FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Huang, W Toma, J Stawiski, E Fransen, S Wrin, T Parkin, N Whitcomb, JM Coakley, E Hecht, FM Deeks, SG Gandhi, RT Eshleman, SH Petropoulos, CJ AF Huang, Wei Toma, Jonathan Stawiski, Eric Fransen, Signe Wrin, Terri Parkin, Neil Whitcomb, Jeannette M. Coakley, Eoin Hecht, Frederick M. Deeks, Steven G. Gandhi, Rajesh T. Eshleman, Susan H. Petropoulos, Christos J. TI Characterization of Human Immunodeficiency Virus Type 1 Populations Containing CXCR4-Using Variants from Recently Infected Individuals SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TREATMENT EXPERIENCED PATIENTS; SYNCYTIUM-INDUCING PHENOTYPE; HIV-1 INFECTION; DISEASE PROGRESSION; CORECEPTOR TROPISM; MULTIDRUG-RESISTANT; CXCR4 TROPISM; TRANSMISSION; AIDS; CCR5 AB We screened 150 individuals from two recent seroconverter cohorts and found that six (4%) had CXCR4-using viruses. Clonal analysis of these six individuals, along with a seventh individual identified during clinical care as a recent seroconverter, revealed the presence of both X4- and dual-tropic variants in these recently infected adults. The ability of individual CXCR4-using variants to infect cells expressing CD4/CXCR4 or CD4/CCR5 varied dramatically. These data demonstrate that virus populations in some newly infected individuals can consist of either heterogeneous populations containing both CXCR4-using and CCR5-tropic viruses, or homogeneous populations containing only CXCR4-using viruses. The presence of CXCR4-using viruses at early stages of infection suggests that testing for viral tropism before using CCR5 antagonists may be important even in persons with known recent infection. The presence of CXCR4-using viruses in a subset of newly infected individuals could impact the efficacies of vaccine and microbicide strategies that target CCR5-tropic viruses. C1 [Huang, Wei; Toma, Jonathan; Stawiski, Eric; Fransen, Signe; Wrin, Terri; Parkin, Neil; Whitcomb, Jeannette M.; Coakley, Eoin; Petropoulos, Christos J.] Monogram Biosci, San Francisco, CA 94080 USA. [Hecht, Frederick M.; Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hecht, Frederick M.; Deeks, Steven G.] San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Huang, W (reprint author), Monogram Biosci, 345 Oyster Point Blvd, San Francisco, CA 94080 USA. EM whuang@monogrambio.com FU National Institutes of Health (NIH)-U.S.; National Institute of Allergy and Infectious Diseases (NIAID); Small Business Innovation Research (SBIR) [R44-AI048990]; NIH-NIAID [P01 A1071713]; Department of Health and Human Services (DHHS) [N01-AI-35173, N01-AI-45200, N0I-AI-35173-417]; HIV Prevention Trials Network (HPTN); National Institutes of Child Health and Human Development (NICH/HD); National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Office of AIDS Research, NIH, DHHS [U01-AI-46745, U01-AI-48054, U01-AI-068613] FX This study was supported in part by (1) National Institutes of Health (NIH)-U.S. National Institute of Allergy and Infectious Diseases (NIAID) Small Business Innovation Research (SBIR) Grant R44-AI048990, (2) NIH-NIAID Program Grant P01 A1071713, (3) the HIV Network for Prevention Trials (HIVNET) sponsored by the Department of Health and Human Services (DHHS) through contract N01-AI-35173 with Family Health International, contract N01-AI-45200 with the Fred Hutchinson Cancer Research Center, and contract N0I-AI-35173-417 with Johns Hopkins University, and (4) the HIV Prevention Trials Network (HPTN), sponsored by the NIAID, National Institutes of Child Health and Human Development (NICH/HD), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), and Office of AIDS Research, NIH, DHHS (U01-AI-46745, U01-AI-48054, and U01-AI-068613). NR 38 TC 24 Z9 25 U1 0 U2 2 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 AUG PY 2009 VL 25 IS 8 BP 795 EP 802 DI 10.1089/aid.2008.0252 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 483BR UT WOS:000268937300008 PM 19678765 ER PT J AU Schneeweiss, S Korzenik, J Solomon, DH Canning, C Lee, J Bressler, B AF Schneeweiss, S. Korzenik, J. Solomon, D. H. Canning, C. Lee, J. Bressler, B. TI Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CROHNS-DISEASE; CLOSTRIDIUM-DIFFICILE; RHEUMATOID-ARTHRITIS; NECROSIS-FACTOR; PERFORMANCE; SCORES; THERAPEUTICS; CONFOUNDERS; ADJUSTMENT; STRATEGIES AB Background There remain concerns about the safety of infliximab therapy in patients with inflammatory bowel disease (IBD). Aim To assess the association between the initiation of infliximab and other immunomodulating drugs and the risk of serious bacterial infection in the treatment of IBD. Methods We assembled a cohort study of patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC). All patients initiating an immunomodulating drug between January 2001 and April 2006 were identified in British Columbia from linked health care utilization databases. Exposure of interest was initiation of infliximab or corticosteroids compared with initiation of other immunosuppressive agents, including azathioprine, mercaptopurine (MP) and methotrexate (MTX). Outcome of interest was serious bacterial infections requiring hospitalization, including Clostridium difficile. Results Among 10 662 IBD patients, the incidence rate of bacteriaemia ranged from 3.8 per 1000 person-years (95% confidence interval 2.1-6.2) for other immunosuppressive agents to 7.4 (3.3-19.3) for infliximab with slightly higher rate for serious bacterial infections resulting in an adjusted relative risk 1.4 (0.47-4.24). Clostridium difficile infections occurred in 0/1000 (0-5.4) among 521 infliximab initiations and 14/1000 (10.6-18.2) for corticosteroids. Corticosteroid initiation tripled the risk of C. difficile infections (RR = 3.4; 1.9-6.1) compared with other immunosuppressant agents. This corticosteroid effect was neither dose-dependent nor duration-dependent. Bacteriaemia and other serious bacterial infections were not increased by corticosteroids or infliximab (5 events). Conclusions In a population-based cohort of patients with IBD, we found no meaningful association between infliximab and serious bacterial infections, although some subgroups had few events. Corticosteroid initiation increased the risk for C. difficile infections in these patients. C1 [Schneeweiss, S.; Solomon, D. H.; Canning, C.; Lee, J.] Harvard Univ, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Korzenik, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crohns & Colitis Ctr, Boston, MA USA. [Solomon, D. H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Bressler, B.] Univ British Columbia, St Pauls Hosp, Div Gastroenterol, Vancouver, BC V5Z 1M9, Canada. RP Schneeweiss, S (reprint author), Harvard Univ, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Dept Med,Brigham & Womens Hosp, 1620 Tremont St,Suite 3030, Boston, MA 02115 USA. EM schneeweiss@post.harvard.edu RI Schneeweiss, Sebastian/C-2125-2013 FU Pfizer; Procter and Gamble; Amgen; Abbott; Division of Pharmacoepidemiology, Brigham and Women's Hospital; Agency for Healthcare Research and Quality FX Dr Schneeweiss has received an investigator-initiated research grant from Pfizer on the safety of selective cox-2 inhibitors. Dr Korzenik has been a consultant for Procter and Gamble, Shire Pharmaceuticals, Eurand, Cytokine Pharma, Zymogenetics and receives research support from Procter and Gamble. Dr. Solomon receives research support from Amgen and Abbott. Dr Bressler has served as a speaker, a consultant and an advisory board member for Abbott, UCB and Schering-Plough. Declaration of funding interests: This study was funded by the Division of Pharmacoepidemiology, Brigham and Women's Hospital. Dr Schneeweiss is Principal Investigator of the Brigham and Women's Hospital DEcIDE Research Center funded by the Agency for Healthcare Research and Quality. NR 26 TC 90 Z9 97 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD AUG 1 PY 2009 VL 30 IS 3 BP 253 EP 264 DI 10.1111/j.1365-2036.2009.04037.x PG 12 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 469DB UT WOS:000267874600007 PM 19438424 ER PT J AU Beste, LA Straits-Troster, K Zickmund, S Larson, M Chapko, M Dominitz, JA AF Beste, L. A. Straits-Troster, K. Zickmund, S. Larson, M. Chapko, M. Dominitz, J. A. TI Specialty care and education associated with greater disease-specific knowledge but not satisfaction with care for chronic hepatitis C SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INJECTION-DRUG USERS; QUALITY-OF-LIFE; VIRUS-INFECTION; UNITED-STATES; MANAGEMENT; VETERANS; IMPACT; IDENTIFICATION; PREVALENCE; PHYSICIANS AB Background Little is known about differences among hepatitis C virus (HCV) patients managed by generalists vs. specialists with respect to patient-centred outcomes, such as disease-specific knowledge, health-related quality of life (HRQoL) and satisfaction with care. Aim To examine selected patient-centred outcomes of HCV-related care provided in primary care, specialty care or both. Methods A total of 629 chronic HCV patients completed a survey including an HCV knowledge assessment and validated instruments for satisfaction and HRQoL. Multivariable linear regression was used to compare outcomes between groups. Results Adjusted total HCV knowledge score was lower among patients who did not attend specialty care (P < 0.01). Primary care and specialty patients did not differ in adjusted general HRQoL or satisfaction. Sixty percent of specialty patients underwent formal HCV education, which was associated with 5% higher knowledge score (P = 0.01). General HRQoL and patient satisfaction did not differ between primary care and specialty groups. Disease-specific knowledge and care satisfaction were independent of mental illness, substance abuse, socio-economic variables, history of antiviral treatment, formal HCV education and duration of time between last visit and survey completion. Conclusions Primary care patients with chronic HCV have lower adjusted disease-specific knowledge than specialty patients, but no difference in general HRQoL or patient satisfaction. C1 [Beste, L. A.; Chapko, M.; Dominitz, J. A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA. [Beste, L. A.; Chapko, M.] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. [Straits-Troster, K.] VA Midatlantic Reg Mental Illness Res Educ & Clin, Durham, NC USA. [Zickmund, S.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Larson, M.; Chapko, M.; Dominitz, J. A.] VA Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, Seattle, WA 98101 USA. RP Beste, LA (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Lauren.beste@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU VA Puget Sound Health Care System, Seattle, Washington; Department of Veterans Affairs Health Services Research and Development research [IAC-06-021]; Schering-Plough FX This study was funded in part by the VA Puget Sound Health Care System, Seattle, Washington. The primary author was supported by Department of Veterans Affairs Health Services Research and Development research and training funds (IAC-06-021). 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. This study protocol was supported by an unrestricted grant from Schering-Plough. This sponsor had no role in the study design, analysis or interpretation of study results. The authors thank the staff and patients of the Northwest Hepatitis C Resource Center, VA Puget Sound for their contributions to this project. NR 28 TC 10 Z9 10 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD AUG 1 PY 2009 VL 30 IS 3 BP 275 EP 282 DI 10.1111/j.1365-2036.2009.04036.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 469DB UT WOS:000267874600009 PM 19438425 ER PT J AU Rosendorff, C Dubiel, R Xu, JB Chavanu, KJ AF Rosendorff, Clive Dubiel, Robert Xu, Jianbo Chavanu, Kathleen J. TI Comparison of Olmesartan Medoxomil Versus Amlodipine Besylate on Regression of Ventricular and Vascular Hypertrophy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HYPERTENSIVE PATIENTS; ANGIOTENSIN-II; RECEPTOR ANTAGONIST; BLACK PATIENTS; MASS; REDUCTION; LIFE AB Reversal of left ventricular (LV) hypertrophy is an important goal of anti hypertensive therapy. This phase 3b study compared the ability of the angiotensin receptor blocker olmesartan medoxomil with the calcium channel blocker amlodipine besylate to induce regression of LV hypertrophy and vascular hypertrophy after achieving blood pressure (BP) goal. After a washout phase, 102 patients with hypertension and LV hypertrophy were randomized to olmesartan medoxomil 20 mg/day, up titrated to 40 mg/day, or amlodipine 5 mg/day, up titrated to 10 mg/day, for up to 4 weeks until a BP goal of <140/90 mm Hg (<130/85 mm Hg for diabetes) was achieved (hydrochlorothiazide 25 mg/day and terazosin 1 to 5 mg/day 2 times/day could be added if needed). Upon achieving the BP goal or by week 8, and again at weeks 26 and 52, assessments of LV mass and compliance and arterial structure and function were performed by echocardiography, Doppler flow, and arterial ultrasonography, respectively. There was no statistically significant percent change in LV mass at 52 weeks in either treatment group (11.6% with olmesartan medoxomil vs 2.9% with amlodipine) and no statistically significant difference between treatment groups. There were no significant changes in LV compliance or carotid or femoral artery wall-to-lumen ratios in either treatment group at 52 weeks. In conclusion, there did not appear to be a clinically significant BP-independent effect with olmesartan medoxomil or amlodipine on LV mass decrease, diastolic function or vascular structure., and compliance in patients with hypertension and LV hypertrophy. Published by Elsevier Inc. (Am J Cardiol 2009; 104:359-365) C1 [Rosendorff, Clive] Mt Sinai Sch Med, Dept Med, Bronx, NY USA. [Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY USA. [Dubiel, Robert; Xu, Jianbo; Chavanu, Kathleen J.] Daiichi Sankyo Inc, Parsippany, NJ USA. RP Rosendorff, C (reprint author), Mt Sinai Sch Med, Dept Med, Bronx, NY USA. EM clive.rosendorff@med.va.gov FU Daiichi Sankyo, Inc., Parsippany, New Jersey FX This study was supported by Daiichi Sankyo, Inc., Parsippany, New Jersey. NR 12 TC 5 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2009 VL 104 IS 3 BP 359 EP 365 DI 10.1016/j.amjcard.2009.03.042 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 480KI UT WOS:000268733000011 PM 19616668 ER PT J AU Dhoble, A Patel, MB Abdelmoneim, SS Puttarajappa, C Abela, GS Bhatt, DL Thakur, RK AF Dhoble, Abhijeet Patel, Mehul B. Abdelmoneim, Sahar S. Puttarajappa, Chethan Abela, George S. Bhatt, Deepak L. Thakur, Ranjan K. TI Relation of Porphyria to Atrial Fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE INTERMITTENT PORPHYRIA; MANAGEMENT; DIAGNOSIS; RISK AB Porphyrias are a group of inherited disorders affecting enzymes in the heme biosynthesis pathway, leading to overproduction and/or accumulation of porphyrin or its precursors. Porphyrias have been associated with autonomic dysfunction, which in turn can develop atrial fibrillation (AF). The purpose of this study was to characterize the prevalence of AF and atrial flutter (AFI) in patients with porphyrias. A single-center retrospective cohort study was designed using data from chart reviews of patients who were admitted to the hospital from January 2000 to June 2008. Fifty-six distinct cases were found with a discharge diagnosis of porphyria including all its subtypes. From the same database, age- and gender-matched controls were identified using computer-generated random numbers. We selected 1 age- and gender-matched control for each case. Electrocardiograms and echocardiograms were reviewed by 2 independent reviewers. Only patients with available 12-lead electrocardiograms that showed AF/AFl were labeled with that diagnosis. All patients with a diagnosis of porphyria were included in the study irrespective of their age. Seven of 56 patients with porphyria met inclusion criteria, yielding a prevalence of AF/AFl of 12.5%. This association was significant (p = 0.028, relative risk 7.45, 95% confidence interval 1.01 to 66.14) compared with the age- and gender-matched control group (2%). In conclusion, our observations suggest that porphyria may be significantly associated with AF/AFl. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:373-376) C1 [Dhoble, Abhijeet; Patel, Mehul B.; Puttarajappa, Chethan; Abela, George S.; Thakur, Ranjan K.] Michigan State Univ, Thorac & Cardiovasc Inst, Lansing, MI USA. [Abdelmoneim, Sahar S.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Abdelmoneim, Sahar S.] Assiut Univ, Assiut, Egypt. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston VA Healthcare Syst, Boston, MA 02115 USA. RP Thakur, RK (reprint author), Michigan State Univ, Thorac & Cardiovasc Inst, Lansing, MI USA. EM thakur@msu.edu OI Puttarajappa, Chethan/0000-0002-4856-9242 FU Graduate Medical Education, Inc., Michigan State University, Lansing, Michigan FX This study was funded by a grant to Dr. Dhoble from Graduate Medical Education, Inc., Michigan State University, Lansing, Michigan. NR 17 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2009 VL 104 IS 3 BP 373 EP 376 DI 10.1016/j.amjcard.2009.03.043 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 480KI UT WOS:000268733000013 PM 19616670 ER PT J AU Clark, JI Eisner, RM Hofmeister, C Norton, J Thomas, S Choudhury, A Petruzzelli, G Lathers, D Young, MRI Lau, A Emami, B AF Clark, Joseph I. Eisner, Robert M. Hofmeister, Craig Norton, John Thomas, Sachdev Choudhury, Abdul Petruzzelli, Guy Lathers, Deanne Young, M. Rita I. Lau, Ann Emami, Bahman TI Phase I Adjuvant Radiation With Docetaxel in High-Risk Head and Neck Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE phase I; radiochemotherapy; docetaxel; high risk; head and neck cancer ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; ACTIVE-DRUG; CHEMOTHERAPY; FLUOROURACIL; CISPLATIN; INFUSION; TRIAL AB Background: This phase I study was designed to determine the maximum tolerated dose (MTD) and preliminary efficacy of docetaxel with concurrent radiotherapy (RT), in high-risk squamous cell carcinoma of the head and neck. Patients and Methods: Eligible patients had resected squamous cell carcinoma of the head and neck, histologically involved lymph nodes, and/or extranodal disease, and/or involved surgical margins and performance status 0 to 1. Treatment included weekly docetaxel with concurrent RT in a dose-finding study; a subsequent small cohort of patients was treated using the MTD of docetaxel. Results: Twenty patients were enrolled. Planned accrual was 25, but the study was closed prematurely because of slow accrual. The MTD was 15 mg/m(2). Dose-limiting toxicity was oral stomatitis. Therapy was well tolerated. Five patients experienced locoregional relapse at a median follow-up of 32 months. Conclusion: Docetaxel with concurrent RT has acceptable toxicity. This approach warrants further investigation in a phase II trial. C1 [Clark, Joseph I.; Eisner, Robert M.; Norton, John; Thomas, Sachdev; Lau, Ann] Loyola Univ, Med Ctr, Dept Med, Div Hematol Oncol,Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. [Clark, Joseph I.; Choudhury, Abdul] Jr Hines VA Hosp, Med Serv, Hines, IL USA. [Hofmeister, Craig] Ohio State Univ, Dept Hematol, Columbus, OH 43210 USA. [Petruzzelli, Guy] Rush Univ, Med Ctr, Dept Otolaryngol, Chicago, IL 60612 USA. [Lathers, Deanne; Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Dept Otolaryngol, Res Serv, Charleston, SC USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Emami, Bahman] Loyola Univ, Med Ctr, Dept Radiat Oncol, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Clark, JI (reprint author), Loyola Univ, Med Ctr, Dept Med, Div Hematol Oncol,Cardinal Bernardin Canc Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. EM jclark@lumc.edu RI Hofmeister, Craig/E-3256-2011 OI Hofmeister, Craig/0000-0003-4816-1607 FU Aventis FX The authors thank Aventis for support with an unrestricted educational grant for this trial. NR 18 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 2009 VL 32 IS 4 BP 396 EP 400 DI 10.1097/COC.0b013e31818da9c7 PG 5 WC Oncology SC Oncology GA 480UF UT WOS:000268761600012 PM 19415031 ER PT J AU Kramer, N Reinelt, C Garcia-Godoy, F Taschner, M Petschelt, A Frankenberger, R AF Kraemer, Norbert Reinelt, Christian Garcia-Godoy, Franklin Taschner, Michael Petschelt, Anselm Frankenberger, Roland TI Nanohybrid composite vs. fine hybrid composite in extended Class II cavities: Clinical and microscopic results after 2 years SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID RESIN COMPOSITE; SELF-ETCH; INDIRECT RESTORATIONS; MARGINAL QUALITY; POSTERIOR TEETH; CERAMIC INLAYS; BOND STRENGTH; ADHESIVES; DENTIN; PERFORMANCE AB Purpose: To evaluate the clinical behavior of two different resin composites in Class II cavities over a period of 2 years in a controlled prospective split-mouth study. Methods: 30 subjects received 68 direct resin composite restorations (Grandio bonded with Solobond M: n= 36, Tetric Ceram bonded with Syntac: n= 32) by one dentist in a private practice. All restorations were replacement restorations, 24 cavities (35%) revealed no enamel at the bottom of the proximal box, in 33 cavities (48%) the proximal enamel width was < 0.5 mm. The restorations were examined according to modified USPHS criteria at baseline, and after 0.5, 1, and 2 years. At each recall, impressions were taken to prepare replicas. Replicas of 44 selected subjects were assessed for marginal quality under a stereo light microscope (SLM) at x 130, and 22 replicas were assessed under a SEM at x200. Results: Both recall rate and survival rate were 100% after 2 years of clinical service. No significant difference was found between the restorative materials (P> 0.05; Mann-Whitney U-test). A significant deterioration was found over time for marginal integrity, tooth integrity, restoration integrity and proximal contact (P< 0.05; Friedman test). SLM and SEM analysis of restoration margins only revealed differences in the amount of detectable perfect margins, in favor of Tetric Ceram (P< 0.05). Both materials performed satisfactorily over the 2-year observation period. (Am J Dent 2009;22:228-234). C1 [Taschner, Michael; Petschelt, Anselm; Frankenberger, Roland] Univ Erlangen Nurnberg, Univ Med Ctr Erlangen, Dent Clin 1, D-91054 Erlangen, Germany. [Kraemer, Norbert] Tech Univ Dresden, Dept Pediat Dent, Univ Med Ctr Carl Gustav Carus, Dresden, Germany. [Garcia-Godoy, Franklin] Nova SE Univ, Coll Dent Med, Ft Lauderdale, FL 33314 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. RP Frankenberger, R (reprint author), Univ Erlangen Nurnberg, Univ Med Ctr Erlangen, Dent Clin Operat Dent & Periodontol 1, Glueckstr 11, D-91054 Erlangen, Germany. EM frankbg@dent.uni-erlangen.de NR 38 TC 3 Z9 3 U1 0 U2 1 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD AUG PY 2009 VL 22 IS 4 BP 228 EP 234 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 501RT UT WOS:000270400100008 PM 19824560 ER PT J AU Khoury, MJ Bertram, L Boffetta, P Butterworth, AS Chanock, SJ Dolan, SM Fortier, I Garcia-Closas, M Gwinn, M Higgins, JPT Janssens, ACJW Ostell, J Owen, RP Pagon, RA Rebbeck, TR Rothman, N Bernstein, JL Burton, PR Campbell, H Chockalingam, A Furberg, H Little, J O'Brien, TR Seminara, D Vineis, P Winn, DM Yu, W Ioannidis, JPA AF Khoury, Muin J. Bertram, Lars Boffetta, Paolo Butterworth, Adam S. Chanock, Stephen J. Dolan, Siobhan M. Fortier, Isabel Garcia-Closas, Montserrat Gwinn, Marta Higgins, Julian P. T. Janssens, A. Cecile J. W. Ostell, James Owen, Ryan P. Pagon, Roberta A. Rebbeck, Timothy R. Rothman, Nathaniel Bernstein, Jonine L. Burton, Paul R. Campbell, Harry Chockalingam, Anand Furberg, Helena Little, Julian O'Brien, Thomas R. Seminara, Daniela Vineis, Paolo Winn, Deborah M. Yu, Wei Ioannidis, John P. A. TI Genome-Wide Association Studies, Field Synopses, and the Development of the Knowledge Base on Genetic Variation and Human Diseases SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE association; database; encyclopedias; epidemiologic methods; genome; human; genome-wide association study; genomics; meta-analysis ID SYSTEMATIC METAANALYSES; BLADDER-CANCER; EPIDEMIOLOGY; VARIANTS; COMMON; SUSCEPTIBILITY; REPLICATION; DATABASE; FALSE; LOCI AB Genome-wide association studies (GWAS) have led to a rapid increase in available data on common genetic variants and phenotypes and numerous discoveries of new loci associated with susceptibility to common complex diseases. Integrating the evidence from GWAS and candidate gene studies depends on concerted efforts in data production, online publication, database development, and continuously updated data synthesis. Here the authors summarize current experience and challenges on these fronts, which were discussed at a 2008 multidisciplinary workshop sponsored by the Human Genome Epidemiology Network. Comprehensive field synopses that integrate many reported gene-disease associations have been systematically developed for several fields, including Alzheimer's disease, schizophrenia, bladder cancer, coronary heart disease, preterm birth, and DNA repair genes in various cancers. The authors summarize insights from these field synopses and discuss remaining unresolved issues-especially in the light of evidence from GWAS, for which they summarize empirical P-value and effect-size data on 223 discovered associations for binary outcomes (142 with P < 10(-7)). They also present a vision of collaboration that builds reliable cumulative evidence for genetic associations with common complex diseases and a transparent, distributed, authoritative knowledge base on genetic variation and human health. As a next step in the evolution of Human Genome Epidemiology reviews, the authors invite investigators to submit field synopses for possible publication in the American Journal of Epidemiology. C1 [Khoury, Muin J.; Gwinn, Marta; Yu, Wei] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Bertram, Lars] Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. [Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Butterworth, Adam S.; Higgins, Julian P. T.] Univ Cambridge, Mol Epidemiol Unit, Cambridge, England. [Chanock, Stephen J.; Garcia-Closas, Montserrat; Rothman, Nathaniel; O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Dolan, Siobhan M.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Fortier, Isabel] McGill Univ, Quebec Innovat Ctr, Montreal, PQ, Canada. [Higgins, Julian P. T.] Univ Cambridge, MRC, Biostat Unit, Cambridge, England. [Janssens, A. Cecile J. W.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Ostell, James] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Owen, Ryan P.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Pagon, Roberta A.] Univ Washington, Sch Med, Seattle, WA USA. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Bernstein, Jonine L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Burton, Paul R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Chockalingam, Anand] Univ Calif Berkeley, Div Epidemiol, Berkeley, CA 94720 USA. [Furberg, Helena] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Little, Julian] Univ Ottawa, Dept Epidemiol & Community Hlth, Ottawa, ON, Canada. [Seminara, Daniela; Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol, London, England. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Ioannidis, John P. A.] Tufts Med Ctr, Ctr Genet Epidemiol & Modeling, Boston, MA USA. RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway NE, Atlanta, GA 30341 USA. EM mukl@cdc.gov RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Garcia-Closas, Montserrat /F-3871-2015; Burton, Paul/H-7527-2016; Bertram, Lars/K-3889-2015; OI Higgins, Julian/0000-0002-8323-2514; Garcia-Closas, Montserrat /0000-0003-1033-2650; Bertram, Lars/0000-0002-0108-124X; Janssens, A Cecile/0000-0002-6153-4976 FU British Heart Foundation [RG/08/014/24067]; Medical Research Council [MC_U105285807]; NCI NIH HHS [K07 CA118412, K07 CA118412-04]; NCRR NIH HHS [UL1 RR025752] NR 53 TC 81 Z9 82 U1 0 U2 8 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 AUG 1 PY 2009 VL 170 IS 3 BP 269 EP 279 DI 10.1093/aje/kwp119 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 475BH UT WOS:000268330300001 PM 19498075 ER PT J AU Karlamangla, AS Miller-Martinez, D Aneshensel, CS Seeman, TE Wight, RG Chodosh, J AF Karlamangla, Arun S. Miller-Martinez, Dana Aneshensel, Carol S. Seeman, Teresa E. Wight, Richard G. Chodosh, Joshua TI Trajectories of Cognitive Function in Late Life in the United States: Demographic and Socioeconomic Predictors SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; cognition; health status disparities; longitudinal studies; social class ID ALZHEIMERS-DISEASE; OLDER-ADULTS; INDIVIDUAL-DIFFERENCES; MARITAL-STATUS; INTELLECTUAL-DEVELOPMENT; METHODOLOGICAL ISSUES; LONGITUDINAL FINDINGS; BRAIN RESERVE; FOLLOW-UP; AGE AB This study used mixed-effects modeling of data from a national sample of 6,476 US adults born before 1924, who were tested 5 times between 1993 and 2002 on word recall, serial 7's, and other mental status items to determine demographic and socioeconomic predictors of trajectories of cognitive function in older Americans. Mean decline with aging in total cognition score (range, 0-35; standard deviation, 6.00) was 4.1 (0.68 standard deviations) per decade (95% confidence interval: 3.8, 4.4) and in recall score (range, 0-20; standard deviation, 3.84) was 2.3 (0.60 standard deviations) per decade (95% confidence interval: 2.1, 2.5). Older cohorts (compared with younger cohorts), women (compared with men), widows/widowers, and those never married (both compared with married individuals) declined faster, and non-Hispanic blacks (compared with non-Hispanic whites) and those in the bottom income quintile (compared with the top quintile) declined slower. Race and income differences in rates of decline were not sufficient to offset larger differences in baseline cognition scores. Educational level was not associated with rate of decline in cognition scores. The authors concluded that ethnic and socioeconomic disparities in cognitive function in older Americans arise primarily from differences in peak cognitive performance achieved earlier in the life course and less from declines in later life. C1 [Karlamangla, Arun S.; Miller-Martinez, Dana; Seeman, Teresa E.; Chodosh, Joshua] Univ Calif Los Angeles, Div Geriatr, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Aneshensel, Carol S.; Wight, Richard G.] Univ Calif Los Angeles, Dept Community Hlth Sci, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Chodosh, Joshua] VA Greater Los Angeles Hlth Syst, Hlth Serv Res, Los Angeles, CA USA. RP Karlamangla, AS (reprint author), Univ Calif Los Angeles, Div Geriatr, David Geffen Sch Med, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM akarlamangla@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU NIA NIH HHS [R01 AG022537] NR 75 TC 73 Z9 73 U1 5 U2 34 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 AUG 1 PY 2009 VL 170 IS 3 BP 331 EP 342 DI 10.1093/aje/kwp154 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 475BH UT WOS:000268330300009 PM 19605514 ER PT J AU Spiegel, B Harris, L Lucak, S Mayer, E Naliboff, B Bolus, R Esrailian, E Chey, WD Lembo, A Karsan, H Tillisch, K Dulai, G Talley, J Chang, L AF Spiegel, Brennan Harris, Lucinda Lucak, Susan Mayer, Emeran Naliboff, Bruce Bolus, Roger Esrailian, Eric Chey, William D. Lembo, Anthony Karsan, Hetal Tillisch, Kirsten Dulai, Gareth Talley, Jennifer Chang, Lin TI Developing Valid and Reliable Health Utilities in Irritable Bowel Syndrome: Results From the IBS PROOF Cohort SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID QUALITY-OF-LIFE; WORK PRODUCTIVITY; ILLNESS SEVERITY; IMPACT; INDEX AB OBJECTIVES: A "utility" is a measure of health-related quality of life (HRQOL) that ranges between 0 (death) and 1 (perfect health). Disease-targeted utilities are mandatory to conduct cost-utility analyses. Given the economic and healthcare burden of irritable bowel syndrome (IBS), cost-utility analyses will play an important role in guiding health economic decision-making. To inform future cost-utility analyses in IBS, we measured and validated the IBS utilities. METHODS: We analyzed data from Rome III IBS patients in the Patient Reported Observed Outcomes and Function (PROOF) Cohort-a longitudinal multi-center IBS registry. At entry, the patients completed a multi-attribute utility instrument (EuroQOL), bowel symptom items, IBS severity measurements (IBS Severity Scale (IBSSS), Functional Bowel Disease Severity Index (FBDSI)), HRQOL indexes (IBS quality-of-life instrument (IBS-QOL), Center for disease control-4 (CDC-4)), and the Worker Productivity Activity Index for IBS (WPAI). We repeated assessments at 3 months. RESULTS: There were 257 patients (79% women; age = 43 +/- 15 years) at baseline and 85 at 3 months. The mean utilities in patients with severe vs. non-severe IBS were 0.70 and 0.80, respectively (P<0.001). There were no differences in utilities among IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and mixed IBS (IBS-M) subgroups. EuroQOL utilities correlated with FBDSI (r=0.31; P<0.01), IBSSS (r=0.36; P<0.01), IBS-QOL (r=0.36; P<0.01), CDC-4 (r=0.44; P<0.01), WPAI presenteeism (r=0.16; P<0.01), abdominal pain (r=0.43; P<0.01), and distension (r=0.18; P=0.01). The utilities in patients reporting "considerable relief" of symptoms at 3 months vs. those without considerable relief were 0.78 and 0.73, respectively (P=0.02). CONCLUSIONS: EuroQOL utilities are valid and reliable in IBS. The utility of severe IBS (0.7) is similar to Class III congestive heart failure and rheumatoid arthritis. These validated utilities can be employed in future IBS cost-utility analyses. C1 [Spiegel, Brennan; Talley, Jennifer] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Spiegel, Brennan; Mayer, Emeran; Naliboff, Bruce; Bolus, Roger; Esrailian, Eric; Tillisch, Kirsten; Chang, Lin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Gastroenterol, Los Angeles, CA 90073 USA. [Spiegel, Brennan; Mayer, Emeran; Naliboff, Bruce; Bolus, Roger; Tillisch, Kirsten; Chang, Lin] Univ Calif Los Angeles, Ctr Neurobiol Stress, Los Angeles, CA USA. [Spiegel, Brennan] Columbia Univ, Dept Gastroenterol, New York, NY USA. [Spiegel, Brennan; Bolus, Roger; Esrailian, Eric; Talley, Jennifer; Chang, Lin] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA 90073 USA. [Harris, Lucinda; Lucak, Susan] Mayo Clin, Scottsdale, AZ USA. [Chey, William D.] Univ Michigan, Dept Gastroenterol, Ann Arbor, MI 48109 USA. [Lembo, Anthony] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Karsan, Hetal] Emory Univ, Dept Gastroenterol, Atlanta, GA 30322 USA. [Karsan, Hetal] Atlanta Gastroenterol Associates, Atlanta, GA USA. [Dulai, Gareth] Kaiser So Calif, Los Angeles, CA USA. RP Spiegel, B (reprint author), Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 11,Room 21E, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Veteran's Affairs Health Services Research and Development Career Development Award [RCD 03-179-2]; CURE Digestive Disease Research Center [2P30 DK 041301-17]; NIH [P50 DK64539, 1 R24 AT002681-NCCAM] FX Spiegel is supported by a Veteran's Affairs Health Services Research and Development Career Development Award (RCD 03-179-2), and the CURE Digestive Disease Research Center (NIH 2P30 DK 041301-17). Chang, Naliboff, and Mayer are supported by NIH grant no. P50 DK64539, and Spiegel, Mayer, and Naliboff are supported by NIH Center Grant 1 R24 AT002681-NCCAM from the UCLA Center for Neurobiology of Stress. NR 29 TC 25 Z9 26 U1 1 U2 7 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 AUG PY 2009 VL 104 IS 8 BP 1984 EP 1991 DI 10.1038/ajg.2009.232 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 483KW UT WOS:000268965300014 PM 19491835 ER PT J AU Ogino, S Nosho, K Baba, Y Kure, S Shima, K Irahara, N Toyoda, S Chen, L Kirkner, GJ Wolpin, BM Chan, AT Giovannucci, EL Fuchs, CS AF Ogino, Shuji Nosho, Katsuhiko Baba, Yoshifumi Kure, Shoko Shima, Kaori Irahara, Natsumi Toyoda, Saori Chen, Li Kirkner, Gregory J. Wolpin, Brian M. Chan, Andrew T. Giovannucci, Edward L. Fuchs, Charles S. TI A Cohort Study of STMN1 Expression in Colorectal Cancer: Body Mass Index and Prognosis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; HUMAN COLON-CARCINOMA; MICROSATELLITE INSTABILITY; LINE-1 HYPOMETHYLATION; DOWN-REGULATION; POOR-PROGNOSIS; BREAST-CANCER; CELL-CYCLE; STATHMIN; MUTATION AB OBJECTIVES: STMN1 (stathmin or oncoprotein-18) destabilizes microtubules and reorganizes cytoskeleton, and functions in cell cycle progression and cell migration. STMN1 activity is influenced by p53, p27, and the PI3K/AKT pathway. However, its prognostic significance in colon cancer is uncertain. METHODS: Utilizing 546 colorectal cancers (stage I-IV) from two independent prospective cohort studies (the Nurses' Health Study and Health Professionals Follow-up Study), STMN1 expression was detected in 297 (54%) tumors by immunohistochemistry. Cox proportional hazard models computed hazard ratios (HRs) of mortality, adjusted for clinical and tumoral features, including microsatellite instability (MSI), CpG island methylation phenotype (CIMP), LINE-1 hypomethylation, KRAS, BRAF, PIK3CA, p53, p21, p27, cyclin D1, beta-catenin, fatty acid synthase, FASN, and COX-2. RESULTS: Five-year colorectal cancer-specific survival was 78% in STMN1-positive patients and 76% in STMN1-negative patients (log-rank P=0.30). STMN1-positivity was not significantly associated with cancer-specific survival in univariate analysis with HR of 0.82 (95% confidence interval (CI), 0.59-1.14), which became significant in multivariate analysis (adjusted HR = 0.60; 95% CI, 0.41-0.87; P=0.0078). Notably, the prognostic effect of obesity (body mass index, BMI >= 30 kg/m(2)) significantly differed by STMN1 (P(interaction)=0.005). Obesity was associated with high cancer-specifi c mortality among STMN1-positive patients (adjusted HR = 2.36; 95% CI, 1.18-4.69), whereas obesity was not associated with high mortality among STMN1-negative patients (adjusted HR=0.51; 95% CI, 0.24-1.07). CONCLUSIONS: STMN1 overexpression in colorectal cancer is independently associated with improved survival. The adverse prognostic effect of obesity was limited to patients with STMN1-positive tumors. Our findings suggest the presence of a tumor (STMN1)-host (BMI) interaction that potentially determines clinical outcome. C1 [Ogino, Shuji] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Nosho, Katsuhiko; Baba, Yoshifumi; Kure, Shoko; Shima, Kaori; Irahara, Natsumi; Toyoda, Saori; Kirkner, Gregory J.; Wolpin, Brian M.; Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Ogino, Shuji; Chen, Li] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kirkner, Gregory J.; Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA055075-070001, P01 CA087969, P01 CA87969, P50 CA127003, K07 CA122826-02, P50 CA127003-01, R01 CA137178, P01 CA055075, K07 CA122826, P01 CA087969-010003, P01 CA55075] NR 54 TC 28 Z9 29 U1 1 U2 9 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 AUG PY 2009 VL 104 IS 8 BP 2047 EP 2056 DI 10.1038/ajg.2009.281 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 483KW UT WOS:000268965300022 PM 19513025 ER PT J AU Jutabha, R Jensen, DM Chavalitdhamrong, D AF Jutabha, Rome Jensen, Dennis M. Chavalitdhamrong, Disaya TI Randomized Prospective Study of Endoscopic Rubber Band Ligation Compared With Bipolar Coagulation for Chronically Bleeding Internal Hemorrhoids SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID INFRARED COAGULATION; SCLEROSANT INJECTION; OUTPATIENT TREATMENT; SINGLE SESSION; SCLEROTHERAPY; ELECTROCOAGULATION; COMPLICATIONS; DIATHERMY; IMPOTENCE; THERAPY AB OBJECTIVES: Our purpose was to compare the efficacy, complications, success rate, recurrence rate at 1 year, and crossovers of rubber band ligation (RBL) with those of bipolar electrocoagulation (BPEC) treatment for chronically bleeding internal hemorrhoids. METHODS: A total of 45 patients of mean age 51.5 years, who had rectal bleeding from grade II or III hemorrhoids and in whom intensive medical therapy failed, were randomized in a prospective study comparing RBL with BPEC. Treatment failure was predefined as continued bleeding, occurrence of a major complication, or failure to reduce the size of all internal hemorrhoidal segments to grade 1 in <= 3 treatments. Patients were followed up for 1 year. RESULTS: With similar patients, rectal bleeding and other symptoms were controlled with significantly fewer treatments of RBL than of BPEC (2.3 +/- 0.2 vs. 3.8 +/- 0.4, P<0.05), and RBL had a significantly higher success rate (92% vs. 62%, P<0.05). RBL had more cases of severe pain during treatment (8% vs. 0%, P>0.05), but significantly fewer failures and crossovers (8% vs. 38%). Symptomatic recurrence at 1 year was 10% RBL and 15% BPEC. CONCLUSIONS: For patients with chronically bleeding grade II or III internal hemorrhoids that are unresponsive to medical therapy, safety and complication rates of banding and BPEC were similar. The success rate was significantly higher with RBL than with BPEC. Symptom recurrence rates at 1 year were similar. C1 [Jensen, Dennis M.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, David Geffen Sch Med, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, David Geffen Sch Med, Greater Los Angeles VA Healthcare Ctr, Blg 115,RM 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM djensen@mednet.ucla.edu FU American Digestive Health Foundation Endoscopy Research Award; NIH [GCRC M01-RR00865, IK24DK02650]; [NIH DK41301] FX This research study was funded in part by NIH DK41301 ( CURE DDRC Human Studies Core), the American Digestive Health Foundation Endoscopy Research Award (Dr Jutabha), NIH-GCRC M01-RR00865, and NIH-IK24DK02650 ( Dr Jensen). NR 32 TC 10 Z9 10 U1 1 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 AUG PY 2009 VL 104 IS 8 BP 2057 EP 2064 DI 10.1038/ajg.2009.292 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 483KW UT WOS:000268965300023 PM 19513028 ER PT J AU Hou, JK El-Serag, H Thirumurthi, S AF Hou, Jason K. El-Serag, Hashem Thirumurthi, Selvi TI Distribution and Manifestations of Inflammatory Bowel Disease in Asians, Hispanics, and African Americans: A Systematic Review SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID CROHNS-DISEASE; ULCERATIVE-COLITIS; CLINICAL CHARACTERISTICS; MONTREAL CLASSIFICATION; FAMILIAL OCCURRENCE; CHINESE POPULATION; RACIAL-DIFFERENCES; EPIDEMIOLOGY; PREVALENCE; RACE AB OBJECTIVES: Although inflammatory bowel disease (IBD) has been reported worldwide, most studies have focused on Caucasian populations. Our aim was to summarize the existing epidemiological literature, identify temporal trends, and highlight areas for future research. METHODS: We carried out a systematic review following standard guidelines to evaluate the incidence, prevalence, temporal trends, disease characteristics, and extra-intestinal manifestations (EIMs) of IBD in African American, Hispanic, and Asian adult patients. Two investigators independently identified eligible studies through 2008 using structured keyword searches in PubMed, applied several inclusion and exclusion criteria, and abstracted the data. RESULTS: Twenty-eight publications were included, encompassing 1,272 Hispanic, 547 African American, and 35,844 Asian patients with IBD. Greater proportions of Hispanic (36.7-84.3%) and Asian (30.6-74.7%) patients were diagnosed with ulcerative colitis (UC) than with Crohn's disease (CD) compared with African Americans (27.6-40.6%). The prevalence rates of IBD in Hispanics in Puerto Rico varied between 5 (rural) and 62 (urban) per 100,000. Crude prevalence rates in Asia varied between 6 (Singapore) and 136 (South Asians in UK) per 100,000 for UC, and between 3 (Singapore) and 33 (South Asians in UK) per 100,000 for CD. Three studies reported a rising annual incidence rate among Hispanics (from 2.6 to 7.5 per 100,000) and Asians (from 0.22 to 3.62 per 100,000). Fistulizing CD was reported in nearly one-third of Hispanic patients, up to one-quarter of African-American patients, and up to one-half of Asian patients. Ileocolonic disease was the most common site of CD among the three racial/ethnic groups, with skin and joint manifestations noted as the most common EIMs. CONCLUSIONS: Prevalence and incidence rates in Hispanics and Asians have recently increased. There are many similarities and differences in disease location and behavior among racial/ethnic groups. There is a paucity of literature on all aspects of the disease in Hispanics, in the incidence and prevalence of IBD in African Americans, and in Asians with IBD outside Asia. C1 [Thirumurthi, Selvi] Baylor Coll Med, Gastroenterol Sect, Houston, TX 77030 USA. [Hou, Jason K.; El-Serag, Hashem; Thirumurthi, Selvi] Michael E DeBakey Vet Adm Med Ctr, Gastroenterol Sect, Houston, TX USA. [Hou, Jason K.; El-Serag, Hashem; Thirumurthi, Selvi] Michael E DeBakey Vet Adm Med Ctr, Sect Hlth Serv Res, Houston, TX USA. RP Thirumurthi, S (reprint author), Baylor Coll Med, Gastroenterol Sect, 1709 Dryden Rd,Suite 8-35, Houston, TX 77030 USA. EM jkhou@bcm.tmc.edu NR 43 TC 82 Z9 83 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2009 VL 104 IS 8 BP 2100 EP 2109 DI 10.1038/ajg.2009.190 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 483KW UT WOS:000268965300029 PM 19471256 ER PT J AU Zhu, X Rivera, A Golub, MS Peng, JB Sha, Q Wu, X Song, XL Kumarathasan, P Ho, M Redman, CM Lee, S AF Zhu, Xiang Rivera, Alicia Golub, Mari S. Peng, Jianbin Sha, Quan Wu, Xu Song, Xiaoling Kumarathasan, Prem Ho, Mac Redman, Colvin M. Lee, Soohee TI Changes in red cell ion transport, reduced intratumoral neovascularization, and some mild motor function abnormalities accompany targeted disruption of the Mouse Kell gene (Kel) SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ENDOTHELIN-B RECEPTOR; BLOOD-GROUP PROTEIN; NITRIC-OXIDE; NERVOUS-SYSTEM; EXPRESSION PROFILES; KNOCKOUT MOUSE; XK; PATHWAYS; PROLIFERATION; ERYTHROCYTES AB Kell (ECE-3), a highly polymorphic blood group glycoprotein, displays more than 30 antigens that produce allo-antibodies and, on red blood cells (RBCs), is complexed through a single disulfide bond with the integral membrane protein, XK. XK is a putative membrane transporter whose absence results in a late onset form of neuromuscular abnormalities known as the McLeod syndrome. Although Kell glycoprotein is known to be an endothelin-3-converting enzyme, the full extent of its physiological function is unknown. To study the functions of Kell glycoprotein, we undertook targeted disruption of the murine Kel gene by homologous recombination. RBCs from Kel(-/-) mice lacked Kell glycoprotein, Kell/XK complex, and endothelin-3-converting enzyme activity and had reduced levels of XK. XK mRNA levels in spleen, brain, and testis were unchanged. In Keg(-/-) mice RBC Gardos channel activity was increased and the normal enhancement by endothelin-3 was blunted. Analysis of the microvessels of tumors produced from LL2 cells indicated that the central portion of tumors from wild-type mice were populated with many mature blood vessels, but that vessels in tumors from Keg(-/-) mice were fewer and smaller. The absence of Kell glycoprotein mildly affected some motor activities identified by foot splay on the drop tests. The targeted disruption of Kel in mouse enabled us to identify phenotypes that would not be easily detected in humans lacking Kell glycoprotein. In this regard, the Kell knockout mouse provides a good animal model for the study of normal and/or pathophysiological functions of Kell glycoprotein. Am. J. Hematol. 84:492-498, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Zhu, Xiang; Peng, Jianbin; Sha, Quan; Wu, Xu; Song, Xiaoling; Redman, Colvin M.; Lee, Soohee] New York Blood Ctr, Dept Pathol, New York, NY 10065 USA. [Rivera, Alicia] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Golub, Mari S.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Kumarathasan, Prem] Dept Hlth & Welf, Ctr Environm Hlth, Ottawa, ON K1A 0L2, Canada. [Ho, Mac] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. RP Lee, S (reprint author), New York Blood Ctr, Dept Pathol, 310 E 67th St, New York, NY 10065 USA. EM solee@nybloodcenter.org FU National Institute of Health, a Specialized Center of Research (SCOR) [HL54459]; NIH [5R01 HL075716] FX Contract grant sponsor: National Institute of Health, a Specialized Center of Research (SCOR) grant in Transfusion Biology and Medicine, HL54459 and an NIH grant, 5R01 HL075716. NR 48 TC 7 Z9 7 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD AUG PY 2009 VL 84 IS 8 BP 492 EP 498 DI 10.1002/ajh.21453 PG 7 WC Hematology SC Hematology GA 479WR UT WOS:000268693000007 PM 19544475 ER PT J AU Carbo, C del Conde, I Duerschmied, D AF Carbo, Carla del Conde, Ian Duerschmied, Daniel TI Petechial bleeding after sunburn in a patient with mild thrombocytopenia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material C1 [Carbo, Carla; Duerschmied, Daniel] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Carbo, Carla] Univ Barcelona, Hosp Clin, Serv Hemoterapia & Hemostasia, E-08007 Barcelona, Spain. [del Conde, Ian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Duerschmied, D (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA. EM duerschmied@idi.harvard.edu NR 3 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD AUG PY 2009 VL 84 IS 8 BP 523 EP 523 DI 10.1002/ajh.21321 PG 1 WC Hematology SC Hematology GA 479WR UT WOS:000268693000012 PM 19021121 ER PT J AU Mehrotra, R Khawar, O Duong, U Fried, L Norris, K Nissenson, A Kalantar-Zadeh, K AF Mehrotra, Rajnish Khawar, Osman Duong, Uyen Fried, Linda Norris, Keith Nissenson, Allen Kalantar-Zadeh, Kamyar TI Ownership Patterns of Dialysis Units and Peritoneal Dialysis in the United States: Utilization and Outcomes SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Peritoneal dialysis; hemodialysis; end-stage renal disease; modality selection; mortality; technique failure; leading dialysis organizations; chains ID MORTALITY AB Background: Peritoneal dialysis (PD) provides outcomes similar to hemodialysis, but its use has decreased in the United States despite its potential for substantial taxpayer savings. We undertook this study to determine the relationship between dialysis unit ownership with PD use and outcomes. Study Design: Observational study. Setting & Participants: All incident dialysis patients (1996 to 2004) from the US Renal Data System. Predictor: Large dialysis organization (LDO), defined as corporations owning 20 or more freestanding dialysis units located in more than 1 state. Outcomes & Measurements: Odds for an incident dialysis patient undergoing PD and hazards for death on follow-up in incident PD patients for each of the 5 LDOs (non-LDO as reference). Results: During the 9-year period, 785,531 patients started maintenance dialysis therapy; the proportion receiving care in LDOs increased from 39% to 63%. There were consistent differences in PD use. It was significantly lower in LDO 2 (adjusted odds ratio [OR], 0.66; 95% confidence interval [CI], 0.64 to 0.68), LDO 3 (OR, 0.82; 95% CI, 0.80 to 0.85), and LDO 4 (OR, 0.96; 95% CI, 0.92 to 0.995) and higher in LDO 1 (adjusted OR, 1.06; 95% CI, 1.02 to 1.11) and LDO 5 (adjusted OR, 1.09; 95% Cl, 1.06 to 1.12). Between 2000 and 2004, LDO 2 had the least use and greatest risk of death (hazard ratio, 1.08; 95% CI, 1.02 to 1.14); LDO 1 had greater use and the lowest death risk (hazard ratio, 0.87; 95% CI, 0.78 to 0.96). Limitations: Only cross-sectional associations can be described. Conclusions: Three of the 5 LDOs had consistently lower PD use. Patients treated in the LIDO with the lowest use of PD had the greatest risk of death. Understanding relationships among providers, physicians, and dialysis modality use may help devise strategies for increasing PD use in appropriate patients. This has the potential to reduce the cost of renal replacement therapy and further improve outcomes. Am J Kidney Dis 54:289-298. (C) 2009 by the National Kidney Foundation, Inc. C1 [Mehrotra, Rajnish; Khawar, Osman; Duong, Uyen; Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Mehrotra, Rajnish; Khawar, Osman; Duong, Uyen; Norris, Keith; Nissenson, Allen; Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fried, Linda] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Norris, Keith] Charles Drew Univ, Los Angeles, CA USA. RP Mehrotra, R (reprint author), 1124 W Carson St, Torrance, CA 90502 USA. EM rmehrotra@labiomed.org OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 FU National Institutes of Health (NIH) [RR18298, RR019234, MD00182, DK078106] FX Dr Mehrotra is supported by Grant RR18298 from the National Institutes of Health (NIH) and grants from Satellite Health and DaVita Inc. Dr Norris is supported by NIH Grants RR019234 and MD00182. Dr Nissenson reports support from the Richard Rosenthal Dialysis Fund. Dr Kalantar-Zadeh is supported by grants from DaVita Inc and NIH (DK078106). NR 13 TC 27 Z9 28 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2009 VL 54 IS 2 BP 289 EP 298 DI 10.1053/j.ajkd.2009.01.262 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 492FL UT WOS:000269640200014 PM 19359081 ER PT J AU Chirunomula, V Kondle, V Vaddey, B Colvin, RB Kambham, N AF Chirunomula, Venumadhav Kondle, Venu Vaddey, Bhavani Colvin, Robert B. Kambham, Neeraja TI Crescentic Glomerulonephritis With Ribbon-like Immunofluorescence Pattern SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Fibrillary glomerulonephritis; crescents; immune complexes ID C VIRAL-INFECTION; FIBRILLARY GLOMERULONEPHRITIS; IMMUNOTACTOID GLOMERULOPATHY; PATHOLOGICAL FEATURES; CHAIN DEPOSITION; IMMUNOGLOBULIN; GLOMERULOSCLEROSIS; ENTITIES C1 [Chirunomula, Venumadhav; Vaddey, Bhavani; Kambham, Neeraja] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. [Kondle, Venu] Sutter N Med Grp, Div Nephrol, Yuba City, CA USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kambham, N (reprint author), Stanford Univ, Med Ctr, Dept Pathol, Rm H2110,300 Pasteur Dr, Stanford, CA 94305 USA. EM nkambham@stanford.edu NR 27 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2009 VL 54 IS 2 BP 381 EP 384 DI 10.1053/j.ajkd.2008.11.011 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 492FL UT WOS:000269640200024 PM 19121555 ER PT J AU Barrett-Connor, E Cox, DA Song, JL Mitlak, B Mosca, L Grady, D AF Barrett-Connor, Elizabeth Cox, David A. Song, Jingli Mitlak, Bruce Mosca, Lori Grady, Deborah TI Raloxifene and Risk for Stroke Based on the Framingham Stroke Risk Score SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Framingham; Raloxifene; SERM; Stroke ID POSTMENOPAUSAL WOMEN; BREAST-CANCER; CARDIOVASCULAR EVENTS; CEREBRAL INFARCTION; PRIMARY PREVENTION; RANDOMIZED-TRIAL; POPULATION; RECURRENCE; PREDICTION; REDUCTION AB PURPOSE: Raloxifene reduces vertebral fracture and invasive breast cancer risks, but increases fatal strokes in postmenopausal women at increased coronary risk. We assessed whether this risk is concentrated in postmenopausal women already at high stroke risk. METHODS: Raloxifene Use for The Heart (RUTH) enrolled 10,101 postmenopausal women (mean age 67 years) with or at increased coronary heart disease risk; Multiple Outcomes of Raloxifene Evaluation ( MORE) enrolled 7705 osteoporotic postmenopausal women ( mean age 66 years). A Framingham Stroke Risk Score (FSRS) was calculated for all women with no prior cerebrovascular events (n = 16,858). The validity of the FSRS was assessed in the placebo groups, and then raloxifene-associated stroke risk was analyzed by FSRS subgroups. RESULTS: FSRS predicted an increased stroke risk in the placebo group of both clinical trials. There was no difference in the incidence of nonfatal strokes between the raloxifene and placebo groups in MORE or RUTH, regardless of baseline Framingham stroke risk. In RUTH, women with FSRS <13 showed no increase in raloxifene-associated fatal stroke risk ( hazard ratio [HR] 1.08; 95% confidence interval [CI], 0.49-2.37). Those with FSRS >= 13 had a 75% increased risk of raloxifene-associated fatal stroke (HR 1.75; 95% CI, 1.01-3.02; interaction P = .33). In MORE, where 80% of women had a FSRS <13, no increase in fatal (HR 0.57; 95% CI, 0.19-1.68) stroke risk was observed. DISCUSSION: Risk of fatal stroke associated with raloxifene was greater in women at high stroke risk. These results might be useful for identifying postmenopausal women at high risk of first stroke who should avoid raloxifene therapy. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 754-761 C1 [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, La Jolla, CA 92093 USA. [Cox, David A.; Song, Jingli; Mitlak, Bruce] Lilly Res Labs, Indianapolis, IN USA. [Mosca, Lori] Columbia Univ, Med Ctr, New York, NY USA. [Grady, Deborah] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. RP Barrett-Connor, E (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, 9500 Gilman Dr 0607, La Jolla, CA 92093 USA. EM ebarrettconnor@ucsd.edu FU Lilly Research Laboratories; Eli Lilly and Company (Indianapolis, IN) FX The RUTH and MORE trials were both supported by Eli Lilly and Company (Indianapolis, IN). We thank the investigators, staff, and the 17,806 women who participated in the RUTH and MORE trials. Complete lists of the investigators and sub-investigators of both trials have been published previously.1,3 We also are indebted to Steve Zheng for statistical programming. NR 19 TC 19 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2009 VL 122 IS 8 BP 754 EP 761 DI 10.1016/j.amjmed.2009.01.033 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 474PD UT WOS:000268295500014 PM 19540454 ER PT J AU Rapalino, O AF Rapalino, O. TI Thalamic Anisotropy and Functional Disability SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID MULTIPLE-SCLEROSIS C1 Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, Boston, MA 02114 USA. RP Rapalino, O (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 2009 VL 30 IS 7 BP 1387 EP 1387 DI 10.3174/ajnr.A1706 PG 1 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 486BE UT WOS:000269169600023 PM 19509070 ER PT J AU Stefancyk, AL AF Stefancyk, Amanda L. TI Vitality and Teamwork SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gen Med Unit, White 10, Boston, MA 02114 USA. RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, Gen Med Unit, White 10, Boston, MA 02114 USA. EM astefancyk@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD AUG PY 2009 VL 109 IS 8 BP 70 EP 71 PG 2 WC Nursing SC Nursing GA 482UM UT WOS:000268914300029 ER PT J AU Gee, RE Mitra, N Wan, F Chavkin, DE Long, JA AF Gee, Rebekah E. Mitra, Nandita Wan, Fei Chavkin, Diana E. Long, Judith A. TI Power over parity: intimate partner violence and issues of fertility control SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE abortion; contraception; intimate partner violence; multiparity ID WOMEN SEEKING ABORTION; DOMESTIC VIOLENCE; RISK-FACTORS; PREVALENCE; PREGNANCY; INTERVENTIONS AB OBJECTIVE: The purpose of this study was to examine the association between intimate partner violence (IPV), abortion, parity, and contraception use. STUDY DESIGN: We recruited 1463 women for this written questionnaire study of IPV. Patient demographics, contraceptive history, and reproductive history were obtained in the waiting room from patients presenting for gynecologic care. RESULTS: Seventy percent of those eligible participated. Twenty-one percent reported a history of IPV. Partner unwillingness to use birth control, partner desirous of conception, partner creating difficulty for subject's use of birth control, and subjects expressing inability to afford contraception were all positively associated with report of IPV. Each additional pregnancy was associated with 10% greater odds of IPV (95% confidence interval, 1.03-1.17). CONCLUSION: Contraception is more difficult to navigate for women experiencing IPV. Providers should consider prescribing contraceptive methods for IPV victims that are not partner dependent. C1 [Gee, Rebekah E.] Univ Penn, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19104 USA. [Gee, Rebekah E.; Long, Judith A.] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Mitra, Nandita; Wan, Fei] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Chavkin, Diana E.] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Long, Judith A.] Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA USA. RP Gee, RE (reprint author), 423 Guardian Dr,13th Floor Blockley Hall 1303A, Philadelphia, PA 19104 USA. EM rebekahgeemd@gmail.com FU Pennsylvania Department of Health FX This study was supported by the Robert Wood Johnson Clinical Scholars Program and the Institute for Translational Medicine and Therapeutics, both at the University of Pennsylvania and under a Grant from the Pennsylvania Department of Health. The Department specifically disclaims responsibility for any analysis, interpretations, or conclusions. NR 26 TC 18 Z9 18 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2009 VL 201 IS 2 AR 148.e1 DI 10.1016/j.ajog.2009.04.048 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 476RI UT WOS:000268460900007 PM 19564020 ER PT J AU Watts, L Joseph, N Velazquez, A Gonzalez, M Munro, E Muzikansky, A Rauh-Hain, JA del Carmen, MG AF Watts, Luisa Joseph, Naima Velazquez, Amanda Gonzalez, Marisa Munro, Elizabeth Muzikansky, Alona Rauh-Hain, Jose A. del Carmen, Marcela G. TI Understanding barriers to cervical cancer screening among Hispanic women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical cancer screening; disparities; Hispanics ID VIETNAMESE-AMERICAN WOMEN; PAP TEST; BREAST; RECOMMENDATION; PREDICTORS; KNOWLEDGE; LATINAS; SMEARS; IMPACT AB OBJECTIVE: We investigated issues affecting Papanicolaou smear screening access, health services utilization, acculturation, social networking, and media venues most conducive to acquiring health information among Hispanics. STUDY DESIGN: Self-identified Hispanics were surveyed. Participants were stratified based on age, time living in the United States, and Papanicolaou screening frequency. RESULTS: Of 318 participants, Hispanics aged 30 years or older and living in the United States less than 5 years prefer speaking Spanish. Women with 5 or more lifetime Papanicolaou smears were 1.610 times more likely to have lived in the United States 5 or more years, 1.706 times more likely to speak a second language, and 1.712 times less likely to need a translator during their health care encounter. CONCLUSION: Age and years living in the United States may be independent risk factors for participation in Papanicolaou screening programs. Social difficulties inherent to acculturation inform health behavior and translate to health disparity among Hispanics. Our results may help design federally funded and community-level programs. C1 [Watts, Luisa; Joseph, Naima; Velazquez, Amanda; Gonzalez, Marisa; Munro, Elizabeth; Rauh-Hain, Jose A.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA USA. [Muzikansky, Alona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA USA. RP del Carmen, MG (reprint author), 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 21 TC 8 Z9 9 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2009 VL 201 IS 2 AR 199.e1 DI 10.1016/j.ajog.2009.05.014 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 476RI UT WOS:000268460900026 PM 19646571 ER PT J AU Lamichane, M Anderson, NK Rigali, PH Seldin, EB Will, LA AF Lamichane, Manish Anderson, Nina Kay Rigali, Paul H. Seldin, Edward B. Will, Leslie A. TI Accuracy of reconstructed images from cone-beam computed tomography scans SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Article ID LANDMARK IDENTIFICATION; CT; NEWTOM; CEPHALOMETRY; DOSIMETRY; DEVICES; FILM AB Introduction: The aim of this study was to determine whether 2-dimensional (2D) images produced from cone-beam computed tomography (CBCT) images taken with an iCAT scanner (Imaging Sciences International, Hatfield, Pa) can substitute for traditional cephalograms. Methods: Lateral and frontal cephalograms were taken of a radiographic phantom with known dimensions. Landmarks on the 2D images were traced and measured manually by 2 examiners and then digitally in Dolphin 10 (Dolphin Imaging Sciences, Chats-worth, Calif) by the same examiners. A CBCT scan was taken of the phantom, and orthogonal and perspective projections were created from the scans. Frontal and lateral cephalograms were created by using the 3-dimensional function in Dolphin 10, digitized into Dolphin, and traced by the same 2 examiners. Linear measurements were compared to assess the accuracy of the generated images from the CBCT scans. Results: Measurements on the orthogonal projections were not significantly different from the actual dimensions of the phantom, and measurements on the perspective projections were highly correlated with those taken on standard 2D films. Conclusions: By constructing a perspective lateral cephalogram from a CBCT scan, one can replicate the inherent magnification of a conventional 2D lateral cephalogram with high accuracy. (Am J Orthod Dentofacial Orthop 2009;136:156.e1-156.e6) C1 [Rigali, Paul H.; Will, Leslie A.] Tufts Univ, Sch Dent Med, Dept Orthodont, Boston, MA 02111 USA. [Anderson, Nina Kay] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Seldin, Edward B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Seldin, Edward B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Will, LA (reprint author), Tufts Univ, Sch Dent Med, Dept Orthodont, 1 Kneeland St, Boston, MA 02111 USA. EM Leslie.Will@tufts.edu NR 20 TC 3 Z9 5 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD AUG PY 2009 VL 136 IS 2 AR 156.e1 DI 10.1016/j.ajodo.2009.01.019 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 478YX UT WOS:000268625800011 PM 19651340 ER PT J AU Boninger, ML Whyte, J DeLisa, J Zafonte, R Chan, L AF Boninger, Michael L. Whyte, John DeLisa, Joel Zafonte, Ross Chan, Leighton TI Building a Research Program in Physical Medicine and Rehabilitation SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Research; Rehabilitation; Academic Medical Center; Mentorship; Research Capacity ID DEPARTMENTS; IMPACT AB There is a clear need for increased rigorous research in physical medicine and rehabilitation. The objective of this article is to describe the decisions, environment, and other factors that can lead to the growth of extramurally funded research at academic institutions. Together with case examples presented in the accompanying article, it is hoped that these articles can help chairs and deans who are attempting to improve medical rehabilitation research efforts at their schools. C1 [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Sch Med, Pittsburgh, PA 15213 USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA USA. [Whyte, John] Moss Rehabil Res Inst, Philadelphia, PA USA. [Whyte, John] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [DeLisa, Joel] UMDNJ, New Jersey Med Sch, Dept Phys Med & Rehabil, Piscataway, NJ USA. [Zafonte, Ross] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Kessler Fdn Res Ctr,Spaulding Rehabil Hosp, Boston, MA USA. RP Boninger, ML (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, Sch Med, 201 Kaufmann Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA. OI Boninger, Michael/0000-0001-6966-919X FU Foundation for PMR FX This study was supported through the Foundation for PM&R. Authors received a small honorarium for their contributions. NR 14 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2009 VL 88 IS 8 BP 659 EP 666 DI 10.1097/PHM.0b013e3181aeab74 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 476VW UT WOS:000268475400007 PM 19620832 ER PT J AU Chan, L Jette, AM Ottenbacher, KJ Robinson, LR Tietsworth, ML Ricker, JH Boninger, ML AF Chan, Leighton Jette, Alan M. Ottenbacher, Kenneth J. Robinson, Lawrence R. Tietsworth, Monica L. Ricker, Joseph H. Boninger, Michael L. TI Building a Research Program in Rehabilitation Sciences, Part II Case Studies: University of Texas Medical Branch, Boston University, University of Pittsburgh, and University of Washington SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Research; Research Activities; Academic Medical Center AB This article presents four case studies of rehabilitation science programs that have created enduring research efforts: one in physical therapy, one in interdisciplinary rehabilitation sciences, and two in physical medicine and rehabilitation. Several themes emerge from these case studies. First, building an enduring research program takes time and significant foundational work. Most importantly, it is crucial to have the support of the dean, academic institution, and medical center. This seems to be a prerequisite for success in this area. C1 [Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA USA. [Ottenbacher, Kenneth J.] Univ Texas Med Branch, Div Rehabil Sci, Galveston, TX USA. [Robinson, Lawrence R.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [Tietsworth, Monica L.; Ricker, Joseph H.; Boninger, Michael L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA USA. RP Chan, L (reprint author), 5511 Lambeth Rd, Bethesda, MD 20814 USA. OI Jette, Alan/0000-0002-2117-9973; Boninger, Michael/0000-0001-6966-919X FU Foundation for PMR FX This study was supported through the Foundation for PM&R. Authors received a small honorarium for their contributions. NR 6 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2009 VL 88 IS 8 BP 667 EP 678 DI 10.1097/PHM.0b013e3181aeab55 PG 12 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 476VW UT WOS:000268475400008 PM 19620833 ER PT J AU Aplin, AC Zhu, WH Fogel, E Nicosia, RF AF Aplin, A. C. Zhu, W. H. Fogel, E. Nicosia, R. F. TI Vascular regression and survival are differentially regulated by MT1-MMP and TIMPs in the aortic ring model of angiogenesis SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE neovascularization; matrix metalloproteinase-14; collagen; endothelial cells; aorta; rarefaction; membrane type 1 matrix metalloproteinase; tissue inhibitors of matrix metalloproteinases ID 3-DIMENSIONAL EXTRACELLULAR-MATRIX; HUMAN ENDOTHELIAL-CELLS; TISSUE INHIBITOR; RAT AORTA; 1-MATRIX METALLOPROTEINASE; QUANTITATIVE ASSAY; INVASIVE CELLS; TUMOR INVASION; IN-VITRO; MEMBRANE AB Aplin AC, Zhu WH, Fogel E, Nicosia RF. Vascular regression and survival are differentially regulated by MT1-MMP and TIMPs in the aortic ring model of angiogenesis. Am J Physiol Cell Physiol 297: C471-C480, 2009. First published June 3, 2009; doi:10.1152/ajpcell.00019.2009.-This study was designed to investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in the reabsorption of neovessels in collagen gel cultures of rat and mouse aortic rings. Aortic angiogenesis was associated with collagen lysis and production of the matrix-degrading enzymes MMP-2, MMP-9, and membrane-type MMP (MT1-MMP, or MMP-14). Vascular growth and regression were not affected by disruption of MMP-2 or MMP-9. In addition, no effect on vascular regression was observed by blocking plasmin, a protease implicated in the activation of MMPs, with epsilon-aminocaproic acid or by adding plasminogen, which caused a modest increase in vascular proliferation. Conversely, angiogenesis was blocked and vessels stabilized by inhibiting MT1-MMP with neutralizing antibodies, TIMP-2, TIMP-3, or TIMP-4. TIMP-1, which blocks MMP-2 and MMP-9 but is a poor inhibitor of MT1-MMP, had no antiangiogenic effect. However, TIMP-1 prolonged the survival of neovessels following angiogenesis. Vascular regression was accelerated in aortic cultures from TIMP-1-and TIMP-2-deficient mice. The vascular survival effect of anti-MT1-MMP antibodies and TIMPs with MT1-MMP inhibitory activity was associated with complete inhibition of collagen lysis. In contrast, TIMP-1 had no anticollagenolytic effect. These results indicate that MT1-MMP plays a critical role not only in angiogenesis but also in vascular regression and demonstrate that TIMPs with anti-MT1-MMP activity have opposite effects on angiogenic outcomes depending on the stage of the angiogenic process. This study also suggests the existence of a TIMP-1-mediated alternate pathway of vascular survival that is unrelated to MT1-MMP inhibitory activity. C1 [Fogel, E.; Nicosia, R. F.] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA 98108 USA. [Aplin, A. C.; Zhu, W. H.; Nicosia, R. F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Nicosia, RF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv S Lab 113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM roberto.nicosia@va.gov FU National Heart, Lung, and Blood Institute [HL52585]; Medical Research Service, Department of Veterans Affairs FX This work was supported by National Heart, Lung, and Blood Institute Grant HL52585 ( R. F. Nicosia) and the Medical Research Service, Department of Veterans Affairs ( R. F. Nicosia). NR 63 TC 25 Z9 26 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD AUG PY 2009 VL 297 IS 2 BP C471 EP C480 DI 10.1152/ajpcell.00019.2009 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 477CI UT WOS:000268494800026 PM 19494241 ER PT J AU Gollisch, KSC Brandauer, J Jessen, N Toyoda, T Nayer, A Hirshman, MF Goodyear, LJ AF Gollisch, Katja S. C. Brandauer, Josef Jessen, Niels Toyoda, Taro Nayer, Ali Hirshman, Michael F. Goodyear, Laurie J. TI Effects of exercise training on subcutaneous and visceral adipose tissue in normal- and high-fat diet-fed rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE cytokines; adipocytes; insulin resistance ID NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; STIMULATES LIPOLYSIS; OBESITY; CELLS; IL-6; ADIPOCYTES; EXPRESSION; MICE; INFLAMMATION AB Gollisch KS, Brandauer J, Jessen N, Toyoda T, Nayer A, Hirshman MF, Goodyear LJ. Effects of exercise training on subcutaneous and visceral adipose tissue in normal-and high-fat diet-fed rats. Am J Physiol Endocrinol Metab 297: E495-E504, 2009. First published June 2, 2009; doi: 10.1152/ajpendo.90424.2008.-Regular physical activity improves glucose tolerance and decreases adiposity. Our aim was to investigate the effects of exercise training on subcutaneous (inguinal) and visceral (parametrial) adipose tissue in rats that were fed a chow diet (13% fat) or made insulin resistant by a high-fat diet (60% fat). Sprague-Dawley rats performed 4 wk of voluntary wheel running or were kept as sedentary controls. The training groups fed chow and the high-fat diet achieved similar running distances (8.8 +/- 1.8 and 9.3 +/- 1.9 km/day, respectively). Training improved oral glucose tolerance in chow-fed rats and prevented the glucose intolerance that occurred in sedentary rats fed the high-fat diet. In both subcutaneous and visceral adipose tissue, the high-fat diet-induced increases in fat pad weight (67% and 133%, respectively), adipocyte size (20% and 43%), and cell number (36% and 65%) were completely prevented by exercise training. Cytokine mRNA expression in visceral fat did not change with exercise training. However, in subcutaneous fat, training actually increased mRNA expression of several cytokines [IL-6: 80% (P < 0.05); TNF-alpha: 100% (P < 0.05); IL-1 receptor antagonist (IL-1Ra): 57% (P = 0.08)] with no detectable increases in serum cytokine concentrations. In summary, exercise training can overcome high-fat diet-induced impairments in glucose tolerance and increases in adipocyte size, cell number, and fat pad mass. Improved glucose tolerance was accompanied by an increase in cytokine gene expression in subcutaneous fat. This finding raises the possibility of a specific role of subcutaneous adipose tissue in adaptive responses to exercise training. C1 [Goodyear, Laurie J.] Joslin Diabet Ctr, Metab Sect, Div Res, Boston, MA 02215 USA. [Gollisch, Katja S. C.; Brandauer, Josef; Jessen, Niels; Toyoda, Taro; Nayer, Ali; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA USA. [Gollisch, Katja S. C.; Brandauer, Josef; Jessen, Niels; Toyoda, Taro; Nayer, Ali; Hirshman, Michael F.; Goodyear, Laurie J.] Dept Med, Boston, MA USA. [Gollisch, Katja S. C.] Univ Munich, Ctr Diabet, Med Clin Innenstadt, Munich, Germany. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Metab Sect, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Jessen, Niels/E-1731-2011; OI Jessen, Niels/0000-0001-5613-7274 FU National Institutes of Health (NIH) [R01-DK-068626, P30-DK-36836]; Joslin Diabetes Center; Postdoc Program of the German Academic Exchange Service (DAAD); NIH [T32-DK-07260-29]; Danish Agency for Science Technology and Innovation [271-07-0719] FX This work was supported by National Institutes of Health (NIH) Grants R01-DK-068626 (L. J. Goodyear) and P30-DK-36836, a Diabetes and Endocrinology Research Center Grant to the Joslin Diabetes Center. K. S. C. Gollisch was supported by a fellowship within the Postdoc Program of the German Academic Exchange Service (DAAD) and J. Brandauer by NIH Training Grant T32-DK-07260-29. N. Jessen was supported by Danish Agency for Science Technology and Innovation Grant 271-07-0719. NR 26 TC 56 Z9 60 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 2009 VL 297 IS 2 BP E495 EP E504 DI 10.1152/ajpendo.90424.2008 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 473ZT UT WOS:000268252700025 PM 19491293 ER PT J AU Buys, ES Cauwels, A Raher, MJ Passeri, JJ Hobai, I Cawley, SM Rauwerdink, KM Thibault, H Sips, PY Thoonen, R Scherrer-Crosbie, M Ichinose, F Brouckaert, P Bloch, KD AF Buys, Emmanuel S. Cauwels, Anje Raher, Michael J. Passeri, Jonathan J. Hobai, Ion Cawley, Sharon M. Rauwerdink, Kristen M. Thibault, Helene Sips, Patrick Y. Thoonen, Robrecht Scherrer-Crosbie, Marielle Ichinose, Fumito Brouckaert, Peter Bloch, Kenneth D. TI sGC alpha(1)beta(1) attenuates cardiac dysfunction and mortality in murine inflammatory shock models SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE soluble guanylate cyclase; left ventricular function; sepsis; mice; nitric oxide ID NITRIC-OXIDE SYNTHASE; SENSITIVE GUANYLYL CYCLASE; HUMAN SEPTIC SHOCK; ENOS-DERIVED NO; MYOCARDIAL DYSFUNCTION; METHYLENE-BLUE; SEVERE SEPSIS; MICE LACKING; PRESSURE-OVERLOAD; CGMP AB Buys ES, Cauwels A, Raher MJ, Passeri JJ, Hobai I, Cawley SM, Rauwerdink KM, Thibault H, Sips PY, Thoonen R, ScherrerCrosbie M, Ichinose F, Brouckaert P, Bloch KD. sGC alpha(1)beta(1) attenuates cardiac dysfunction and mortality in murine inflammatory shock models. Am J Physiol Heart Circ Physiol 297: H654-H663, 2009. First published June 5, 2009; doi:10.1152/ajpheart.00367.2009.-Altered cGMP signaling has been implicated in myocardial depression, morbidity, and mortality associated with sepsis. Previous studies, using inhibitors of soluble guanylate cyclase (sGC), suggested that cGMP generated by sGC contributed to the cardiac dysfunction and mortality associated with sepsis. We used sGC alpha(1)-deficient (sGC alpha(-/-)(1)) mice to unequivocally determine the role of sGC alpha(1)beta(1) in the development of cardiac dysfunction and death associated with two models of inflammatory shock: endotoxin-and TNF-induced shock. At baseline, echocardiographic assessment and invasive hemodynamic measurements of left ventricular (LV) dimensions and function did not differ between wild-type (WT) mice and sGC alpha(-/-)(1) mice on the C57BL/6 background (sGC alpha(-/-B6)(1) mice). At 14 h after endotoxin challenge, cardiac dysfunction was more pronounced in sGC alpha(-/-B6)(1) than WT mice, as assessed using echocardiographic and hemodynamic indexes of LV function. Similarly, Ca(2+) handling and cell shortening were impaired to a greater extent in cardiomyocytes isolated from sGC alpha(-/-B6)(1) than WT mice after endotoxin challenge. Importantly, morbidity and mortality associated with inflammatory shock induced by endotoxin or TNF were increased in sGC alpha(-/-B6)(1) compared with WT mice. Together, these findings suggest that cGMP generated by sGC alpha(1)beta(1) protects against cardiac dysfunction and mortality in murine inflammatory shock models. C1 [Buys, Emmanuel S.; Raher, Michael J.; Hobai, Ion; Rauwerdink, Kristen M.; Sips, Patrick Y.; Ichinose, Fumito; Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia & Crit Care,Sch Med, Boston, MA 02114 USA. [Passeri, Jonathan J.; Thibault, Helene; Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Dept Med,Sch Med,Cardiol Div, Boston, MA 02114 USA. [Buys, Emmanuel S.; Raher, Michael J.; Cawley, Sharon M.; Scherrer-Crosbie, Marielle; Bloch, Kenneth D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Cauwels, Anje; Thoonen, Robrecht; Brouckaert, Peter] Univ Ghent VIB, Dept Med Mol Biol, Ghent, Belgium. [Cauwels, Anje; Thoonen, Robrecht; Brouckaert, Peter] Univ Ghent, Dept Mol Biol, B-9000 Ghent, Belgium. RP Buys, ES (reprint author), Harvard Univ, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia & Crit Care,Sch Med, 50 Blossom St,Thier 505, Boston, MA 02114 USA. EM ebuys@partners.org OI Sips, Patrick/0000-0001-9241-5980 FU American Heart Association Northeast Affiliate; Massachusetts Biomedical Research Corporation; Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO-Vlaanderen); Geconcerteerde Onderzoeksacties; National Heart, Lung, and Blood Institute [HL-42397, HL-70896, HL-71987] FX This study was supported by a postdoctoral fellowship award of the American Heart Association Northeast Affiliate and a postdoctoral fellowship from the Massachusetts Biomedical Research Corporation (E. S. Buys), grants from the Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO-Vlaanderen) and the Geconcerteerde Onderzoeksacties (P. Brouckaert), and National Heart, Lung, and Blood Institute Grants HL-42397, HL-70896, and HL-71987. A. Cauwels is a postdoctoral fellow of the FWO Vlaanderen. NR 59 TC 33 Z9 33 U1 1 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 AUG PY 2009 VL 297 IS 2 BP H654 EP H663 DI 10.1152/ajpheart.00367.2009 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 475HC UT WOS:000268348200021 PM 19502556 ER PT J AU Wray, C Mao, Y Pan, J Chandrasena, A Piasta, F Frank, JA AF Wray, Charlie Mao, Ying Pan, Jue Chandrasena, Anita Piasta, Frank Frank, James A. TI Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE alveolar epithelium; ion transport; paracellular transport; tight junction; pulmonary edema; acute respiratory distress syndrome ID CLOSTRIDIUM-PERFRINGENS ENTEROTOXIN; JUNCTIONAL PERMEABILITY; DECREASES EXPRESSION; FLUID TRANSPORT; CELLS; SODIUM; KINASE; EDEMA; ACTIVATION; RESOLUTION AB Wray C, Mao Y, Pan J, Chandrasena A, Piasta F, Frank JA. Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury. Am J Physiol Lung Cell Mol Physiol 297: L219-L227, 2009. First published May 15, 2009; doi:10.1152/ajplung.00043.2009.-Intact alveolar barrier function is associated with better outcomes in acute lung injury patients; however, the regulation of alveolar epithelial paracellular transport during lung injury has not been extensively investigated. This study was undertaken to determine whether changes in tight junction claudin expression affect alveolar epithelial barrier properties and to determine the mechanisms of altered expression. In anesthetized mice exposed to ventilator-induced lung injury, claudin-4 was specifically induced among tight junction structural proteins. Real-time PCR showed an eightfold increase in claudin-4 expression in the lung injury model. To examine the role of this protein in barrier regulation, claudin-4 function was inhibited with small interfering RNA (siRNA) and a blocking peptide derived from the binding domain of Clostridium perfringens enterotoxin (CPE(BD)). Inhibition of claudin-4 decreased transepithelial electrical resistance but did not alter macromolecule permeability in primary rat and human epithelial cells. In mice, CPEBD decreased air space fluid clearance >33% and resulted in pulmonary edema during moderate tidal volume ventilation that did not induce edema in control peptide-treated mice. In vitro phorbol ester induced a ninefold increase in claudin-4 expression that was dependent on PKC activation and the JNK MAPK pathway. These data establish that changes in alveolar epithelial claudin expression influence paracellular transport, alveolar fluid clearance rates, and susceptibility to pulmonary edema. We hypothesize that increased claudin-4 expression early in acute lung injury represents a mechanism to limit pulmonary edema and that the regulation of alveolar epithelial claudin expression may be a novel target for acute lung injury therapy. C1 [Pan, Jue; Chandrasena, Anita; Frank, James A.] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Chandrasena, Anita; Piasta, Frank; Frank, James A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Wray, Charlie; Mao, Ying; Frank, James A.] Vet Hlth Res Inst, NCIRE, San Francisco, CA USA. RP Frank, JA (reprint author), 4150 Clement St,Box 111D, San Francisco, CA 94121 USA. EM james.frank@ucsf.edu FU National Heart, Lung, and Blood Institute [HL-88440] FX This work was funded by National Heart, Lung, and Blood Institute Grant HL-88440 ( J. A. Frank). NR 37 TC 72 Z9 77 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2009 VL 297 IS 2 BP L219 EP L227 DI 10.1152/ajplung.00043.2009 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 474IE UT WOS:000268276200004 PM 19447895 ER PT J AU Alexopoulos, GS Reynolds, CF Bruce, ML Katz, IR Raue, PJ Mulsant, BH Oslin, DW Ten Have, T AF Alexopoulos, George S. Reynolds, Charles F., III Bruce, Martha L. Katz, Ira R. Raue, Patrick J. Mulsant, Benoit H. Oslin, David W. Ten Have, Thomas CA Prospect Grp TI Reducing Suicidal Ideation and Depression in Older Primary Care Patients: 24-Month Outcomes of the PROSPECT Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LATE-LIFE DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; ADULTS; MANAGEMENT; REMISSION; MORTALITY; DISEASE; MODELS; SCALE; AGE AB OBJECTIVE: The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) evaluated the impact of a care management intervention on suicidal ideation and depression in older primary care patients. This is the first report of outcomes over a 2-year period. METHOD: Study participants were patients 60 years of age or older (N=599) with major or minor depression selected after screening 9,072 randomly identified patients of 20 primary care practices randomly assigned to provide either the PROSPECT intervention or usual care. The intervention consisted of services of 15 trained care managers, who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 24 months. RESULTS: Compared with patients receiving usual care, those receiving the intervention had a higher likelihood of receiving antidepressants and/or psychotherapy (84.9%-89% versus 49%-62%) and had a 2.2 times greater decline in suicidal ideation over 24 months. Treatment response occurred earlier on average in the intervention group and increased from months 18 to 24, while no appreciable increase in treatment response occurred in the usual care group during the same period. Among patients with major depression, a greater number achieved remission in the intervention group than in the usual-care group at 4 months (26.6% versus 15.2%), 8 months (36% versus 22.5%), and 24 months (45.4% versus 31.5%). Patients with minor depression had favorable outcomes regardless of treatment assignment. CONCLUSIONS: Sustained collaborative care maintains high utilization of depression treatment, reduces suicidal ideation, and improves the outcomes of major depression over 2 years. C1 [Alexopoulos, George S.] Weill Cornell Med Coll, Dept Psychiat, White Plains, NY 10605 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON M5S 1A1, Canada. Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada. RP Alexopoulos, GS (reprint author), Weill Cornell Med Coll, Dept Psychiat, 21 Bloomingdale Rd, White Plains, NY 10605 USA. EM gsalexop@med.cornell.edu OI Alexopoulos, George/0000-0001-5677-7001 FU NIMH [RO1 MH59366, R01 MH059380, RO37 MH51842, RO1 MH59318, P30 MH68638, P30 MH52247, P30 MH066270]; Hartford Foundation; Forest Pharmaceuticals; [R01 MH59366]; [R01 MH59380]; [P30 MH52129]; [R01 MH59381] FX The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) was a collaborative research study funded by NIMH. The three groups included the Advanced Centers for Intervention and Services Research of the following: Cornell University (PROSPECT Coordinating Center; principal investigator, George S. Alexopoulos, M. D.; co-principal investigators, Martha L. Bruce, Ph. D., M. P. H., and Herbert C. Schulberg, Ph. D.; grants R01 MH59366, P30 MH68638); University of Pennsylvania (principal investigator, Ira Katz, M. D., Ph. D.; co-principal investigators: Thomas Ten Have, Ph. D., and Gregory K. Brown, Ph. D.; grants R01 MH59380, P30 MH52129); and University of Pittsburgh (principal investigator, Charles F. Reynolds III, M. D.; co-principal investigator, Benoit H. Mulsant, M. D.; grants R01 MH59381, P30 MH52247). PROSPECT was supported by NIMH grants RO1 MH59366, R01 MH059380, RO37 MH51842, RO1 MH59318, P30 MH68638, P30 MH52247, and P30 MH066270; the Hartford Foundation; and Forest Pharmaceuticals. NR 30 TC 118 Z9 120 U1 2 U2 20 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2009 VL 166 IS 8 BP 882 EP 890 DI 10.1176/appi.ajp.2009.08121779 PG 9 WC Psychiatry SC Psychiatry GA 479DC UT WOS:000268638900010 PM 19528195 ER PT J AU Medarova, Z Moore, A AF Medarova, Zdravka Moore, Anna TI MRI in Diabetes: First Results SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE autoimmune attack; beta cell mass; diabetes; islet vasculature; MRI; noninvasive imaging ID TRANSPLANTED PANCREATIC-ISLETS; CD8(+) T-CELLS; IN-VIVO; BLOOD-FLOW; CONTRAST AGENT; TUMOR ANGIOGENESIS; MAGNETIC-SUSCEPTIBILITY; EDMONTON PROTOCOL; RAT PANCREAS; REAL-TIME AB OBJECTIVE. This article will highlight the latest accomplishments in the area of MRI of diabetes including imaging of beta cell mass, imaging of autoimmune attack in type 1 diabetes, imaging of islet vasculature, and imaging of islet transplantation. CONCLUSION. Diabetes is a devastating disease in which the body does not produce or properly use insulin. Noninvasive imaging could greatly aid in the diagnosis, staging, and treatment efficiency of this disease. C1 [Medarova, Zdravka; Moore, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Mol Imaging Lab,MGH, HMS Athinoula A Martinos Ctr Biomed Imaging,MIT, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Mol Imaging Lab,MGH, HMS Athinoula A Martinos Ctr Biomed Imaging,MIT, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu NR 71 TC 11 Z9 13 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2009 VL 193 IS 2 BP 295 EP 303 DI 10.2214/AJR.08.2156 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 472RB UT WOS:000268148600005 PM 19620424 ER PT J AU Otero, HJ Yap, JT Patak, MA Erturk, SM Israel, DA Johnston, CJ Sakellis, C Rybicki, FJ Van den Abbeele, AD Ros, PR AF Otero, Hansel J. Yap, Jeffrey T. Patak, Michael A. Erturk, Sukru M. Israel, David A. Johnston, Ciaran J. Sakellis, Chris Rybicki, Frank J. Van den Abbeele, Annick D. Ros, Pablo R. TI Evaluation of Low-Density Neutral Oral Contrast Material in PET/CT for Tumor Imaging: Results of a Randomized Clinical Trial SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE contrast media; neutral contrast material; nuclear imaging; oncologic imaging; oral contrast material; PET/CT ID POSITRON-EMISSION-TOMOGRAPHY; ENHANCED CT; ATTENUATION CORRECTION; INTEGRATED PET/CT; SMALL-BOWEL; INTRAVENOUS CONTRAST; LIVER METASTASES; NONENHANCED CT; DIAGNOSTIC CT; CANCER AB OBJECTIVE. The objective of this study was to determine the impact on image quality and risks in terms of artifacts and side effects of a low-density barium-based suspension as oral contrast material for CT during PET/CT examinations of an oncologic patient population. SUBJECTS AND METHODS. Eighty-five patients (51 men and 34 women; mean age, 53 years; age range, 21-87 years) were prospectively randomized to receive either 0.1% barium sulfate oral suspension or no oral contrast material during PET/CT. Patients in the oral contrast group were given 1,350 mL over 60-75 minutes. The (18)F-FDG PET component of each examination was reviewed for the presence of artifacts by two nuclear medicine physicians and was classified as adequate (no presence of artifactual focal FDG uptake attributed to attenuation-correction errors) or inadequate (focal uptake in attenuation-correction PET images with no corresponding uptake in non-attenuation-corrected PET images). Two radiologists reviewed the CT studies and scored the degree of bowel opacification using a 5-point scale, ranging from 0 for no opacification (i.e., not possible to delineate the bowel structures from the surrounding tissues) to 4 for excellent opacification (i.e., bowel structure identifiable and bowel wall clearly visible). The attenuation values (in Hounsfield units) were recorded in the stomach, duodenum, mid jejunum, and terminal ileum for quantitative analysis. Interobserver variability was assessed using kappa coefficients. RESULTS. None of the patients who received oral contrast material experienced side effects. All 85 PET examinations were considered adequate with no observable artifacts. The mean bowel opacification scores of the oral contrast group (2.59 and 2.93) as evaluated by radiologists 1 and 2, respectively, were significantly higher (p < 0.01) than those of the control group (1.55 and 1.59). The level of attenuation achieved in the contrast group was significantly higher than in the control group. The interobserver variability was moderate (kappa = 0.32). CONCLUSION. The use of low-density neutral oral contrast material for CT during combined FDG PET/CT studies significantly improves visualization of the bowel structures compared with no contrast material without causing side effects or clinically detectable errors in the attenuation correction of the FDG PET study. C1 [Otero, Hansel J.; Rybicki, Frank J.; Ros, Pablo R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02120 USA. [Otero, Hansel J.; Israel, David A.; Johnston, Ciaran J.; Van den Abbeele, Annick D.; Ros, Pablo R.] Harvard Univ, Sch Med, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yap, Jeffrey T.; Israel, David A.; Sakellis, Chris; Van den Abbeele, Annick D.] Harvard Univ, Sch Med, Dept Nucl Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Patak, Michael A.] Univ Hosp Bern, Inselspital, Dept Intervent & Diagnost Radiol, CH-3010 Bern, Switzerland. [Erturk, Sukru M.] Sisli Etfal Training & Res Hosp, Dept Radiol, Istanbul, Turkey. RP Otero, HJ (reprint author), Brigham & Womens Hosp, Dept Radiol, 1620 Tremont St,3rd Fl,Radiol Ste, Boston, MA 02120 USA. EM hotero@partners.org FU Departments of Radiology and Nuclear Medicine; Dana-Farber Cancer Institute FX We thank Greg Lefever, Madhavi Kamma, Triscia Locascio, Aldo Gonzalez-Beicos, Pamela Dipiro, and Nikhil Ramaiya, of the Departments of Radiology and Nuclear Medicine at the Dana-Farber Cancer Institute, for their valuable assistance and support in this study. NR 38 TC 4 Z9 4 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2009 VL 193 IS 2 BP 326 EP 332 DI 10.2214/AJR.08.1565 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 472RB UT WOS:000268148600008 PM 19620427 ER PT J AU Otero, HJ Jagannathan, JP Prevedello, LM Johnston, CJ Ramaiya, NH Van den Abbeele, AD DiPiro, PJ AF Otero, Hansel J. Jagannathan, Jyothi P. Prevedello, Luciano M. Johnston, Ciaran J. Ramaiya, Nikhil H. Van den Abbeele, Annick D. DiPiro, Pamela J. TI CT and PET/CT Findings of T-Cell Lymphoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; extranodal involvement; PET/CT; T-cell lymphoma ID POSITRON-EMISSION-TOMOGRAPHY; FDG-PET/CT; NEOPLASMS AB OBJECTIVE. The purpose of this study was to describe the extranodal features of T-cell lymphoma at CT and PET/CT. CONCLUSION. The extranodal features of T-cell lymphoma are not specific and usually cannot be used to differentiate T-cell lymphoma from other aggressive types of lymphoma. Noncutaneous subtypes frequently manifest with visceral involvement. The goal of CT in initial staging is to exclude visceral involvement. Evidence on the utility of PET/CT is promising, showing high diagnostic value in evaluation of occult disease and treatment response, but the role of PET/CT is evolving. C1 [Otero, Hansel J.; Jagannathan, Jyothi P.; Johnston, Ciaran J.; Ramaiya, Nikhil H.; Van den Abbeele, Annick D.; DiPiro, Pamela J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Otero, Hansel J.; Prevedello, Luciano M.] Brigham & Womens Hosp, Dept Radiol, Appl Imaging Sci Lab, Boston, MA 02115 USA. RP Otero, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. EM hotero@partners.org RI Prevedello, Luciano/G-8650-2014; OI Prevedello, Luciano/0000-0002-6768-6452 NR 19 TC 13 Z9 16 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2009 VL 193 IS 2 BP 349 EP 358 DI 10.2214/AJR.08.1398 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 472RB UT WOS:000268148600012 PM 19620431 ER PT J AU Birdwell, RL Mountford, CE Iglehart, JD AF Birdwell, Robyn L. Mountford, Carolyn E. Iglehart, J. Dirk TI Molecular Imaging of the Breast SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast cancer; breast cancer screening; molecular imaging; MR spectroscopy; nuclear medicine ID PROTON-MAGNETIC-RESONANCE; GENE-EXPRESSION PATTERNS; FINE-NEEDLE BIOPSY; IN-VIVO; MR SPECTROSCOPY; H-1 MRS; CANCER; LESIONS; DIAGNOSIS; CHOLINE AB OBJECTIVE. Personalized health care centers around the concept that each tumor and its host environment is unique; optimal treatment and expected response for any given woman presenting with a newly diagnosed breast cancer differ from the care and response of other women. CONCLUSION. As more is understood about the molecular subtypes of breast cancer and as development of targeted therapies progresses, the possibility of earlier treatment response assessment and even improved detection will be realized. C1 [Birdwell, Robyn L.] Brigham & Womens Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02129 USA. [Birdwell, Robyn L.; Mountford, Carolyn E.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Mountford, Carolyn E.] Brigham & Womens Hosp, Ctr Clin Spectroscopy, Dept Radiol, Boston, MA 02129 USA. [Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02129 USA. [Iglehart, J. Dirk] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Birdwell, RL (reprint author), Brigham & Womens Hosp, Dept Radiol, Div Breast Imaging, 75 Francis St, Boston, MA 02129 USA. EM rbirdwell@partners.org NR 63 TC 6 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2009 VL 193 IS 2 BP 367 EP 376 DI 10.2214/AJR.09.3079 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 472RB UT WOS:000268148600014 PM 19620433 ER PT J AU O'Donnell, DH Abbara, S Chaithiraphan, V Yared, K Killeen, RP Cury, RC Dodd, JD AF O'Donnell, David H. Abbara, Suhny Chaithiraphan, Vithaya Yared, Kibar Killeen, Ronan P. Cury, Ricardo C. Dodd, Jonathan D. TI Cardiac Tumors: Optimal Cardiac MR Sequences and Spectrum of Imaging Appearances SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE heart diagnosis; heart neoplasms; MRI; neoplasm metastasis ID CARDIOVASCULAR MAGNETIC-RESONANCE; LEFT-VENTRICULAR THROMBUS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; TRANSTHORACIC ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY; CT ANGIOGRAPHY; ATRIAL MASS; HEART; ENHANCEMENT; DISEASE AB OBJECTIVE. This article reviews the optimal cardiac MRI sequences for and the spectrum of imaging appearances of cardiac tumors. CONCLUSION. Recent technologic advances in cardiac MRI have resulted in the rapid acquisition of images of the heart with high spatial and temporal resolution and excellent myocardial tissue characterization. Cardiac MRI provides optimal assessment of the location, functional characteristics, and soft-tissue features of cardiac tumors, allowing accurate differentiation of benign and malignant lesions. C1 [O'Donnell, David H.; Killeen, Ronan P.; Dodd, Jonathan D.] St Vincents Hosp, Dept Radiol & Cardiol, Cardiac CT & MRI Program, Dublin 4, Ireland. [Abbara, Suhny; Chaithiraphan, Vithaya; Yared, Kibar; Cury, Ricardo C.; Dodd, Jonathan D.] CIMIT, Cardiac MR PET CT Program, Boston, MA USA. [Abbara, Suhny; Yared, Kibar; Cury, Ricardo C.; Dodd, Jonathan D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abbara, Suhny; Yared, Kibar; Cury, Ricardo C.; Dodd, Jonathan D.] Harvard Univ, Sch Med, Boston, MA USA. [Cury, Ricardo C.] Baptist Hosp Miami, Miami, FL USA. [Cury, Ricardo C.] Baptist Miami Cardiac & Vasc Inst, Miami, FL USA. RP Dodd, JD (reprint author), St Vincents Hosp, Dept Radiol & Cardiol, Cardiac CT & MRI Program, Elm Pk, Dublin 4, Ireland. NR 60 TC 56 Z9 62 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2009 VL 193 IS 2 BP 377 EP 387 DI 10.2214/AJR.08.1895 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 472RB UT WOS:000268148600015 PM 19620434 ER PT J AU Randall, GJ Zald, PB Cohen, JI Hamilton, BE AF Randall, Geneva J. Zald, Philip B. Cohen, James I. Hamilton, Bronwyn E. TI Contrast-Enhanced MDCT Characteristics of Parathyroid Adenomas SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Neuroradiology CY MAY 31-JUN 05, 2008 CL New Orleans, LA SP Amer Soc Neuroradiol DE adenoma; hypercalcemia; hyperparathyroidism; parathyroid ID MINIMALLY INVASIVE SURGERY; PRIMARY HYPERPARATHYROIDISM; PREOPERATIVE ULTRASOUND; COMPUTED-TOMOGRAPHY; SUPPLEMENTAL CT; LOCALIZATION; TUMORS; US AB OBJECTIVE. Minimally invasive directed parathyroidectomy has replaced conventional surgical techniques aimed at exploring all four glands in the bilateral neck. These changes have created the need for better preoperative imaging localization techniques. In this article, we describe the CT imaging characteristics of surgically confirmed adenomas and review anatomy and embryology to aid the radiologist in successfully identifying adenomas using contrast-enhanced CT. CONCLUSION. Knowledge of normal CT appearance, contrast enhancement, and expected location are critical to correct interpretation of parathyroid adenoma at CT. C1 [Randall, Geneva J.; Hamilton, Bronwyn E.] Oregon Hlth & Sci Univ, Dept Diagnost Radiol, Portland, OR 97239 USA. [Zald, Philip B.] Oregon Hlth & Sci Ctr, Dept Otolaryngol Head & Neck Surg, Portland, OR USA. [Cohen, James I.] Portland VA Med Ctr, Dept Otolaryngol Head & Neck Surg, Portland, OR USA. RP Randall, GJ (reprint author), Oregon Hlth & Sci Univ, Dept Diagnost Radiol, Mail Code CR 135,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. NR 13 TC 20 Z9 21 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2009 VL 193 IS 2 BP W139 EP W143 DI 10.2214/AJR.08.2098 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 472RB UT WOS:000268148600053 PM 19620416 ER PT J AU Martin, RL Mohtadi, NG Safran, MR Leunig, M Martin, HD McCarthy, J Guanche, CA Kelly, BT Byrd, JWT Clohisy, JC Philippon, MJ Sekiya, JK AF Martin, RobRoy L. Mohtadi, Nicholas G. Safran, Marc R. Leunig, Michael Martin, Hal D. McCarthy, Joseph Guanche, Carlos A. Kelly, Bryan T. Byrd, J. W. Thomas Clohisy, John C. Philippon, Marc J. Sekiya, Jon K. TI Differences in Physician and Patient Ratings of Items Used to Assess Hip Disorders SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE outcome; questionnaire; self-report; instrument; patient perspective ID QUALITY-OF-LIFE; KNEE; DISABILITIES; VALIDATION; SYMPTOMS AB Background: The purpose of this study was to determine what issues are important to active individuals with hip lesions and to assess whether these issues are different from those that surgeons think are important. Hypothesis: A discrepancy will be noted between what patients and surgeons believe to be important. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This study comprised 150 consecutive patients (73 men, 77 women) from the international practices of 9 orthopaedic surgeons specializing in the management of hip disorders. All participants were seeking treatment for musculoskeletal hip disease. Average patient age was 42 +/- 11 years (range, 18-60). Patients and surgeons rated the importance of 146 potential hip outcome assessment items on a 6-point Likert-type scale. Results: Of the 23 items identified as being important to patients, 16 were in the sports and recreation category. The top 11 items that the clinicians thought were most important were rated significantly lower by patients (P < .0005). Specifically, surgeons rated several items as being important that fell into the symptoms, functional limitations, and occupational issues categories, whereas patients did not. That is, a difference was found between patients and clinicians in how they rated items related to symptoms, functional limitations, and occupation (P < .01). A difference was not found between patients and surgeons in how they rated items related to sports and recreation and social-emotional lifestyle (P > .01). Conclusion: The hypothesis of this study was affirmed: a discrepancy was found between what issues patients believe are important and what surgeons perceive as being important to patients. This information may be particularly important when assessing treatment outcomes from a patient's perspective. Clinicians must be careful in presuming that the issues that they are attempting to improve with treatment are issues that are important to patients. These findings also emphasize the importance of discussing appropriate postoperative expectations for those considering surgery. C1 [Sekiya, Jon K.] Univ Michigan, MedSport Dept Orthopaed Surg, Ann Arbor, MI 48106 USA. [Martin, RobRoy L.] Duquesne Univ, Pittsburgh, PA 15219 USA. [Mohtadi, Nicholas G.] Univ Calgary, Calgary, AB, Canada. [Safran, Marc R.] Stanford Univ, Stanford, CA 94305 USA. [Leunig, Michael] Schulthess Clin, Zurich, Switzerland. [Martin, Hal D.] Oklahoma Sports Sci & Orthopaed, Oklahoma City, OK USA. [McCarthy, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guanche, Carlos A.] So Calif Orthoped Inst, Van Nuys, CA USA. [Kelly, Bryan T.] Hosp Special Surg, New York, NY 10021 USA. [Byrd, J. W. Thomas] Nashville Sports Med Fdn, Nashville, TN USA. [Clohisy, John C.] Washington Univ, St Louis, MO USA. [Philippon, Marc J.] Steadman Hawkins Res Fdn, Vail, CO USA. RP Sekiya, JK (reprint author), Univ Michigan, MedSport Dept Orthopaed Surg, 24 Frank Lloyd Wright Dr,POB 0391, Ann Arbor, MI 48106 USA. EM sekiya@umich.edu RI Leunig, Michael/E-7951-2017 OI Leunig, Michael/0000-0002-2036-5416 NR 9 TC 13 Z9 15 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD AUG PY 2009 VL 37 IS 8 BP 1508 EP 1512 DI 10.1177/0363546509333851 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 474MY UT WOS:000268289400006 PM 19417122 ER PT J AU Alpert, JM Kozanek, M Li, GA Kelly, BT Asnis, PD AF Alpert, Joshua M. Kozanek, Michal Li, Guoan Kelly, Bryan T. Asnis, Peter D. TI Cross-Sectional Analysis of the Iliopsoas Tendon and Its Relationship to the Acetabular Labrum An Anatomic Study SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE iliopsoas; acetabulum; hip arthroscopy; cross-sectional anatomy ID INTERNAL SNAPPING HIP; SURGICAL-CORRECTION; TEARS; ARTHROSCOPY; RELEASE AB Background: Hip pain in patients with normal bony anatomy and anterior labral injury may be related to compression of the iliopsoas tendon across the anterior capsulolabral complex. No attempts to characterize the 3-dimensional anatomy of the iliopsoas tendon and its relationship to the acetabular labrum have been reported to date. Hypothesis: The iliopsoas tendon directly overlies the capsulolabral complex. Contribution of the muscle belly and tendon to the overall circumference at the level of the labrum is approximately the same. Study Design: Descriptive laboratory study. Materials and Methods: Eight hip joints were dissected and cross-sectional measurements of the iliopsoas muscle-tendon complex were performed using digital calipers and image analysis software. Results: The iliopsoas tendon in all specimens was located directly anterior to the anterosuperior capsulolabral complex at the 2 to 3 o'clock position. The overall length of the iliopsoas tendon from the lesser trochanter to the acetabular labrum was 75.4 +/- 0.9 mm. The circumference of the iliopsoas tendon at the lesser trochanter was 25.5 +/- 2.6 mm, the iliopsoas tendon at the level of the labrum was 28.4 +/- 2.8 mm, and the iliopsoas tendon-muscle belly complex at the level of the labrum was 63.8 +/- 7.4 mm. At the level of the labrum, the iliopsoas is composed of 44.5% tendon and 55.5% muscle belly. Conclusion: The close anatomic relationship of the iliopsoas tendon to the anterior capsulolabral complex suggests that iliopsoas pathologic changes at this level may lead to labral injury. Additionally, these data suggest that at the level of the labrum, 45% of the tendon-muscle belly complex should be released to release the entire tendinous portion. Clinical Relevance: Knowledge of the cross-sectional anatomy of the iliopsoas tendon and its relationship to the acetabular labrum will better assist surgeons in treating lesions associated with iliopsoas injury. C1 [Li, Guoan] Harvard Univ, Sch Med, Bioengn Lab, MGH, Boston, MA 02114 USA. [Alpert, Joshua M.; Kozanek, Michal; Li, Guoan; Asnis, Peter D.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Alpert, Joshua M.] Midwest Bone & Joint Inst, Barrington, IL USA. [Kelly, Bryan T.] Hosp Special Surg, Dept Orthopaed Surg, New York, NY 10021 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Bioengn Lab, MGH, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU Academic Enrichment Fund of the Department of Orthopaedic Surgery at Massachusetts General Hospital FX We thank the Academic Enrichment Fund of the Department of Orthopaedic Surgery at Massachusetts General Hospital for funding this study. We also acknowledge the donors of the cadaveric specimens. NR 14 TC 22 Z9 22 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD AUG PY 2009 VL 37 IS 8 BP 1594 EP 1598 DI 10.1177/0363546509332817 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 474MY UT WOS:000268289400017 PM 19357107 ER PT J AU Stone, DH Albadawi, H Conrad, MF Entabi, F Stoner, MC Casey, PJ Cambria, RP Watkins, MT AF Stone, David H. Albadawi, Hassan Conrad, Mark F. Entabi, Fateh Stoner, Michael C. Casey, Patrick J. Cambria, Richard P. Watkins, Michael T. TI PJ34, a poly-ADP-ribose polymerase inhibitor, modulates visceral mitochondrial activity and CD14 expression following thoracic aortic ischemia-reperfusion SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Thoracic aortic aneurysm; Visceral ischemia; Reperfusion injury; Inflammation ID TOLL-LIKE RECEPTOR-4; MOLECULAR-MECHANISMS; LIVER-INJURY; RAT; CELLS; CYTOTOXICITY; DAMAGE; DYSFUNCTION; HEPATOCYTES; METABOLISM AB BACKGROUND: Visceral ischemia-reperfusion injury (VI) contributes to adverse outcomes following the repair of thoracoabdominal aneurysms. Experiments were designed to determine whether a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor modulates indexes of metabolic function (mitochondrial activity), inflammatory cell activation, and tissue inflammation (lipopolysaccharide receptor CD14 messenger ribonucleic acid) following VI. METHODS: 129S1/SvImj mice were subjected to thoracic aortic occlusion followed by 48 hours of reperfusion. Normal saline was administered to 25 untreated control mice and PJ34 to 21 mice before and immediately after thoracic aortic ischemia-reperfusion. Sham mice (n = 13) underwent median sternotomy alone. At 48 hours, all animals were euthanized and tissues harvested for quantitative analysis. RESULTS: PJ34 improved intestinal (P < .05) but not hepatic mitochondrial activity following reperfusion. CD14 messenger ribonucleic acid levels in liver (P < .004), kidney (P < .003), and spinal cord (P < .03) tissue were less in PJ34-treated mice. CONCLUSIONS: PJ34 preserved the metabolic function of intestinal but not hepatic tissue during reperfusion. PJ34 uniformly decreased the expression of an important marker of inflammatory cell activation and tissue inflammation in visceral tissue following VI. PARP inhibitors may serve as a therapeutic modality to abrogate the stress response to VI. (c) 2009 Elsevier Inc. All rights reserved. C1 [Stone, David H.; Albadawi, Hassan; Conrad, Mark F.; Entabi, Fateh; Stoner, Michael C.; Casey, Patrick J.; Cambria, Richard P.; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Dept Surg, Boston, MA 02115 USA. RP Watkins, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Dept Surg, Boston, MA 02115 USA. EM mtwatkins@partners.org RI Ji, Haofeng/G-6206-2012 FU EVEREST Foundation; Pacific Vascular Research Foundation; Department of Surgery and Division of Vascular and Endovascular Surgery, Massachusetts General Hospital FX This work was supported by a grant from the EVEREST Foundation, the Pacific Vascular Research Foundation (Wylie Scholar Award), and the Department of Surgery and Division of Vascular and Endovascular Surgery, Massachusetts General Hospital. NR 38 TC 5 Z9 5 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD AUG PY 2009 VL 198 IS 2 BP 250 EP 255 DI 10.1016/j.amjsurg.2008.09.013 PG 6 WC Surgery SC Surgery GA 481GK UT WOS:000268795300018 PM 19268911 ER PT J AU Geyer, JT Lopez-Garcia, MA Sanchez-Estevez, C Sarrio, D Moreno-Bueno, G Franceschetti, I Palacios, J Oliva, E AF Geyer, Julia Turbiner Angeles Lopez-Garcia, Maria Sanchez-Estevez, Carolina Sarrio, David Moreno-Bueno, Gema Franceschetti, Ilaria Palacios, Jose Oliva, Esther TI Pathogenetic Pathways in Ovarian Endometrioid Adenocarcinoma A Molecular Study of 29 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol DE ovary; low and high grade endometrioid carcinoma; beta-catenin; PTEN; KRAS; MSI; p53 ID BETA-CATENIN GENE; MICROSATELLITE INSTABILITY; SEROUS CARCINOMA; P53 GENE; CLINICOPATHOLOGICAL FEATURES; EXPRESSION PATTERN; MUTATIONS; CANCER; TUMORS; PTEN AB It has been recently suggested that ovarian serous carcinoma follows a dualistic pathway with low-grade carcinomas arising from borderline tumors and high-grade carcinomas originating de novo. Similarly, our group has shown that based on their molecular profile endometrioid borderline tumors could predate low-grade endometrioid ovarian carcinomas (EOC). It is not clearly understood if low-grade EOC is in turn related to high-grade EOC, or if high-grade EOC may also arise de novo. The aim of our study was to compare the molecular profile of grade 1, 2, and 3 EOCs. Twenty-nine EOCs were selected including 10 grade 1 (G 1), 11 grade 2 (G2), and 8 grade 3 (G3). Selected blocks were immunostained with P-catenin and p53, and also microdissected, DNA extracted and amplified by polymerase chain reaction with primers for exon 3 of the P-catenin gene, codons 12 and 13 of KRAS and codons I to 9 of PTEN. The length of BAT-26 and BAT-25 was analyzed to determine microsatellite instability (NISI). Patients with G1 EOC ranged from 21 to 71 (mean 52) years, those with G2 tumors ranged from 43 to 66 (mean 56) years, and patients with G3 EOC ranged from 41 to 67 (mean 57) years. Immunohistochemical analysis for beta-catenin showed nuclear staining in 14 cases (7 G 1, 5 G2, and 2 G3 tumors), whereas the rest showed membranous staining. Beta-catenin mutations were found in only 3 G I tumors. KRAS mutations were seen in 5 EOCs (2 G1 and 3 G2). MSI and mutations of PTEN were both detected in 1 G1 and I G2 tumor, respectively. There was no overlapping expression of MSI, beta-catenin, PTEN, or KRAS mutations. Finally, p53 overexpression was present in 6 EOCs (5 G3 and 1 G2),. all G3 p53 positive tumors being negative for all other markers, whereas the G2 tumor also showed a KRAS mutation. In conclusion, beta-catenin and KRAS mutations, and MSI were strongly associated with low-grade EOC. In contrast, p53 overexpression characterized high-grade EOC, with no other molecular alterations present in the vast majority of these tumors. On the basis of these results, we suggest that there may also be a dual pathogenetic pathway for EOC. C1 [Geyer, Julia Turbiner; Franceschetti, Ilaria; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Moreno-Bueno, Gema] Inst Invest Biomed Alberto Sols, Madrid, Spain. [Angeles Lopez-Garcia, Maria; Palacios, Jose] Hosp Univ Virgen del Rocio, Seville, Spain. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org RI Moreno-Bueno, Gema/K-9354-2016 OI Moreno-Bueno, Gema/0000-0002-5030-6687 NR 44 TC 34 Z9 34 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2009 VL 33 IS 8 BP 1157 EP 1163 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 481YR UT WOS:000268850300005 PM 19542870 ER PT J AU Staats, PN Garcia, JJ Dias-Santagata, DC Kuhlmann, G Stubbs, H McCluggage, WG De Nictolis, M Kommoss, F Soslow, RA Iafrate, AJ Oliva, E AF Staats, Paul N. Garcia, Joaquin J. Dias-Santagata, Dora C. Kuhlmann, Georgiana Stubbs, Hannah McCluggage, W. Glenn De Nictolis, Michele Kommoss, Friedrich Soslow, Robert A. Iafrate, A. John Oliva, Esther TI Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCT) Lack the JAZF1-JJAZ1 Translocation Frequently Seen in Endometrial Stromal Tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE uterine tumor resembling ovarian sex-cord tumor (UTROSCT); JAZF1; JJAZ1; SUZ12; fluorescence in situ hybridization (FISH); reverse transcriptase polymerase chain reaction (RT-PCR) ID SMOOTH-MUSCLE DIFFERENTIATION; OF-THE-LITERATURE; JAZF1/JJAZ1 GENE FUSION; IN-SITU HYBRIDIZATION; SARCOMA-CELL-LINE; IMMUNOHISTOCHEMICAL ANALYSIS; CLINICOPATHOLOGIC ANALYSIS; MOLECULAR ANALYSIS; CHROMOSOME CHANGE; NEOPLASMS AB Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare uterine neoplasm composed predominantly or exclusively of cells which resemble those seen in sex cord tumors of the ovary. Since its initial morphologic description, it has been unclear whether UTROSCT represents a variant within the spectrum of endometrial stromal tumors (ESTs), which may rarely exhibit areas of sex cord-like differentiation, or whether it is a distinct uterine neoplasm unrelated to ESTs. Recently, several studies have revealed a recurrent t(7;17) translocation resulting in a JAZF1-JJAZ1 gene fusion in over 60% of EST and its variants, including 2 out of 4 endometrial stromal tumors with sex cord-like elements (ESTSCLE). We examined UTROSCTs for evidence of the JAZF1-JJAZ1 gene fusion by fluorescence in situ hybridization and by reverse transcriptase polymerase chain reaction in 24 and 20 cases, respectively. The JAZF1-JJAZ1 gene fusion was not identified in any tumor by either method. Although we cannot entirely exclude that UTROSCT represents a variant of ESTSCLE which lacks this translocation, our findings suggest that UTROSCT does not share the genetic mechanism common to the majority of ESTs with or without sex cord-like differentiation, and therefore most likely represents a distinct neoplasm unrelated to ESTSCLE. C1 [Staats, Paul N.; Dias-Santagata, Dora C.; Kuhlmann, Georgiana; Stubbs, Hannah; Iafrate, A. John; Oliva, Esther] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Garcia, Joaquin J.; Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [McCluggage, W. Glenn] Royal Grp Hosp Trust, Dept Pathol, Belfast, Antrim, North Ireland. [De Nictolis, Michele] Univ Ancona, Inst Anat & Istol Patol, Ancona, Italy. [Kommoss, Friedrich] Inst Pathol, Mannheim, Germany. RP Staats, PN (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM pstaats@partners.org NR 51 TC 24 Z9 28 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2009 VL 33 IS 8 BP 1206 EP 1212 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 481YR UT WOS:000268850300012 PM 19542872 ER PT J AU Cotten, JF Husain, SS Forman, SA Miller, KW Kelly, EW Nguyen, HH Raines, DE AF Cotten, Joseph F. Husain, S. Shaukat Forman, Stuart A. Miller, Keith W. Kelly, Elizabeth W. Nguyen, Hieu H. Raines, Douglas E. TI Methoxycarbonyl-etomidate A Novel Rapidly Metabolized and Ultra-short-acting Etomidate Analogue that Does Not Produce Prolonged Adrenocortical Suppression SO ANESTHESIOLOGY LA English DT Article ID MULTIPLE TRAUMA PATIENTS; ADULT MALE-VOLUNTEERS; GATED ION CHANNELS; ADRENAL STEROIDOGENESIS; REMIFENTANIL GI87084B; MENINGOCOCCAL SEPSIS; ANESTHETIC ETOMIDATE; SURGICAL PATIENTS; MAJOR METABOLITE; PHARMACOKINETICS AB Background: Etomidate is a rapidly acting sedative-hypnotic that provides hemodynamic stability. it causes prolonged suppression of adrenocortical steroid synthesis; therefore, its clinical utility and safety are limited. The authors describe the results of studies to define the pharmacology of (R)-3-methoxy-3-oxopropyll-(1-phenylethyl)-1H-imidazole-5-carboxylate (MOC-etomidate), the first etomidate analogue designed to be susceptible to ultra-rapid metabolism. Methods: The gamma-aminobutyric acid type A receptor activities of MOC-etomidate and etomidate were compared by using electrophysiological techniques in human alpha(1)beta(2)gamma(2I), receptors. MOC-etomidate's hypnotic concentration was determined in tadpoles by using a loss of righting reflex assay. its in vitro metabolic half-life was measured in human liver S9 fraction, and the resulting metabolite was provisionally identified by using high-performance liquid chromatography/mass spectrometry techniques. The hypnotic and hemodynamic actions of MOC-etomidate, etomidate, and propofol were defined in rats. The abilities of MOC-etomidate and etomidate to inhibit corticosterone production were assessed in rats. Results: MOC-etomidate potently enhanced gamma-aminobutyric acid type A receptor function and produced loss of righting reflex in tadpoles. Metabolism in human liver S9 fraction was first-order, with an in vitro half-fife of 4.4 min versus more than 40 min for etomidate. MOC-etomidate's only detectable metabolite was a car-boxylic acid. in rats, MOC-etomidate produced rapid loss of righting reflex that was extremely brief and caused minimal hemodynamic changes. Unlike etomidate, MOC-etomidate produced no adrenocortical suppression 30 min after administration. Conclusions: MOC-etomidate is an etomidate analogue that retains etomidate's important favorable pharmacological properties. However, it is rapidly metabolized, ultra-short-acting, and does not produce prolonged adrenocortical suppression after bolus administration. C1 [Cotten, Joseph F.; Husain, S. Shaukat; Forman, Stuart A.; Miller, Keith W.; Kelly, Elizabeth W.; Nguyen, Hieu H.; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,GRB444, Boston, MA 02114 USA. EM draines@partners.org FU National Institutes of Health, Bethesda, Maryland [P01-GM58448]; Foundation for Anesthesia Education and Research, Rochester, Minnesota; Department of Anesthesia and Critical Care; Massachusetts General Hospital, Boston, Massachusetts FX Supported by grant P01-GM58448 from the National Institutes of Health, Bethesda, Maryland, by the Foundation for Anesthesia Education and Research, Rochester, Minnesota, and by the Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts. The Massachusetts General Hospital has submitted a patent application for MOC-etomidate and related analogues. Five authors (Drs. Raines, Cotten, Forman, Husain, and Miller), their laboratories, the Department of Anesthesia and Critical Care at the Massachusetts General Hospital, and the Massachusetts General Hospital could receive royalties relating to the development or sale of these drugs. NR 47 TC 51 Z9 54 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 2009 VL 111 IS 2 BP 240 EP 249 PG 10 WC Anesthesiology SC Anesthesiology GA 475FB UT WOS:000268342700005 PM 19625798 ER PT J AU Wiik, AC Thoresen, SI Wade, C Lindblad-Toh, K Lingaas, F AF Wiik, A. C. Thoresen, S. I. Wade, C. Lindblad-Toh, K. Lingaas, F. TI A population study of a mutation allele associated with cone-rod dystrophy in the standard wire-haired dachshund SO ANIMAL GENETICS LA English DT Article DE age of mutation; cone-rod dystrophy; NPHP4; standard wire-haired dachshund AB P>Cone-rod dystrophy in the standard wire-haired dachshund (SWHD) is inherited as a simple autosomal recessive trait and the recently discovered mutation is widespread within the SWHD population in Norway and other Scandinavian countries. The gene frequency was estimated to be 4.8%. On the basis of the assumption that the size of the ancestral haplotype around a mutation is inversely correlated with the number of generations since the mutation arose, we have found that the mutation is of a relatively recent origin. The conserved haplotype was found to be 8 Mb in size and therefore we estimate that the mutation arose roughly eight generations (approximately 37 years) ago. This indicates that the mutation arose after breed separation. C1 [Wiik, A. C.; Lingaas, F.] Norwegian Sch Vet Sci, Dept Basic Sci & Aquat Med, Div Genet, N-0033 Oslo, Norway. [Thoresen, S. I.] Norwegian Sch Vet Sci, Dept Basic Sci & Aquat Med, Sect Clin Pathol, Cent Lab, N-0033 Oslo, Norway. [Wade, C.; Lindblad-Toh, K.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02141 USA. [Wade, C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lindblad-Toh, K.] Uppsala Univ, Dept Med Biochem & Microbiol, S-75124 Uppsala, Sweden. RP Wiik, AC (reprint author), Norwegian Sch Vet Sci, Dept Basic Sci & Aquat Med, Div Genet, POB 8146 Dep, N-0033 Oslo, Norway. EM anne.wiik@veths.no FU Norwegian School of Veterinary Science; EURYI award; Swedish MRC; Foundation for Strategic Research FX This study was supported by the Norwegian School of Veterinary Science. KLT is supported by a EURYI award, the Swedish MRC and Foundation for Strategic Research. NR 8 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0268-9146 J9 ANIM GENET JI Anim. Genet. PD AUG PY 2009 VL 40 IS 4 BP 572 EP 574 DI 10.1111/j.1365-2052.2009.01877.x PG 3 WC Agriculture, Dairy & Animal Science; Genetics & Heredity SC Agriculture; Genetics & Heredity GA 471BO UT WOS:000268028100029 PM 19392817 ER PT J AU Patel, SN Tsai, CL Boudreaux, ED Kilgannon, JH Sullivan, AF Blumenthal, D Camargo, CA AF Patel, Sundip N. Tsai, Chu-Lin Boudreaux, Edwin D. Kilgannon, J. Hope Sullivan, Ashley F. Blumenthal, David Camargo, Carlos A., Jr. TI Multicenter study of cigarette smoking among patients presenting to the emergency department with acute asthma SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID QUALITY-OF-LIFE; LUNG-FUNCTION; ANTIBIOTIC USE; FOLLOW-UP; RESPIRATORY-INFECTIONS; ADULTS; CESSATION; SYMPTOMS; DECLINE; HEALTH AB Background: Many studies have focused on smoking and chronic asthma severity. However, research on the relationship between smoking and acute asthma severity in an acute care setting is sparse. Objectives: To determine the smoking prevalence among emergency department (ED) patients with acute asthma and to investigate the relationships between smoking and acute asthma severity. Methods: A 63-site medical record review study of ED patients, ages 14 to 54 years, with a principal diagnosis of acute asthma was performed. Patients with chronic obstructive pulmonary disease were excluded. Measurements for acute asthma severity included sociodemographic factors, asthma medical history, ED presentation, clinical Course, medications administered, and return visit within 48 hours. Results: A total of 4,052 patient medical records were reviewed. A total of 1,332 patients (33%; 95% confidence interval, 31%-34%) were documented as smokers. No statistically significant differences were found between smokers and nonsmokers in vital signs, oxygen saturation, peak expiratory flow, and administration of asthma medications. By contrast, smokers were more likely than nonsmokers to receive antibiotics in the ED (12% vs 9%, P < .001) or at discharge (23% vs 14%, P < .001). A multivariate analysis confirmed that smoking status was independently associated with antibiotic administration (odds ratio, 1.6; 95% confidence interval, 1.3-1.8). Conclusions: One-third of ED patients with acute asthma smoked cigarette. Smokers and nonsmokers did not differ in their acute asthma severity. Asthmatic smokers, however, were more likely to receive antibiotics, even when adjusting for other possible confounders. Ann Allergy Asthma Immunol. 2009;103:121-127. C1 [Patel, Sundip N.; Boudreaux, Edwin D.; Kilgannon, J. Hope] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, Camden, NJ 08103 USA. [Tsai, Chu-Lin; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Boudreaux, Edwin D.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, Camden, NJ 08103 USA. [Blumenthal, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Blumenthal, David; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA USA. RP Patel, SN (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden Cooper Univ Hosp, Dept Emergency Med, 1 Cooper Plaza, Camden, NJ 08103 USA. EM patel-sundip@cooperhealth.edu OI Boudreaux, Edwin/0000-0002-3223-6371; TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality (Rockville, Maryland) [R01 HS-13099] FX The National Emergency Department Safety Study Was Supported by grant R01 HS-13099 from the Agency for Healthcare Research and Quality (Rockville, Maryland). NR 43 TC 12 Z9 14 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD AUG PY 2009 VL 103 IS 2 BP 121 EP 127 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 480KC UT WOS:000268732300006 PM 19739424 ER PT J AU Beam, DM Courtney, DM Kabrhel, C Moore, CL Richman, PB Kline, JA AF Beam, Daren M. Courtney, D. Mark Kabrhel, Christopher Moore, Christopher L. Richman, Peter B. Kline, Jeffrey A. TI Risk of Thromboembolism Varies, Depending on Category of Immobility in Outpatients SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID PULMONARY-EMBOLISM; VENOUS THROMBOEMBOLISM; AIR-TRAVEL; HYPOXIA; RULE AB Study objective: Immobility predisposes to venous thromboembolism, but this risk may vary, depending on the underlying cause of immobility. Methods: This was a prospective, longitudinal outcome study of self-presenting emergency department (ED) patients who were from 12 hospitals and had suspected venous thromboembolism. Using explicit written criteria, clinicians recorded clinical features of each patient in the ED by using a Web-based data form. The form required one of 6 types of immobility: no immobility, general or whole-body immobility greater than 48 hours, limb (orthopedic) immobility, travel greater than 8 hours causing immobility within the previous 7 days, neurologic paralysis, or other immobility not listed above. Patients were followed for 45 days for outcome of venous thromboembolism, which required positive imaging results and clinical plan to treat. Odds ratios (ORs) were derived from logistic regression including 12 covariates. Results: From 7,940 patients enrolled, 545 of 7,940 (6.9%) were diagnosed with venous thromboembolism (354 pulmonary embolism, 72 deep venous thrombosis, 119 pulmonary embolism and deep venous thrombosis). Risk of venous thromboembolism varied, depending on immobility type: limb (OR=2.24; 95% confidence interval [CI] 1.40 to 3.60), general (OR=1.76; 95% CI 1.26 to 2.44), other (OR=1.97; 95% CI 1.25 to 3.09), neurologic (OR=2.23; 95% CI 1.01 to 4.92), and travel (OR=1.19; 95% CI 0.85 to 1.67). Other significant risk factors from multivariate analysis included age greater than 50 years (OR =1.5; 95% CI 1.25 to 1.82), unilateral leg swelling (OR=2.68; 95% CI 2.13 to 3.37), previous venous thromboembolism (OR=2.99; 95% CI 2.41 to 3.71), active malignancy (OR=2.23; 95% CI 1.69 to 2.95), and recent surgery (OR=2.12; 95% CI 1.61 to 2.81). Conclusion: In a large cohort of symptomatic ED patients, risk of venous thromboembolism was substantially increased by presence of limb, whole-body, or neurologic immobility but not by travel greater than 8 hours. These data show the importance of clarifying the cause of immobility in risk assessment of venous thromboembolism. [Ann Emerg Med. 2009;54:147-152.] C1 [Kline, Jeffrey A.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28323 USA. [Beam, Daren M.] E Carolina Univ, Brody Sch Med, Greenville, NC USA. [Courtney, D. Mark] NW Mem Hosp, Chicago, IL 60611 USA. [Kabrhel, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moore, Christopher L.] Yale Univ, Sch Med, New Haven, CT USA. [Richman, Peter B.] Mayo Clin, Scottsdale, AZ USA. RP Kline, JA (reprint author), Carolinas Med Ctr, Dept Emergency Med, POB 32861, Charlotte, NC 28323 USA. EM jkline@carolinas.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU Emergency Medicine Foundation FX Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. Supported by a Resident Research Award from the Emergency Medicine Foundation. NR 9 TC 20 Z9 21 U1 0 U2 1 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 AUG PY 2009 VL 54 IS 2 BP 147 EP 152 DI 10.1016/j.annemergmed.2008.10.033 PG 6 WC Emergency Medicine SC Emergency Medicine GA 479YA UT WOS:000268696900003 PM 19135280 ER PT J AU Green, SM Cote, CJ AF Green, Steven M. Cote, Charles J. TI Ketamine and Neurotoxicity: Clinical Perspectives and Implications for Emergency Medicine SO ANNALS OF EMERGENCY MEDICINE LA English DT Review ID METHYL-D-ASPARTATE; PERITONSILLAR-ABSCESS-DRAINAGE; PEDIATRIC PROCEDURAL SEDATION; DEPARTMENT SAFETY PROFILE; NEURON-SPECIFIC ENOLASE; DEVELOPING RAT-BRAIN; INFANT MOUSE-BRAIN; ADVERSE EVENTS; CELL-DEATH; INTRAMUSCULAR KETAMINE AB Rodent and monkey research has shown that ketamine can induce accelerated programmed nerve cell death (apoptosis) when administered in high doses, for prolonged periods, or both. Concern about similar neurotoxicity with human therapeutic use has prompted ongoing investigations by the Food and Drug Administration and National Institutes of Health. If the results of these inquiries are unfavorable to ketamine, such action could ultimately lead to restricted availability of this drug or even its discontinuation from the market. This article discusses the limitations of the published animal research, the challenges in extrapolating such data to humans, the need for further animal and human investigations, and the potential adverse effect on current clinical practice that might result, should the use of ketamine be restricted or the drug removed from the market. [Ann Emerg Med. 2009;54: 181-190.] C1 [Green, Steven M.] Loma Linda Univ, Med Ctr, Dept Emergency Med, Loma Linda, CA USA. [Green, Steven M.] Childrens Hosp, Loma Linda, CA USA. [Cote, Charles J.] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Cote, Charles J.] Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. RP Green, SM (reprint author), Loma Linda Univ, Med Ctr A108, 11234 Anderson St, Loma Linda, CA 92354 USA. EM steve@viridissimo.com FU Annals policy FX Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. NR 119 TC 28 Z9 29 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2009 VL 54 IS 2 BP 181 EP 190 DI 10.1016/j.annemergmed.2008.10.003 PG 10 WC Emergency Medicine SC Emergency Medicine GA 479YA UT WOS:000268696900010 PM 18990467 ER PT J AU Carr, BG Branas, CC Metlay, JP Sullivan, AF Camargo, CA AF Carr, Brendan G. Branas, Charles C. Metlay, Joshua P. Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Access to Emergency Care in the United States SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ACUTE ISCHEMIC-STROKE; TRAUMA CENTERS; SEVERE SEPSIS; SEPTIC SHOCK; ANGIOPLASTY; GUIDELINES; MANAGEMENT; MORTALITY; THERAPY AB Study objective: Rapid access to emergency services is essential for emergency care-sensitive conditions such as acute myocardial infarction, stroke, sepsis, and major trauma. We seek to determine US population access to an emergency department (ED). Methods: The National Emergency Department Inventories-USA was used to identify the location, annual visit volume, and teaching status of all EDs in the United States. EDs were categorized as any ED, by patient volume, and by teaching status. Driving distances, driving speeds, and out-of-hospital times were estimated with validated models and adjusted for population density. Access was determined by summing the population that could reach an ED within the specified intervals. Results: Overall, 71% of the US population has access to an ED within 30 minutes, and 98% has access within 60 minutes. Access to teaching hospitals was more limited, with 16% having access within 30 minutes and 44% within 60 minutes. Rural states had lower access to all types of EDs. Conclusion: Although the majority of the US population has access to an ED, there are regional disparities in ED access, especially by rurality. Future efforts should measure the relationship between access to emergency services and outcomes for emergency care-sensitive conditions. The development of a regionalized emergency care delivery system should be explored. [Ann Emerg Med. 2009;54:261-269.] C1 [Carr, Brendan G.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Carr, Brendan G.; Branas, Charles C.; Metlay, Joshua P.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Carr, Brendan G.; Metlay, Joshua P.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Carr, Brendan G.; Branas, Charles C.; Metlay, Joshua P.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Carr, Brendan G.; Branas, Charles C.; Metlay, Joshua P.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] VA Med Ctr, Philadelphia, PA USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Carr, BG (reprint author), 932 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM Carrb@upenn.edu FU Annals policy; Robert Wood Johnson Foundation; National Library of Medicine [R21LM008700] FX Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. The study was supported by the Robert Wood Johnson Foundation and the National Library of Medicine (R21LM008700). NR 33 TC 55 Z9 55 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2009 VL 54 IS 2 BP 261 EP 269 DI 10.1016/j.annemergmed.2008.11.016 PG 9 WC Emergency Medicine SC Emergency Medicine GA 479YA UT WOS:000268696900022 PM 19201059 ER PT J AU Verbeek, MM Kremer, BPH Rikkert, MO van Domburg, PHMF Skehan, ME Greenberg, SM AF Verbeek, Marcel M. Kremer, Berry P. H. Rikkert, Marcel Olde van Domburg, Peter H. M. F. Skehan, Maureen E. Greenberg, Steven M. TI Cerebrospinal Fluid Amyloid beta(40) Is Decreased in Cerebral Amyloid Angiopathy SO ANNALS OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; ACCUMULATION; BRAIN; HEMORRHAGE; PRECURSOR; PATHOLOGY; DEMENTIA; DEPOSITS; MUTATION; PLAQUES AB Cerebral amyloid angiopathy is caused by deposition of the amyloid P protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid beta(40) (P < 0.01 vs controls or Alzheimer disease) and amyloid beta(42) concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid beta(42) and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid beta(40) as well as amyloid beta(42) protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid P proteins toward the cerebrospinal fluid. C1 [Verbeek, Marcel M.; Kremer, Berry P. H.] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Donders Ctr Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Verbeek, Marcel M.] Radboud Univ Nijmegen, Med Ctr, Lab Pediat & Neurol, Donders Ctr Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Verbeek, Marcel M.; Kremer, Berry P. H.; Rikkert, Marcel Olde] Radboud Univ Nijmegen, Med Ctr, Alzheimer Ctr Nijmegen, Donders Ctr Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Rikkert, Marcel Olde] Radboud Univ Nijmegen, Med Ctr, Dept Geriatr Med, Donders Ctr Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [van Domburg, Peter H. M. F.] Maasland Hosp, Dept Neurol, Sittard, Netherlands. [Skehan, Maureen E.; Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Ctr, Boston, MA 02114 USA. [Skehan, Maureen E.; Greenberg, Steven M.] Harvard Univ, Sch Med, Boston, MA USA. RP Verbeek, MM (reprint author), Radboud Univ Nijmegen, Med Ctr, Lab Pediat & Neurol LKN 830, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM m.verbeek@cukz.umcn.nl RI Verbeek, Marcel/D-1971-2010; Olde Rikkert, Marcel/D-9773-2012; Olde Rikkert, M.G.M./H-8078-2014 OI Olde Rikkert, M.G.M./0000-0003-1397-1677 FU Zon-MW (Vidi-Vernieuwingsimpuls) [917.46.331]; US National Institutes of Health [R01 AG26484] FX Supported by a grant from Zon-MW (Vidi-Vernieuwingsimpuls, 917.46.331) to M.M.V. and the US National Institutes of Health (R01 AG26484) to S.M.G. NR 20 TC 62 Z9 63 U1 1 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 AUG PY 2009 VL 66 IS 2 BP 245 EP 249 DI 10.1002/ana.21694 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 494UX UT WOS:000269845400018 PM 19743453 ER PT J AU Goldhirsch, A Ingle, JN Gelber, RD Coates, AS Thurlimann, B Senn, HJ AF Goldhirsch, A. Ingle, J. N. Gelber, R. D. Coates, A. S. Thuerlimann, B. Senn, H. -J. TI Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009 SO ANNALS OF ONCOLOGY LA English DT Article DE early breast cancer; St Gallen Consensus; therapies ID CARCINOMA IN-SITU; CIRCULATING TUMOR-CELLS; SENTINEL LYMPH-NODE; POSTMENOPAUSAL WOMEN; LOCAL RECURRENCE; GENE-EXPRESSION; ADJUVANT CHEMOTHERAPY; ESTROGEN-RECEPTOR; PREOPERATIVE CHEMOTHERAPY; CONSERVING THERAPY AB The 11(th) St Gallen (Switzerland) expert consensus meeting on the primary treatment of early breast cancer in March 2009 maintained an emphasis on targeting adjuvant systemic therapies according to subgroups defined by predictive markers. Any positive level of estrogen receptor (ER) expression is considered sufficient to justify the use of endocrine adjuvant therapy in almost all patients. Overexpression or amplification of HER2 by standard criteria is an indication for anti-HER2 therapy for all but the very lowest risk invasive tumours. The corollary is that ER and HER2 must be reliably and accurately measured. Indications for cytotoxic adjuvant therapy were refined, acknowledging the role of risk factors with the caveat that risk per se is not a target. Proliferation markers, including those identified in multigene array analyses, were recognised as important in this regard. The threshold for indication of each systemic treatment modality thus depends on different criteria which have been separately listed to clarify the therapeutic decision-making algorithm. C1 [Goldhirsch, A.] European Inst Oncol, Int Breast Canc Study Grp, I-20141 Milan, Italy. [Goldhirsch, A.] Oncol Inst So Switzerland, Int Breast Canc Study Grp, Bellinzona, Switzerland. [Ingle, J. N.] Mayo Clin, Ctr Canc, Breast Canc Res Program, Rochester, MN USA. [Gelber, R. D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Coates, A. S.] Univ Sydney, Sch Publ Hlth, Int Breast Canc Study Grp, Sydney, NSW 2006, Australia. [Thuerlimann, B.] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Senn, H. -J.] Tumor & Breast Ctr ZeTuP, St Gallen, Switzerland. RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org OI Gnant, Michael/0000-0003-1002-2118; Gligorov, Joseph/0000-0002-9900-6386 NR 85 TC 763 Z9 822 U1 8 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2009 VL 20 IS 8 BP 1319 EP 1329 DI 10.1093/annonc/mdp322 PG 11 WC Oncology SC Oncology GA 481JR UT WOS:000268806700004 PM 19535820 ER PT J AU Colleoni, M Sun, Z Martinelli, G Basser, RL Coates, AS Gelber, RD Green, MD Peccatori, F Cinieri, S Aebi, S Viale, G Price, KN Goldhirsch, A AF Colleoni, M. Sun, Z. Martinelli, G. Basser, R. L. Coates, A. S. Gelber, R. D. Green, M. D. Peccatori, F. Cinieri, S. Aebi, S. Viale, G. Price, K. N. Goldhirsch, A. CA Int Breast Canc Study Grp TI The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant treatment; dose-intensive chemotherapy; early breast cancer; endocrine responsiveness ID STEM-CELL SUPPORT; CONVENTIONAL ADJUVANT CHEMOTHERAPY; CLINICAL-TRIALS; PROGNOSTIC IMPACT; RANDOMIZED-TRIAL; PRIMARY THERAPY; SURVIVAL; WOMEN; INTENSIFICATION; AMENORRHEA AB Patients and methods: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features. Results: At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58-1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03). Conclusions: After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged. C1 [Colleoni, M.] European Inst Oncol, Dept Med, Res Unit Med Senol, I-20141 Milan, Italy. [Gelber, R. D.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr,Frontier Sci &, Boston, MA 02115 USA. [Martinelli, G.; Peccatori, F.; Cinieri, S.] European Inst Oncol, Dept Med, Div Hematol Oncol, I-20141 Milan, Italy. [Basser, R. L.] Royal Melbourne Hosp, Ctr Dev Canc Therapy, Parkville, Vic 3050, Australia. [Coates, A. S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, A. S.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Green, M. D.] Royal Melbourne & Western Hosp, Dept Hematol & Med Oncol, Melbourne, Vic, Australia. [Cinieri, S.] San Antonio Perrino Hosp, Div Med Oncol, Brindisi, Italy. [Cinieri, S.] San Antonio Perrino Hosp, Breast Unit, Brindisi, Italy. [Aebi, S.] Univ Hosp, Dept Med Oncol, Bern, Switzerland. [Aebi, S.] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Viale, G.] Univ Milan, European Inst Oncol, Div Pathol & Lab Med, Milan, Italy. [Goldhirsch, A.] Oncol Inst So Switzerland, Dept Res, Bellinzona, Switzerland. RP Colleoni, M (reprint author), European Inst Oncol, Dept Med, Res Unit Med Senol, Via Ripamonti 435, I-20141 Milan, Italy. EM marco.colleoni@ieo.it RI friedlander, michael/G-3490-2013; Aebi, Stefan/F-2004-2010; Wyld, David/B-8893-2015 OI friedlander, michael/0000-0002-6488-0604; Aebi, Stefan/0000-0002-3383-9449; Wyld, David/0000-0001-9523-4333 FU Swiss Group for Clinical Cancer Research; Frontier Science and Technology Research Foundation; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; National Cancer Institute [CA-75362]; Swedish Cancer Society; Foundation for Clinical Research of Eastern Switzerland; Amgen, Australia; Pharmacia (now Pfizer) Australia; National Health and Medical Research Council of Australia FX Swiss Group for Clinical Cancer Research; Frontier Science and Technology Research Foundation; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; National Cancer Institute (CA-75362); Swedish Cancer Society; Foundation for Clinical Research of Eastern Switzerland; Amgen, Australia; Pharmacia (now Pfizer) Australia; National Health and Medical Research Council of Australia. NR 31 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2009 VL 20 IS 8 BP 1344 EP 1351 DI 10.1093/annonc/mdp024 PG 8 WC Oncology SC Oncology GA 481JR UT WOS:000268806700007 PM 19468030 ER PT J AU Temple, LK Romanus, D Niland, J Veer, AT Weiser, MR Skibber, J Wilson, J Rajput, A Benson, A Wong, YN Schrag, D AF Temple, Larissa K. Romanus, Dorothy Niland, Joyce Veer, Anna Ter Weiser, Martin R. Skibber, John Wilson, John Rajput, Ashwani Benson, Al Wong, Yu Ning Schrag, Deborah TI Factors Associated With Sphincter-Preserving Surgery for Rectal Cancer at National Comprehensive Cancer Network Centers SO ANNALS OF SURGERY LA English DT Article ID RANDOMIZED MULTICENTER TRIAL; QUALITY-OF-LIFE; HOSPITAL VOLUME; ABDOMINOPERINEAL EXCISION; ANTERIOR RESECTION; TERM OUTCOMES; PRESERVATION; RADIOTHERAPY; MANAGEMENT; CASELOAD AB Objective: To determine rate and predictors of sphincter-preserving surgery (SPS) for rectal cancer patients treated at specialty institutions. Summary Background Data: SPS has been considered a surrogate for surgical quality, and sphincter preservation is tremendously important to patients. Evidence of association between case volume and SPS rate has prompted recommendations that all rectal cancer patients undergo surgery at specialty institutions. However, rates of SPS, and the factors associated with ability to perform SPS, have not been well-characterized. Methods: A prospective registry of all colorectal cancer patients treated at 7 National Comprehensive Cancer Network institutions was used to identify patients with clinical stage I-III rectal cancer undergoing surgery (n = 674) between September 2005 and October 2007. Patient, tumor and treatment factors were abstracted; patients' clinical characteristics with and without SPS were compared using descriptive statistics and multivariable logistic regression. Results: Of 674 identified patients (median age, 58.2; 60% male), 520 (77%) had SPS. Of these, 240 had low anterior resection with coloanal anastomosis, 268 low anterior resection without coloanal anastomosis; 12 had other SPS procedures. Sixty-two percent had a temporary diverting stoma. On multivariable analyses, independent predictors of SPS included younger age at diagnosis, proximal location in the rectum, nonfixed tumor, and institution. Conclusions: SPS rates at National Comprehensive Cancer Network institutions exceed those seen in population-based samples and clinical trials. In addition to expected variation in SPS rates based on patient and tumor characteristics, we identified variation among institutions. Although the optimal rate of SPS remains unknown, this provides areas for further research and potential performance improvement. C1 [Temple, Larissa K.] Mem Sloan Kettering Canc Ctr, Dept Surg, Colorectal Serv, New York, NY 10065 USA. [Romanus, Dorothy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Niland, Joyce; Veer, Anna Ter] City Hope Canc Ctr, Dept Biostat, Duarte, CA USA. [Skibber, John] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wilson, John] Ohio State Univ, Richard J Solove Res Inst, Columbus, OH 43210 USA. [Wilson, John] Ohio State Univ, Dept Urol, Arthur G James Canc Hosp, Columbus, OH 43210 USA. [Rajput, Ashwani] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Benson, Al] Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Wong, Yu Ning; Schrag, Deborah] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Temple, LK (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Colorectal Serv, 1275 York Ave,Room C-1079, New York, NY 10065 USA. EM templel@mskcc.org FU NCCN FX The authors thank the NCCN and its financial and material support in the development of the NCCN Outcomes Database. In particular, we thank the following people for their contributions to this project: all of the study participants, the clinical research associates for careful abstraction of these data, Janet Nikowitz for administrative assistance; and the NCCN CRC Disease-Specific Executive committee for helpful comments and suggestions throughout this study. NR 28 TC 26 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 2009 VL 250 IS 2 BP 260 EP 267 DI 10.1097/SLA.0b013e3181ae330e PG 8 WC Surgery SC Surgery GA 482GS UT WOS:000268873400014 PM 19638922 ER PT J AU Scherer, SS Pietramaggiori, G Matthews, J Perry, S Assmann, A Carothers, A Demcheva, M Muise-Helmericks, RC Seth, A Vournakis, JN Valeri, RC Fischer, TH Hechtman, HB Orgill, DP AF Scherer, Saja Sandra Pietramaggiori, Giorgio Matthews, Jasmine Perry, Samuel Assmann, Anke Carothers, Adelaide Demcheva, Marina Muise-Helmericks, Robin C. Seth, Arun Vournakis, John N. Valeri, Robert C. Fischer, Thomas H. Hechtman, Herbert B. Orgill, Dennis P. TI Poly-N-Acetyl Glucosamine Nanofibers A New Bioactive Material to Enhance Diabetic Wound Healing by Cell Migration and Angiogenesis SO ANNALS OF SURGERY LA English DT Article ID MEDIATED HEMOSTASIS; ANGIOGENESIS; DYSFUNCTION; ACTIVATION; MECHANISMS; P63 AB Introduction: In several fields of surgery, the treatment of complicated tissue defects is an unsolved clinical problem. In particular, the use of tissue scaffolds has been limited by poor revascularization and integration. In this study, we developed a polymer, poly-N-acetyl-glucosamine (sNAG), with bioactive properties that may be useful to overcome these limitations. Objective: To develop a scaffold-like membrane with bioactive properties and test the biologic effects in vitro and in vivo in diabetic wound healing. Methods: In vitro, cells-nanofibers interactions were tested by cell metabolism and migration assays. In vivo, full thickness wounds in diabetic mice (n = 15 per group) were treated either with sNAG scaffolds, with a cellulosic control material, or were left untreated. Wound healing kinetics, including wound reepithelialization and wound contraction as well as microscopic metrics such as tissue growth, cell proliferation (Ki67), angiogenesis (PECAM-1), cell migration (MAP-Kinase), and keratinocyte migration (p 63) were monitored over a period of 28 days. Messenger RNA levels related to migration (uPAR), angiogenesis (VEGF), inflammatory response (IL-1 beta), and extracellular matrix remodeling (MMP3 and 9) were measured in wound tissues. Results: sNAG fibers stimulated cell metabolism and the in vitro migratory activity of endothelial cells and fibroblasts. sNAG membranes profoundly accelerated wound closure mainly by reepithelialization and increased keratinocyte migration (7.5-fold), granulation tissue formation (2.8-fold), cell proliferation (4-fold), and vascularization (2.7-fold) compared with control wounds. Expression of markers of angiogenesis (VEGF), cell migration (uPAR) and ECM remodeling (MMP3, MMP9) were up-regulated in sNAG treated wounds compared with controls. Conclusions: The key mechanism of the bioactive membranes is the cell-nanofiber stimulatory interaction. Engineering of bioactive materials may represent the clinical solution for a number of complex tissue defects. C1 [Scherer, Saja Sandra; Pietramaggiori, Giorgio; Matthews, Jasmine; Orgill, Dennis P.] Harvard Univ, Div Plast Surg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Perry, Samuel; Hechtman, Herbert B.] Harvard Univ, Dept Surg, Vasc Biol Program, Sch Med,Childrens Hosp Boston, Boston, MA 02115 USA. [Assmann, Anke] Harvard Univ, Joslin Diabet Ctr, Sch Med, Boston, MA 02115 USA. [Carothers, Adelaide] Harvard Univ, Dept Surg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Demcheva, Marina; Vournakis, John N.] Marine Polymer Technol, Danvers, MA USA. [Muise-Helmericks, Robin C.] Med Univ S Carolina, Hollings Canc Ctr, Dept Cell Biol & Anat, Charleston, SC 29425 USA. [Seth, Arun] Sunnybrook Hlth Sci Ctr, Toronto, CA USA. [Valeri, Robert C.] USN, Blood Res Lab Inc, Boston, MA USA. [Fischer, Thomas H.] Univ N Carolina, Francis Owen Blood Lab, Chapel Hill, NC USA. RP Orgill, DP (reprint author), Harvard Univ, Div Plast Surg, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM dorgill@partners.org OI Orgill, Dennis/0000-0002-8279-7310 FU Marine Polymer Technologies, Inc., Danvers, MA; [R01 HL84565] FX Supported by Marine Polymer Technologies, Inc., Danvers, MA (material and financial) and R01 HL84565 (to R.M.H.). NR 22 TC 39 Z9 40 U1 0 U2 9 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 AUG PY 2009 VL 250 IS 2 BP 322 EP 330 DI 10.1097/SLA.0b013e3181ae9d45 PG 9 WC Surgery SC Surgery GA 482GS UT WOS:000268873400025 PM 19638916 ER PT J AU McGory, ML Kao, KK Shekelle, PG Rubenstein, LZ Leonardi, MJ Parikh, JA Fink, A Ko, CY AF McGory, Marcia. L. Kao, Kenneth K. Shekelle, Paul G. Rubenstein, Laurence Z. Leonardi, Michael J. Parikh, Janak A. Fink, Arlene Ko, Clifford Y. TI Developing Quality Indicators for Elderly Surgical Patients SO ANNALS OF SURGERY LA English DT Article ID CORONARY REVASCULARIZATION; VULNERABLE ELDERS; ASSESSING CARE; OF-CARE; SURGERY; CRITERIA; POPULATION; UNDERUSE; CANCER; PANEL AB Objective: To develop process-based quality indicators to improve perioperative care for elderly surgical patients. Background: The population is aging and expanding, and physicians must continue to optimize elderly surgical care to meet the anticipated increase in surgical services. We sought to develop process-based quality indicators applicable to virtually all disciplines of surgery to identify necessary and meaningful ways to improve surgical care and outcomes in the elderly. Methods: We identified candidate perioperative quality indicators for elderly patients undergoing ambulatory, or major elective or nonelective inpatient surgery through structured interviews with thought leaders and systematic reviews of the literature. An expert panel of physicians in surgery, geriatrics, anesthesia, critical care, internal, and rehabilitation medicine formally rated the indicators using a modification of the RAND/UCLA Appropriateness Methodology. Results: Ninety-one of 96 candidate indicators were rated as valid. They were categorized into 8 domains: comorbidity assessment, elderly issues, medication use, patient-provider discussions, intraoperative care, postoperative management, discharge planning, and ambulatory surgery. Of note, 71 (78%) of the indicators rated as valid address processes of care not routinely performed in younger surgical populations. Conclusions: Attention to the quality of care in elderly patients is of great importance due to the increasing numbers of elderly undergoing surgery. This project used a validated methodology to identify and rate process measures to achieve high quality perioperative care for elderly surgical patients. C1 [McGory, Marcia. L.; Kao, Kenneth K.; Leonardi, Michael J.; Parikh, Janak A.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rubenstein, Laurence Z.] VA Greater Los Angeles Healthcare Syst, Dept Med, David Geffen Sch Med, Los Angeles, CA USA. [Fink, Arlene] VA Greater Los Angeles Healthcare Syst, Dept Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, Los Angeles, CA USA. RP McGory, ML (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, 72-215 Ctr Hlth Sci,Box 956904,10833 Conte Ave, Los Angeles, CA 90095 USA. EM mmcgory@mednet.ucla.edu FU NIA NIH HHS [5R21AG028121-02] NR 23 TC 48 Z9 48 U1 0 U2 0 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 AUG PY 2009 VL 250 IS 2 BP 338 EP 347 DI 10.1097/SLA.0b013e3181ae575a PG 10 WC Surgery SC Surgery GA 482GS UT WOS:000268873400027 PM 19638913 ER PT J AU Ahmadiyeh, N Stoleru, MA Raza, S Lester, SC Golshan, M AF Ahmadiyeh, Nasim Stoleru, Mariana A. Raza, Sughra Lester, Susan C. Golshan, Mehra TI Management of Intraductal Papillomas of the Breast: An Analysis of 129 Cases and Their Outcome SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 62nd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 05-08, 2009 CL Phoenix, AZ SP Soc Surg Oncol ID CORE-NEEDLE-BIOPSY; PAPILLARY LESIONS; RISK; CARCINOMA; HYPERPLASIA AB The management of intraductal papillomas of the breast has been controversial; some advocate surgical excision of all lesions despite benign pathologic features, whereas others excise only those specimens with atypia. We conducted a retrospective review of 129 core-biopsy-proven papillomas of the breast with atypia (n = 43) and without atypia (n = 86) and determined the rate of missed carcinoma in surgically excised specimen in each group. Carcinoma was found in 22.5% of the surgically excised specimens in the atypia group (9/40) and in 3% of the surgically excised specimens in the no atypia group (1/29). Our findings confirm the practice that papillomas with atypical features should be excised, and suggest that in patients with adequate follow-up, benign papillomas may be managed conservatively. C1 [Ahmadiyeh, Nasim; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Ahmadiyeh, Nasim; Golshan, Mehra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stoleru, Mariana A.; Lester, Susan C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Raza, Sughra] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Ahmadiyeh, N (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 12 TC 43 Z9 45 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD AUG PY 2009 VL 16 IS 8 BP 2264 EP 2269 DI 10.1245/s10434-009-0534-1 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 472AQ UT WOS:000268101900028 PM 19484312 ER PT J AU Posner, MC Niedzwiecki, D Venook, AP Hollis, DR Kindler, HL Martin, EW Schilsky, RL Goldberg, RM Mayer, RJ AF Posner, Mitchell C. Niedzwiecki, Donna Venook, Alan P. Hollis, Donna R. Kindler, Hedy L. Martin, Edward W. Schilsky, Richard L. Goldberg, Richard M. Mayer, Robert J. TI A Phase II Prospective Multi-Institutional Trial of Adjuvant Active Specific Immunotherapy Following Curative Resection of Colorectal Cancer Hepatic Metastases: Cancer and Leukemia Group B Study 89903 (vol 15, pg 158, 2008) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Correction C1 [Posner, Mitchell C.; Kindler, Hedy L.; Schilsky, Richard L.] Univ Chicago, Chicago, IL 60637 USA. [Niedzwiecki, Donna; Hollis, Donna R.] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Venook, Alan P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goldberg, Richard M.] Univ N Carolina, Chapel Hill, NC USA. [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, Edward W.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. RP Posner, MC (reprint author), Univ Chicago, Chicago, IL 60637 USA. EM mposner@surgery.bsd.uchicago.edu RI Goldberg , Richard/M-1311-2013 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD AUG PY 2009 VL 16 IS 8 BP 2381 EP 2381 DI 10.1245/s10434-009-0466-9 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 472AQ UT WOS:000268101900049 ER PT J AU Singh, JA Hodges, JS Asch, SM AF Singh, J. A. Hodges, J. S. Asch, S. M. TI Opportunities for improving medication use and monitoring in gout SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID QUALITY-OF-CARE; ACUTE CORONARY SYNDROMES; DRUG-THERAPY; MANAGED CARE; III GUIDELINES; ALLOPURINOL; HYPERURICEMIA; COLCHICINE; ADHERENCE; VETERANS AB Purpose: To study patterns and predictors of medication use and laboratory monitoring in gout. Methods: In a cohort of veterans with a diagnosis of gout prescribed allopurinol, colchicine or probenecid, quality of care was assessed by examining adherence to the following evidence-based recommendations: (1) whether patients starting a new allopurinol prescription (a) received continuous allopurinol, (b) received colchicine prophylaxis, (c) achieved the target uric acid level of <= 6 mg/dl; and (2) whether doses were adjusted for renal insufficiency. The association of sociodemographic characteristics, healthcare utilisation and comorbidity with the recommendations was examined by logistic/Poisson regression. Results: Of the 643 patients with gout receiving a new allopurinol prescription, 297 (46%) received continuous allopurinol, 66 (10%) received colchicine prophylaxis and 126 (20%) reached the target uric acid level of <= 6 mg/dl. During episodes of renal insufficiency, appropriate dose reduction/discontinuation of probenecid was done in 24/31 episodes (77%) and of colchicine in 36/52 episodes (69%). Multivariable regression showed that higher outpatient utilisation, more rheumatology care and lower comorbidity were associated with better quality of care; more rheumatology clinic or primary care visits were associated with less frequent allopurinol discontinuation; more total outpatient visit days or most frequent visits to a rheumatology clinic were associated with a higher likelihood of receiving colchicine prophylaxis; and a lower Charlson Comorbidity Index or more outpatient visit days were associated with higher odds of reaching the target uric acid level of <= 6 mg/dl. Conclusions: Important variations were found in patterns of medication use and monitoring in patients with gout with suboptimal care. A concerted effort is needed to improve the overall care of gout. C1 [Singh, J. A.] VA Med Ctr, Rheumatol Sect, Med Serv, Minneapolis, MN USA. [Singh, J. A.; Hodges, J. S.] VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Singh, J. A.] Univ Minnesota, Dept Med, Div Rheumatol, Minneapolis, MN 55455 USA. [Hodges, J. S.] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Asch, S. M.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, S. M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Singh, JA (reprint author), Minneapolis VA Med Ctr, Rheumatol 111R,1 Vet Dr, Minneapolis, MN 55417 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Center for Epidemiological and Clinical Research, Minneapolis VA Medical Center, Minneapolis, MN; TAP Pharmaceuticals FX We thank Ms Ann Emery, administrative assistant, Minneapolis VA Medical Center for her help in typing the manuscript. This was investigator-initiated research supported by VA Scholar Grant from the Center for Epidemiological and Clinical Research, Minneapolis VA Medical Center, Minneapolis, MN and a research grant from TAP Pharmaceuticals. TAP Pharmaceuticals or its representatives did not contribute to the design, conduct or data analyses or to writing, editing or approving the manuscript. NR 40 TC 44 Z9 45 U1 1 U2 1 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 AUG PY 2009 VL 68 IS 8 BP 1265 EP 1270 DI 10.1136/ard.2008.092619 PG 6 WC Rheumatology SC Rheumatology GA 470VS UT WOS:000268010500006 PM 18701554 ER PT J AU Lanuti, M De Delva, PE Gaissert, HA Wright, CD Wain, JC Allan, JS Donahue, DM Mathisen, DJ AF Lanuti, Michael De Delva, Pierre E. Gaissert, Henning A. Wright, Cameron D. Wain, John C. Allan, James S. Donahue, Dean M. Mathisen, Douglas J. TI Review of Superior Vena Cava Resection in the Management of Benign Disease and Pulmonary or Mediastinal Malignancies SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 26-28, 2009 CL San Francisco, CA SP Soc Thorac Surg ID CELL LUNG-CANCER; SINGLE-CENTER EXPERIENCE; PROSTHETIC REPLACEMENT; EXTENDED OPERATION; GREAT-VESSELS; LEFT ATRIUM; TUMORS; CARCINOMA; GRAFT AB Background. Obstruction of the superior vena cava (SVC) by tumor or benign disease implies unreconstructable disease and poor outcome. We analyzed the operative results, graft patency, and survival in patients undergoing SVC resection and reconstruction for benign disease and pulmonary or mediastinal malignancy. Methods. Patients undergoing SVC resection from 1997 to 2007 for surgical management of benign and invasive neoplasms were retrospectively reviewed. Results. We identified 19 patients requiring SVC resection. Malignant disease was resected in 17: lung cancer in 9 and mediastinal malignancy in 8. Two patients (10%) with benign processes required reconstruction for chronic SVC syndrome. Ringed Gore-Tex conduit (W.L. Gore and Associates, Flagstaff, AZ) was used for 12 reconstructions (63%) of the SVC, and 7 patients underwent primary closure or autologous pericardial patch repair. Preoperative chemoradiotherapy was administered to 9 patients (53%). There was one perioperative death (5%). Major postoperative morbidities included atrial fibrillation in 5, stroke in 2, respiratory failure in 3, myocardial infarction in 1, and Horner syndrome in 1. Median survival for the entire cohort was 45.5 months (range, 0.2 to 147 months), with a mean follow-up of 45.8 months. Five-year survival probability was 30% for patients with resected lung cancer and 56% for patients with resected anterior mediastinal malignancies. Conclusions. Resection and reconstruction may be safely performed in selected patients for benign and malignant obstruction or infiltration of the SVC. Survival and intermediate-term patency after tubular grafting of the SVC are acceptable. (Ann Thorac Surg 2009; 88: 392-8) (C) 2009 by The Society of Thoracic Surgeons C1 [Lanuti, Michael; De Delva, Pierre E.; Gaissert, Henning A.; Wright, Cameron D.; Wain, John C.; Allan, James S.; Donahue, Dean M.; Mathisen, Douglas J.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Lanuti, M (reprint author), 55 Fruit St,Blake 1570, Boston, MA 01748 USA. EM mlanuti@partners.org NR 22 TC 14 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2009 VL 88 IS 2 BP 392 EP 398 DI 10.1016/j.athoracsur.2009.04.068 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 474WW UT WOS:000268316400006 PM 19632380 ER PT J AU White, JK Jagannath, A Titus, J Yoneyama, R Madsen, J Agnihotri, AK AF White, Jennifer K. Jagannath, Anand Titus, Jim Yoneyama, Ryuichi Madsen, Joren Agnihotri, Arvind K. TI Funnel-Tipped Aortic Cannula for Reduction of Atheroemboli SO ANNALS OF THORACIC SURGERY LA English DT Article ID BYPASS GRAFT-SURGERY; ISCHEMIC BRAIN-LESIONS; CARDIAC-SURGERY; CARDIOPULMONARY BYPASS; THORACIC AORTA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CEREBRAL EMBOLIZATION; TRANSCRANIAL DOPPLER; ATHEROMATOUS PLAQUE; ARCH AB Background. Atheroemboli caused by aortic manipulation poses a risk for stroke in patients undergoing cardiopulmonary bypass (CPB) surgery. One potential cause is the high velocity jet from aortic perfusion cannulae. This study describes the flow patterns of a novel funnel-tip cannula designed to reduce emboli by decreasing fluid velocity and resultant shear force on the aortic wall. Methods. A funnel-tip cannula was constructed and compared with standard straight-tip cannulae and the Dispersion (Research Medical Inc, Midvale, UT) and Sarns Soft Flow (Terumo Cardiovascular Systems Corp, Ann Arbor, MI) cannulae. Pressure drop measurements were collected at 1 to 6 L/minute flows. Velocity flow profiles were created using phase contrast magnetic resonance imaging. Absolute velocity was measured in a phantom aorta at 5 L/minute flow. Each cannula was further studied in a synthetic model of an atherosclerotic aorta to determine the mass of dislodged particulate matter generated at 2, 3, and 5 L/minute flows. Results. The funnel-tip cannula demonstrated significantly lower values (p < 0.05) in pressure drop (55 mm Hg), exit velocity (309 cm/second, 167 cm/second for center axis and wall, respectively), and particulate dislodgement (0.15 +/- 0.05 g) than other tested cannulae. The Soft Flow cannula generated the next lowest pressure drop but exhibited twice the exit velocity and particulate dislodgement of the funnel-tip cannula. The Dispersion cannula did not demonstrate a reduction in velocity or particulate dislodgement compared with the standard straight-tip cannulae. Conclusions. The results of this study suggest that a low-angled funnel-tip cannula has favorable flow characteristics warranting further investigation. Design development may reduce the risk of atheroemboli generation during CPB surgery. (Ann Thorac Surg 2009; 88: 551-7) (C) 2009 by The Society of Thoracic Surgeons C1 [Agnihotri, Arvind K.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Boston, MA 02114 USA. RP Agnihotri, AK (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Cox Bldg,Room 642,55 Fruit St, Boston, MA 02114 USA. EM aagnihotri@partners.org FU Center for Integration of Medicine and Innovative Technology (CIMIT, Boston, MA); United States Patent Office [20050107817] FX This study was supported by the Center for Integration of Medicine and Innovative Technology (CIMIT, Boston, MA). The funnel-tip design concept has been filed with the United States Patent Office (Application # 20050107817). No commercial companies were involved in the completion of this study. NR 34 TC 10 Z9 10 U1 0 U2 0 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 AUG PY 2009 VL 88 IS 2 BP 551 EP 557 DI 10.1016/j.athoracsur.2009.04.108 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 474WW UT WOS:000268316400028 PM 19632411 ER PT J AU Tom, TSM Kruse, MW Reichman, RT AF Tom, Trisha S. M. Kruse, Michael W. Reichman, Robert T. TI Update: Methicillin-Resistant Staphylococcus aureus Screening and Decolonization in Cardiac Surgery SO ANNALS OF THORACIC SURGERY LA English DT Review ID INTENSIVE-CARE-UNIT; SURGICAL-SITE INFECTION; BYPASS GRAFT-SURGERY; CHLORHEXIDINE GLUCONATE; NOSOCOMIAL INFECTION; INTRANASAL MUPIROCIN; HOSPITAL ADMISSION; NASAL CARRIAGE; MRSA INFECTION; RISK AB Methicillin-resistant Staphylococcus aureus (MRSA) has become a concerning multidrug-resistant organism, expanding further outside the hospital setting. Cardiothoracic surgery patients are at an increased risk for mediastinitis and other surgical site infections, which may be further complicated by MRSA. To reduce MRSA surgical site infections, multidisciplinary active surveillance should be implemented in at least high-risk patients, incorporating basic infection control practices, appropriate antibiotic prophylaxis, and decolonization. This article will review the various guidelines, addressing the role of MRSA active surveillance in cardiothoracic surgery, and provide guidance for cardiothoracic surgeons. (Ann Thorac Surg 2009; 88: 695-702) (C) 2009 by The Society of Thoracic Surgeons C1 Palomar Med Ctr, Dept Pharm, Escondido, CA 92025 USA. Palomar Med Ctr, Dept Surg, Escondido, CA 92025 USA. Washington State Univ, Deaconess Med Ctr, Dept Pharm, Spokane, WA USA. RP Kruse, MW (reprint author), Palomar Med Ctr, Dept Pharm, 555 E Valley Pkwy, Escondido, CA 92025 USA. EM michael.kruse@pph.org NR 55 TC 21 Z9 21 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2009 VL 88 IS 2 BP 695 EP 702 DI 10.1016/j.athoracsur.2009.02.010 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 474WW UT WOS:000268316400069 PM 19632455 ER PT J AU Nguyen, KT Ta, P Hoang, BT Cheng, S Hao, BH Nguyen, MH Clancy, CJ AF Nguyen, Katherine T. Ta, Philip Hoang, Bich Thu Cheng, Shaoji Hao, Binghua Nguyen, M. Hong Clancy, Cornelius J. TI Anidulafungin Is Fungicidal and Exerts a Variety of Postantifungal Effects against Candida albicans, C. glabrata, C. parapsilosis, and C. krusei isolates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DOUBLE-BLIND TRIAL; TIME-KILL METHODS; AMPHOTERICIN-B; INVASIVE CANDIDIASIS; CASPOFUNGIN; MICAFUNGIN; ECHINOCANDIN; FLUCONAZOLE; SPP.; SUSCEPTIBILITY AB Anidulafungin targets the cell walls of Candida species by inhibiting beta-1,3-glucan synthase, thereby killing isolates and exerting prolonged postantifungal effects (PAFEs). We performed time-kill and PAFE experiments on Candida albicans (n = 4), C. glabrata (n = 3), C. parapsilosis (n = 3), and C. krusei (n = 2) isolates and characterized the PAFEs in greater detail. MICs were 0.008 to 0.125 mu g/ml against C. albicans, C. glabrata, and C. krusei and 1.0 to 2.0 mu g/ml against C. parapsilosis. During time-kill experiments, anidulafungin caused significant kills at 16x MIC (range, log 2.68 to 3.89) and 4x MIC (log 1.87 to 3.19), achieving fungicidal levels (>= log 3) against nine isolates. A 1-hour drug exposure during PAFE experiments resulted in kills ranging from log 1.55 to 3.47 and log 1.18 to 2.89 (16x and 4x MIC, respectively), achieving fungicidal levels against four isolates. Regrowth of all 12 isolates was inhibited for >= 12 h after drug washout. Isolates of each species collected 8 h after a 1-hour exposure to anidulafungin (16x and 4x MIC) were hypersusceptible to sodium dodecyl sulfate (0.01 to 0.04%) and calcofluor white (40 mu g/ml). Moreover, PAFEs were associated with major cell wall disturbances, as evident in electron micrographs of viable cells, and significant reductions in adherence to buccal epithelial cells (P <= 0.01). Finally, three of four PAFE isolates tested were hypersusceptible to killing by J774 macrophages (P <= 0.007). Our data suggest that the efficacy of anidulafungin in the treatment of candidiasis might stem from both direct fungicidal activity and indirect PAFEs that lessen the ability of Candida cells to establish invasive disease and to persist within infected hosts. C1 [Hao, Binghua; Nguyen, M. Hong; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Nguyen, Katherine T.; Ta, Philip; Hoang, Bich Thu; Cheng, Shaoji; Hao, Binghua; Nguyen, M. Hong; Clancy, Cornelius J.] Univ Florida, Coll Med, Dept Med, Gainesville, FL USA. [Nguyen, M. Hong] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Nguyen, M. Hong; Clancy, Cornelius J.] N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Dept Med, 867 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM cjc76@pitt.edu FU Pfizer, Inc.; Medical Research Service of the Department of Veterans Affairs; Astellas Pharmaceuticals; Merck Co., Inc. FX This project was funded by a research grant to C. J. C. from Pfizer, Inc. C. J. C. and M. H. N. were supported by the Medical Research Service of the Department of Veterans Affairs. Their research was conducted as part of the University of Florida Mycology Research Unit. C. J. C. has received research funding from Astellas Pharmaceuticals, Pfizer, Inc., and Merck & Co., Inc. C. J. C. and M. H. N. have received funds to speak at a symposium organized on behalf of Three Rivers Pharmaceuticals, Inc. NR 25 TC 24 Z9 25 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2009 VL 53 IS 8 BP 3347 EP 3352 DI 10.1128/AAC.01480-08 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 471ZW UT WOS:000268098300024 PM 19364856 ER PT J AU Bin Kim, H Wang, MH Park, CH Kim, EC Jacoby, GA Hooper, DC AF Bin Kim, Hong Wang, Minghua Park, Chi Hye Kim, Eui-Chong Jacoby, George A. Hooper, David C. TI oqxAB Encoding a Multidrug Efflux Pump in Human Clinical Isolates of Enterobacteriaceae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; ESCHERICHIA-COLI; PLASMID; PREVALENCE; OLAQUINDOX AB The genes for multidrug efflux pump OqxAB, which is active on fluoroquinolones, were found in human clinical isolates on a plasmid in Escherichia coli and on the chromosome of Klebsiella pneumoniae. IS26-like sequences flanked the plasmid-mediated oqxAB genes, suggesting that they had been mobilized as part of a composite transposon. C1 [Bin Kim, Hong; Wang, Minghua; Park, Chi Hye; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bin Kim, Hong] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. [Bin Kim, Hong] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Wang, Minghua] Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200433, Peoples R China. [Kim, Eui-Chong] Seoul Natl Univ, Coll Med, Dept Lab Med, Seoul, South Korea. [Jacoby, George A.] Lahey Clin Fdn, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org RI Kim, Hong Bin/J-5452-2012; Kim, Eu Chong/J-5424-2012 OI Kim, Hong Bin/0000-0001-6262-372X; FU National Institute of Health, U. S. Public Health Service [R01 AI057576, R01AI043312] FX This work was supported in part by grants R01 AI057576 (to D. C. H.) and R01AI043312 (to G. A. J.) from the National Institute of Health, U. S. Public Health Service.; We thank Que Chi Truong-Bolduc, Yanpeng Ding, and Debra M. Mills for technical advice. NR 12 TC 63 Z9 64 U1 0 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2009 VL 53 IS 8 BP 3582 EP 3584 DI 10.1128/AAC.01574-08 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 471ZW UT WOS:000268098300067 ER PT J AU Krieser, RJ White, K AF Krieser, Ronald J. White, Kristin TI Inside an enigma: do mitochondria contribute to cell death in Drosophila? SO APOPTOSIS LA English DT Article DE Apoptosis; Mitochondria; Drosophila ID OUTER-MEMBRANE PERMEABILIZATION; APOPTOSIS-INDUCING FACTOR; STRESS-INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; PARKINSONS-DISEASE; CASPASE ACTIVATION; SERINE-PROTEASE; REGULATES APOPTOSIS; PATHWAY; FISSION AB Mitochondria have been shown to play an important role in cell death in mammalian cells. However, the importance of mitochondria in Drosophila apoptosis is still under investigation. Many proteins involved in the regulation of apoptosis in mammals act at mitochondria or are released from mitochondria, resulting in caspase activation. In addition, these organelles undergo significant ultrastructural changes during apoptosis. This review highlights similarities and differences in the roles of mitochondria and mitochondrial factors in apoptosis between Drosophila and mammals. In Drosophila, many key regulators of apoptosis also appear to localize to this organelle, which also undergoes ultrastructural changes during apoptosis. Although many of the proteins important for the control of apoptosis in mammalian cells are conserved in Drosophila, the role that mitochondria play in apoptosis in this model system remains an area of controversy and active research. C1 [White, Kristin] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Krieser, Ronald J.] Fitchburg State Coll, Fitchburg, MA USA. RP White, K (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 129 13th St, Charlestown, MA 02129 USA. EM Kristin.White@CBRC2.MGH.Harvard.edu RI White, Kristin/D-7936-2013 FU N.I.H [GM55568, GM69541] FX KW is supported by grants GM55568 and GM69541 from N.I.H. NR 75 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD AUG PY 2009 VL 14 IS 8 BP 961 EP 968 DI 10.1007/s10495-009-0362-6 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 477HP UT WOS:000268510200005 PM 19479378 ER PT J AU Thalacker-Mercer, AE Petrella, JK Bamman, MM AF Thalacker-Mercer, Anna E. Petrella, John K. Bamman, Marcas M. TI Does habitual dietary intake influence myofiber hypertrophy in response to resistance training? A cluster analysis SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE NUTRITION ET METABOLISME LA English DT Article DE diet; amino acids; exercise; muscle hypertrophy ID MUSCLE PROTEIN-SYNTHESIS; ESSENTIAL AMINO-ACIDS; SKELETAL-MUSCLE; OLDER MEN; MYONUCLEAR ADDITION; BODY-COMPOSITION; ENERGY-INTAKE; YOUNG MEN; EXERCISE; INGESTION AB Although resistance exercise training (RT) is a common intervention to stimulate muscle protein synthesis and increase skeletal muscle mass, the optimal daily protein and total energy intakes sufficient to support RT-mediated muscle growth are as yet unclear. Further, the efficacy of RT varies widely among adults of all ages and whether this is attributable to interindividual differences in nutrition is not known. To determine if self-selected daily intake of macronutrients and specific components of dietary protein and fat are predictive of the magnitude of RT-mediated muscle growth, detailed 4-day dietary records were analyzed on 60 subjects previously clustered (K-means cluster analysis) as non-, modest, and extreme responders (non, n = 16; mod, n = 29; xtr, n = 15), based on the magnitudes of change in vastus lateralis myofiber cross-sectional area following a 16-week, 3-day-per-week, high-intensity RT. Despite the marked contrast between 60% myofiber hypertrophy in xtr and zero growth in non, we found no differences among response clusters in daily intakes of energy (mean +/- SEM: non 102 +/- 8; mod 111 +/- 6; xtr 109 +/- 5 kJ.kg(-1).day(-1)), protein (non 0.97 +/- 0.08; mod 1.07 +/- 0.07; xtr 1.05 +/- 0.06 g.kg(-1).day(-1)), carbohydrate (non 3.02 +/- 0.24; mod 3.18 +/- 0.20; xtr 3.14 +/- 0.17 g.kg(-1).day(-1)), and fat (non 0.95 +/- 0.09; mod 1.05 +/- 0.08; xtr 1.03 +/- 0.08 g.kg(-1).day(-1)), which generally met or exceeded dietary recommendations. There were no cluster differences in intakes of branched chain amino acids known to stimulate muscle protein synthesis. Using the novel K-means clustering approach, we conclude from this preliminary study that protein and energy intakes were sufficient to facilitate modest and extreme muscle growth during RT and intrinsic or extrinsic factors other than nutrient ingestion apparently impaired the anabolic response in nonresponders. C1 [Thalacker-Mercer, Anna E.; Petrella, John K.; Bamman, Marcas M.] UAB, Dept Physiol & Biophys, Birmingham, AL 35294 USA. [Thalacker-Mercer, Anna E.; Petrella, John K.; Bamman, Marcas M.] UAB, Dept Nutr Sci, Birmingham, AL 35294 USA. [Bamman, Marcas M.] Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL 35294 USA. RP Bamman, MM (reprint author), UAB, Dept Physiol & Biophys, Birmingham, AL 35294 USA. EM mbamman@uab.edu FU National Institutes of Health/National Institute [1R01 AG017896]; Veterans Affairs Merit Grant; General Clinical Research Center [M01-RR-0032]; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [5T32 DK062710-01A1] FX We are indebted to the research subjects for their invaluable contributions to this work. We thank S. C. Tuggle and S. Hall for conducting RT sessions and the staff of the Pittman General Clinical Research Center at UAB for entering dietary food records. Funding for this work was provided by National Institutes of Health/National Institute on Aging Grant 1R01 AG017896 (M. M. B.), Veterans Affairs Merit Grant (M. M. B.), General Clinical Research Center Grant M01-RR-0032, and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases 5T32 DK062710-01A1 (A. E. T.-M.). NR 48 TC 16 Z9 16 U1 2 U2 2 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 1715-5312 J9 APPL PHYSIOL NUTR ME JI Appl. Physiol. Nutr. Metab. PD AUG PY 2009 VL 34 IS 4 BP 632 EP 639 DI 10.1139/H09-038 PG 8 WC Nutrition & Dietetics; Physiology; Sport Sciences SC Nutrition & Dietetics; Physiology; Sport Sciences GA 496KP UT WOS:000269972200010 PM 19767798 ER PT J AU Lyoo, IK Yoon, SJ Musen, G Simonson, DC Weinger, K Bolo, N Ryan, CM Kim, JE Renshaw, PF Jacobson, AM AF Lyoo, In Kyoon Yoon, Sujung J. Musen, Gail Simonson, Donald C. Weinger, Katie Bolo, Nicolas Ryan, Christopher M. Kim, Jieun E. Renshaw, Perry F. Jacobson, Alan M. TI Altered Prefrontal Glutamate-Glutamine-gamma-Aminobutyric Acid Levels and Relation to Low Cognitive Performance and Depressive Symptoms in Type 1 Diabetes Mellitus SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; BRAIN METABOLIC ALTERATIONS; NERVE GROWTH-FACTOR; MAJOR DEPRESSION; BIPOLAR DISORDER; CEREBRAL GLUCOSE; NMDA RECEPTORS; PROTON MRS; DECARBOXYLASE; HYPERGLYCEMIA AB Context: Neural substrates for low cognitive performance and depression, common long-term central nervous system-related changes in patients with type 1 diabetes mellitus, have not yet been studied. Objective: To investigate whether prefrontal glutamate levels are higher in patients with type 1 diabetes and whether an elevation is related to lower cognitive performance and depression. Design: Cross-sectional study. Setting: General clinical research center. Participants: One hundred twenty-three patients with adult type 1 diabetes with varying degrees of lifetime glycemic control and 38 healthy participants. Main Outcome Measures: With the use of proton magnetic resonance spectroscopy, prefrontal glutamateglutamine- gamma-aminobutyric acid (Glx) levels were compared between patients and control subjects. Relationships between prefrontal Glx levels and cognitive function and between Glx levels and mild depressive symptoms were assessed in patients with type 1 diabetes. Results: Prefrontal Glx concentrations were 9.0% (0.742 mmol/ L; P=.005) higher in adult patients with type 1 diabetes than in healthy control subjects. There were positive linear trends for the effects of lifetime glycemic control on prefrontal Glx levels (P for trend=.002). Cognitive performances in memory, executive function, and psychomotor speed were lower in patients (P=.003, .01, and <.001, respectively) than in control subjects. Higher prefrontal Glx concentrations in patients were associated with lower performance in assessment of global cognitive function (0.11 change in z score per 1-mmol/L increase in Glx) as well as with mild depression. Conclusions: The high prefrontal glutamate levels documented in this study may play an important role in the genesis of the low cognitive performance and mild depression frequently observed in patients with type 1 diabetes. Therapeutic options that alter glutamatergic neurotransmission may be of benefit in treating central nervous system-related changes in patients with adult type 1 diabetes. C1 [Lyoo, In Kyoon; Kim, Jieun E.] Seoul Natl Univ, Dept Psychiat, Seoul 110744, South Korea. [Lyoo, In Kyoon; Kim, Jieun E.] Seoul Natl Univ, Interdisciplinary Program Brain Sci, Seoul 110744, South Korea. [Lyoo, In Kyoon; Musen, Gail; Weinger, Katie; Bolo, Nicolas; Jacobson, Alan M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Yoon, Sujung J.] Catholic Univ, Korea Sch Med, Dept Psychiat, Seoul, South Korea. [Musen, Gail; Weinger, Katie; Jacobson, Alan M.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Simonson, Donald C.] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. [Ryan, Christopher M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Renshaw, Perry F.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Renshaw, Perry F.] Univ Utah, Inst Brain, Salt Lake City, UT USA. [Renshaw, Perry F.] Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network 19, Dept Vet Affairs, Salt Lake City, UT USA. RP Lyoo, IK (reprint author), Seoul Natl Univ, Dept Psychiat, 28 Yongon Dong, Seoul 110744, South Korea. EM inkylyoo@snu.ac.kr FU National Institutes of Health [DK-060754]; Independent Investigator Awards; National Alliance for Schizophrenia and Depression [KRF-2008-220-E00021]; Korea Research Foundation; Korean Ministry of Education, Science, and Technology [2009K001272] FX This study was supported by grant DK-060754 from the National Institutes of Health (Dr Jacobson), Independent Investigator Awards (Drs Lyoo and Renshaw) from the National Alliance for Schizophrenia and Depression, grant KRF-2008-220-E00021 from the Korea Research Foundation (Dr Lyoo), and grant 2009K001272 from the Brain Research Center of the 21st Century Frontier Research Program funded by the Korean Ministry of Education, Science, and Technology (Dr Lyoo). NR 74 TC 37 Z9 39 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2009 VL 66 IS 8 BP 878 EP 887 PG 10 WC Psychiatry SC Psychiatry GA 479BT UT WOS:000268634500008 PM 19652127 ER PT J AU Tyler, KL AF Tyler, Kenneth L. TI Emerging Viral Infections of the Central Nervous System Part 1 SO ARCHIVES OF NEUROLOGY LA English DT Article; Proceedings Paper CT 132nd Annual Meeting of the American-Neurological-Association CY OCT 07-10, 2007 CL Washington, DC SP Amer Neurol Assoc ID WEST-NILE-VIRUS; VACCINE-DERIVED POLIOVIRUS; 4 TRANSPLANT RECIPIENTS; MR-IMAGING FINDINGS; JAPANESE ENCEPHALITIS; TOSCANA VIRUS; UNITED-STATES; NEUROINVASIVE DISEASE; LIMBIC ENCEPHALITIS; HUMAN HERPESVIRUS-6 AB In this 2-part review, I will focus on emerging virus infections of the central nervous system (CNS). Part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of CNS involvement. Important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by West Nile virus (WNV), Japanese encephalitis (JE) virus, Toscana virus, and enterovirus 71 (EV71). Emerging infections also result from opportunistic spread of viruses into known niches, often resulting from attenuated host resistance to infection. This process is exemplified by transplant-associated cases of viral CNS infection caused by WNV, rabies virus, lymphocytic choriomeningitis, and lymphocytic choriomeningitis-like viruses and by the syndrome of human herpesvirus 6 (HHV6)-associated posttransplantation acute limbic encephalitis. The second part of this review begins with a discussion of JC virus and the occurrence of progressive multifocal leukoencephalopathy in association with novel immunomodulatory therapies and then continues with an overview of the risk of infection introduced by imported animals (eg, monkeypox virus) and examples of emerging diseases caused by enhanced competence of viruses for vectors and the spread of vectors (eg, chikungunya virus) and then concludes with examples of novel viruses causing CNS infection as exemplified by Nipah and Hendra viruses and bat lyssaviruses. Arch Neurol. 2009;66(8):939-948 C1 [Tyler, Kenneth L.] Univ Colorado Denver, Hlth Sci Ctr, Dept Neurol, Aurora, CO 80045 USA. [Tyler, Kenneth L.] Univ Colorado Denver, Hlth Sci Ctr, Dept Med Infect Dis, Aurora, CO 80045 USA. [Tyler, Kenneth L.] Univ Colorado Denver, Hlth Sci Ctr, Dept Microbiol, Aurora, CO 80045 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado Denver, Hlth Sci Ctr, Dept Neurol, Neurol B-182,Res Complex 2,12700 E 19th Ave, Aurora, CO 80045 USA. EM ken.tyler@ucdenver.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS NIH HHS [R01 NS051403, R01 NS051403-05, R01 NS050138-05, R01 NS050138, R01 NS050138-05S1] NR 76 TC 59 Z9 62 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9942 EI 1538-3687 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2009 VL 66 IS 8 BP 939 EP 948 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 481YA UT WOS:000268848100003 PM 19667214 ER PT J AU Orta, DS Chiappa, KH Quiroz, AZ Costello, DJ Cole, AJ AF Orta, Daniel San Juan Chiappa, Keith H. Quiroz, Alejandro Z. Costello, Daniel J. Cole, Andrew J. TI Prognostic Implications of Periodic Epileptiform Discharges SO ARCHIVES OF NEUROLOGY LA English DT Article ID TRANSITIONAL RHYTHMIC DISCHARGES; CLINICAL-SIGNIFICANCE; PEDIATRIC-PATIENTS; EEG PATTERNS; WHITE-MATTER; PLEDS; SEIZURES; ELECTROENCEPHALOGRAM; ASSOCIATION; EVOLUTION AB Background: Periodic epileptiform discharges (PEDs) are an abnormal finding on electroencephalograms (EEGs), the significance of which is uncertain. Objective: To investigate long-term outcome in patients with PEDs. Design: We retrospectively analyzed the outcomes of patients who had PEDs diagnosed during a 7-year period. We abstracted and tabulated clinical parameters from the time of EEG, imaging findings, EEG measurements, and subsequent clinical outcome from medical records. We used descriptive, inferential, and logistic regression analysis to determine the factors associated with clinical outcomes in patients with PEDs. We divided PEDs into the following subgroups: periodic lateralized epileptiform discharges (PLEDs), generalized PEDs, and bilateral PEDs and analyzed these subgroups individually. Setting: University-affiliated teaching hospital. Subjects: One hundred sixty-two patients with PEDs. Results: We obtained complete clinical, neuroimaging, neurophysiologic, and long-term outcome data in 118 patients. In the subgroup of patients with PLEDs, absence of seizures at onset (odds ratio, 0.21 per point; 95% confidence interval, 0.04-0.97) and an acute etiology for the PLEDs (odds ratio, 0.14 per point; 95% confidence interval, 0.03-0.72) were associated with death. A nonneoplastic cause for PLEDs was associated with independent functionality (odds ratio, 0.45 per point; 95% confidence interval, 0.3-0.67). Conclusion: In patients with PLEDs, the absence of clinical seizures at the time of detection and presumed acute etiology are associated with death, whereas a nonneoplastic etiology was associated with a good clinical outcome. C1 [Orta, Daniel San Juan; Chiappa, Keith H.; Costello, Daniel J.; Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [Quiroz, Alejandro Z.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Orta, DS (reprint author), Massachusetts Gen Hosp, Epilepsy Serv, 55 Fruit St, Boston, MA 02114 USA. EM investigacionclinica@innn.edu.mx NR 31 TC 40 Z9 41 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2009 VL 66 IS 8 BP 985 EP 991 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 481YA UT WOS:000268848100010 PM 19667220 ER PT J AU Scarmeas, N Honig, LS Choi, H Cantero, J Brandt, J Blacker, D Albert, M Amatniek, JC Marder, K Bell, K Hauser, A Stern, Y AF Scarmeas, Nikolaos Honig, Lawrence S. Choi, Hyunmi Cantero, Julio Brandt, Jason Blacker, Deborah Albert, Marilyn Amatniek, Joan C. Marder, Karen Bell, Karen Hauser, Allen Stern, Yaakov TI Seizures in Alzheimer Disease Who, When, and How Common? SO ARCHIVES OF NEUROLOGY LA English DT Article ID UNPROVOKED SEIZURES; MOTOR SIGNS; EARLY-ONSET; DEMENTIA; PREDICTORS; EPILEPSY; ASSOCIATION; MINNESOTA; ROCHESTER; SYMPTOMS AB Background: Transient symptoms in Alzheimer disease (AD) are frequent and include seizures, syncope, and episodes of inattention or confusion. The incidence of seizures in AD and predictors of which patients with AD might be more predisposed to them is based primarily on retrospective studies and is not well established. Objective: To determine the incidence and predictors of new-onset unprovoked seizures. Design: Prospective cohort study. Setting: Three academic centers. Patients: Four hundred fifty-three patients with probable AD observed prospectively from mild disease stages since 1992. Main Outcome Measure: Informant interviews every 6 months included questions about whether the patient had a seizure (convulsion, fainting, or "funny" spell) and whether diagnosis or treatment for epilepsy or seizure was made. Two epileptologists independently retrospectively reviewed all available medical records for 52 patients with positive responses to either of these questions, and using a specific checklist form, events were diagnosed as to whether they were unprovoked seizures (intrarater concordance, kappa = 0.67). Diagnosis of unprovoked seizures constituted the event in survival analyses. Potential predictors included sex, age, race/ethnicity, educational achievement, duration of illness, baseline cognition and function, depression, medical comorbidities, and time-dependent use of cholinesterase inhibitors and neuroleptic agents, apolipoprotein E genotype, and previous electroencephalographic findings. Results: Over the course of 3518 visit-assessments (per patient: mean, 7.8; maximum, 27), 7 patients (1.5%) developed seizures. Younger age was associated with higher risk (hazard ratio, 1.23; 95% confidence interval, 1.08-1.41; P=.003 for each additional year of age) of seizure incidence. No other predictor was significant. The overall incidence of seizures was low (418 per 100 000 person-years of observation) although significantly higher than expected for idiopathic unprovoked seizures in similar age ranges of the general population (hazard ratio, 8.06; 95% confidence interval, 3.23-16.61). Conclusions: Unprovoked seizures are uncommon in AD, but they do occur more frequently than in the general population. Younger age is a risk factor for seizures in AD. C1 [Scarmeas, Nikolaos; Honig, Lawrence S.; Choi, Hyunmi; Cantero, Julio; Marder, Karen; Bell, Karen; Hauser, Allen; Stern, Yaakov] Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10032 USA. [Scarmeas, Nikolaos; Honig, Lawrence S.; Marder, Karen; Bell, Karen; Hauser, Allen; Stern, Yaakov] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Scarmeas, Nikolaos; Honig, Lawrence S.; Marder, Karen; Bell, Karen; Hauser, Allen; Stern, Yaakov] Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10027 USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Amatniek, Joan C.] Ortho McNeil Janssen Sci Affairs LLC, Titusville, NJ USA. RP Scarmeas, N (reprint author), Columbia Univ, Dept Neurol, Med Ctr, 622 W 168 St,PH Bldg,19th Floor, New York, NY 10032 USA. EM ns257@columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU National Institutes of Health [AG07370, RR00645, AG 08702]; Henry Panasci Fund FX This study was supported by grants AG07370, RR00645, and AG 08702 from the National Institutes of Health and by the Henry Panasci Fund (Dr Honig). NR 36 TC 80 Z9 85 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2009 VL 66 IS 8 BP 992 EP 997 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 481YA UT WOS:000268848100011 PM 19667221 ER PT J AU Jakobiec, FA Colby, K Bajart, AM Saragas, SJ Moulin, A AF Jakobiec, Frederick A. Colby, Kathryn Bajart, Ann M. Saragas, S. John Moulin, Alexandre TI Immunohistochemical Studies of Atypical Conjunctival Melanocytic Nevi SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BALLOON CELL NEVUS; MALIGNANT-MELANOMA; MONOCLONAL-ANTIBODY; KI-67 EXPRESSION; DYSPLASTIC NEVI; S100 PROTEIN; SPITZ NEVUS; BLUE NEVI; LESIONS; HMB-45 AB Objective: To evaluate with immunohistochemical methods 5 atypical melanocytic conjunctival lesions. Methods: This was a retrospective clinicoimmunopathologic study. Routine histochemical staining was performed with multiparametric immunohistochemical analysis with monoclonal antibodies immunoreacted on paraffin sections to identify the following cell antigens: S-100, MART-1, HMB-45, CD45, CD68, CD1a, lysozyme, and Ki-67 (nuclear proliferation protein). Results: A unique granular cell nevus contained periodic acid-Schiff-positive, diastase-resistant granules and immunoreacted with monoclonal antibodies against S-100 protein and melanocytic-associated antigens MART-1 and HMB-45. Results for CD45, CD1a, CD68, and lysozyme immunostaining of the granular cells were negative. Two epithelioid cell (clonal or inverted) nevi exhibited an identical immunohistochemical profile. Only the balloon cell nevus was MART-1-positive and HMB-45-negative. The granular cell and blue nevi immunoreacted negligibly with Ki-67 (approximately 1% of cells). Conclusions: S100 and MART-1 reliably immunostained all nevocytic morphologic variants. HMB-45 immunoreactivity of the granular, epithelioid/clonal, and blue nevi did not indicate a more active or proliferative lesion but instead suggested abnormal melanogenesis. Ki-67 was the most valuable immunohistochemical adjunct to morphology for the diagnosis of these benign variant conjunctival nevi, because melanomas display a much higher proliferation index (> 10% nuclear positivity among all cells counted) than the current nevi (approximately 1%). C1 [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Dept Ophthalmol, Boston, MA 02114 USA. [Colby, Kathryn] Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Bajart, Ann M.] Ophthalm Consultants Boston, Boston, MA USA. [Saragas, S. John] Saragas Eye Ctr, Somerville, MA USA. [Moulin, Alexandre] Hop Ophtalm Jules Gonin, Lausanne, Switzerland. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Dept Ophthalmol, 243 Charles St,Room 321, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 58 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2009 VL 127 IS 8 BP 970 EP 980 PG 11 WC Ophthalmology SC Ophthalmology GA 481YB UT WOS:000268848200003 PM 19667333 ER PT J AU Mehta, M Jakobiec, F Fay, A AF Mehta, Manisha Jakobiec, Frederick Fay, Aaron TI Idiopathic Fibroinflammatory Disease of the Face, Eyelids, and Periorbital Membrane With Immunoglobulin G4-Positive Plasma Cells SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID IGG4-RELATED SCLEROSING DISEASE; DACRYOADENITIS; PANCREATITIS AB Progressive sclerosing orbital pseudotumors are a subset of usually primary and localized idiopathic fibroinflammatory disorders. We report on a 66-year-old man who developed this condition along the facial tissue planes with extension into the orbit and preferential involvement of the periorbital membrane. Fibrocollagenous tissue with scattered lymphoid aggregates without follicle formation dominated the process. There was a light dispersion of B and T lymphocytes and histiocytes in the stroma. Immunoglobulin G4 (IgG4)-positive plasma cells (>35 per high-power field) were identified mostly in the lymphoid clusters, as has been discovered in similar IgG4-related fibrosclerosing conditions of other nonorbital sites. No associated systemic disease emerged during a 20-year clinical course. Previously reported orbital cases of IgG4-positive disease have all involved the lacrimal gland, usually bilaterally, and more closely resembled hypercellular reactive lymphoid hyperplasias with moderate interlobular fibrosis, rather than representing an essentially sclerosing process from the beginning. (Arch Pathol Lab Med. 2009; 133: 1251-1255) C1 [Mehta, Manisha; Jakobiec, Frederick] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Fay, Aaron] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Facial Plast & Reconstruct Surg Serv, Boston, MA 02114 USA. RP Jakobiec, F (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 16 TC 41 Z9 44 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 2009 VL 133 IS 8 BP 1251 EP 1255 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 482TA UT WOS:000268910400021 PM 19653720 ER PT J AU Moriarty, AT Darragh, TM Fatheree, LA Souers, R Wilbur, DC AF Moriarty, Ann T. Darragh, Teresa M. Fatheree, Lisa A. Souers, Rhona Wilbur, David C. TI Performance of Candida-Fungal-Induced Atypia and Proficiency Testing Observations From the College of American Pathologists Proficiency Testing Program SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INTERLABORATORY COMPARISON PROGRAM; CERVICOVAGINAL CYTOLOGY; VALIDATION AB Context.-Candida may elicit cellular changes on otherwise negative screening Papanicolaou tests that may be misinterpreted as atypical squamous cells of undetermined significance. Although these changes have been correctly interpreted in the educational program of the College of American Pathologists, the Interlaboratory Comparison Program in Gynecologic Cytology, the performance of negative slides with Candida faltered when the same field validated slides were included in proficiency testing (PT). Objective.-To identify the performance differences of negative for intraepithelial lesion (NILM) Candida challenges before and after PT. Design.-We compare the performance of NILM College of American Pathologists slides with Candida as a single reference diagnosis, prior to PT (1991-2006) and after PT (2006-2007). Results.-There were 147 186 responses for slides with NILM Candida from the College of American Pathologists programs from 1991 through 2007. After PT, 79.7% of incorrect participant responses identified Candida as Category C (low-grade squamous intraepithelial lesion), whereas prior to PT only 59.5% of the incorrect diagnoses were low-grade squamous intraepithelial lesion (P<.001) in the field-validated component of the program. Validated Candida slides performed significantly more poorly in PT (97.2%) than prior to PT (98.3%) (P<.001). Candida challenges performed better in the educational component post-PT (98.3% versus 97.2%; P<.001). Cytotechnologists (97.9%) identified Candida more frequently than pathologists (97.3%) (P<.001) and ThinPrep preparations performed the best of all preparation types. Conclusions.-Proficiency testing adversely affects the performance of participants in the identification of NILM Candida. Slides with Candida are more likely to be identified as low-grade squamous intraepithelial lesion in a PT exercise. Misidentification is not due to lack of recognition but most likely an attempt of test takers to optimize their likelihood of passing the examination. (Arch Pathol Lab Med. 2009; 133: 1272-1275) C1 [Moriarty, Ann T.] AmeriPath Indiana, Dept Pathol, Indianapolis, IN 46219 USA. [Darragh, Teresa M.] Univ Calif San Francisco, Mt Zion Med Ctr, Dept Pathol & Cytol, San Francisco, CA 94120 USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Fatheree, Lisa A.; Souers, Rhona] Coll Amer Pathologists, Northfield, IL USA. RP Moriarty, AT (reprint author), AmeriPath Indiana, Dept Pathol, 2560 N Shadeland Ave,Suite A, Indianapolis, IN 46219 USA. EM amoriarty@ameripath.com NR 6 TC 2 Z9 2 U1 1 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 2009 VL 133 IS 8 BP 1272 EP 1275 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 482TA UT WOS:000268910400025 PM 19653724 ER PT J AU Pozdnyakova, O Hoang, MMP Dresser, KA Mahalingam, M AF Pozdnyakova, Olga Hoang, Mai M. P. Dresser, Karen A. Mahalingam, Meera TI Prognostic Value of E-Cadherin, beta-Catenin, CD44v6, and HER2/neu in Metastatic Cutaneous Adenocarcinoma SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CELL-ADHESION MOLECULE; COLORECTAL-CANCER; EXPRESSION; INVASION; PROGRESSION; CARCINOMA; TUMORS AB Context.-Our recent experience with a patient developing cutaneous metastases within 3 months of diagnosis of esophageal adenocarcinoma suggests that altered expression of the cellular adhesion molecules, E-cadherin and CD44v6, may have had a role to play in the rapid onset of metastases. Objective.-To corroborate these findings, we designed a cross-sectional study to investigate the expression of select molecules involved in the metastatic cascade. Design.-E-cadherin, beta-catenin, CD44v6, and HER2/neu immunohistochemical stains were performed on archival materials of metastatic adenocarcinoma to the skin from 27 patients and the available corresponding primary tumors in 10 patients. The primary sites included breast (n = 10; 37%), gastrointestinal tract (n = 10; 37%), ovary (n = 1; 4%), thyroid (n = 2; 7%), lung (n = 1; 4%), and unknown primary (n = 3; 11%). Results.-Expression of all markers was noted with the most significant increases observed in beta-catenin (26 of 27 cases; 96%), followed by CD44v6 (24 of 27 cases; 89%), E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27 cases; 41%). Contrasting expression of these molecules in the primary versus the metastatic tumors, enhanced expression of CD44v6 was observed in the cutaneous metastases relative to the primary in 6 of 10 (60%) cases. Of interest, 2 of these 6 cases (33%) also showed reduction in E-cadherin-a member of the cadherin family functioning as an invasion suppressor molecule. Conclusions.-These findings reinforce the complexities of the metastatic cascade and imply that the variation in adhesive properties of tumor cells is, perhaps, a consequence of the difference in density of the molecules mediating this process. (Arch Pathol Lab Med. 2009; 133: 1285-1290) C1 [Mahalingam, Meera] Boston Univ, Sch Med, Dept Dermatol, Dermatopathol Sect, Boston, MA 02118 USA. [Pozdnyakova, Olga; Dresser, Karen A.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Hoang, Mai M. P.] Harvard Univ, Sch Med, Boston, MA USA. [Hoang, Mai M. P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mahalingam, M (reprint author), Boston Univ, Sch Med, Dept Dermatol, Dermatopathol Sect, 609 Albany St,J-301, Boston, MA 02118 USA. EM mmahalin@bu.edu NR 20 TC 5 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 2009 VL 133 IS 8 BP 1285 EP 1290 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 482TA UT WOS:000268910400028 PM 19653727 ER PT J AU Wecht, JM Radulovic, M LaFountaine, MF Rosado-Rivera, D Zhang, RL Bauman, WA AF Wecht, Jill M. Radulovic, Miroslav LaFountaine, Michael F. Rosado-Rivera, Dwindally Zhang, Run-Lin Bauman, William A. TI Orthostatic Responses to Nitric Oxide Synthase Inhibition in Persons With Tetraplegia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Hypotension, orthostatic; Rehabilitation; Spinal cord injuries; Tilt-table test ID SPINAL-CORD-INJURY; SYMPATHETIC PREGANGLIONIC NEURONS; PLASMA-RENIN ACTIVITY; SIMULATED MICROGRAVITY; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; HYPOTENSION; MECHANISMS; RISK; EXPRESSION AB Wecht JM, Radulovic M, LaFountaine MF, Rosado-Rivera D, Zhang R-L, Bauman WA. Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia. Arch Phys Med Rehabil 2009;90:1428-34. Objectives: To determine the effects of 1.0mg/kg nitro-L-arginine methyl ester (L-NAME) on orthostatic mean arterial pressure (MAP), serum aldosterone, and plasma renin concentrations in persons with chronic tetraplegia compared with nonspinal cord-injured controls. Design: Prospective placebo-controlled intervention study. Setting: James J. Peters Veterans Affairs Medical Center. Participants: Patients (n=5) with tetraplegia and controls (n=7) participated. The groups were matched for age, height, and weight; the average duration of injury in the tetraplegia group was 22 +/- 14 years. Intervention: Subjects with tetraplegia visited the laboratory twice, receiving placebo on day 1 and L-NAME (1.0mg/kg) on day 2. The agents were infused via an intravenous catheter over 60 minutes with the patient in the supine position. Data were collected during the infusion and then during head-up tilt to 45 degrees for 30 minutes. Control subjects visited the laboratory once for placebo infusion and the head-up tilt maneuver. Main Outcome Measure: Orthostatic MAP. Results: Orthostatic MAP was reduced after placebo infusion in subjects with tetraplegia compared with controls (69 +/- 11 vs 89 +/- 9mmHg, respectively; P <.01) and compared with L-NAME infusion (90 +/- 16mmHg; P <.01). Orthostatic MAP did not differ when comparing the tetraplegia group with controls after L-NAME infusion. Orthostatic aldosterone levels were increased after placebo compared with L-NAME infusion in persons with tetraplegia; plasma renin levels did not differ among the groups. Conclusions: These data suggest that nitric oxide synthase inhibition may have clinical potential for treatment of orthostatic hypotension in persons with chronic tetraplegia. C1 [Wecht, Jill M.; Radulovic, Miroslav; LaFountaine, Michael F.; Rosado-Rivera, Dwindally; Zhang, Run-Lin; Bauman, William A.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Wecht, Jill M.; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Wecht, Jill M.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM jm.wecht@VA.gov FU Veterans Affairs Rehabilitation Research and Development Service [B3203R, B4162C]; United Spinal Association FX Supported by the Veterans Affairs Rehabilitation Research and Development Service (grant no. B3203R and B4162C) and by the United Spinal Association. NR 41 TC 9 Z9 9 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 2009 VL 90 IS 8 BP 1428 EP 1434 DI 10.1016/j.apmr.2009.02.004 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 483PY UT WOS:000268981000022 PM 19651280 ER PT J AU Gleysteen, JJ AF Gleysteen, John J. TI Mesh-Reinforced Ventral Hernia Repair Preference for 2 Techniques SO ARCHIVES OF SURGERY LA English DT Article ID INCISIONAL HERNIA; SUTURE REPAIR; EXPERIENCE; HERNIOPLASTY; OUTCOMES AB Hypothesis: Long-term (5-year) recurrence rates are comparable between onlay vs retrorectus mesh-reinforced ventral hernia repairs. Design: Retrospective study of prospective data collection. Setting: University and Veterans Affairs hospitals. Patients: One hundred twenty-five patients treated between February 1988 and September 2001. Ninety-four patients were male. The mean patient age was 56 years (age range, 29-80 years). Fifty percent of patients were smokers, and 32.0% were obese; comorbidities were similar in the 2 cohorts studied. Interventions: Open surgical extraperitoneal prosthetic mesh reinforcement of the incisional closure among 75 patients (onlay repair [cohort OR]) or in the retrorectus position among 50 patients (retrorectus repair [cohort RR]). Main Outcome Measures: Recurrent hernia, wound infection, and intestinal fistulas. Results: Nine patients in cohort OR and 2 patients in cohort RR (8.8%) had wound infections; no fistulas occurred. Complications were similar in the 2 cohorts. One mortality occurred. All hernias recurred at the cranial or caudal edge of the mesh. The median recurrence rates were 20.0% at 15 months in the OR cohort and 4.0% at 9 months in cohort RR (P < .02). Follow-up periods averaged 64 months. Three other patients in cohort OR developed subsequent hernia adjacent to their mesh reinforcement at 72, 73, and 86 months. Conclusions: Extraperitoneal mesh reinforcement avoids intestinal complications and subsequent operations to remove mesh. Recurrence is more frequent after onlay mesh reinforcement and usually occurs at the cranial or caudal edge of the mesh within the first 2 years after hernia repair. Retrorectus repair is the preferred open surgical treatment of incisional hernia, but it has not been universally applicable. Hernias developing 6 to 7 years after surgery are not the result of failed earlier repairs. C1 [Gleysteen, John J.] Birmingham Vet Affairs Med Ctr, Surg Serv, Birmingham, AL 35233 USA. [Gleysteen, John J.] Univ Alabama, Sch Med, Dept Surg, Gastrointestinal Sect, Birmingham, AL USA. RP Gleysteen, JJ (reprint author), Birmingham Vet Affairs Med Ctr, Surg Serv, Room 4343,700 S 19th St, Birmingham, AL 35233 USA. EM jgleyst@bellsouth.net NR 19 TC 13 Z9 13 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD AUG PY 2009 VL 144 IS 8 BP 740 EP 745 PG 6 WC Surgery SC Surgery GA 484RD UT WOS:000269063800010 PM 19687378 ER PT J AU Walshe, TE Dole, VS Maharaj, ASR Patten, IS Wagner, DD D'Amore, PA AF Walshe, Tony E. Dole, Vandana S. Maharaj, Arindel S. R. Patten, Ian S. Wagner, Denisa D. D'Amore, Patricia A. TI Inhibition of VEGF or TGF-beta Signaling Activates Endothelium and Increases Leukocyte Rolling SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE VEGF; TGF-beta; P-selectin; nitric oxide; inflammation ID GROWTH-FACTOR-BETA; E-SELECTIN EXPRESSION; TUMOR-NECROSIS-FACTOR; PLASMA P-SELECTIN; NITRIC-OXIDE; IN-VIVO; TRANSFORMING GROWTH-FACTOR-BETA-1; MURINE MEGAKARYOCYTOPOIESIS; THROMBOTIC MICROANGIOPATHY; ADHESION MOLECULES AB Objective-Motivated by the central roles that vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta play in the assembly and maintenance of the vasculature, we examined the impact of systemic VEGF or TGF-beta signal inhibition on endothelial activation as detected by leukocyte-endothelial interactions. Methods and Results-VEGF or TGF-beta inhibition, accomplished using adenovirus expression of soluble Flt1 (Ad-sFlt1) or soluble endoglin (Ad-sEng), resulted in a significant increase in the number of leukocytes rolling along the mesenteric venous endothelium and a significant decrease in rolling velocity in Ad-sEng mice. Neutralization of VEGF or TGF-beta resulted in endothelial surface expression of P-selectin and impaired peripheral vasodilatation. Neither inhibition of VEGF nor TGF-beta was associated with platelet or leukocyte activation, as detected by the activation markers platelet P-selectin and the active integrin alpha IIb beta III, or by leukocyte expression of L-selectin. Soluble vascular cell adhesion molecule (VCAM)-1 and E-selectin were increased in sEng-expressing mice, indicating higher levels of these adhesion receptors. Conclusions-VEGF or TGF-beta neutralization leads to impaired endothelium-mediated vasodilatation and elevated expression of surface adhesion molecules, resulting in increased leukocyte adhesion. These results indicate an essential role for both VEGF and TGF-beta in maintaining the endothelium in a nonactivated state and have implications for therapeutic approaches that neutralize VEGF or TGF-beta. (Arterioscler Thromb Vasc Biol. 2009; 29: 1185-1192.) C1 [Walshe, Tony E.; Maharaj, Arindel S. R.; D'Amore, Patricia A.] Schepens Eye Res Inst, Boston, MA 02114 USA. [Dole, Vandana S.; Wagner, Denisa D.; D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Dole, Vandana S.; Patten, Ian S.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02114 USA. RP D'Amore, PA (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM wagner@idi.harvard.edu FU NIH [EY05318, POI HL066105]; Knights Templar Eye Foundation award FX This work was supported by NIH grant EY05318 (to P. A. D.), POI HL066105 (to D. D. W.), and Knights Templar Eye Foundation award (to T. E. W.). NR 66 TC 32 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2009 VL 29 IS 8 BP 1185 EP U70 DI 10.1161/ATVBAHA.109.186742 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 470UU UT WOS:000268007500007 PM 19461051 ER PT J AU Stangenberg, L Ellson, C Cortez-Retamozo, V Ortiz-Lopez, A Yuan, H Blois, J Smith, RA Yaffe, MB Weissleder, R Benoist, C Mathis, D Josephson, L Mahmood, U AF Stangenberg, Lars Ellson, Chris Cortez-Retamozo, Virna Ortiz-Lopez, Adriana Yuan, Hushan Blois, Joseph Smith, Ralph A. Yaffe, Michael B. Weissleder, Ralph Benoist, Christophe Mathis, Diane Josephson, Lee Mahmood, Umar TI Abrogation of Antibody-Induced Arthritis in Mice by a Self-Activating Viridin Prodrug and Association With Impaired Neutrophil and Endothelial Cell Function SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; RHEUMATOID-ARTHRITIS; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; INFLAMMATORY ARTHRITIS; B-CELL; MURINE MODEL; PI3K-GAMMA; WORTMANNIN AB Objective. To test a novel self-activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3-kinase inhibitor, in a model of antibody-mediated inflammatory arthritis. Methods. The SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10-day disease course (serum-transfer arthritis). Protease activity was measured by a near-infrared imaging approach using a cleavable cathepsin-selective probe. Further near-infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil-endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay. Results. SAV prevented ankle swelling in mice with serum-transfer arthritis in a dose-dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor alpha was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease-laden vesicles, were decreased by SAV administration. Conclusion. A novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody-induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions. C1 [Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Stangenberg, Lars; Cortez-Retamozo, Virna; Ortiz-Lopez, Adriana; Yuan, Hushan; Blois, Joseph; Smith, Ralph A.; Weissleder, Ralph; Benoist, Christophe; Mathis, Diane; Josephson, Lee; Mahmood, Umar] Harvard Univ, Sch Med, Boston, MA USA. [Ellson, Chris; Ortiz-Lopez, Adriana; Yaffe, Michael B.; Benoist, Christophe; Mathis, Diane] MIT, Cambridge, MA 02139 USA. [Ortiz-Lopez, Adriana; Mathis, Diane; Josephson, Lee] Broad Inst Harvard, Cambridge, MA USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU NIH [P01-AI-054904, R01-EB-001872, R01-AR-046580, R24-CA-92782, P50-CA-86355] FX Supported in part by NIH grants P01-AI-054904, R01-EB-001872, R01-AR-046580, R24-CA-92782, and P50-CA-86355. NR 43 TC 8 Z9 8 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2009 VL 60 IS 8 BP 2314 EP 2324 DI 10.1002/art.24704 PG 11 WC Rheumatology SC Rheumatology GA 483NL UT WOS:000268973600013 PM 19644878 ER PT J AU Matsui, Y Iwasaki, N Kon, S Takahashi, D Morimoto, J Matsui, Y Denhardt, DT Rittling, S Minami, A Uede, T AF Matsui, Yuichiro Iwasaki, Norimasa Kon, Shigeyuki Takahashi, Daisuke Morimoto, Junko Matsui, Yutaka Denhardt, David T. Rittling, Susan Minami, Akio Uede, Toshimitsu TI Accelerated Development of Aging-Associated and Instability-Induced Osteoarthritis in Osteopontin-Deficient Mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CRUCIATE LIGAMENT TRANSECTION; ARTICULAR-CARTILAGE; METABOLIC ABNORMALITIES; KNEE OSTEOARTHRITIS; MECHANICAL-STRESS; MURINE MODEL; IN-VITRO; BONE; MATRIX; EXPRESSION AB Objective. To investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions. Methods. Both instability-induced and aging-associated OA models were generated using OPN-deficient (OPN(-/-)) and control wild-type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage. Results. OPN deficiency exacerbated both aging-associated and instability-induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP-13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen-degrading enzyme MMP-13 facilitated the development of OA. Conclusion. OPN plays a pivotal role in the progression of both instability-induced and aging-associated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP-13 expression and proteoglycan loss. C1 [Uede, Toshimitsu] Hokkaido Univ, Div Mol Immunol, Inst Med Genet, Kita Ku, Sapporo, Hokkaido 0600815, Japan. [Matsui, Yuichiro; Iwasaki, Norimasa; Takahashi, Daisuke; Minami, Akio] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido 0600815, Japan. [Denhardt, David T.] Rutgers State Univ, Piscataway, NJ USA. [Rittling, Susan] Forsyth Inst, Boston, MA USA. RP Uede, T (reprint author), Hokkaido Univ, Div Mol Immunol, Inst Med Genet, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0600815, Japan. EM toshi@igm.hokudai.ac.jp RI Kon, Shigeyuki/A-3809-2012; uede, toshimitsu/A-4273-2012; Iwasaki, Norimasa/D-6448-2012 NR 43 TC 46 Z9 49 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2009 VL 60 IS 8 BP 2362 EP 2371 DI 10.1002/art.24705 PG 10 WC Rheumatology SC Rheumatology GA 483NL UT WOS:000268973600018 PM 19644889 ER PT J AU Yun, CH Schlett, CL Rogers, IS Truong, QA Toepker, M Donnelly, P Brady, TJ Hoffmann, U Bamberg, F AF Yun, Chun-Ho Schlett, Christopher L. Rogers, Ian S. Truong, Quynh A. Toepker, Michael Donnelly, Patrick Brady, Thomas J. Hoffmann, Udo Bamberg, Fabian TI Association between diabetes and different components of coronary atherosclerotic plaque burden as measured by coronary multidetector computed tomography SO ATHEROSCLEROSIS LA English DT Article DE Diabetes; Cardiovascular risk factors; Coronary artery disease; Coronary MDCT ID REVASCULARIZATION INVESTIGATION BARI; SILENT-MYOCARDIAL-ISCHEMIA; INTRAVASCULAR ULTRASOUND; NONINVASIVE ASSESSMENT; ARTERY-DISEASE; INFARCTION; PATHOPHYSIOLOGY; INTERVENTION; ANGIOGRAPHY; MORTALITY AB Objective: The aim of the study was to assess differences in the presence, extent, and composition of coronary atherosclerotic plaque burden as detected by coronary multidetector computed tomography (MDCT) between patients with and without diabetes mellitus. Methods: We compared coronary atherosclerotic plaques (any plaque, calcified [CAP], non-calcified [NCAP, and mixed plaque [MCAP]]) between 144 symptomatic diabetic and non-diabetic patients (36 diabetics, mean age: 54.4 +/- 12, 64% females) who underwent coronary 64-slice MDCT (Siemens Medical Solutions, Forchheim, Germany) for the evaluation of acute chest pain but proven absence of myocardial ischemia. Results: Patients with diabetes had a higher prevalence of any plaque, CAP, MCAP, and NCAP (p = 0.08, 0.07, 0.05, and 0.05, respectively) and a significantly higher extent of any plaque, CAP, MCAP, and NCAP (3.8 +/- 4.2 vs. 2.0 +/- 3.2, p = 0.01; 3.3 +/- 4.0 vs. 1.7 +/- 3.0, p = 0.03; 1.4 +/- 2.6 vs. 0.6 +/- 1.5. p = 0.03; and 1.9 +/- 3.0 vs. 1.0 +/- 1.9, p = 0.03, respectively) as compared to controls. In addition, patients with diabetes had a significant higher prevalence of significant coronary artery stenosis (42% vs. 14%, p = 0.0004) and an approximately 3.5-fold higher risk of significant coronary stenosis independent of the presence of hypertension and BMI (OR: 3.46, 95% Cl: 1.37-8.74, p = 0.009). Conclusion: Patients with diabetes have an approximately 3.5-fold higher risk of coronary stenosis independent of other cardiovascular risk factors and an overall increased coronary atherosclerotic plaque burden. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Yun, Chun-Ho; Schlett, Christopher L.; Rogers, Ian S.; Truong, Quynh A.; Toepker, Michael; Donnelly, Patrick; Brady, Thomas J.; Hoffmann, Udo; Bamberg, Fabian] Harvard Univ, Cardiac MR PET CT Program, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yun, Chun-Ho] Mackay Mem Hosp, Dept Radiol, Taipei, Taiwan. [Yun, Chun-Ho] Mackay Med Nursing & Management Coll, Taipei, Taiwan. RP Bamberg, F (reprint author), Harvard Univ, Cardiac MR PET CT Program, Sch Med, Massachusetts Gen Hosp, 165 Cambridge St,4th Floor,Suite 400, Boston, MA 02114 USA. EM fbamberg@partners.org NR 27 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2009 VL 205 IS 2 BP 481 EP 485 DI 10.1016/j.atherosclerosis.2009.01.015 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487QI UT WOS:000269289500025 PM 19230889 ER PT J AU Shusterman, A Feld, L Baer, L Keuthen, N AF Shusterman, Anna Feld, Lauren Baer, Lee Keuthen, Nancy TI Affective regulation in trichotillomania: Evidence from a large-scale internet survey SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Trichotillomania; Hair-pulling; Affective regulation; Emotion; Internet survey; Anxiety ID MGH HAIRPULLING SCALE; EXPERIENTIAL AVOIDANCE; EMOTION REGULATION; PHENOMENOLOGY; IMPACT; DYSREGULATION; PREVALENCE; VALIDATION; SEVERITY; SAMPLES AB Trichotillomania (TTM), a repetitive hair-pulling disorder, is underrepresented in the clinical literature. The current project explores the relationship between affective regulation and disordered hair-pulling. Previous research Suggests that cycles of emotional states are correlated with the disorder and may induce, reinforce, or otherwise contribute to hair-pulling behavior. We use anonymous internet survey responses from 1162 self-identified hair-pullers to address four questions about affective regulation in people with TTM: (1) Do hair-pullers experience greater difficulty "snapping out" of affective states than non-pullers? (2) Does difficulty with emotional control correlate with TTM severity? (3) Are subtypes identifiable based on the emotions that trigger hair-pulling behavior? (4) Does difficulty "snapping out" of an emotion predict whether that emotion triggers pulling behavior? The results showed a small-tomoderate relationship between affective regulation and problematic hair-pulling. In addition, individual patterns of emotion regulation were systematically related to emotional cues for hair-pulling as well as overall hair-pulling severity. These findings contribute to an understanding of the phenomenology of TTM and provide empirical support for treatments focused on affect regulation. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Shusterman, Anna; Feld, Lauren] Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. [Baer, Lee; Keuthen, Nancy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Shusterman, A (reprint author), Wesleyan Univ, Dept Psychol, 207 High St, Middletown, CT 06459 USA. EM ashusterman@wesleyan.edu; lfeld@wesleyan.edu; lbaer@partners.org; nkeuthen@partners.org RI Citations, TLC SAB/C-4006-2011 NR 30 TC 38 Z9 38 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD AUG PY 2009 VL 47 IS 8 BP 637 EP 644 DI 10.1016/j.brat.2009.04.004 PG 8 WC Psychology, Clinical SC Psychology GA 478VG UT WOS:000268616000001 PM 19467648 ER PT J AU Hagopian, K Ramsey, JJ Weindruch, R AF Hagopian, Kevork Ramsey, Jon J. Weindruch, Richard TI Caloric restriction counteracts age-related changes in the activities of sorbitol metabolizing enzymes from mouse liver SO BIOGERONTOLOGY LA English DT Article DE Aldose reductase; Sorbitol dehydrogenase; Polyol; Glucose; Fructose; Redox state ID INDUCED DIABETIC-RATS; ALDOSE REDUCTASE; OXIDATIVE STRESS; GENE-EXPRESSION; POLYOL PATHWAY; DEHYDROGENASE; COMPLICATIONS; LENS; INHIBITION; MICE AB The influence of caloric restriction (CR) on hepatic sorbitol-metabolizing enzyme activities was investigated in young and old mice. Aldose reductase and sorbitol dehydrogenase activities were significantly lower in old CR mice than in old controls. Young CR mice showed decreased aldose reductase activity and a trend towards decreased sorbitol dehydrogenase when compared to controls. Metabolites of the pathway, namely sorbitol, glucose and fructose were decreased by CR in young and old mice. Pyruvate levels were decreased by CR in both young and old mice, while lactate decreased only in old CR. Malate levels increased in old CR but remained unchanged in young CR, when compared with controls. Accordingly, the lactate/pyruvate and malate/pyruvate ratios in young and old CR mice were increased, indicating increased NADH/NAD and NADPH/NADP redox couples, respectively. The results indicate that decreased glucose levels under CR conditions lead to decreased sorbitol pathway enzyme activities and metabolite levels, and could contribute to the beneficial effects of long-term CR through decreased sorbitol levels and NADPH sparing. C1 [Hagopian, Kevork; Ramsey, Jon J.] Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA. [Weindruch, Richard] Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. [Weindruch, Richard] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. RP Hagopian, K (reprint author), Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, 1 Shields Ave, Davis, CA 95616 USA. EM khagopian@ucdavis.edu FU National Institutes of Health [PO1 AG11915, RO1 AG028125] FX The work was supported by the National Institutes of Health grants PO1 AG11915 and RO1 AG028125. NR 37 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-5729 J9 BIOGERONTOLOGY JI Biogerontology PD AUG PY 2009 VL 10 IS 4 BP 471 EP 479 DI 10.1007/s10522-008-9191-1 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 461TC UT WOS:000267293400009 PM 18953666 ER PT J AU Loberiza, FR Lee, SJ Freytes, CO Giralt, SA Van Besien, K Kurion, S del Cerro, P Toro, JJ Williams, LA Ketelsen, SW Navarro, WH Rizzo, JD AF Loberiza, Fausto R., Jr. Lee, Stephanie J. Freytes, Cesar O. Giralt, Sergio A. Van Besien, Koen Kurion, Seira del Cerro, Paula Toro, Juan J. Williams, Loretta A. Ketelsen, Seth W. Navarro, Willis H. Rizzo, J. Douglas TI Methodological and Logistical Considerations to Study Design and Data Collection in Racial/Ethnic Minority Populations Evaluating Outcome Disparity in Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Hematopoietic cell transplantation; Racial/ethnic disparity ID BONE-MARROW-TRANSPLANTATION; BREAST-CANCER SURVIVAL; ETHNIC-MINORITIES; CHRONIC LEUKEMIA; UNITED-STATES; HEALTH-CARE; SERVICES; INCOME; RACE; MORTALITY AB Outcome disparity associated with race or ethnicity in the United States has been observed in hematopoietic cell transplantation (HCT). The underlying reasons for such disparity are not known. In the United States, an optimal study of health care disparity by race or ethnicity involves consideration of both biologic and psychosocial determinants, which requires an adequately powered, prospective cohort study design. To better characterize the nature and quantify the magnitude of the many impediments relevant to conducting a successful prospective study involving racial or ethnic minorities in HCT, we conducted a feasibility study to help guide planning of a larger scale outcome and disparity study in HCT The primary questions to be addressed in the study were: (1) can we establish a racially or ethnically diverse patient sample that will respond to a survey focused on sociodemographic, economic, health insurance, cultural, spiritual, and religious well-being, and social support information? (2) What is the retention rate in the study over time? (3) What is the quality of the data collected from the patients over time? The challenges we faced in conducting this multicenter feasibility study are summarized in this report. Despite the difficulty in conducting disparity studies in racial and ethnic minorities, such studies are essential to ensure that people of all ethnic and racial backgrounds have the best chance possible of benefiting from HCT Biol Blood Marrow Transplant 15: 903-909 (2009) (C) 2009 Elsevier Inc. All rights reserved. C1 [Loberiza, Fausto R., Jr.] Univ Nebraska, Med Ctr, Onc Hem Sect, Omaha, NE 68198 USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Freytes, Cesar O.; Toro, Juan J.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Freytes, Cesar O.; Toro, Juan J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Giralt, Sergio A.; Williams, Loretta A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Van Besien, Koen; del Cerro, Paula] Univ Chicago, Chicago, IL 60637 USA. [Kurion, Seira] Dept Publ Hlth, Los Angeles, CA USA. [Ketelsen, Seth W.; Rizzo, J. Douglas] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Navarro, Willis H.] Natl Marrow Donor Program, Phoenix, AZ USA. RP Loberiza, FR (reprint author), Univ Nebraska, Med Ctr, Onc Hem Sect, 600 S 42nd St, Omaha, NE 68198 USA. EM floberiza@unmc.edu RI van Besien, Koen/G-4221-2012 OI van Besien, Koen/0000-0002-8164-6211 FU Medical College of Wisconsin Cancer Center Institutional Research Fund FX This work was supported by the Medical College of Wisconsin Cancer Center Institutional Research Fund. NR 25 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2009 VL 15 IS 8 BP 903 EP 909 DI 10.1016/j.bbmt.2009.04.005 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 477PH UT WOS:000268530500002 PM 19589479 ER PT J AU Maas, MB Furie, KL AF Maas, Matthew B. Furie, Karen L. TI Molecular biomarkers in stroke diagnosis and prognosis SO BIOMARKERS IN MEDICINE LA English DT Review DE biomarkers; cytokines; diagnosis; inflammation; prognosis; severity; stroke; worsening ID ACUTE ISCHEMIC-STROKE; NEURON-SPECIFIC ENOLASE; C-REACTIVE PROTEIN; FIBRILLARY ACIDIC PROTEIN; MYELIN BASIC-PROTEIN; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; TISSUE-PLASMINOGEN ACTIVATOR; N-ACETYL-ASPARTATE; MATRIX-METALLOPROTEINASE EXPRESSION; ADMISSION FIBRINOLYTIC PROFILE AB Serum biomarkers related to the cascade of inflammatory, hemostatic, glial and neuronal perturbations have been identified to diagnose and characterize intracerebral hemorrhage and cerebral ischemia. Interpretation of most markers is confounded by their latent rise, blood-brain barrier effects, the heterogeneity of etiologies and the wide range of normal values, limiting their application for early diagnosis, lesion size estimation and long-term outcome prediction. Certain hemostatic and inflammatory constituents have been found to predict response to thrombolysis and worsening due to infarct progression and secondary hemorrhage, offering a potential role for improved treatment selection and individualization of therapy. Biomarkers will become increasingly relevant for developing targets for neuroprotective therapies, monitoring response to treatment and as surrogate end points for treatment trials. C1 [Maas, Matthew B.; Furie, Karen L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Maas, MB (reprint author), 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM mmaas@partners.org FU NIH [P50NS051343] FX Mathew B Maas and Karen L Furie are supported by NIH (grant P50NS051343). 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 175 TC 30 Z9 33 U1 1 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD AUG PY 2009 VL 3 IS 4 BP 363 EP 383 DI 10.2217/BMM.09.30 PG 21 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 486EP UT WOS:000269179000015 PM 20160867 ER PT J AU Zhang, L Spector, M AF Zhang, Lu Spector, Myron TI Comparison of three types of chondrocytes in collagen scaffolds for cartilage tissue engineering SO BIOMEDICAL MATERIALS LA English DT Article ID SMOOTH-MUSCLE ACTIN; CANINE ARTICULAR CHONDROCYTES; MATRICES IN-VITRO; EXTRACELLULAR-MATRIX; BOVINE MENISCUS; SYNOVIAL-FLUID; PASSAGE NUMBER; CROSS-LINKING; GAG MATRICES; CELLS AB The objective of this study was to compare the chondrogenesis in type I and II collagen scaffolds seeded with chondrocytes from three types of cartilage, after four weeks of culture: auricular (AU), articular (AR) and meniscal (ME). Related aims were to investigate the expression of a contractile muscle actin isoform, alpha-smooth muscle actin (SMA), in the cells in the scaffold and to determine the presence of a lubricating glycoprotein, lubricin, in the constructs. Adult goat AU, AR and ME chondrocytes were seeded into two types of collagen scaffolds: type II collagen and type I/III collagen. After four weeks of culture, the constructs were prepared for histochemical and immunohistochemical analysis of the distribution of glycosaminoglycan (GAG), types I and II collagen, elastin, SM and lubricin. AU constructs contained substantially more tissue than the AR and ME samples. The AU constructs exhibited neocartilage, but no elastin. There were no notable differences between the type I and II collagen scaffolds. Novel findings were the expression of SMA by the AU cells in the scaffolds and the presence of lubricin in the AR and AU constructs. AU cells have the capability to produce cartilage in collagen scaffolds under conditions in which there is little histogenesis by AR and ME cells. C1 [Zhang, Lu] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg,Shanghai Tissue Eng, Shanghai 200030, Peoples R China. [Zhang, Lu; Spector, Myron] VA Boston Healthcare Syst, Boston, MA USA. [Zhang, Lu; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Zhang, L (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg,Shanghai Tissue Eng, Shanghai 200030, Peoples R China. EM luzhangmd@gmail.com FU China Scholarship Council [2007100913] FX This study was financially supported by Department of Veterans Affairs. Lu Zhang MD was supported by China Scholarship Council (2007) 3020 (no 2007100913) as a research fellow in Harvard Medical School in 2008. The authors thank T Schmid of Rush University Medical Center, Chicago, IL for the anti-lubricin antibody and James Kretlow from Rice University for some helpful suggestions for the manuscript. NR 37 TC 21 Z9 21 U1 1 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 J9 BIOMED MATER JI Biomed. Mater. PD AUG PY 2009 VL 4 IS 4 AR 045012 DI 10.1088/1748-6041/4/4/045012 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 482FW UT WOS:000268871000021 PM 19636108 ER PT J AU Yuan, H Pupo, MT Blois, J Smith, A Weissleder, R Clardy, J Josephson, L AF Yuan, Hushan Pupo, Monica T. Blois, Joe Smith, Adam Weissleder, Ralph Clardy, Jon Josephson, Lee TI A stabilized demethoxyviridin derivative inhibits PI3 kinase SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Viridins; P13 kinase; Natural products; Inhibitors ID PHOSPHATIDYLINOSITOL 3-KINASE; WORTMANNIN AB The viridins like demethoxyviridin (Dmv) and wortmannin (Wm) are nanomolar inhibitors of the PI3 kinases, a family of enzymes that play key roles in a host of regulatory processes. Central to the use of these compounds to investigate the role of PI3 kinase in biological systems, or as scaffolds for drug development, are the interrelated issues of stability, chemical reactivity, and bioactivity as inhibitors of PI3 kinase. We found that Dmv was an even more potent inhibitor of PI3 kinase than Wm. However, Dmv was notably less stable than Wm in PBS, with a half-life of 26 min versus Wm's half-life of 3470 min. Dmv, like Wm, disappeared in culture media with a half-life of less than 1 min. To overcome Dmv's instability, it was esterified at the C1 position, and then reacted with glycine at the C20 position. The resulting Dmv derivative, termed SA-DmvC20-Gly had a half-life of 218 min in PBS and 64 min in culture media. SA-DmvC20-Gly underwent an exchange reaction at the C20 position with N-acetyl lysine in a manner similar to a WmC20 derivative, WmC20-Proline. SA-DmvC20-Gly inhibited PI3 kinase with an IC(50) of 44 nM, compared to Wm's IC(50) of 12 nM. These results indicate that the stability of Dmv can be manipulated by reactions at the C1 and C20 positions, while substantially maintaining its ability to inhibit PI3 kinase. Our results indicate it may be possible to obtain stabilized Dmv derivatives for use as PI3 kinase inhibitors in biological systems. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Yuan, Hushan; Blois, Joe; Smith, Adam; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Pupo, Monica T.] Univ Sao Paulo, BR-14049 Ribeirao Preto, SP, Brazil. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Josephson, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. EM mtpupo@fcfrp.usp.br; ljosephson@mgh.harvard.edu RI Pupo, Monica/D-8628-2012; 4, INCT/H-4499-2013; Inbeqmedi, Inct/I-1929-2013; Wang, Gaoqian/K-8528-2015 OI Pupo, Monica/0000-0003-2705-0123; FU [P50-CA86355]; [CA24487] FX This work was supported in part by P50-CA86355 (R. W.) and, CA24487 (J. C.). NR 13 TC 5 Z9 5 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 1 PY 2009 VL 19 IS 15 BP 4223 EP 4227 DI 10.1016/j.bmcl.2009.05.105 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 469LQ UT WOS:000267900900049 PM 19523825 ER PT J AU Choi, Y Syeda, F Walker, JR Finerty, PJ Cuerrier, D Wojciechowski, A Liu, QS Dhe-Paganon, S Gray, NS AF Choi, Yongmun Syeda, Farisa Walker, John R. Finerty, Patrick J., Jr. Cuerrier, Dominic Wojciechowski, Amy Liu, Qingsong Dhe-Paganon, Sirano Gray, Nathanael S. TI Discovery and structural analysis of Eph receptor tyrosine kinase inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Eph kinase; Ephrin; Type II kinase inhibitor ID BCR-ABL; DESIGN; CANCER; EXPRESSION; LEUKEMIA; INVASION; IMATINIB; SYSTEM; POTENT; CELLS AB The Eph family of receptor tyrosine kinases has drawn growing attention due to their role in regulating diverse biological phenomena. However, pharmacological interrogation of Eph kinase function has been hampered by a lack of potent and selective Eph kinase inhibitors. Here we report the discovery of compounds 6 and 9 using a rationally designed kinase-directed library which potently inhibit Eph receptor tyrosine kinases, particularly EphB2 with cellular EC(50)s of 40 nM. Crystallographic data of EphA3 and EphA7 in complex with the inhibitors show that they bind to the 'DFG-out' inactive kinase conformation and provide valuable information for structure-based design of second generation inhibitors. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Syeda, Farisa; Cuerrier, Dominic; Dhe-Paganon, Sirano] Univ Toronto, Dept Physiol, Toronto, ON M5G 1L5, Canada. [Syeda, Farisa; Walker, John R.; Finerty, Patrick J., Jr.; Cuerrier, Dominic; Dhe-Paganon, Sirano] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L5, Canada. [Choi, Yongmun; Wojciechowski, Amy; Liu, Qingsong; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Choi, Yongmun; Wojciechowski, Amy; Liu, Qingsong; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Dhe-Paganon, S (reprint author), Univ Toronto, Dept Physiol, 100 Coll St, Toronto, ON M5G 1L5, Canada. EM sirano.dhepaganon@utoronto.ca; nathanael_gray@dfci.harvard.edu OI liu, qing song/0000-0002-7829-2547 FU U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; NIH [GM079575-02]; The Structural Genomics Consortium [1097737]; Canadian Institutes for Health Research; the Canadian Foundation for Innovation Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut; Alice Wallenberg Foundation; Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust FX We thank Ambit Biosciences for performing KinomeScan profiling, Invitrogen's SelectScreen (R) Service for performing enzymatic biochemical kinase activity pro. ling, Ivona Kozieradzki and her team for providing cloning services for structural biology, and to the Genomics Institute of the Novartis Research Foundation for performing Ba/F3 cellular assays. Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. This work was funded by NIH grant GM079575-02. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research and the Wellcome Trust. NR 23 TC 40 Z9 41 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 1 PY 2009 VL 19 IS 15 BP 4467 EP 4470 DI 10.1016/j.bmcl.2009.05.029 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 469LQ UT WOS:000267900900104 PM 19553108 ER PT J AU Tohen, M Frank, E Bowden, CL Colom, F Ghaemi, SN Yatham, LN Malhi, GS Calabrese, JR Nolen, WA Vieta, E Kapczinski, F Goodwin, GM Suppes, T Sachs, GS Chengappa, KNR Grunze, H Mitchell, PB Kanba, S Berk, M AF Tohen, Mauricio Frank, Ellen Bowden, Charles L. Colom, Francesc Ghaemi, S. Nassir Yatham, Lakshmi N. Malhi, Gin S. Calabrese, Joseph R. Nolen, Willem A. Vieta, Eduard Kapczinski, Flavio Goodwin, Guy M. Suppes, Trisha Sachs, Gary S. Chengappa, K. N. Roy Grunze, Heinz Mitchell, Philip B. Kanba, Shigenobu Berk, Michael TI The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders SO BIPOLAR DISORDERS LA English DT Review DE affective switch; bipolar disorder; course and outcome; functional outcome; ISBD; nomenclature; predominant polarity; recovery; recurrence; relapse; remission; response ID DEPRESSION RATING-SCALE; PROSPECTIVE FOLLOW-UP; LITHIUM MAINTENANCE TREATMENT; TREATMENT ENHANCEMENT PROGRAM; MONTGOMERY-ASBERG DEPRESSION; CONTROLLED 18-MONTH TRIAL; WEEKLY SYMPTOMATIC STATUS; REPORT QIDS-SR; I DISORDER; FUNCTIONAL IMPAIRMENT AB Objectives: Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. Methods: Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. Results: Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. Conclusion: Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature. C1 [Tohen, Mauricio] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. [Tohen, Mauricio] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. [Frank, Ellen; Chengappa, K. N. Roy] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Colom, Francesc; Vieta, Eduard] Univ Barcelona, IDIBAPS, CIBERSAM, Dept Psychiat, Barcelona, Spain. [Ghaemi, S. Nassir] Tufts Univ, Dept Psychiat, Boston, MA 02111 USA. [Yatham, Lakshmi N.] Univ British Columbia, Dept Psychiat, Div Mood Disorders, Vancouver, BC, Canada. [Malhi, Gin S.] Univ Sydney, Dept Psychiat, CADE Clin, Sydney, NSW 2006, Australia. [Malhi, Gin S.] Univ Sydney, Discipline Psychol Med, Sydney, NSW 2006, Australia. [Calabrese, Joseph R.] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Psychiat, Sch Med, Cleveland, OH 44106 USA. [Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Kapczinski, Flavio] Fed Univ, UFRGS, HCPA, INCT Translat Med,Dept Psychiat, Porto Alegre, RS, Brazil. [Goodwin, Guy M.] Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. [Suppes, Trisha] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA. [Sachs, Gary S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Grunze, Heinz] Newcastle University, Inst Neurosci, Dept Psychiat, Royal Victoria Infirm, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Mitchell, Philip B.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Mitchell, Philip B.] Black Dog Inst, Sydney, NSW, Australia. [Kanba, Shigenobu] Kyushu Univ, Dept Neuropsychiat, Fukuoka, Japan. [Berk, Michael] Univ Melbourne, Dept Clin & Biomed Sci, Melbourne, Vic, Australia. RP Tohen, M (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr,MC 7792, San Antonio, TX 78229 USA. EM tohen@uthscsa.edu RI Kapczinski, Flavio/D-3175-2013; Vieta, Eduard/I-6330-2013; Ghaemi, Nassir/J-4934-2013; Nolen, Willem/E-9006-2014; Kapczinski, Flavio/J-5803-2014; OI Vieta, Eduard/0000-0002-0548-0053; Mitchell, Philip/0000-0002-7954-5235; Berk, Michael/0000-0002-5554-6946; Colom, Francesc/0000-0002-9516-9030 FU The International Society FX This work was conducted under the auspices of The International Society for Bipolar Disorders. Editorial assistance was provided by Caron Modeas. NR 91 TC 170 Z9 172 U1 2 U2 16 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2009 VL 11 IS 5 BP 453 EP 473 PG 21 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 469DD UT WOS:000267874900001 PM 19624385 ER PT J AU Baethge, C Tondo, L Lepri, B Baldessarini, RJ AF Baethge, Christopher Tondo, Leonardo Lepri, Beatrice Baldessarini, Ross J. TI Coffee and cigarette use: association with suicidal acts in 352 Sardinian bipolar disorder patients SO BIPOLAR DISORDERS LA English DT Article DE alcohol; bipolar disorders; caffeine; nicotine; substance abuse; suicidal behavior ID COMORBID SUBSTANCE USE; PSYCHIATRIC-DISORDERS; CLINICAL PREDICTORS; 1ST HOSPITALIZATION; MENTAL-DISORDERS; MOOD DISORDERS; ALCOHOL-ABUSE; II DISORDERS; RISK-FACTORS; CAFFEINE AB Objective: Abuse of illicit drugs and alcohol is prevalent in bipolar disorder (BPD) patients, and is an adverse prognostic factor. Much less is known about correlates of nicotine and caffeine consumption, but tobacco smoking is tentatively associated with suicidal behavior. Methods: Retrospective analysis of demographic and clinical factors among 352 longitudinally assessed DSM-IV types I and II BPD patients contrasted patients with versus without consumption of nicotine or caffeine, based on univariate comparisons and multiple regression modeling. Results: Current smoking (46%) and coffee drinking (74% of cases) were common, and significantly and independently associated with suicidal acts [coffee: odds ratio (OR) = 2.42, 95% confidence interval (CI): 1.15-5.09; smoking: OR = 1.79, CI: 1.02-3.15; both p < 0.001]. Risk increased with more smoking (cigarettes/day; r(s) = 0.383; p < 0.0001) and greater coffee consumption (cups/day; r(s) = 0.312; p = 0.008). Neither intake was related to yearly rates of all episodes, depressions, or manias. Conclusions: This is the first report to associate suicidal acts with coffee consumption in BPD patients, and it confirmed an association with smoking. Pending further evidence, the findings underscore the importance of monitoring use of even legal and mildly psychotropic substances by BPD patients. C1 [Baethge, Christopher] Univ Cologne, Sch Med, Dept Psychiat & Psychotherapy, D-50924 Cologne, Germany. [Tondo, Leonardo; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Tondo, Leonardo; Baldessarini, Ross J.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Tondo, Leonardo; Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Boston, MA 02114 USA. [Tondo, Leonardo; Lepri, Beatrice] Univ Cagliari, Dept Psychol, Sardinia, Italy. [Tondo, Leonardo; Lepri, Beatrice] Lucio Bini Mood Disorders Res Ctr, Cagliari, Italy. RP Baethge, C (reprint author), Univ Cologne, Sch Med, Dept Psychiat & Psychotherapy, Kerpener Str 62, D-50924 Cologne, Germany. EM christopher.baethge@web.de FU Bruce J. Anderson Foundation; McLean Private Donors Research Fund; Janssen; Eli Lilly & Co. FX This study was supported in part by a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Research Fund (RJB).; LT has received research support from Janssen and Eli Lilly & Co.; and has served as a consultant to GlaxoSmithKline and Merck. RJB was recently (>= 5 years) a consultant or investigator-initiated research collaborator with AstraZeneca, Auritec, Biotrofix, Janssen, JDS-Noven, Eli Lilly & Co., Luitpold, NeuroHealing, Novartis, Pfizer, and SK-BioPharmaceutical. CB and BL have no conflicts of interest with regard to this research. None of the authors has other financial relations or equity holdings with pharmaceutical or biomedical corporations. NR 67 TC 22 Z9 23 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2009 VL 11 IS 5 BP 494 EP 503 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 469DD UT WOS:000267874900004 PM 19624388 ER PT J AU Desikan, RS Cabral, HJ Hess, CP Dillon, WP Glastonbury, CM Weiner, MW Schmansky, NJ Greve, DN Salat, DH Buckner, RL Fischl, B AF Desikan, Rahul S. Cabral, Howard J. Hess, Christopher P. Dillon, William P. Glastonbury, Christine M. Weiner, Michael W. Schmansky, Nicholas J. Greve, Douglas N. Salat, David H. Buckner, Randy L. Fischl, Bruce CA Alzheimers Dis Neuroimaging TI Automated MRI measures identify individuals with mild cognitive impairment and Alzheimers disease SO BRAIN LA English DT Article DE MRI; mild cognitive impairment; Alzheimers disease; diagnostic marker ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; ENTORHINAL CORTEX; COORDINATE SYSTEM; CEREBRAL-CORTEX; CLASSIFICATION; SEGMENTATION; DIAGNOSIS; DEMENTIA; PET AB Mild cognitive impairment can represent a transitional state between normal ageing and Alzheimers disease. Non-invasive diagnostic methods are needed to identify mild cognitive impairment individuals for early therapeutic interventions. Our objective was to determine whether automated magnetic resonance imaging-based measures could identify mild cognitive impairment individuals with a high degree of accuracy. Baseline volumetric T(1)-weighted magnetic resonance imaging scans of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with mild cognitive impairment, while the second cohort included 94 older controls and 57 mild cognitive impairment individuals. Sixty-five patients with probable Alzheimers disease were also included for comparison. For the discrimination of mild cognitive impairment, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94, sensitivity 74, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91, sensitivity 90, positive likelihood ratio 10.0, negative likelihood ratio 0.11) for the second cohort. For the discrimination of Alzheimers disease, these three measures demonstrated an area under the curve of 1.0. The three magnetic resonance imaging measures demonstrated significant correlations with clinical and neuropsychological assessments as well as with cerebrospinal fluid levels of tau, hyperphosphorylated tau and abeta 42 proteins. These results demonstrate that automated magnetic resonance imaging measures can serve as an in vivo surrogate for disease severity, underlying neuropathology and as a non-invasive diagnostic method for mild cognitive impairment and Alzheimers disease. C1 [Desikan, Rahul S.; Schmansky, Nicholas J.; Greve, Douglas N.; Salat, David H.; Buckner, Randy L.; Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Desikan, Rahul S.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hess, Christopher P.; Dillon, William P.; Glastonbury, Christine M.; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Weiner, Michael W.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Fischl, Bruce] MIT, CSAIL, Cambridge, MA 02139 USA. [Fischl, Bruce] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Fischl, B (reprint author), Massachusetts Gen Hosp, NMR Ctr, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM fischl@nmr.mgh.harvard.edu OI Cabral, Howard/0000-0002-1185-8331; GLASTONBURY, CHRISTINE/0000-0002-9611-1287 FU American Federation for Aging Research (RSD); National Center for Research Resources [P41-RR14075, R01 RR 16594-01A1, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550]; Mental Illness and Neuroscience Discovery (MIND) Institute; National Institute on Aging [P50 AG05681, P01 AG03991, AG021910]; Alzheimer's Disease Neuroimaging Initiative; NIH [U01 AG024904]; Howard Hughes Medical Institute; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering (NIBIB) FX Medical Student Training in Aging Research Program from the American Federation for Aging Research (RSD); National Center for Research Resources grants (P41-RR14075, R01 RR 16594-01A1 and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382); the National Institute for Biomedical Imaging and Bioengineering (R01 EB001550); the Mental Illness and Neuroscience Discovery (MIND) Institute and the National Institute on Aging (P50 AG05681, P01 AG03991, and AG021910). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (Alzheimer's disease NI; Principal Investigator: Michael Weiner; NIH grant U01 AG024904) and the Howard Hughes Medical Institute (OASIS project). Alzheimer's disease NI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and through generous contributions from the following: Pfizer Inc., Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck & Co. Inc., AstraZeneca AB, Novartis Pharmaceuticals Corporation, Alzheimer's Association, Eisai Global Clinical Development, Elan Corporation plc, Forest Laboratories and the Institute for the Study of Aging, with participation from the US Food and Drug Administration. Industry partnerships are coordinated through the Foundation for the National Institutes of Health. 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. Alzheimer's disease NI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles. NR 51 TC 164 Z9 168 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2009 VL 132 BP 2048 EP 2057 DI 10.1093/brain/awp123 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 475BJ UT WOS:000268330500006 PM 19460794 ER PT J AU Feng, P Yee, KK Rawson, NE Feldman, LM Feldman, RS Breslin, PAS AF Feng, Pu Yee, Karen K. Rawson, Nancy E. Feldman, Lauren M. Feldman, Roy S. Breslin, Paul A. S. TI Immune cells of the human peripheral taste system: Dominant dendritic cells and CD4 T cells SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Taste tissue; Taste bud; Dendritic cell; Langerhans cell; Lymphocyte; Fungiform papillae; Cell population ID UNILATERAL NERVE INJURY; HIV-INFECTED PATIENTS; ORAL LICHEN-PLANUS; UP-REGULATION; TISSUE SPECIMENS; LANGERHANS CELLS; SMELL; MUCOSA; DISORDERS; SUBSETS AB Taste loss or alterations can seriously impact health and quality of life due to the resulting negative influence on eating habits and nutrition. Infection and inflammation are thought to be some of the most common causes of taste perception disorders. Supporting this view, neuro-immune interactions in the peripheral gustatory system have been identified, underlying the importance of this tissue in mucosal immunity, but we have little understanding of how these interactions influence taste perception directly or indirectly. This limited understanding is evident by the lack of even a basic knowledge of the resident immune cell populations in or near taste tissues. The present study characterized the distribution and population of the major immune cells and their subsets in healthy human anterior, lingual, fungiform papillae (FP) using immunohistochemistry. Dendritic cells (DCs) were the predominant innate immune cells in this tissue, including four subtypes: CD11c(+) DCs, DC-SIGN+ immature DCs, CD83(+) mature DCs, and CD1a(+) DCs (Langerhans cells). While most DCs were localized beneath the lamina propria and only moderately in the epithelium, CD1a(+) Langerhans cells were exclusively present within the epithelium and not in sub-strata. A small number of macrophages were observed. T lymphocytes were present throughout the FP with CD4(+) T cells more prevalent than CD8(+)T cells. Very few CD19(+) B lymphocytes were detected. The results show that DCs, macrophages, and T lymphocytes are the constitutive guardians of human FP taste tissue, with DCs and CD4 T cells being dominant, while B lymphocytes are rare under normal, healthy conditions. These observations provide a basic anatomical foundation for the immune response in the healthy human tongue as a basis for subsequent disease-related studies, but none of the present data indicate that the immune cell populations identified are, in fact, altered in individuals with abnormal taste perception. (C) 2009 Elsevier Inc. All rights reserved. C1 [Feng, Pu; Yee, Karen K.; Rawson, Nancy E.; Feldman, Roy S.; Breslin, Paul A. S.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Feng, Pu] Acad Med Sci Gansu Prov, Lanzhou 730050, Gansu, Peoples R China. [Rawson, Nancy E.] WellGen Inc, N Brunswick, NJ USA. [Feldman, Lauren M.] Barnard Coll, New York, NY USA. [Feldman, Roy S.] Philadelphia Vet Affairs Med Ctr, Dent Serv, Philadelphia, PA USA. [Feldman, Roy S.; Breslin, Paul A. S.] Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. RP Breslin, PAS (reprint author), Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA. EM breslin@monell.org FU NIH [DC 02995, P50DC 06760] FX This work was supported by NIH DC 02995 to PASB and P50DC 06760 to PASB and NER. We thank Biostatistician Jesse Chittams for data analysis, Linda Wysocki for her technical help in histology, and Luba Dankulich, Suzanne Alarcon, and Anne Ledyard for their invaluable assistance. NR 37 TC 15 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD AUG PY 2009 VL 23 IS 6 BP 760 EP 766 DI 10.1016/j.bbi.2009.02.016 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 474SR UT WOS:000268304800007 PM 19268521 ER PT J AU Pagani, O Gelber, S Simoncini, E Castiglione-Gertsch, M Price, KN Gelber, RD Holmberg, SB Crivellari, D Collins, J Lindtner, J Thurlimann, B Fey, MF Murray, E Forbes, JF Coates, AS Goldhirsch, A AF Pagani, Olivia Gelber, Shari Simoncini, Edda Castiglione-Gertsch, Monica Price, Karen N. Gelber, Richard D. Holmberg, Stig B. Crivellari, Diana Collins, John Lindtner, Jurij Thuerlimann, Beat Fey, Martin F. Murray, Elizabeth Forbes, John F. Coates, Alan S. Goldhirsch, Aron CA Int Breast Canc Study Grp TI Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Chemoendocrine therapy; Estrogen receptors; Postmenopausal ID ESTROGEN-RECEPTOR STATUS; PREDICTING RESPONSE; RANDOMIZED-TRIAL; GENE-EXPRESSION; TAMOXIFEN; THERAPY; COMBINATION; TUMOR; SURVIVAL; SUBSETS AB To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high. C1 [Pagani, Olivia] Osped Italiano, Oncol Inst So Switzerland, Lugano, Switzerland. [Fey, Martin F.] Univ Bern, Inselspital, Swiss Grp Clin Canc Res SAKK, Dept Med Oncol, CH-3010 Bern, Switzerland. [Gelber, Shari; Gelber, Richard D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Gelber, Shari; Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Simoncini, Edda] Spedali Civil Brescia, I-25125 Brescia, Italy. [Castiglione-Gertsch, Monica] IBCSG Coordinating Ctr, Bern, Switzerland. [Price, Karen N.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Holmberg, Stig B.] Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden. [Crivellari, Diana] Ctr Riferimento Oncol, I-33081 Aviano, Italy. [Collins, John] Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. [Lindtner, Jurij] Inst Oncol, Ljubljana, Slovenia. [Thuerlimann, Beat] Kantonsspital, Swiss Grp Clin Canc Res SAKK, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. [Murray, Elizabeth] Univ Cape Town, Groote Shuur Hosp, ZA-7925 Cape Town, South Africa. [Forbes, John F.] Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. [Coates, Alan S.] Univ Sydney, Int Breast Canc Study Grp, Sydney, NSW 2006, Australia. [Goldhirsch, Aron] European Inst Oncol, Dept Med, Milan, Italy. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. Int Breast Canc Study Grp, Bern, Switzerland. RP Pagani, O (reprint author), Osped Italiano, Oncol Inst So Switzerland, Lugano, Switzerland. EM olivia.pagani@ibcsg.org; shari@jimmy.harvard.edu; bscivile@ns.numerica.it; monica.castiglione@bluewin.ch; price@jimmy.harvard.edu; gelber@jimmy.harvard.edu; stig.holmberg@vgregion.se; dcrivellari@cro.it; johncol@bigpond.net.au; JLindtner@onko-i.si; beat.thuerlimann@kssg.ch; martin.fey@insel.ch; Elizabeth.Murray@uct.ac.za; john.forbes@anzbctg.newcastle.edu.au; alan.coates@ibcsg.org; aron.goldhirsch@ibcsg.org RI Aebi, Stefan/F-2004-2010; OI Aebi, Stefan/0000-0002-3383-9449; Hultborn, Ragnar/0000-0002-4289-9339 FU Swiss Group for Clinical Cancer Research (SAKK); Frontier Science and Technology Research Foundation (FSTRF); The Cancer Council Australia; National Health Medical Research Council; National Cancer Institute [CA-75362]; Swedish Cancer Society; Cancer Research Switzerland/Oncosuisse; Cancer Association of South Africa; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX We thank the patients, physicians, nurses, and data managers who have participated in the International Breast Cancer Study Group (see Appendix) trials, now and for the past 30 years. The IBCSG is funded in part by: Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation (FSTRF), The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council), National Cancer Institute (CA-75362), Swedish Cancer Society, Cancer Research Switzerland/Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). NR 33 TC 23 Z9 24 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2009 VL 116 IS 3 BP 491 EP 500 DI 10.1007/s10549-008-0225-9 PG 10 WC Oncology SC Oncology GA 471KA UT WOS:000268055100008 PM 18953651 ER PT J AU Payne, E Look, T AF Payne, Elspeth Look, Thomas TI Zebrafish modelling of leukaemias SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE leukaemia; zebrafish; genetics; transgenics; haematopoiesis ID ZINC-FINGER NUCLEASES; REGULATED TRANSGENIC ZEBRAFISH; ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LEUKEMIA; INSERTIONAL MUTAGENESIS; IN-VIVO; DEFINITIVE HEMATOPOIESIS; EXPRESSION; GENES; PROLIFERATION AB P>The use of animal models has revealed important mechanisms relevant to the development and treatment of human cancer. In recent years the zebrafish has emerged as an exciting new organism in which to model leukaemogenesis. The zebrafish model has distinct advantages over other animal models, most notably a capacity for forward genetic studies and rapid small molecule screens which can be used to dissect novel genetic pathways contributing to the development of leukaemia. Additionally, the high fecundity and optical clarity of the zebrafish make it an attractive organism in which to directly visualize the localization and development of normal and abnormal haematopoiesis in vivo. Until recently, targeting mutations to specific genes was technically difficult in the zebrafish, but new technology using chimeric zinc fingers to create targeted gene knockouts has made reverse genetic modelling possible and promises to deliver many new and exciting models. This review summarizes the benefits of using the zebrafish to study leukaemogenesis, reviews current zebrafish models of specific leukaemias, and gives an overview of future direction for the zebrafish in the study of cancer. C1 [Payne, Elspeth; Look, Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Payne, Elspeth] Barts & London Inst Canc, London, England. RP Payne, E (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Elspeth_Payne@DFCI.HARVARD.EDU FU LRF (UK) FX Elspeth Payne is the recipient of a Clinical Research Training Fellowship from the LRF (UK). NR 43 TC 24 Z9 25 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2009 VL 146 IS 3 BP 247 EP 256 DI 10.1111/j.1365-2141.2009.07705.x PG 10 WC Hematology SC Hematology GA 470BT UT WOS:000267948400002 PM 19466976 ER PT J AU Friedberg, JW Kelly, JL Neuberg, D Peterson, DR Kutok, JL Salloum, R Brenn, T Fisher, DC Ronan, E Dalton, V Rich, L Marquis, D Sims, P Rothberg, PG Liesveld, J Fisher, RI Coffman, R Mosmann, T Freedman, AS AF Friedberg, Jonathan W. Kelly, Jennifer L. Neuberg, Donna Peterson, Derick R. Kutok, Jeffery L. Salloum, Rabih Brenn, Thomas Fisher, David C. Ronan, Elizabeth Dalton, Virginia Rich, Lynn Marquis, Diana Sims, Paul Rothberg, Paul G. Liesveld, Jane Fisher, Richard I. Coffman, Robert Mosmann, Tim Freedman, Arnold S. TI Phase II study of a TLR-9 agonist (1018 ISS) with rituximab in patients with relapsed or refractory follicular lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE lymphoma; CpG oligonucleotides; TLR-9; microenvironment; rituximab ID NON-HODGKINS-LYMPHOMA; DEPENDENT CELLULAR CYTOTOXICITY; EVENT-FREE SURVIVAL; CPG OLIGODEOXYNUCLEOTIDES; COMBINATION IMMUNOTHERAPY; MONOCLONAL-ANTIBODIES; CANCER; CELLS; TRIAL; INDOLENT AB P>Toll-like receptor-9 (TLR-9) agonists have pleotropic effects on both the innate and adaptive immune systems, including increased antigen expression, enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and T helper cell type 1 shift in the immune response. We combined a TLR-9 agonist (1018 ISS, 0 center dot 2 mg/kg sc weekly x 4 beginning day 8) with standard rituximab (375 mg/m(2) weekly x 4) in patients (n = 23) with relapsed/refractory, histologically confirmed follicular lymphoma, and evaluated immunological changes following the combination. Treatment was well-tolerated with no significant adverse events attributable to therapy. Clinical responses were observed in 48% of patients; the overall median progression-free survival was 9 months. Biologically relevant increases in ADCC and circulating CD-3 positive T cells were observed in 35% and 39% of patients, respectively. Forty-five percent of patients had increased T cells and dendritic cells in skin biopsies of 1018 ISS injection sites 24 h post-therapy. Pre- and post-biopsies of tumour tissue demonstrated an infiltration of CD8(+) T cells and macrophages following treatment. This group of patients had favourable clinical outcome despite adverse prognostic factors. This study is the first to histologically confirm perturbation of the local immune microenvironment following systemic biological therapy of follicular lymphoma. C1 [Friedberg, Jonathan W.; Kelly, Jennifer L.; Peterson, Derick R.; Salloum, Rabih; Rich, Lynn; Marquis, Diana; Rothberg, Paul G.; Liesveld, Jane; Fisher, Richard I.; Mosmann, Tim] Univ Rochester, James P Wilmot Canc Ctr, Med Ctr, Rochester, NY 14642 USA. [Neuberg, Donna; Kutok, Jeffery L.; Brenn, Thomas; Fisher, David C.; Ronan, Elizabeth; Dalton, Virginia; Freedman, Arnold S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sims, Paul; Coffman, Robert] Dynavax Technol, Berkeley, CA USA. RP Friedberg, JW (reprint author), Univ Rochester, James P Wilmot Canc Ctr, Med Ctr, 601 Elmwood Ave,POB 704, Rochester, NY 14642 USA. EM Jonathan_Friedberg@urmc.rochester.edu RI Kelly, Jennifer/E-5512-2012 FU NIH [CA-102216, CA-103244, HL-007152, A1054953, RR 024160] FX We thank the patients who participated in this study, and all of the nurses and physicians involved in their care. We thank Sally Quataert for assistance in sample organization and preparation, Matt Cochran for performing flow cytometric analysis, and Shelley Secor-Socha for ELISPOT analysis, and Karen Rosell for ADCC studies. Supported by CA-102216 (to JWF); CA-103244 (to ASF); HL-007152 (to JK), A1054953 (to TM) and RR 024160. JWF is a Clinical Scholar of the Leukemia and Lymphoma Society. NR 43 TC 50 Z9 50 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2009 VL 146 IS 3 BP 282 EP 291 DI 10.1111/j.1365-2141.2009.07773.x PG 10 WC Hematology SC Hematology GA 470BT UT WOS:000267948400005 PM 19519691 ER PT J AU Kohno, RI Hata, Y Kawahara, S Kita, T Arita, R Mochizuki, Y Aiello, LP Ishibashi, T AF Kohno, R-i Hata, Y. Kawahara, S. Kita, T. Arita, R. Mochizuki, Y. Aiello, L. P. Ishibashi, T. TI Possible contribution of hyalocytes to idiopathic epiretinal membrane formation and its contraction SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID COLLAGEN GEL CONTRACTION; RHO-KINASE PATHWAY; GROWTH-FACTOR; VITREORETINOPATHY; VITREOSCHISIS; INVOLVEMENT; EXPRESSION; CYTOKINES; DISEASES; SURGERY AB Aim: To address the cellular components and the contractile mechanisms of the idiopathic epiretinal membrane (ERM). Methods: Ten surgically removed ERMs were fixed in 4% paraformaldehyde and analysed by whole-mount immunohistochemistry with anti-glial fibrillar acidic protein (GFAP) and alpha smooth-muscle actin (alpha SMA) antibodies. Type I collagen gel contraction assay, an established wound-healing assay in vitro, was performed using cultured bovine hyalocytes or normal human astrocytes (NHA) to evaluate the contractile property of the cells in the presence of tissue growth factor (TGF)-beta 2. The expression of alpha SMA was also analysed by western blot analysis to examine myofibroblastic transdifferentiation of the cells. Vitreous-induced collagen gel contraction was also evaluated. Results: All membranes were composed of alpha SMA immunopositive cells in contracted foci and GFAP immunopositive cells in the periphery. No apparent double positive cells were observed in any membranes examined. Cultured hyalocytes showed overexpression of alpha SMA and hypercontraction of collagen gels in response to TGF-beta 2, while glial cells showed marginal change. The vitreous from ERM patients also caused overexpression of alpha SMA and hypercontraction of the gels embedding hyalocytes, which were almost completely inhibited in the presence of anti-TGF-beta 2 neutralising antibody. Conclusions: Hyalocytes might be one of the critical components of ERM mediating its contractile property through the effect of TGF-beta 2 in the vitreous fluid. C1 [Hata, Y.] Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Higashi Ku, Fukuoka 8128582, Japan. [Aiello, L. P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Aiello, L. P.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Aiello, L. P.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Hata, Y (reprint author), Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM hatachan@med.kyushu-u.ac.jp FU Ministry of Education, Science, Sports and Culture, Japan [19592026] FX The study was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japan (Grant-in-Aid for Scientific Research #19592026). NR 26 TC 37 Z9 39 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD AUG PY 2009 VL 93 IS 8 BP 1020 EP 1026 DI 10.1136/bjo.2008.155069 PG 7 WC Ophthalmology SC Ophthalmology GA 474RP UT WOS:000268302000008 PM 19429593 ER PT J AU Craddock, N Kerdler, K Neale, M Nurnberger, J Purcell, S Rietschel, M Perlis, R Santangelo, SL Schulze, T Smoller, JW Thapar, A AF Craddock, Nick Kerdler, Kenneth Neale, Michael Nurnberger, John Purcell, Shaun Rietschel, Marcella Perlis, Roy Santangelo, Susan L. Schulze, Thomas Smoller, Jordan W. Thapar, Anita CA Psychiat GWAS Consortium TI Dissecting the phenotype in genome-wide association studies of psychiatric illness SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID GENETICS; DISEASE; FRAMEWORK; INSIGHTS; LOCI AB Over the past 2 years genome-wide association studies have made major contributions to understanding the genetic architecture of many common human diseases. This editorial outlines the development of such studies in psychiatry and highlights the opportunities for advancing understanding of the biological underpinnings and nosological structure of psychiatric disorders. C1 [Craddock, Nick; Thapar, Anita] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff CF14 4XN, S Glam, Wales. [Kerdler, Kenneth; Neale, Michael] Virginia Commonwealth Univ, Med Coll Virginia, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Kerdler, Kenneth; Neale, Michael] Virginia Commonwealth Univ, Med Coll Virginia, Dept Psychiat, Richmond, VA 23298 USA. [Kerdler, Kenneth; Neale, Michael] Virginia Commonwealth Univ, Med Coll Virginia, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Nurnberger, John] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Purcell, Shaun; Perlis, Roy; Santangelo, Susan L.; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Purcell, Shaun] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. [Rietschel, Marcella; Schulze, Thomas] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Perlis, Roy] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Santangelo, Susan L.; Smoller, Jordan W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Santangelo, Susan L.; Smoller, Jordan W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schulze, Thomas] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, DHHS, Bethesda, MD 20892 USA. RP Craddock, N (reprint author), Cardiff Univ, Sch Med, Dept Psychol Med & Neurol, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM craddockn@cardiff.ac.uk OI Nurnberger, John/0000-0002-7674-1767; Thapar, Anita/0000-0002-3689-737X NR 19 TC 37 Z9 37 U1 0 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD AUG PY 2009 VL 195 IS 2 BP 97 EP 99 DI 10.1192/bjp.bp.108.063156 PG 3 WC Psychiatry SC Psychiatry GA 479WF UT WOS:000268691700001 ER PT J AU Hawkins, DS Conrad, EU Butrynski, JE Schuetze, SM Eary, JF AF Hawkins, Douglas S. Conrad, Ernest U., III Butrynski, James E. Schuetze, Scott M. Eary, Janet F. TI [F-18]-Fluorodeoxy-D-Glucose-Positron Emission Tomography Response Is Associated With Outcome for Extremity Osteosarcoma in Children and Young Adults SO CANCER LA English DT Article DE osteosarcoma; fluorodeoxyglucose positron emission tomography; outcome ID PRIMARY OSTEOGENIC-SARCOMA; SOFT-TISSUE SARCOMA; NONMETASTATIC OSTEOSARCOMA; PREOPERATIVE CHEMOTHERAPY; PROGNOSTIC FACTORS; DELAYED SURGERY; BONE; TUMORS; METHOTREXATE; DOXORUBICIN AB BACKGROUND: Response to neoadjuvant chemotherapy is I of the most powerful prognostic factors for extremity osteosarcoma. [F-18]-fluorodeoxy-D-glucose-positron emission tomography (FDG-PET) is a non-invasive imaging modality that is used to predict histopathologic response. To determine the prognostic value of FDG-PET response for progression-free survival (PFS) in osteosarcoma, the authors of this report reviewed the University of Washington Medical Center experience. METHODS: Forty patients with extremity osteosarcoma were evaluated by FDG-PET. All patients received neoadjuvant and adjuvant chemotherapy. FDG-PET standard uptake values (SUVs) before neoadjuvant chemotherapy (SUV1) and after neoadjuvant chemotherapy (SUV2) were analyzed and correlated with histopathologic response. RESULTS: The median SUV1 was 6.8 (range, 3.0-24.1), the median SUV2 was 2.3 (range, 1.2-12.8), and the median SUV2 to SUV1 ratio (SUV2:1), was 0.36 (range, 0.12-1.10). A good FDG-PET response was defined as an SUV2 <2.5 or an SUV2:1 <= 0.5. FDG-PET responses according to SUV2 and SUV2:1 were concordant with histologic response in 58% and 68% of patients, respectively. SUV2 was associated with outcome (4-year PFS, 73% for SUV2 <2.5 vs 39% for SUV2 >= 2.5; P = .021). Both the initial disease stage and the histologic response were associated with outcome. CONCLUSIONS: FDG-PET imaging of extremity osteosarcoma was correlated only partially with a histologic response to neoadjuvant chemotherapy. An SUV2 <2.5 was associated with improved PFS. Future prospective studies are warranted to determine whether FDG-PET imaging may be used as a predictor of outcome independent of initial disease stage. Cancer 2009;115:3519-25. (C) 2009 American Cancer Society. C1 [Hawkins, Douglas S.] Seattle Childrens Hosp, Dept Pediat, Seattle, WA 98105 USA. [Conrad, Ernest U., III; Eary, Janet F.] Univ Washington, Med Ctr, Dept Orthoped, Washington, DC USA. [Conrad, Ernest U., III; Eary, Janet F.] Univ Washington, Med Ctr, Dept Radiol, Washington, DC USA. [Butrynski, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Schuetze, Scott M.] Univ Michigan, Dept Med Oncol, Ann Arbor, MI 48109 USA. RP Hawkins, DS (reprint author), Seattle Childrens Hosp, Dept Pediat, 4800 Sandpoint Way,Mailstop B-6553, Seattle, WA 98105 USA. EM doug.hawkins@seattlechildrens.org FU National Institutes of Health/National Cancer Institute [CA87721, CA65537] FX Supported by National Institutes of Health/National Cancer Institute Grants CA87721 and CA65537. NR 26 TC 59 Z9 60 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2009 VL 115 IS 15 BP 3519 EP 3525 DI 10.1002/cncr.24421 PG 7 WC Oncology SC Oncology GA 471LZ UT WOS:000268060500020 PM 19517457 ER PT J AU Okechukwu, CA Krieger, N Sorensen, G Li, Y Barbeau, EM AF Okechukwu, Cassandra A. Krieger, Nancy Sorensen, Glorian Li, Yi Barbeau, Elizabeth M. TI MassBuilt: effectiveness of an apprenticeship site-based smoking cessation intervention for unionized building trades workers SO CANCER CAUSES & CONTROL LA English DT Article DE Smoking cessation; Smoking; Worksite health promotion; Tobacco control; Labor unions ID BLUE-COLLAR WORKERS; UNITED-STATES; CIGARETTE-SMOKING; HEALTH-PROMOTION; CONSTRUCTION-INDUSTRY; TOBACCO USE; PROGRAMS; US; DISPARITIES; PREVALENCE AB Blue-collar workers are difficult to reach and less likely to successfully quit smoking. The objective of this study was to test a training site-based smoking cessation intervention. This study is a randomized-controlled trial of a smoking cessation intervention that integrated occupational health concerns and was delivered in collaboration with unions to apprentices at 10 sites (n = 1,213). We evaluated smoking cessation at 1 and 6 months post-intervention. The baseline prevalence of smoking was 41%. We observed significantly higher quit rates in the intervention versus control group (26% vs. 16.8%; p = 0.014) 1 month after the intervention. However, the effects diminished over time so that the difference in quit rate was not significant at 6 month post-intervention (9% vs. 7.2%; p = 0.48). Intervention group members nevertheless reported a significant decrease in smoking intensity (OR = 3.13; 95% CI: 1.55-6.31) at 6 months post-intervention, compared to controls. The study demonstrates the feasibility of delivering an intervention through union apprentice programs. Furthermore, the notably better 1-month quit rate results among intervention members and the greater decrease in smoking intensity among intervention members who continued to smoke underscore the need to develop strategies to help reduce relapse among blue-collar workers who quit smoking. C1 [Okechukwu, Cassandra A.] Univ Calif San Francisco & Berkeley, Robert Wood Johnson Hlth & Soc Scholars Program, San Francisco, CA 94709 USA. [Krieger, Nancy; Sorensen, Glorian; Barbeau, Elizabeth M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sorensen, Glorian; Barbeau, Elizabeth M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Barbeau, Elizabeth M.] Hlth Dialog Inc, Boston, MA USA. RP Okechukwu, CA (reprint author), Univ Calif San Francisco & Berkeley, Robert Wood Johnson Hlth & Soc Scholars Program, 3333 Calif St,Suite 465, San Francisco, CA 94709 USA. EM cassandrao@post.harvard.edu FU National Institutes of Occupational Safety and Health [1R01 DP000097-01] FX The research was supported by grant 1R01 DP000097-01 from the National Institutes of Occupational Safety and Health (PI. Dr. Barbeau). C. A. Okechukwu is supported by Robert Wood Johnson Health and Society Scholars program. We would like to thank the president, program directors, staff, and apprentices affiliated with the Massachusetts Building Trades Council for their participation in this study, the Massachusetts Coalition of Occupational Safety and Health (MassCOSH) for assisting us with delivering the Toxics and Tobacco Curriculum and for leading behavioral therapy groups. We gratefully acknowledge the contributions of project staff, including Michael Ostler, Cathy Hartman, Ruth Lederman, David Wilson, Jennifer Kelly, Janice Perates, and Mary Ellen Chambers. NR 39 TC 29 Z9 29 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2009 VL 20 IS 6 BP 887 EP 894 DI 10.1007/s10552-009-9324-0 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 457EB UT WOS:000266910200010 PM 19301135 ER PT J AU Bao, Y Giovannucci, E Fuchs, CS Michaud, DS AF Bao, Ying Giovannucci, Edward Fuchs, Charles S. Michaud, Dominique S. TI Passive Smoking and Pancreatic Cancer in Women: a Prospective Cohort Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; CIGARETTE-SMOKING; RISK; INFLAMMATION; EXPOSURE AB Background: Active smoking is an established risk factor for pancreatic cancer, but the role of passive smoking in pancreatic carcinogenesis remains unclear. We aimed to examine whether environmental tobacco smoke is associated with pancreatic cancer risk. Methods: We prospectively examined 86,673 women in the Nurses' Health Study. History of exposure to environmental tobacco smoke was assessed through questionnaires in 1982. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Results: During 24 years of follow-up (1982-2006), 384 women were diagnosed with pancreatic cancer. Maternal smoking significantly increased the risk of pancreatic cancer (RR, 1.42; 95% CI, 1.07-1.89), whereas paternal smoking was not related to the risk (RR, 0.97; 95% CI, 0.77-1.21). The risk associated with maternal smoking remained elevated, albeit not significant, among never smokers (RR, 1.52; 95% CI, 0.97-2.39). No association was found for adult passive exposure at work or at home. Conclusions: The positive association with maternal smoking suggests that environmental tobacco smoke, potentially in utero or in early life, may be associated with pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2292-6) C1 [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Dept Epidendol & Publ Hlth, London W2 1PG, England. [Bao, Ying; Giovannucci, Edward; Michaud, Dominique S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. [Bao, Ying; Giovannucci, Edward; Fuchs, Charles S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bao, Ying; Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Michaud, DS (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Epidendol & Publ Hlth, St Marys Campus,Norfolk Pl, London W2 1PG, England. EM d.michaud@imperial.ac.uk RI Michaud, Dominique/I-5231-2014 FU National Cancer Institute, NIH, Bethesda, MD, USA [CA124908] FX Grant support: National Cancer Institute, NIH, Bethesda, MD, USA (grant number CA124908). NR 17 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2009 VL 18 IS 8 BP 2292 EP 2296 DI 10.1158/1055-9965.EPI-09-0352 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 483IW UT WOS:000268958600023 PM 19602702 ER PT J AU Weichselbaum, RR Kufe, D AF Weichselbaum, R. R. Kufe, D. TI Translation of the radio- and chemo-inducible TNFerade vector to the treatment of human cancers SO CANCER GENE THERAPY LA English DT Review DE TNF-alpha; gene therapy; ionizing radiation; chemotherapy; TNFerade; adenoviral vector ID TUMOR-NECROSIS-FACTOR; ALPHA GENE-THERAPY; IONIZING-RADIATION; TNF-ALPHA; IN-VITRO; PHASE-I; CELL-DEATH; INDUCED APOPTOSIS; RANDOMIZED TRIAL; EGR-1 PROMOTER AB Radiotherapy is a widely used treatment for localized malignancies that is often delivered in combination with cytotoxic chemotherapeutic agents. The concept that treatment of localized tumors can be improved with a radio- and chemo-inducible gene therapy strategy has been investigated in the laboratory and now translated to the clinic. The TNFerade (Ad.Egr-TNF11D) adenoviral vector was engineered by inserting radio- and chemo-inducible elements from the Egr-1 promoter upstream to a cDNA encoding tumor necrosis factor-alpha (TNF-alpha). Transduction of tumor cells with TNFerade and then treatment with radiation or chemotherapy is associated with spatial and temporal control of TNF-alpha secretion and enhanced antitumor activity. TNFerade has been evaluated in trials for patients with sarcomas, melanomas and cancers of the pancreas, esophagus, rectum and head and neck. If the ongoing phase III trial for pancreatic cancer is successful, TNFerade will likely become the first gene therapy approved for cancer in the United States. Cancer Gene Therapy (2009) 16, 609-619; doi:10.1038/cgt.2009.37; published online 15 May 2009 C1 [Weichselbaum, R. R.] Univ Chicago, Med Ctr, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. [Kufe, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Med Ctr, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. EM rrw@radonc.uchicago.edu NR 86 TC 28 Z9 36 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD AUG PY 2009 VL 16 IS 8 BP 609 EP 619 DI 10.1038/cgt.2009.37 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 471ZJ UT WOS:000268096900001 PM 19444302 ER PT J AU Meijer, DH Maguire, CA LeRoy, SG Sena-Esteves, M AF Meijer, D. H. Maguire, C. A. LeRoy, S. G. Sena-Esteves, M. TI Controlling brain tumor growth by intraventricular administration of an AAV vector encoding IFN-beta SO CANCER GENE THERAPY LA English DT Article DE brain tumor; AAV; gene delivery; ICV; intracerebroventricular; interferon-beta ID CONVECTION-ENHANCED DELIVERY; INTERFERON-BETA; GENE-THERAPY; IN-VIVO; GLIOBLASTOMA-MULTIFORME; LYSOSOMAL STORAGE; TIGHT REGULATION; MAMMALIAN BRAIN; MOUSE-BRAIN; PATTERNS AB Glioblastoma multiforme (GBM) is the most aggressive type of all primary brain tumors, with an overall median survival < 1 year after diagnosis. Despite introduction of multimodal treatment approaches, the prognosis has not improved significantly over the past 50 years. In this study we investigated the effect of intracerebroventricular (ICV) injection of an adeno-associated virus (AAV) vector encoding human interferon-beta (AAV-hIFN-beta) on glioblastoma growth. Recently, we found that peritumoral parenchymal transduction with an AAV-hIFN-beta was exceptionally efficient in eradicating GBM brain tumors. However, the extensive infiltration and migration displayed by glioblastoma cells in patients may leave a significant number of tumor cells outside a local therapeutic zone created by intraparenchymal delivery of AAV vectors. Here we show that pretreatment of mice by ICV infusion of an AAV-IFN-beta completely prevents tumor growth in an orthotopic model of GBM. Furthermore, ICV infusion of AAV-IFN-beta into mice bearing preestablished U87 intracranial tumors improved their survival compared to mice infused through the same route with a control AAV vector. These data suggest that ICV injection of AAV vectors encoding antitumor proteins is a promising approach deserving further consideration for the treatment of GBM. Cancer Gene Therapy (2009) 16, 664-671; doi:10.1038/cgt.2009.8; published online 6 February 2009 C1 [Meijer, D. H.; Maguire, C. A.; LeRoy, S. G.; Sena-Esteves, M.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Meijer, D. H.; Maguire, C. A.; LeRoy, S. G.; Sena-Esteves, M.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Meijer, D. H.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurosci & Pharmacol, Utrecht, Netherlands. RP Sena-Esteves, M (reprint author), Massachusetts Gen Hosp, Dept Neurol, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM msesteves@partners.org FU Alliance for Cancer Gene Therapy (MSE); NIH [5 T32 CA073479-09]; Massachusetts General Hospital Neuroscience Center Microscopy and Image Analysis Core [P30NS045776] FX This work was supported by a Young Investigator Award from the Alliance for Cancer Gene Therapy (MSE), and NIH 5 T32 CA073479-09 ( CM). We acknowledge the Massachusetts General Hospital Neuroscience Center Microscopy and Image Analysis Core ( NIH grant P30NS045776) for the use of the Nikon scanner, and we thank Dr Ralph Weissleder, Director of the Center for Molecular Imaging Research, for the use of the bioluminescence imager. NR 30 TC 17 Z9 19 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD AUG PY 2009 VL 16 IS 8 BP 664 EP 671 DI 10.1038/cgt.2009.8 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 471ZJ UT WOS:000268096900007 PM 19197327 ER PT J AU Huang, JX Wu, SL Wu, CL Manning, BD AF Huang, Jingxiang Wu, Shulin Wu, Chin-Lee Manning, Brendan D. TI Signaling Events Downstream of Mammalian Target of Rapamycin Complex 2 Are Attenuated in Cells and Tumors Deficient for the Tuberous Sclerosis Complex Tumor Suppressors SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; MTOR COMPLEX; MOTIF PHOSPHORYLATION; TSC1-TSC2 COMPLEX; AKT; GROWTH; ACTIVATION; CANCER; RICTOR; ALPHA AB Mutations in the TSC1 and TSC2 tumor suppressor genes give rise to the neoplastic disorders tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis. Their gene products form a complex that is a critical negative regulator of mammalian target of rapamycin (mTOR) complex I (mTORC1) and cell growth. We recently found that the TSC1-TSC2 complex promotes the activity of mTOR complex 2 (mTORC2), an upstream activator of Akt, and this occurs independent of its inhibitory effects on mTORC1. Loss of mTORC2 activity in cells lacking the TSC1-TSC2 complex, coupled with mTORC1-mediated feedback mechanisms, leads to strong attenuation of the growth factor-stimulated phosphorylation of Akt on S473. In this study, we show that both phosphatidylinositol 3-kinase-dependent and phosphatidylinositol 3-kinase-independent mTORC2 substrates are affected by loss of the TSC1-TSC2 complex in cell culture models and kidney tumors from both Tsc2(+/-) mice (adenoma) and TSC patients (angiomyolipoma). These mTORC2 targets are all members of the AGC kinase family and include Akt, protein kinase C alpha, and serum and glucocorticoid-induced protein kinase 1. We also show that the TSC1-TSC2 complex can directly stimulate the in vitro kinase activity of mTORC2. The interaction between these two complexes is mediated primarily through regions on TSC2 and a core component of mTORC2 called Rictor. Hence, loss of the TSC tumor suppressors results in elevated mTORC1 signaling and attenuated mTORC2 signaling. These findings suggest that the TSC1-TSC2 complex plays opposing roles in tumor progression, both blocking and promoting specific oncogenic pathways through its effects on mTORC1 inhibition and mTORC2 activation, respectively. [Cancer Res 2009;69(15):6107-14] C1 [Huang, Jingxiang; Manning, Brendan D.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Wu, Shulin; Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,Urol Res Lab, Boston, MA 02115 USA. RP Manning, BD (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave,SPH2-117, Boston, MA 02115 USA. EM bmanning@hsph.harvard.edu RI Huang, Jingxiang/B-4515-2008 FU NIH [R01-CA122617, P01-CA120964]; Agency for Science, Technology and Research (Singapore) national science scholarship FX Grant support: NIH grants R01-CA122617 (B.D. Manning) and P01-CA120964 (B.D. Manning and C.-L Wu) and Agency for Science, Technology and Research (Singapore) national science scholarship (J. Huang). NR 40 TC 76 Z9 78 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2009 VL 69 IS 15 BP 6107 EP 6114 DI 10.1158/0008-5472.CAN-09-0975 PG 8 WC Oncology SC Oncology GA 480MC UT WOS:000268737900014 PM 19602587 ER PT J AU Maurer, M Su, T Saal, LH Koujak, S Hopkins, BD Barkley, CR Wu, JP Nandula, S Dutta, B Xie, YL Chin, YR Kim, DI Ferris, JS Gruvberger-Saal, SK Laakso, M Wang, XM Memeo, L Rojtman, A Matos, T Yu, JS Cordon-Cardo, C Isola, J Terry, MB Toker, A Mills, GB Zhao, JJ Murty, VVVS Hibshoosh, H Parsons, R AF Maurer, Matthew Su, Tao Saal, Lao H. Koujak, Susan Hopkins, Benjamin D. Barkley, Christina R. Wu, Jiaping Nandula, Subhadra Dutta, Bhaskar Xie, Yuli Chin, Y. Rebecca Kim, Da-In Ferris, Jennifer S. Gruvberger-Saal, Sofia K. Laakso, Mervi Wang, Xiaomei Memeo, Lorenzo Rojtman, Albert Matos, Tulio Yu, Jennifer S. Cordon-Cardo, Carlos Isola, Jorma Terry, Mary Beth Toker, Alex Mills, Gordon B. Zhao, Jean J. Murty, Vundavalli V. V. S. Hibshoosh, Hanina Parsons, Ramon TI 3-Phosphoinositide-Dependent Kinase 1 Potentiates Upstream Lesions on the Phosphatidylinositol 3-Kinase Pathway in Breast Carcinoma SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; COMPARATIVE GENOMIC HYBRIDIZATION; PROTEIN-KINASE; IN-VIVO; PIK3CA MUTATIONS; STEM-CELLS; CANCER; PDK1; ACTIVATION; PTEN AB Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase (PI3K) pathway during cancer development by increasing levels of phosphatidylinositol-3,4,5-triphosphate (PIP(3)). 3-Phosphoinositide-dependent kinase 1 (PDK1) is the first node of the PI3K signal output and is required for activation of AKT. PIP(3) recruits PDK1 and AKT to the cell membrane through interactions with their pleckstrin homology domains, allowing PDK1 to activate AKT by phosphorylating it at residue threonine-308. We show that total PDK1 protein and mRNA were overexpressed in a majority of human breast cancers and that 21% of tumors had five or more copies of the gene encoding PDK1, PDPK1. We found that increased PDPK1 copy number was associated with upstream pathway lesions (ERBB2 amplification, PTEN loss, or PIK3CA mutation), as well as patient survival. Examination of an independent set of breast cancers and tumor cell lines derived from multiple forms of human cancers also found increased PDK1 protein levels associated with such upstream pathway lesions. In human mammary cells, PDK1 enhanced the ability of upstream lesions to signal to ART, stimulate cell growth and migration, and rendered cells more resistant to PDK1 and PI3K inhibition. After orthotopic transplantation, PDK1 overexpression was not oncogenic but dramatically enhanced the ability of ERBB2 to form tumors. Our studies argue that PDK1 overexpression and increased PDPK1 copy number are common occurrences in cancer that potentiate the oncogenic effect of upstream lesions on the PI3K pathway. Therefore, we conclude that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast cancer. [Cancer Res 2009;69(15):6299-306] C1 [Saal, Lao H.; Koujak, Susan; Hopkins, Benjamin D.; Kim, Da-In; Gruvberger-Saal, Sofia K.; Yu, Jennifer S.; Parsons, Ramon] Columbia Univ, Inst Canc Genet, Coll Phys & Surg, New York, NY 10032 USA. [Maurer, Matthew; Xie, Yuli; Parsons, Ramon] Columbia Univ, Dept Med, New York, NY 10032 USA. [Nandula, Subhadra; Rojtman, Albert; Matos, Tulio; Yu, Jennifer S.; Cordon-Cardo, Carlos; Murty, Vundavalli V. V. S.; Hibshoosh, Hanina; Parsons, Ramon] Columbia Univ, Dept Pathol, New York, NY 10032 USA. [Maurer, Matthew; Su, Tao; Wang, Xiaomei; Cordon-Cardo, Carlos; Murty, Vundavalli V. V. S.; Hibshoosh, Hanina; Parsons, Ramon] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Ferris, Jennifer S.; Terry, Mary Beth] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Barkley, Christina R.; Wu, Jiaping; Zhao, Jean J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Barkley, Christina R.] Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Chin, Y. Rebecca; Toker, Alex] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Dutta, Bhaskar; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Laakso, Mervi] Seinajoki Cent Hosp, Seinajoki, Finland. [Laakso, Mervi; Isola, Jorma] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. [Laakso, Mervi; Isola, Jorma] Tampere Univ Hosp, Tampere, Finland. [Memeo, Lorenzo] Mediterranean Inst Oncol, Pathol Unit, Catania, Italy. RP Parsons, R (reprint author), Columbia Univ, Inst Canc Genet, Coll Phys & Surg, ICRC407A,1130 St Nicholas Ave, New York, NY 10032 USA. EM rep15@columbia.edu RI Saal, Lao/A-2919-2011; OI Saal, Lao/0000-0002-0815-1896; CHIN, Yuet Ming Rebecca/0000-0001-8976-3466 FU NIH/National Cancer Institute [R01CA082783, R01CA122099, P01CA97403]; Avon Foundation; OctoberWomen Foundation; Susan G. Komen Breast Cancer Foundation; AACR-AMGEN, Inc.; American Society of Clinical Oncology (ASCO) Cancer Foundation; Breast Cancer Research Foundation; Kleberg Center for Molecular Markers; Komen Foundation; NCI [PO1CA099031] FX Grant support: NIH/National Cancer Institute grants R01CA082783, R01CA122099, and P01CA97403, Avon Foundation (which funded research and Columbia Breast Macromolecule Bank), OctoberWomen Foundation, Susan G. Komen Breast Cancer Foundation, AACR-AMGEN, Inc., Fellowship, American Society of Clinical Oncology (ASCO) Cancer Foundation Young Investigator Award, and Breast Cancer Research Foundation. Reverse-phase proteomic profiling and some sequencing studies were supported by Kleberg Center for Molecular Markers, Komen Foundation, and NCI PO1CA099031. NR 48 TC 60 Z9 62 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2009 VL 69 IS 15 BP 6299 EP 6306 DI 10.1158/0008-5472.CAN-09-0820 PG 8 WC Oncology SC Oncology GA 480MC UT WOS:000268737900038 PM 19602588 ER PT J AU Wang, HB Zhao, AL Chen, L Zhong, XY Liao, J Gao, M Cai, MH Lee, DH Li, J Chowdhury, D Yang, YG Pfeifer, GP Yen, Y Xu, XZ AF Wang, Haibo Zhao, Ailian Chen, Lin Zhong, Xueyan Liao, Ji Gao, Min Cai, Minghua Lee, Dong-Hyun Li, Jing Chowdhury, Dipanjan Yang, Yun-gui Pfeifer, Gerd P. Yen, Yun Xu, Xingzhi TI Human RIF1 encodes an anti-apoptotic factor required for DNA repair SO CARCINOGENESIS LA English DT Article ID MAMMALIAN-CELLS; PATHWAYS; DAMAGE; PHOSPHORYLATION; METASTASIS; NETWORKS; MELANOMA; REVEALS; COMPLEX AB Human Rap1-interacting protein 1 (RIF1) contributes to the ataxia telangiectasia, mutated-mediated DNA damage response against the dexterous effect of DNA lesions and plays a critical role in the S-phase checkpoint. However, the molecular mechanisms by which human RIF1 conquers DNA aberrations remain largely unknown. We here showed that inhibition of RIF1 expression by small interfering RNA led to defective homologous recombination-mediated DNA double-strand break repair and sensitized cancer cells to camptothecin or staurosporine treatment. RIF1 underwent caspase-dependent cleavage upon apoptosis. We further found that RIF1 was highly expressed in human breast tumors, and its expression status was positively correlated with differentiation degrees of invasive ductal carcinoma of the breast. Our results suggest that RIF1 encodes an anti-apoptotic factor required for DNA repair and is a potential target for cancer treatment. C1 [Wang, Haibo; Chen, Lin; Liao, Ji; Cai, Minghua; Li, Jing; Xu, Xingzhi] Capital Normal Univ, Coll Life Sci, Canc Biol Lab, Beijing 100048, Peoples R China. [Zhao, Ailian] Peking Univ, Sch Oncol, Beijing Canc Hosp & Ins,Dept Pathol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China. [Zhong, Xueyan; Pfeifer, Gerd P.] City Hope Natl Med Ctr, Div Biol, Duarte, CA 91010 USA. [Gao, Min; Yang, Yun-gui] Chinese Acad Sci, Beijing Inst Genom, Genome Stabil Grp, Beijing 100029, Peoples R China. [Lee, Dong-Hyun; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Yen, Yun] City Hope Natl Med Ctr, Div Mol & Clin Pharmacol, Duarte, CA 91010 USA. RP Xu, XZ (reprint author), Capital Normal Univ, Coll Life Sci, Canc Biol Lab, 105 Xi San Huan Rd N, Beijing 100048, Peoples R China. EM xingzhi_xu@mail.cnu.edu.cn RI xu, xingzhi/E-8158-2012; Wang, Haibo/H-3151-2012; Li, Jing/C-2031-2013 OI xu, xingzhi/0000-0002-4459-2082; Li, Jing/0000-0002-3977-1641 FU NCI NIH HHS [R01CA084469] NR 18 TC 22 Z9 23 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2009 VL 30 IS 8 BP 1314 EP 1319 DI 10.1093/carcin/bgp136 PG 6 WC Oncology SC Oncology GA 478KG UT WOS:000268586400006 PM 19483192 ER PT J AU Cheung, WY Zhai, RH Kulke, MH Heist, RS Asomaning, K Ma, C Wang, ZX Su, L Lanuti, M Tanabe, KK Christiani, DC Liu, G AF Cheung, Winson Y. Zhai, Rihong Kulke, Matthew H. Heist, Rebecca S. Asomaning, Kofi Ma, Clement Wang, Zhaoxi Su, Li Lanuti, Michael Tanabe, Kenneth K. Christiani, David C. Liu, Geoffrey TI Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk SO CARCINOGENESIS LA English DT Article ID FACTOR RECEPTOR; LUNG-CANCER; EGF GENE; FUNCTIONAL POLYMORPHISM; HISTOLOGY DIFFERENCES; GASTRIC CANCERS; UNITED-STATES; SMOKING; PROGRESSION; SALIVARY AB Background: Single-nucleotide polymorphisms of key cancer genes, such as EGF A61G, are associated with an elevated risk of esophageal adenocarcinoma (EAC). As gastroesophageal reflux disease (GERD) is an established risk factor for EAC, we evaluated whether the association between epidermal growth factor (EGF) polymorphism and EAC development is altered by the presence of GERD. Methods: EGF genotyping of DNA samples was performed and GERD history was collected for 309 EAC patients and 275 matched healthy controls. Associations between genotypes and EAC risk were evaluated using adjusted logistic regression. Genotype-GERD relationships were explored using analyses stratified by GERD history and joint effects models that considered severity and duration of GERD symptoms. Results: EGF variants (A/G or G/G) were more common (P = 0.02) and GERD was more prevalent (P < 0.001) in cases than in controls. When compared with the EGF wild-type A/A genotype, the G/G variant was associated with a substantial increase in EAC risk among individuals with GERD [Odds ratio 9.7; 95% confidence interval (CI), 3.8-25.0; P < 0.001] and a slight decrease in risk for GERD-free individuals (odds ratio 0.4; 95% CI = 0.22-0.90; P = 0.02). In the joint effects models, the odds of EAC was also highest for G/G patients (when compared with A/A) who either experienced frequent GERD of more than once per week (odds ratio 21.8; 95% CI = 5.1-94.0; P < 0.001) or suffered GERD for longer than 15 years (odds ratio 22.4; 95% CI = 6.5-77.6; P < 0.001). There was a highly significant interaction between the G/G genotype and the presence of GERD (P < 0.001). Conclusions: EGF A61G polymorphism may alter EAC susceptibility through an interaction with GERD. C1 [Cheung, Winson Y.] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Cheung, Winson Y.; Zhai, Rihong; Asomaning, Kofi; Wang, Zhaoxi; Su, Li; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Heist, Rebecca S.; Lanuti, Michael; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ma, Clement; Liu, Geoffrey] Princess Margaret Hosp, Div Med Oncol, Toronto, ON M5G 2M9, Canada. [Liu, Geoffrey] Univ Toronto, Dept Med, Toronto, ON M5G 2M9, Canada. RP Cheung, WY (reprint author), British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. EM geoffrey.liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU National Institutes of Health/National Cancer Institute [R01CA109193, R03CA110822, R01CA074386]; Kevin Jackson Memorial Fund; Alan B. Brown Chair in Molecular Genomics; Posluns Family Fund Foundation; Flight Attendant Medical Research Institute Award [062459_YCSA] FX National Institutes of Health/National Cancer Institute (R01CA109193, R03CA110822, R01CA074386); Kevin Jackson Memorial Fund; Alan B. Brown Chair in Molecular Genomics; Posluns Family Fund Foundation; Flight Attendant Medical Research Institute Award (062459_YCSA). NR 26 TC 9 Z9 11 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2009 VL 30 IS 8 BP 1363 EP 1367 DI 10.1093/carcin/bgp126 PG 5 WC Oncology SC Oncology GA 478KG UT WOS:000268586400013 PM 19520791 ER PT J AU Sloan, KA Marquez, HA Li, J Cao, YX Hinds, A O'Hara, CJ Kathuria, S Ramirez, MI Williams, MC Kathuria, H AF Sloan, Karin A. Marquez, Hector A. Li, Jun Cao, Yuxia Hinds, Anne O'Hara, Carl J. Kathuria, Satinder Ramirez, Maria I. Williams, Mary C. Kathuria, Hasmeena TI Increased PEA3/E1AF and decreased Net/Elk-3, both ETS proteins, characterize human NSCLC progression and regulate caveolin-1 transcription in Calu-1 and NCI-H23 NSCLC cell lines SO CARCINOGENESIS LA English DT Article ID D7S522 LOCUS 7Q31.1; LUNG-CANCER; PROSTATE-CANCER; GENE-TRANSCRIPTION; MOUSE LUNG; EXPRESSION; ADENOCARCINOMA; PROMOTER; METASTASIS; NET AB Caveolin-1 protein has been called a 'conditional tumor suppressor' because it can either suppress or enhance tumor progression depending on cellular context. Caveolin-1 levels are dynamic in non-small-cell lung cancer, with increased levels in metastatic tumor cells. We have shown previously that transactivation of an erythroblastosis virus-transforming sequence (ETS) cis-element enhances caveolin-1 expression in a murine lung epithelial cell line. Based on high sequence homology between the murine and human caveolin-1 promoters, we proposed that ETS proteins might regulate caveolin-1 expression in human lung tumorigenesis. We confirm that caveolin-1 is not detected in well-differentiated primary lung tumors. Polyoma virus enhancer activator 3 (PEA3), a pro-metastatic ETS protein in breast cancer, is expressed at low levels in well-differentiated tumors and high levels in poorly differentiated tumors. Conversely, Net, a known ETS repressor, is expressed at high levels in the nucleus of well-differentiated primary tumor cells. In tumor cells in metastatic lymph node sites, caveolin-1 and PEA3 are highly expressed, whereas Net is now expressed in the cytoplasm. We studied transcriptional regulation of caveolin-1 in two human lung cancer cell lines, Calu-1 (high caveolin-1 expressing) and NCI-H23 (low caveolin-1 expressing). Chromatin immunoprecipitation-binding assays and small interfering RNA experiments show that PEA3 is a transcriptional activator in Calu-1 cells and that Net is a transcriptional repressor in NCI-H23 cells. These results suggest that Net may suppress caveolin-1 transcription in primary lung tumors and that PEA3 may activate caveolin-1 transcription in metastatic lymph nodes. C1 [Sloan, Karin A.; Li, Jun; Cao, Yuxia; Hinds, Anne; Ramirez, Maria I.; Williams, Mary C.; Kathuria, Hasmeena] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Marquez, Hector A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [O'Hara, Carl J.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Kathuria, Satinder] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Pathol, Hines, IL 60141 USA. RP Sloan, KA (reprint author), Boston Univ, Sch Med, Ctr Pulm, 72 E Concord St,R304, Boston, MA 02118 USA. EM kasloan@bu.edu OI Kathuria, Hasmeena/0000-0002-9062-409X; Sloan, Karin/0000-0003-0733-927X FU American Cancer Society [IRG-72-001-34-IRG]; American Lung Association Lungevity; National Institute of Health/National Heart, Lung, and Blood Institute FX American Cancer Society (IRG-72-001-34-IRG) to H. K.; American Lung Association Lungevity to H. K.; National Institute of Health/National Heart, Lung, and Blood Institute Training Grant to K. A. S. NR 53 TC 18 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2009 VL 30 IS 8 BP 1433 EP 1442 DI 10.1093/carcin/bgp129 PG 10 WC Oncology SC Oncology GA 478KG UT WOS:000268586400023 PM 19483189 ER PT J AU Cubeddu, RJ Jneid, H Don, CW Witzke, CF Cruz-Gonzalez, I Gupta, R Rengifo-Moreno, P Maree, AO Inglessis, I Palacios, IF AF Cubeddu, Roberto J. Jneid, Hani Don, Creighton W. Witzke, Christian F. Cruz-Gonzalez, Ignacio Gupta, Rakesh Rengifo-Moreno, Pablo Maree, Andrew O. Inglessis, Ignacio Palacios, Igor F. TI Retrograde Versus Antegrade Percutaneous Aortic Balloon Valvuloplasty: Immediate, Short- and Long-Term Outcome at 2 Years SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE percutaneous aortic balloon valvuloplasty; vascular complications; antegrade; retrograde ID CARDIOGENIC-SHOCK; STENOSIS; VALVE; EXPERIENCE; IMPLANTATION; FAILURE AB Background: The short- and long-term vascular risks and hemodynamic benefits of antegrade versus retrograde percutaneous aortic balloon valvuloplasty (PAV) have not been clearly established. With the advent of percutaneous aortic valve replacement strategies, more valvuloplasties are being performed. The antegrade approach may reduce vascular complications, particularly in patients with peripheral vascular disease (PVD). Comparing the clinical efficacy and complications of each technique is warranted. Methods: A cohort of 157 consecutive patients undergoing PAV between 2000 and 2006 were included in the study. Of these, 46 (29%) patients underwent antegrade PAV and 111 (71%) retrograde PAV. Choice of vascular approach (antegrade or retrograde) were determined by operator preference. The rate of death, nonfatal vascular complications, and 2-year survival was explored. Results: The mean age of the study population was 79 years. Patients undergoing antegrade PAV were more likely hypertensive (56% vs. 39%, P = 0.001) with PVD (41% vs. 18%, P = 0.004). Nevertheless, logistic Euroscores were no different between the groups (antegrade 18% vs. retrograde 14%; P = 0.30). Baseline and postprocedural valve areas were also similar. However, patients undergoing antegrade PAV had significantly fewer vascular complications (2% vs. 19%; P = 0.005). Two-year follow-up revealed no significant difference in death (antegrade 81% vs. retrograde 69%; P = 0.16), stroke, congestive heart failure, and surgical aortic valve replacement. Conclusions: The hemodynamic benefit of PAV occurs regardless of the selected vascular approach. The antegrade technique results in significantly fewer vascular complications and similar long-term outcomes. Antegrade PAV is feasible and safe, particularly in patients with PVD. (C) 2009 Wiley-Liss, Inc. C1 [Cubeddu, Roberto J.; Jneid, Hani; Don, Creighton W.; Witzke, Christian F.; Cruz-Gonzalez, Ignacio; Gupta, Rakesh; Rengifo-Moreno, Pablo; Maree, Andrew O.; Inglessis, Ignacio; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, GRB 800,55 Fruit St,GRB-800, Boston, MA 02114 USA. EM ipalacios@partners.org RI 2009, Secribsal/A-1266-2012 NR 21 TC 17 Z9 17 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD AUG 1 PY 2009 VL 74 IS 2 BP 225 EP 231 DI 10.1002/ccd.22085 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 484TD UT WOS:000269069500003 PM 19434744 ER PT J AU Yeh, RW Baron, SJ Healy, JL Pomerantsev, E McNulty, IA Cruz-Gonzalez, I Jang, IK AF Yeh, Robert W. Baron, Suzanne J. Healy, Joanne L. Pomerantsev, Eugene McNulty, Iris A. Cruz-Gonzalez, Ignacio Jang, Ik-Kyung TI Anticoagulation With the Direct Thrombin Inhibitor Argatroban in Patients Presenting With Acute Coronary Syndromes SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE percutaneous coronary intervention; argatroban; direct thrombin inhibitor; anticoagulation; acute coronary syndrome ID ELEVATION MYOCARDIAL-INFARCTION; OUTCOMES; INTERVENTION; BIVALIRUDIN; ANTIBODIES AB Objectives: This study examined the efficacy and safety of the direct thrombin inhibitor argatroban in patients presenting with acute coronary syndromes undergoing cardiac catheterization. Background: Argatroban is a direct-thrombin inhibitor approved for use in percutaneous coronary intervention in patients with heparin-induced thrombocytopenia. Few studies have examined its use in patients undergoing cardiac catheterization for acute coronary syndromes. We performed a retrospective cohort study of patients presenting with acute coronary syndromes who received argatroban anticoagulation during cardiac catheterization. Methods: Consecutive patients presenting with acute coronary syndromes who received argatroban while undergoing cardiac catheterization from 2002 to 2005 were included. Patient characteristics and in-hospital outcomes were examined retrospectively via detailed chart review. The primary endpoints of the study were combined death, myocardial infarction or urgent revascularization, and major bleeding during the index hospitalization. Results: A total of 144 patients presenting with an acute coronary syndrome received argatroban during cardiac catheterization within the study period: 25% presented with ST-elevation myocardial infarction and 75% presented with non-ST-elevation acute coronary syndrome. The combined endpoint of death, myocardial infarction or urgent revascularization occurred in 13.2% of patients during the hospitalization. Major bleeding occurred in 2.1% of patients. Conclusions: In this cohort of patients presenting with acute coronary syndromes, patients receiving argatroban during cardiac catheterization had a moderate rate of adverse cardiac events and a very low rate of major bleeding. (C) 2009 Wiley-Liss, Inc. C1 [Baron, Suzanne J.; Healy, Joanne L.; Pomerantsev, Eugene; McNulty, Iris A.; Jang, Ik-Kyung] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Baron, Suzanne J.; Healy, Joanne L.; Pomerantsev, Eugene; McNulty, Iris A.; Jang, Ik-Kyung] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yeh, Robert W.] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. [Cruz-Gonzalez, Ignacio] Univ Salamanca, Univ Hosp Salamanca, Dept Cardiol, E-37008 Salamanca, Spain. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org RI 2009, Secribsal/A-1266-2012 FU Mitsubishi Pharma FX Grant sponsor: Mitsubishi Pharma. NR 14 TC 3 Z9 4 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD AUG 1 PY 2009 VL 74 IS 2 BP 359 EP 364 DI 10.1002/ccd.21999 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 484TD UT WOS:000269069500029 PM 19213062 ER PT J AU Fishman, JA Strong, DM Kuehnert, MJ AF Fishman, Jay A. Strong, D. Michael Kuehnert, Matthew J. TI Organ and tissue safety workshop 2007: advances and challenges SO CELL AND TISSUE BANKING LA English DT Article DE Transplantation; Infectious disease transmission; Tissue; Organs; Cornea; Adverse events; Surveillance ID TRANSPLANT RECIPIENTS; VIRUS-INFECTION; UNITED-STATES; DONOR; TRANSMISSION; ALLOGRAFT; DISEASE; HCV AB A workshop in June 2005 ("Preventing Organ and Tissue Allograft-Transmitted Infection: Priorities for Public Health Intervention") identified gaps in organ and tissue safety in the US. Participants developed a series of allograft safety initiatives. "The Organ and Tissue Safety Workshop 2007: Advances and Challenges" assessed progress and identified priorities for future interventions. Awareness of the challenges of allograft-associated disease transmission has increased. The Transplantation Transmission Sentinel Network will enhance communication surrounding allograft-associated disease transmission. Other patient safety initiatives have focused on adverse event reporting and microbiologic screening technologies. Despite progress, improved recognition and prevention of donor-derived transmission events is needed. This requires systems integration across the organ and tissue transplantation communities including organ procurement organizations, eye and tissue banks, and transplant infectious disease experts. Commitment of resources and improved coordination of efforts are required to develop essential tools to enhance safety for allograft recipients. C1 [Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA. [Strong, D. Michael] Univ Washington, Sch Med, Dept Orthopaed & Sports Med, Seattle, WA USA. [Strong, D. Michael] Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. [Kuehnert, Matthew J.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis Program, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org NR 37 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9333 J9 CELL TISSUE BANK JI Cell Tissue Banking PD AUG PY 2009 VL 10 IS 3 BP 271 EP 280 DI 10.1007/s10561-008-9114-z PG 10 WC Cell Biology; Engineering, Biomedical SC Cell Biology; Engineering GA 470TF UT WOS:000268002600012 PM 19016348 ER PT J AU Sun, T Yang, M Kantoff, P Lee, GSM AF Sun, Tong Yang, Ming Kantoff, Philip Lee, Gwo-Shu Mary TI Role of microRNA-221/-222 in cancer development and progression SO CELL CYCLE LA English DT Editorial Material DE microRNA-221/-222; prostate cancer; CRPC; microRNA; cancer ID PROSTATE-CANCER; MICRORNA; EXPRESSION; P27(KIP1); RESISTANCE; MIR-222; CELLS C1 [Sun, Tong; Yang, Ming; Kantoff, Philip; Lee, Gwo-Shu Mary] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, GSM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM gwo-shu_lee@dfci.harvard.edu RI Yang, Ming/G-4705-2012 OI Yang, Ming/0000-0002-7722-7487 NR 15 TC 15 Z9 15 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD AUG 1 PY 2009 VL 8 IS 15 BP 2315 EP 2316 DI 10.4161/cc.8.15.9221 PG 2 WC Cell Biology SC Cell Biology GA 477RH UT WOS:000268535700003 PM 19625765 ER PT J AU Ferreira, JC Chipman, DW Hill, NS Kacmarek, RM AF Ferreira, Juliana C. Chipman, Daniel W. Hill, Nicholas S. Kacmarek, Robert M. TI Bilevel vs ICU Ventilators Providing Noninvasive Ventilation: Effect of System Leaks A COPD Lung Model Comparison SO CHEST LA English DT Article ID ACUTE RESPIRATORY-FAILURE; POSITIVE-PRESSURE VENTILATION; MECHANICAL VENTILATION; CONTROLLED-TRIAL; PERFORMANCE; BENCH; EXTUBATION; DISEASE; RISK AB Background: Noninvasive positive-pressure ventilation (NPPV) modes are currently available on bilevel and ICU ventilators. However, little data comparing the performance of the NPPV modes on these ventilators are available. Methods: In an experimental bench study, the ability of nine ICU ventilators to function in the presence of leaks was compared with a bilevel ventilator using the IngMar ASL5000 lung simulator (IngMar Medical; Pittsburgh, PA) set at a compliance of 60 mL/cm H(2)O, an inspiratory resistance of 10 cm H(2)O/L/s, an expiratory resistance of 20 cm H(2)O/L/s, and a respiratory rate of 15 breaths/min. All of the ventilators were set at 12 cm H(2)O pressure support and 5 cm H(2)O positive end-expiratory pressure. The data were collected at baseline and at three customized leaks. Main results: At baseline, all of the ventilators were able to deliver adequate tidal volumes, to maintain airway pressure, and to synchronize with the simulator, without missed efforts or auto-triggering. As the leak was increased, all of the ventilators (except the Vision [Respironics; Murrysville, PA] and Servo I [Maquet; Solna, Sweden]) needed adjustment of sensitivity or cycling criteria to maintain adequate ventilation, and some transitioned to backup ventilation. Significant differences in triggering and cycling were observed between the Servo I and the Vision ventilators. Conclusions: The Vision and Servo I were the only ventilators that required no adjustments as they adapted to increasing leaks. There were differences in performance between these two ventilators, although the clinical significance of these differences is unclear. Clinicians should be aware that in the presence of leaks, most ICU ventilators require adjustments to maintain an adequate tidal volume. (CHEST 2009; 136:448-456) C1 [Ferreira, Juliana C.] Univ Sao Paulo, Hosp Clin, Dept Anesthesia & Crit Care, Sao Paulo, Brazil. [Chipman, Daniel W.; Kacmarek, Robert M.] Univ Sao Paulo, Hosp Clin, Dept Resp Care, Sao Paulo, Brazil. [Ferreira, Juliana C.] Inst Coracao, Sao Paulo, Brazil. [Hill, Nicholas S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org RI Ferreira, Juliana/F-3455-2011 OI Ferreira, Juliana/0000-0001-6548-1384 NR 22 TC 37 Z9 39 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2009 VL 136 IS 2 BP 448 EP 456 DI 10.1378/chest.08-3018 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 481VS UT WOS:000268841000021 PM 19429723 ER PT J AU Bajwa, EK Khan, UA Januzzi, JL Gong, MN Thompson, T Christiani, DC AF Bajwa, Ednan K. Khan, Uzma A. Januzzi, James L. Gong, Michelle N. Thompson, Taylor Christiani, David C. TI Plasma C-Reactive Protein Levels Are Associated With Improved Outcome in ARDS SO CHEST LA English DT Article ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; ACUTE PHASE REACTANTS; NEUTROPHIL ALVEOLITIS; VASCULAR-PERMEABILITY; NITRIC-OXIDE; APACHE-III; PROCALCITONIN; SEPSIS AB Background: C-reactive protein (CRP) has been studied as a marker or systemic inflammation and outcome in a number of diseases, but little is known about its characteristics in ARDS. We sought to examine plasma levels of CRP in patients with ARDS and their relationship to outcome and measures of illness severity. Methods: We measured CRP levels in 1,77 patients within 48 h of disease onset and tested the association of protein level with 60-day mortality, 28-day daily organ dysfunction scores, and number of ventilator-free days. Results: We found that CRP levels were significantly lower in nonsurvivors when Compared with survivors (p = 0.02). Mortality rate decreased with increasing CRP decile (p = 0.02). An increasing CRP level was associated with a significantly higher probability of survival at 60 days (p = 0.005). This difference persisted after adjustment for age and severity of illness in a multivariable model (p = 0.009). Multivariable models were also used to show that patients in the group with higher CRP levels had significantly lower organ dysfunction scores (p = 0.001) and more ventilator-free days (p = 0.02). Conclusions: Increasing plasma levels of CRP within 48 h of ARDS onset are associated with improved survival, lower organ failure scores, and fewer days of mechanical ventilation. These data appear to be contrary to the established view that CRP is solely a marker of systemic inflammation. (CHEST 2009; 136:471-480) C1 [Khan, Uzma A.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Bajwa, Ednan K.; Thompson, Taylor; Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02115 USA. [Januzzi, James L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Unit, Boston, MA 02115 USA. [Gong, Michelle N.] Mt Sinai Sch Med, Div Pulm & Crit Care, New York, NY USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU NHLBI NIH HHS [R01 HL060710, K23 HL087934, K23-HL087934, R01-HL60710] NR 46 TC 27 Z9 30 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2009 VL 136 IS 2 BP 471 EP 480 DI 10.1378/chest.08-2413 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 481VS UT WOS:000268841000024 PM 19411291 ER PT J AU Akylbekova, EL Crow, RS Johnson, WD Buxbaum, SG Njemanze, S Fox, E Sarpong, DF Taylor, HA Newton-Cheh, C AF Akylbekova, Ermeg L. Crow, Richard S. Johnson, William D. Buxbaum, Sarah G. Njemanze, Stephanie Fox, Ervin Sarpong, Daniel F. Taylor, Herman A. Newton-Cheh, Christopher TI Clinical Correlates and Heritability of QT Interval Duration in Blacks The Jackson Heart Study SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE QT interval; genetics; heritability; Jackson Heart Study ID SUDDEN CARDIAC DEATH; LEFT-VENTRICULAR HYPERTROPHY; GENERAL-POPULATION; QUANTITATIVE-TRAIT; AFRICAN-AMERICANS; DISEASE MORTALITY; LINKAGE ANALYSIS; FAMILY-HISTORY; UNITED-STATES; CORRECTED QT AB Background-Electrocardiographic QT interval prolongation is a risk factor for sudden cardiac death and drug-induced arrhythmia. The clinical correlates and heritability of QT interval duration in blacks have not been well studied despite their higher risk for sudden cardiac death compared with non-Hispanic whites. We sought to investigate potential correlates of the QT interval and estimate its heritability in the Jackson Heart Study. Methods and Results-The Jackson Heart Study comprises a sample of blacks residing in Jackson, Miss, of whom 5302 individuals with data at the baseline examination were available for study. Jackson Heart Study participants on QT-altering medications, with bundle-branch block, paced rhythm, atrial fibrillation/flutter, or other arrhythmias were excluded, resulting in a sample of 4660 individuals eligible for analyses. The relation between QT and potential covariates was tested using multivariable stepwise linear regression. Heritability was estimated using Sequential Oligogenic Linkage Analysis Routine in a subset of 1297 Jackson Heart Study participants in 292 families; the remaining sample included unrelated individuals. In stepwise multivariable linear regression analysis, covariates significantly associated with QT interval duration included R-R interval, sex, QRS duration, age, serum potassium, hypertension, body mass index, coronary heart disease, diuretic use, and Sokolow-Lyon voltage (P <= 0.01 for all). The heritability of QT interval duration in the age-, sex-, and R-R interval-adjusted model and in the fully adjusted model was 0.41 (SE, 0.07) and 0.40 (SE, 0.07; P <= 10(-11) for both), respectively. Conclusions-There is substantial heritability of adjusted QT interval in blacks, supporting the need for further investigation to identify its genetic determinants. (Circ Arrhythmia Electrophysiol. 2009;2:427-432.) C1 [Akylbekova, Ermeg L.; Buxbaum, Sarah G.; Sarpong, Daniel F.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA. [Crow, Richard S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. [Johnson, William D.; Fox, Ervin; Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Njemanze, Stephanie] Wellesley Coll, Wellesley, MA 02181 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA. EM cnewtoncheh@chgr.mgh.harvard.edu RI Buxbaum, Sarah/E-1970-2013 OI Buxbaum, Sarah/0000-0002-4886-3564 FU National Institutes of Health, National Heart, Lung, and Blood Institute [N01-HC-95170, N01-HC-95171, N01-HC-95172]; National Center for Minority Health and Health Disparities; NHLBI K23 [HL080025]; Doris Duke Charitable Foundation Clinical Scientist Development Award; Burroughs Wellcome Fund Career Award for Medical Scientists FX This study was supported by the National Institutes of Health through contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172 from the National Heart, Lung, and Blood Institute and the National Center for Minority Health and Health Disparities. Dr Newton-Cheh was supported by an NHLBI K23 award (HL080025), a Doris Duke Charitable Foundation Clinical Scientist Development Award, and a Burroughs Wellcome Fund Career Award for Medical Scientists. NR 41 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD AUG PY 2009 VL 2 IS 4 BP 427 EP U171 DI 10.1161/CIRCEP.109.858894 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 485YN UT WOS:000269162400011 PM 19808499 ER PT J AU Verrier, RL Josephson, ME AF Verrier, Richard L. Josephson, Mark E. TI Impact of Sleep on Arrhythmogenesis SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article ID POSITIVE AIRWAY PRESSURE; INFANT-DEATH-SYNDROME; SUDDEN CARDIAC DEATH; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; CHEYNE-STOKES RESPIRATION; HEART-RATE-VARIABILITY; T-WAVE ALTERNANS; LONG-QT SYNDROME; PERSISTENT ATRIAL-FIBRILLATION C1 [Verrier, Richard L.; Josephson, Mark E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Cardiovasc Inst, Boston, MA 02215 USA. RP Verrier, RL (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,Room 148, Boston, MA 02115 USA. EM rverrier@bidmc.harvard.edu FU National Institutes of Health [R21 HL085720]; Center for Integration of Medicine and Innovative Technology (CIMIT) FX This study was supported by R21 HL085720 from the National Institutes of Health and by the Center for Integration of Medicine and Innovative Technology (CIMIT). NR 88 TC 33 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD AUG PY 2009 VL 2 IS 4 BP 450 EP 459 DI 10.1161/CIRCEP.109.867028 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 485YN UT WOS:000269162400014 PM 19808502 ER PT J AU Blendea, D Barrett, CD Heist, EK Ruskin, JN Mansour, MC AF Blendea, Dan Barrett, Conor D. Heist, E. Kevin Ruskin, Jeremy N. Mansour, Moussa C. TI Right Atrial Thrombus Aspiration Guided by Intracardiac Echocardiography During Catheter Ablation for Atrial Fibrillation SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Editorial Material ID ANTICOAGULATION C1 [Mansour, Moussa C.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, Boston, MA 02114 USA. RP Mansour, MC (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, 55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 7 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD AUG PY 2009 VL 2 IS 4 BP E18 EP E20 DI 10.1161/CIRCEP.109.859918 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 485YN UT WOS:000269162400017 PM 19808487 ER PT J AU Deo, RC Roth, FP AF Deo, Rahul C. Roth, Frederick P. TI Pathways of the Heart SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Editorial Material ID EXPRESSION PATTERNS; SIGNATURES; DISEASE; GUIDE C1 [Deo, Rahul C.; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Deo, Rahul C.; Roth, Frederick P.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Deo, RC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM rdeo@partners.org RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU NHGRI NIH HHS [R01 HG003224-01A2, HG0017115, HG003224, HG004233, P50 HG004233, R01 HG003224, R01 HG003224-02, R01 HG003224-03, R01 HG003224-04, R01 HG003224-05]; NHLBI NIH HHS [HL081341, T32 HL007208, U01 HL081341]; NINDS NIH HHS [NS035611, P01 NS035611] NR 11 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD AUG PY 2009 VL 2 IS 4 BP 303 EP 305 DI 10.1161/CIRCGENETICS.109.892588 PG 3 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 574HG UT WOS:000275979400001 PM 20031600 ER PT J AU Mii, A Shimizu, A Masuda, Y Fujita, E Aki, K Ishizaki, M Sato, S Griesemer, A Fukuda, Y AF Mii, Akiko Shimizu, Akira Masuda, Yukinari Fujita, Emiko Aki, Kaoru Ishizaki, Masamichi Sato, Shigeru Griesemer, Adam Fukuda, Yuh TI Current status and issues of C1q nephropathy SO CLINICAL AND EXPERIMENTAL NEPHROLOGY LA English DT Review DE C1q nephropathy; Complement; C1q ID FOCAL-SEGMENTAL GLOMERULOSCLEROSIS; NEPHROTIC SYNDROME; CLINICOPATHOLOGICAL CORRELATION; LUPUS NEPHRITIS; RENAL-ALLOGRAFT; GLOMERULONEPHRITIS; DISEASE; INFECTION; CHILDREN; IMMUNOFLUORESCENCE AB C1q nephropathy, first proposed by Jennette and Hipp [Am J Clin Pathol 83:415-420, 1985; Am J Kidney Dis 6:103-110, 1985], was described as a distinct glomerular disease entity characterized by extensive mesangial deposition of C1q, with associated mesangial immune complexes, and the absence of any clinical and laboratory evidence of systemic lupus erythematosus. Now, 20 years since the first report, the disease entity is gradually attaining recognition, particularly in the field of pediatrics. C1q is the subcomponent of C1 in the classical pathway of complement activation. Generally, C1q deposition is caused by the activation of C1 by immunoglobulin G (IgG) and IgM; therefore, C1q nephropathy is considered as an immune complex glomerulonephritis. However, in C1q nephropathy, it remains unclear whether the deposition of C1q in the glomeruli is in response to the deposition of immunoglobulin or immune complex, or whether deposition is non-specific trapping that accompanies increased glomerular protein trafficking associated with proteinuria. Since not only the pathogenesis of C1q deposition in glomeruli but also its significance are still uncertain, it has not yet been established as an independent disease. From recent publications of the clinical and pathological characterizations, C1q nephropathy has been thought to be a subgroup of primary focal segmental glomerular sclerosis. However, many reports describe different symptoms, histopathologies, therapeutic responses and prognoses, suggesting that C1q nephropathy is not a single disease entity, but that it may be a combination of several disease groups. There are many uncertain areas requiring further investigation, though it is hoped that a detailed examination of future cases will clarify the subgroups making up C1q nephropathy and their clinicopathological characteristics, and will lead to the establishment of C1q nephropathy as an independent disease entity. C1 [Mii, Akiko; Shimizu, Akira; Masuda, Yukinari; Fujita, Emiko; Aki, Kaoru; Ishizaki, Masamichi; Fukuda, Yuh] Nippon Med Sch, Dept Analyt Human Pathol, Bunkyo Ku, Tokyo 1130031, Japan. [Sato, Shigeru] Nippon Med Sch, Cent Inst Elect Microscop Res, Tokyo 1130031, Japan. [Griesemer, Adam] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Shimizu, A (reprint author), Nippon Med Sch, Dept Analyt Human Pathol, Bunkyo Ku, 1-25-2 Nezu, Tokyo 1130031, Japan. EM ashimizu@nms.ac.jp NR 47 TC 14 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1342-1751 J9 CLIN EXP NEPHROL JI Clin. Exp. Nephrol. PD AUG PY 2009 VL 13 IS 4 BP 263 EP 274 DI 10.1007/s10157-009-0159-5 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 480NW UT WOS:000268743700002 PM 19373520 ER PT J AU Wecht, JM Weir, JP DeMeersman, RE Schilero, GJ Handrakis, JP LaFountaine, MF Cirnigliaro, CM Kirshblum, SC Bauman, WA AF Wecht, Jill M. Weir, Joseph P. DeMeersman, Ronald E. Schilero, Gregory J. Handrakis, John P. LaFountaine, Michael F. Cirnigliaro, Christopher M. Kirshblum, Steven C. Bauman, William A. TI Cold face test in persons with spinal cord injury: age versus inactivity SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Heart rate variability; Bradycardia; Facial cooling; Sympathetic activity; Vagal activity; Spinal cord injury ID HEART-RATE-VARIABILITY; CARDIOVASCULAR-RESPONSES; VAGAL FUNCTION; DIVING REFLEX; FITNESS; HUMANS; IMMERSION; STRESS; TETRAPLEGIA; BRADYCARDIA AB Persons with spinal cord injury (SCI) reflect a model of precocious aging and inactivity; as such, these individuals manifest well-appreciated cardiovascular abnormalities. We aimed to determine the influence of inactivity in persons with SCI, and the influence of age in healthy controls, on cardiovascular autonomic responses to the cold face test (CFT). Subjects recruited (n = 42) included 18 controls: 10 young (25 +/- A 2 years) and 8 old (50 +/- A 6 years), and 24 subjects with chronic SCI: 17 with tetraplegia (C3-C8 44 +/- A 7 years) and 7 with paraplegia (T5-T10 36 +/- A 8 years). Heart rate (HR) and blood pressure were collected continuously: 2-min pre-CFT, 1-min CFT and 2-min post-CFT. Time-frequency (wavelet) analysis of HR (HFln) was used as an estimate of vagal cardiac modulation. The HR response to the CFT differed significantly among the SCI group (4.1 +/- A 8.8 bpm) and the young (-7.7 +/- A 5.9 bpm; P < 0.001) and old (-6.8 +/- A 10.7 bpm; P < 0.01). The HFln response was reduced in the SCI (0.01 +/- A 1.59) as compared with the young controls (1.50 +/- A 1.50; P < 0.05), but was not different from the old controls (0.69 +/- A 1.39). The bradycardia did not differ among the young and old controls; however, the vagal response was attenuated in the old compared with the young. These data suggest that age does not significantly alter the heart rate response to the CFT, but attenuates the vagal response. In the SCI group, the paradoxical heart rate response to facial cooling and the lack of vagal activation suggest that abnormal autonomic cardiovascular reflexive control may result from profound inactivity and/or from the spinal cord injury per se. C1 [Wecht, Jill M.; Schilero, Gregory J.; LaFountaine, Michael F.; Cirnigliaro, Christopher M.; Bauman, William A.] James J Peters VA Med Ctr, Rehabil Res & Dev Ctr Excellence Med Consequences, Bronx, NY 10468 USA. [Wecht, Jill M.; Schilero, Gregory J.; Bauman, William A.] James J Peters VA Med Ctr, Med & Spinal Cord Injury Serv, Bronx, NY 10468 USA. [Wecht, Jill M.; Schilero, Gregory J.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Wecht, Jill M.; Schilero, Gregory J.; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Weir, Joseph P.] Des Moines Univ, Osteopath Med Ctr, Des Moines, IA USA. [Handrakis, John P.] Sch Hlth Profess Behav & Life Sci, NYIT, Old Westbury, NY USA. [Cirnigliaro, Christopher M.; Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [DeMeersman, Ronald E.] Columbia Univ Teachers Coll, New York, NY 10027 USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Rehabil Res & Dev Ctr Excellence Med Consequences, Rm 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM jm.wecht@va.gov FU Veteran Affairs Rehabilitation Research & Development Service; Center of Excellence for the Medical Consequences of SCI; Vidda Foundation; United Spinal Association FX We acknowledge financial and institutional support from the Veteran Affairs Rehabilitation Research & Development Service, Center of Excellence for the Medical Consequences of SCI, James J. Peters VAMC, the Vidda Foundation, and United Spinal Association. We recognize Joel T. Crammer, Ph.D., for his development of the time frequency analysis program. NR 38 TC 8 Z9 8 U1 0 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD AUG PY 2009 VL 19 IS 4 BP 221 EP 229 DI 10.1007/s10286-009-0009-2 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 483OR UT WOS:000268977600004 PM 19418115 ER PT J AU Aqel, R Dorfman, TA AF Aqel, Raed Dorfman, Todd A. TI The Brain First or the Heart: The Approach to Revascularizing Severe Co-Existing Carotid and Coronary Artery Disease SO CLINICAL CARDIOLOGY LA English DT Review ID SINGLE-CENTER; BYPASS; ENDARTERECTOMY; IMMEDIATE; SURGERY; RISK; ANGIOPLASTY; STENOSIS; STRATEGY AB Combined symptomatic severe cerebralvascular disease and significant obstructive coronary artery disease frequently exist.(1,2) For the past few decades, clinicians have debated the various treatment strategies for these high-risk patients including staged procedures and hybrid revascularization. While some recommend addressing the more unstable vascular territory first, others prefer to intervene on the carotids prior to performing coronary revascularization. Both surgical and percutaneous options have been explored in various clinical settings, but there are no treatment guidelines to date. Given the frequency and magnitude of this problem, we performed an extensive review of the literature in an attempt to add some much needed clarity. An illustrative case and recommendations are provided. C1 [Aqel, Raed] Birmingham Vet Affairs Med Ctr, Div Cardiovasc Dis, Birmingham, AL 35233 USA. Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Aqel, R (reprint author), Birmingham Vet Affairs Med Ctr, Div Cardiovasc Dis, 700 19th St S, Birmingham, AL 35233 USA. EM RaedAqel@med.va.gov NR 20 TC 3 Z9 3 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD AUG PY 2009 VL 32 IS 8 BP 418 EP 425 DI 10.1002/clc.20443 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 491GM UT WOS:000269566500002 PM 19685511 ER PT J AU Siegel, CA Marden, SM Persing, SM Larson, RJ Sands, BE AF Siegel, Corey A. Marden, Sadie M. Persing, Sarah M. Larson, Robin J. Sands, Bruce E. TI Risk of Lymphoma Associated With Combination Anti-Tumor Necrosis Factor and Immunomodulator Therapy for the Treatment of Crohn's Disease: A Meta-Analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; POPULATION-BASED COHORT; MAINTENANCE THERAPY; COMBINING INFLIXIMAB; CLINICAL-EXPERIENCE; RADIATION-EXPOSURE; RANDOMIZED-TRIAL; OPEN-LABEL; FOLLOW-UP; SAFETY AB BACKGROUND & AIMS: Although anti-tumor necrosis factor (TNF) therapy can effectively treat Crohn's disease (CD), there is concern that it might increase the risk of non-Hodgkin's lymphoma (NHL). A meta-analysis was performed to determine the rate of NHL in adult CD patients who have received anti-TNF therapy and to compare this rate with that of a population-based registry and a population of CD patients treated with immunomodulators. METHODS: MEDLINE, EMBASE, Cochrane Collaboration, and Web of Science were searched. Inclusion criteria included randomized controlled trials, cohort studies, or case series reporting on anti-TNF therapy in adult CD patients. Standardized incidence ratios (SIR) were calculated by comparing the pooled rate of NHL with the expected rate of NHL derived from the Surveillance Epidemiology & End Results (SEER) database and a meta-analysis of CD patients treated with immunomodulators. RESULTS: Twenty-six studies involving 8905 patients and 21,178 patient-years of follow-up were included. Among anti-TNF treated subjects, 13 cases of NHL were reported (6.1 per 10,000 patient-years). The majority of these patients had previous immunomodulator exposure. Compared with the expected rate of NHL in the SEER database (1.9 per 10,000 patient-years), anti-TNF treated subjects had a significantly elevated risk (SIR, 3.23; 95% confidence interval, 1.5-6.9). When compared with the NHL rate in CD patients treated with immunomodulators alone (4 per 10,000 patient-years), the SIR was 1.7 (95% confidence interval, 0.5-7.1). CONCLUSIONS: The use of anti-TNF agents with immunomodulators is associated with an increased risk of NHL in adult CD patients, but the absolute rate of these events remains low and should be weighed against the substantial benefits associated with treatment. C1 [Siegel, Corey A.] Dartmouth Hitchcock Med Ctr, Sect Gastroenterol & Hepatol, Lebanon, NH 03756 USA. [Siegel, Corey A.] Dartmouth Hitchcock IBD Ctr, Lebanon, NH 03756 USA. [Siegel, Corey A.; Marden, Sadie M.; Persing, Sarah M.; Larson, Robin J.] Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Sands, Bruce E.] Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. RP Siegel, CA (reprint author), Dartmouth Hitchcock Med Ctr, Sect Gastroenterol & Hepatol, Lebanon, NH 03756 USA. EM corey.a.siegel@hitchcock.org FU National Institute of Diabetes and Digestive and Kidney Diseases [K23DK078678] FX Dr Siegel Is supported by a CCFA career development award and by grant number K23DK078678 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and dose not necessarily represent the official views of the National Institute of Diabetes And Digestive and Kidney Diseases or the National Institute of Health. NR 47 TC 252 Z9 256 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2009 VL 7 IS 8 BP 874 EP 881 DI 10.1016/j.cgh.2009.01.004 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 488EM UT WOS:000269332000016 PM 19558997 ER PT J AU Aspinall, SL Good, CB Jiang, R McCarren, M Dong, D Cunningham, FE AF Aspinall, Sherrie L. Good, Chester B. Jiang, Rong McCarren, Madeline Dong, Diane Cunningham, Francesca E. TI Severe Dysglycemia with the Fluoroquinolones: A Class Effect? SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GATIFLOXACIN-INDUCED HYPERGLYCEMIA; RESISTANT HYPOGLYCEMIA; HOSPITALIZED-PATIENTS; LEVOFLOXACIN; THERAPY; CIPROFLOXACIN AB Background. Although gatifloxacin is no longer available, other fluoroquinolones may significantly interfere with glucose homeostasis. The objective of the present study was to compare the risk of severe hypo-and hyperglycemia in a cohort of patients treated with gatifloxacin, levofloxacin, ciprofloxacin, or azithromycin. Methods. This was a retrospective inception cohort study of outpatients with a new prescription for gatifloxacin, levofloxacin, ciprofloxacin, or azithromycin from 1 October 2000 through 30 September 2005 in the Veterans Affairs health care system. For patients who received one of these antibiotics, we identified outcomes of hospitalization with a primary diagnosis of hypo-or hyperglycemia. Multivariable logistic regression was used to determine the odds of hypo-and hyperglycemia with the individual fluoroquinolones versus azithromycin. Results. The crude incidence rates for severe hypo-and hyperglycemia among those who received gatifloxacin, levofloxacin, ciprofloxacin, and azithromycin were 0.35 and 0.45, 0.19 and 0.18, 0.10 and 0.12, and 0.07 and 0.10 cases per 1000 patients, respectively. Among patients with diabetes, the odds ratios for hypoglycemia compared with azithromycin were 4.3 (95% confidence interval [CI], 2.7-6.6) for gatifloxacin, 2.1 (95% CI, 1.4-3.3) for levofloxacin, and 1.1 (95% CI, 0.6-2.0) for ciprofloxacin. The odds ratios for hyperglycemia were 4.5 (95% CI, 3.0-6.9) for gatifloxacin, 1.8 (95% CI, 1.2-2.7) for levofloxacin, and 1.0 (95% CI, 0.6-1.8) for ciprofloxacin. Conclusions. The odds of severe hypo-and hyperglycemia were significantly greater with gatifloxacin and levofloxacin, but not ciprofloxacin, than with azithromycin. Thus, the risk of a clinically relevant dysglycemic event appears to vary among the fluoroquinolones. C1 [Aspinall, Sherrie L.; Good, Chester B.; Jiang, Rong; McCarren, Madeline; Dong, Diane; Cunningham, Francesca E.] Vet Affairs Ctr Medicat Safety, Hines, IL USA. [Aspinall, Sherrie L.; Good, Chester B.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Cunningham, FE (reprint author), Pharm Benefits Management Serv 119D, Vet Hlth Adm, Hines, IL 60141 USA. EM fran.cunningham@va.gov FU Veterans Affairs Center for Medication Safet FX In-kind support for this project was provided by the Veterans Affairs Center for Medication Safety. S. L. A. was a Veterans Affairs Health Services Research and Development Research Career Development awardee when the project was conducted. The contents of this article do not represent the views of the Department of Veterans Affairs or the US Government. NR 34 TC 32 Z9 35 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2009 VL 49 IS 3 BP 402 EP 408 DI 10.1086/600294 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 468LK UT WOS:000267819700014 PM 19545207 ER PT J AU Kelly, JL Toothaker, SR Ciminello, L Hoelzer, D Holte, H LaCasce, AS Mead, G Thomas, D Van Imhoff, GW Kahl, BS Cheson, BD Magrath, IT Fisher, RI Friedberg, JW AF Kelly, Jennifer L. Toothaker, Stephen R. Ciminello, Lauren Hoelzer, Dieter Holte, Harald LaCasce, Ann S. Mead, Graham Thomas, Deborah Van Imhoff, Gustaaf W. Kahl, Brad S. Cheson, Bruce D. Magrath, Ian T. Fisher, Richard I. Friedberg, Jonathan W. TI Outcomes of Patients With Burkitt Lymphoma Older Than Age 40 Treated With Intensive Chemotherapeutic Regimens SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article DE HIV-negative acute lymphocytic leukemia; Non-Hodgkin lymphoma; Non-Hodgkin's lymphoma; Older patients ID ACUTE-LYMPHOBLASTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; ADULT BURKITT; CELL LYMPHOMA; HYPER-CVAD; PLUS RITUXIMAB; ADOLESCENTS; CHILDREN; THERAPY; TRIAL AB Burkitt lymphoma is a highly curable disorder when treated with modern intensive chemotherapy regimens. The majority of adult patients with Burkitt lymphoma in the United States are over age 40 years. Older patients have historically been underrepresented in published clinical trials of modern intensive therapy, and the outcome of these patients has not been systematically reported. We therefore obtained and analyzed primary data from 14 Burkitt lymphoma treatment series and confirmed that older patients (age > 40 years) are underrepresented in the literature. Historically inferior outcomes of this age subgroup have improved substantially over time. We conclude that (1) modern intensive chemotherapy regimens should remain the standard of care for patients > age 40 with Burkitt lymphoma; (2) selected patients > age 40 now have highly favorable outcomes; and (3) future studies should include formal analysis of this subgroup of patients. C1 [Kelly, Jennifer L.; Toothaker, Stephen R.; Ciminello, Lauren; Fisher, Richard I.; Friedberg, Jonathan W.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Hoelzer, Dieter] Univ Frankfurt, Frankfurt, Germany. [Holte, Harald] Univ Oslo, Rikshosp, Norwegian Radium Hosp, Canc Clin, N-0027 Oslo, Norway. [LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mead, Graham] Royal S Hants Hosp, Southampton SO9 4PE, Hants, England. [Thomas, Deborah] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Van Imhoff, Gustaaf W.] Acad Ziekenhuis, Groningen, Netherlands. [Kahl, Brad S.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Kahl, Brad S.] Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. [Cheson, Bruce D.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Magrath, Ian T.] Inst Pasteur, INCTR, Brussels, Belgium. RP Friedberg, JW (reprint author), Univ Rochester, James P Wilmot Canc Ctr, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. EM jonathan_friedberg@urmc.rochester.edu RI Kelly, Jennifer/E-5512-2012 FU National Heart Lung and Blood Institute [HL007152]; Cancer and Leukemia Group B [CA31946] FX This research was carried out at the James P. Wilmot Cancer Center, University of Rochester, Rochester, New York. NR 27 TC 20 Z9 22 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD AUG PY 2009 VL 9 IS 4 BP 307 EP 310 DI 10.3816/CLM.2009.n.060 PG 4 WC Oncology SC Oncology GA 489NL UT WOS:000269426800007 PM 19717381 ER PT J AU McLean, CP Anderson, ER AF McLean, Carmen P. Anderson, Emily R. TI Brave men and timid women? A review of the gender differences in fear and anxiety SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE Gender; Anxiety; Gender socialization ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; COMMON INDIGENOUS ANIMALS; DSM-III DISORDERS; SEX-ROLE IDENTITY; PANIC DISORDER; DISGUST SENSITIVITY; SOCIAL ANXIETY; UNITED-STATES AB Substantial evidence indicates that women report greater fear and are more likely to develop anxiety disorders than men. Women's greater vulnerability for anxiety disorders can be partly understood by examining gender differences in the etiological factors known to contribute to anxiety. This review examines evidence for gender differences across a broad range of relevant factors, including biological influences, temperamental factors, stress and trauma, cognitive factors, and environmental factors. Gender differences are observed with increasing consistency as the scope of analysis broadens to molar levels of functioning. Socialization processes cultivate and promote processes related to anxiety. and moderate gender differences across levels of analysis. (C) 2009 Elsevier Ltd. All rights reserved. C1 [McLean, Carmen P.] Boston VA Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Anderson, Emily R.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. RP McLean, CP (reprint author), Boston VA Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-5, Boston, MA 02130 USA. EM carmen.mclean@va.gov NR 170 TC 190 Z9 195 U1 17 U2 61 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD AUG PY 2009 VL 29 IS 6 BP 496 EP 505 DI 10.1016/j.cpr.2009.05.003 PG 10 WC Psychology, Clinical SC Psychology GA 486CM UT WOS:000269173100004 PM 19541399 ER PT J AU Schoenfeld, DA Zheng, H Finkelstein, DM AF Schoenfeld, David A. Zheng, Hui Finkelstein, Dianne M. TI Bayesian design using adult data to augment pediatric trials SO CLINICAL TRIALS LA English DT Article ID CLINICAL-TRIALS; METAANALYSIS; EFFICACY; CHILDREN; MODELS; FEVER AB Background It can be difficult to conduct pediatric clinical trials because there is often a low incidence of the disease in children, making accrual slow or infeasible. In addition, low mortality and morbidity in this population make it impractical to achieve adequate power. In this case, the only evidence for treatment efficacy comes from adult trials. Since pediatric care providers are accustomed to relying on evidence from adult studies, it is natural to consider borrowing information from adult trials. Purpose The goal of this article is to propose a Bayesian approach to the design and analysis of pediatric trials to allow borrowing strength from previous or simultaneous adult trials. Methods We apply a hierarchical model for which the efficacy parameter from the adult trial and that of the pediatric trail are considered to be draws from a normal distribution. The choice of (the variance of) this distribution is guided by discussion with medical experts. We show that with this information, one can calculate the sample size required for the pediatric trial. We discuss how inference of these studies in pediatric populations depends on the parameter that captures the similarity of the treatment efficacy in adults compared to children Results The Bayesian approach can substantially increase the power of a pediatric clinical trial (or equivalently decrease the number of subjects required) by formally leveraging the data from the adult trial. Limitations Our method relies on obtaining a value for the inter-study variability, nu, which may be difficult to describe to a clinical investigator. Conclusions The Bayesian approach has the potential of making pediatric clinical trials feasible because it has the effect of borrowing strength from adult trials, thus requiring a smaller pediatric trial to show efficacy of a drug in children. Clinical Trials 2009;6:297-304.http://ctj.sagepub.com C1 [Schoenfeld, David A.; Zheng, Hui; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 560, Boston, MA 02114 USA. EM dfinkelstein@partners.org FU [HHSN268200536179C]; [HHSN268200425210C]; [CA74302]; [HD05520] FX The authors wish to acknowledge grants HHSN268200536179C, HHSN268200425210C, CA74302, and HD055201. NR 22 TC 25 Z9 25 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD AUG PY 2009 VL 6 IS 4 BP 297 EP 304 DI 10.1177/1740774509339238 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 481UD UT WOS:000268836600001 PM 19667026 ER PT J AU Kogan, JN Bauer, MS Dennehy, EB Miklowitz, DJ Gonzalez, JM Thompson, PM Sachs, GS AF Kogan, Jane N. Bauer, Mark S. Dennehy, Ellen B. Miklowitz, David J. Gonzalez, Jodi M. Thompson, Peter M. Sachs, Gary S. TI Increasing minority research participation through collaboration with community outpatient clinics: the STEP-BD Community Partners Experience SO CLINICAL TRIALS LA English DT Article ID HEALTH-SERVICES RESEARCH; PRIMARY-CARE PATIENTS; BIPOLAR DISORDER; AFRICAN-AMERICAN; PSYCHIATRIC-DISORDERS; ETHNIC-MINORITIES; WHITE PATIENTS; UNITED-STATES; RECRUITMENT; RETENTION AB Background Minority populations have been under-represented in mental health research studies. The systematic treatment enhancement program for bipolar disorder developed the Community Partners Program (CPP) to address this issue in a large, prospective treatment study of persons with bipolar disorder. Purpose The primary goal of CPP was to develop a community-based infrastructure for studying bipolar disorder that would enhance the ethnic/racial and socioeconomic diversity of participants. Methods Selected academic sites partnered with local clinics (n=6 partnerships in five cities). This report describes the conceptualization, implementation, and qualitative evaluation of CPP, as well as quantitative analysis of clinical and sociodemographic differences between the samples recruited at academic versus community sites. Results Quantitative analysis of the 155 participants from the six partnerships revealed enrollment of 45% from minority populations (vs. 15% in academic sites). Significant sociodemographic differences were evident not only between academic and community sites, but within minority and non-minority groups across site types. Notably, clinical differences were not evident between participants from academic and community sites. Review of qualitative data suggests that certain factors around implementation of research protocols may enhance community participation. Conclusions Moving research recruitment and participation into community sites was more successful in increasing minority enrollment than efforts to attract such individuals to academic sites. Recommendations for creating and maintaining academic/community partnerships are given. Limitations Several important variables were not considered including mood severity, hospitalization, or treatment differences. Minority participants were grouped by combining African American and Hispanics, which may have obscured subgroup differences. A derivation of standard qualitative methods was used in this study. Clinical Trials 2009;6:344-354.http://ctj.sagepub.com C1 [Kogan, Jane N.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Brockton Div, Boston, MA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Harvard S Shore Psychiat Residency Training Progr, Cambridge, MA 02138 USA. [Dennehy, Ellen B.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. [Miklowitz, David J.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Miklowitz, David J.] Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. [Gonzalez, Jodi M.; Thompson, Peter M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Sachs, Gary S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, Gary S.] Harvard Univ, Sch Med, Boston, MA USA. RP Kogan, JN (reprint author), 112 Washington Pl,1 Chatham Ctr,Suite 700, Pittsburgh, PA 15219 USA. EM koganjn@upmc.edu NR 43 TC 6 Z9 6 U1 5 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD AUG PY 2009 VL 6 IS 4 BP 344 EP 354 DI 10.1177/1740774509338427 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 481UD UT WOS:000268836600005 PM 19587069 ER PT J AU Abdel-Kader, K Palevsky, PM AF Abdel-Kader, Khaled Palevsky, Paul M. TI Acute Kidney Injury in the Elderly SO CLINICS IN GERIATRIC MEDICINE LA English DT Review DE Acute kidney injury; Acute renal failure; Elderly; Geriatric ID ACUTE-RENAL-FAILURE; ACUTE INTERSTITIAL NEPHRITIS; CONTRAST-INDUCED NEPHROPATHY; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CONVERTING-ENZYME-INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; AORTIC-ANEURYSM SURGERY; VOID RESIDUAL URINE AB The aging kidney undergoes several important anatomic and physiologic changes that increase the risk of acute kidney injury (formerly acute renal failure) in the elderly. This article reviews these changes and discusses the diagnoses frequently encountered in the elderly patient with acute kidney injury. The incidence, staging, evaluation, management, and prognosis of acute kidney injury are also examined with special focus given to older adults. C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Abdel-Kader, Khaled; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Room 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Abdel-Kader, Khaled/0000-0002-6412-8498; Palevsky, Paul/0000-0002-7334-5400 FU Ruth L. Kirschstein National Research Service Award Institutional Research Training Grants [T32-DK061296] FX This work was supported by a Ruth L. Kirschstein National Research Service Award Institutional Research Training Grants, T32-DK061296 (Abdel-Kader). NR 189 TC 31 Z9 32 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2009 VL 25 IS 3 BP 331 EP + DI 10.1016/j.cger.2009.04.001 PG 29 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 506IW UT WOS:000270769500004 PM 19765485 ER PT J AU Chen, LC Brown, RE McKenna, JT McCarley, RW AF Chen, Lichao Brown, Ritchie E. McKenna, James T. McCarley, Robert W. TI Animal Models of Narcolepsy SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Review DE Narcolepsy; Cataplexy; Sleep; EEG; Animal model; Rodent; Canine; REM ID PONTINE RETICULAR-FORMATION; OREXIN-KNOCKOUT MICE; EYE-MOVEMENT SLEEP; THYROTROPIN-RELEASING-HORMONE; INDUCED IMMOBILITY EPISODES; M2 MUSCARINIC RECEPTORS; CANINE NARCOLEPSY; REM-SLEEP; CHOLINERGIC MECHANISMS; CSF HYPOCRETIN-1 AB Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic systems in canine narcolepsy. In 1999, two independent studies revealed that orexin neurotransmission deficiency was pivotal to the development of narcolepsy with cataplexy. This scientific leap fueled the generation of several genetically engineered mouse and rat models of narcolepsy. To facilitate further research, it is imperative that researchers reach a consensus concerning the evaluation of narcoleptic behavioral and EEG phenomenology in these models. C1 [Chen, Lichao; Brown, Ritchie E.; McKenna, James T.; McCarley, Robert W.] Harvard Univ, Sch Med, Res Serv, VA Boston Healthcare Syst,Dept Psychiat, Brockton, MA 02301 USA. RP Chen, LC (reprint author), Harvard Univ, Sch Med, Res Serv, VA Boston Healthcare Syst,Dept Psychiat, 151C,940 Belmont St, Brockton, MA 02301 USA. EM Lichao_chen@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU VA Merit Award; NIMH [062522, 01798] FX Supported by VA Merit Award and NIMH grants 062522 (RWM), 01798 (RWM). NR 179 TC 14 Z9 15 U1 2 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD AUG PY 2009 VL 8 IS 4 BP 296 EP 308 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 513SN UT WOS:000271343800008 PM 19689311 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Psychiatry and Neuropsychiatry as a Craft SO CNS SPECTRUMS LA English DT Editorial Material C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD AUG PY 2009 VL 14 IS 8 BP 408 EP 409 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 499IB UT WOS:000270211200001 PM 19890233 ER PT J AU Brooks, WW Conrad, CH AF Brooks, Wesley W. Conrad, Chester H. TI Isoproterenol-Induced Myocardial Injury and Diastolic Dysfunction in Mice: Structural and Functional Correlates SO COMPARATIVE MEDICINE LA English DT Article ID SPONTANEOUSLY HYPERTENSIVE-RAT; PRESSURE-OVERLOAD; FIBROSIS; HYPERTROPHY; RECEPTOR; HEART; MOUSE; STIMULATION; EXPRESSION; INFARCTION AB The objective of this study was to determine whether a simple, noninvasive method involving administration of isoproterenol could be used to produce myocardial injury and cardiac dysfunction in the mouse heart with a low incidence of mortality. Adult Swiss-Webster mice were injected with isoproterenol (100 mg/kg SC) once daily for 5 d. Myocardial histology and left ventricular (LV) function were assessed 10 to 14 d after the last isoproterenol injection in 14 surviving isoproterenol-treated mice and 15 saline-treated control mice. Left ventricular systolic and diastolic pressures were evaluated in vitro by means of isovolumically contracting, perfused Langendorff preparations. Isoproterenol induced marked endocardial injury, associated with hypertrophy of surviving myocytes, and an increase in myocardial fibrosis (collagen types I and III according to picrosirius red microscopy). The hearts from isoproterenol-treated mice demonstrated decreased IV compliance, as evidenced by an upward shift in the diastolic pressure-volume relationship, with normal LV systolic function. Isoproterenol administration provides a simple, noninvasive means to induce endocardial injury and diastolic dysfunction without significant impairment of systolic function. This model has a low incidence of mortality and may be useful to assess the effects of gene or stem cell therapy on cardiac dysfunction without the potential confounding effects of invasive procedures. C1 [Brooks, Wesley W.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Brooks, WW (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. EM wesley.brooks@va.gov FU Medical Research Funds from the Department of Veterans Affairs FX This work was supported by Medical Research Funds from the Department of Veterans Affairs (REAP and VA Merit review grants). NR 31 TC 38 Z9 50 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2009 VL 59 IS 4 BP 339 EP 343 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 489IF UT WOS:000269413000005 PM 19712573 ER PT J AU Ament, JD Spurr-Michaud, SJ Dohlman, CH Gipson, IK AF Ament, Jared D. Spurr-Michaud, Sandra J. Dohlman, Claes H. Gipson, Ilene K. TI The Boston Keratoprosthesis: Comparing Corneal Epithelial Cell Compatibility with Titanium and PMMA SO CORNEA LA English DT Article DE Boston Keratoprosthesis; biomaterials; titanium; corneal cell compatibility ID INTRAOCULAR LENSES; RESIDUAL MONOMER; BIOMATERIALS; CYTOTOXICITY; PARTICLES; RESINS AB Purpose: To determine in vitro whether titanium is superior corneal cell compatibility to standard polymethyl-methacryl ate (PMMA) for the Boston Keratoprosthesis (KPro). Methods: Human corneal-limbal epithelial (HCLE) cells were Cultured 24, 48, 72 96, 120, 144. or 168 hours in culture plates alone (controls) or with PMMA or titanium discs. Experiments were performed in triplicate and repeated (final n = 6). To determine if a Soluble, toxic factor is emitted from materials, concurrent experiments at 48 and 144 hours were performed with discs placed in Transwell Supports, with HCLE cells plated beneath. As an additional test for soluble factors, cells were incubated 24 hours with disc-conditioned media, and number of viable cells per well was quantified at each timepoint by proliferation assay. To determine if delayed cell proliferation was attributable to cell death, HCLE cell death was measured under all conditions and quantified at each timepoint by cytotoxicity assay. The effects of material on HCLE cell proliferation over time was determined by repeated measures ANOVA. P < 0.05 was statistically significant. Results: HCLE cell proliferation was greater in wells with titanium discs compared to PMMA. Differences between the test discs and control non-disc cocultures were statistically significant over time for both cell proliferation (P = 0.001) and death (P = 0.0025). No significant difference Was found using Transwells (P = 0.9836) or disc-conditioned media (P = 0.36). Conclusion: This in vitro HCLE cell model demonstrates significantly increased cell proliferation and decreased cell death with cell/titanium contact compared to cell/PMNA contact. Moreover, differences are unlikely attributable to a soluble factor. Prospective in vivo analysis of the two KPro biomaterials is indicated. C1 [Ament, Jared D.; Spurr-Michaud, Sandra J.; Dohlman, Claes H.; Gipson, Ilene K.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Ament, Jared D.; Dohlman, Claes H.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ament, JD (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. EM Jared_Ament@MEEI.harvard.edu FU Dr. Claes Dohlman's keratoprosthesis research fund FX Funding was provided by Dr. Claes Dohlman's keratoprosthesis research fund, in which he (CD) has no commercial or financial interest. NR 24 TC 17 Z9 18 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD AUG PY 2009 VL 28 IS 7 BP 808 EP 811 PG 4 WC Ophthalmology SC Ophthalmology GA 478YI UT WOS:000268624300018 PM 19574903 ER PT J AU Konig, A Bleie, O Dudek, D Marso, S Rogers, JH Dave, R Tanaka, K Siebert, U Wijns, W Klauss, V AF Koenig, Andreas Bleie, Oyvind Dudek, Darius Marso, Steve Rogers, Jason H. Dave, Rajesh Tanaka, Kaoru Siebert, Uwe Wijns, William Klauss, Volker TI Coronary plaque dimensions and composition by intravascular ultrasound radio frequency lesion segment analysis in stable and unstable angina patients SO CORONARY ARTERY DISEASE LA English DT Article DE acute coronary syndrome; culprit lesion plaque composition; intravascular ultrasound; radio frequency analysis ID ACUTE MYOCARDIAL-INFARCTION; RADIOFREQUENCY DATA-ANALYSIS; THIN-CAP FIBROATHEROMA; OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO; VIRTUAL HISTOLOGY; VULNERABLE PLAQUE; RUPTURE; MORPHOLOGY; CLASSIFICATION AB Aims We hypothesized that the plaque composition and plaque type classification differs between acute coronary syndrome (ACS) and stable angina (SA) patients. Methods and results We analyzed culprit lesion (CL) and nonculprit lesion (NCL) of ACS patients compared with target lesion (TL) and nontarget lesion (NTL) of SA patients by intravascular ultrasound radio frequency analysis in 874 lesion segments of 424 patients (ACS: 193 patients/SA: 231 patients). Comparing all lesion segments in ACS and SA patients did not show significant differences in absolute or relative plaque composition. However, necrotic core area was larger in CL versus TL (0.9 +/- 0.7 vs. 0.7 +/- 0.5 mm(2), P=0.005) and all plaque components were significantly higher in CL compared with NCL and TL compared with NTL, respectively. A higher amount of thin cap fibroatheroma lesions (115.2 vs. 5.1%, P<0.0001) was detected in ACS compared with SA patients. Fibrocalcific lesions were lower in ACS patients (3 vs. 10.5%, P<0.0001). Conclusion The differentiation in CL/NCL of ACS and TL/NTL of SA patients revealed significant differences in plaque composition and plaque types when examined by intravascular ultrasound radiofrequency analysis. However, considerable overlap between plaque characteristics exists for ACS and SA patients. Coron Artery Dis 20:309-316 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Koenig, Andreas; Klauss, Volker] Univ Munich, Med Klin & Poliklin Innenstadt, Dept Med, Div Cardiol, D-80336 Munich, Germany. [Bleie, Oyvind] Haukeland Hosp, Dept Heart Dis, N-5021 Bergen, Norway. [Dudek, Darius] Jagiellonian Univ, Inst Cardiol, Krakow, Poland. [Marso, Steve] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Rogers, Jason H.] UC Davis Med Ctr, Div Cardiovasc Med, Sacramento, CA USA. [Dave, Rajesh] Pinnacle Hlth Heart & Vasc Inst, Dept Endovasc Med, Harrisburg, PA USA. [Tanaka, Kaoru] Columbia Univ, Med Ctr, Clin Med Intravasc Imaging & Physiol Core Lab, Cardiovasc Res Fdn, New York, NY USA. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Cambridge, MA 02138 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. [Wijns, William] Cardiovasc Ctr Aalst, Aalst, Belgium. RP Konig, A (reprint author), Univ Munich, Med Klin & Poliklin Innenstadt, Dept Med, Div Cardiol, Ziemssenstr 1, D-80336 Munich, Germany. EM Andreas.Koenig@med.uni-muenchen.de FU Volcano Corporation; Abbott Laboratories FX Andreas Konig, MD, Oyvind Blele, MD, PhD, Rajesh Dave, MD, FACC, FSCAJ, Kaoru Tanaka, MD, PhD, Uwe Siebert, MD, MPH, MSc, ScD, William Wjns, MD, PhD and Volker Klauss, MD have no conflicts of interest. Darius Dudek, MD, PhD, FESC has received research grant from Volcano Corporation. Jason H. Rogers, MD and Steve Marso, MD are consultants and received research grant from Volcano Corporation and Abbott Laboratories. NR 38 TC 1 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD AUG PY 2009 VL 20 IS 5 BP 309 EP 316 DI 10.1097/MCA.0b013e32832ac5d3 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 472VD UT WOS:000268159700002 PM 19543087 ER PT J AU Elmoazzen, HY Lee, GY Li, MW McGinnis, LK Lloyd, KCK Toner, M Biggers, JD AF Elmoazzen, Heidi Y. Lee, Gloria Y. Li, Ming W. McGinnis, Lynda K. Lloyd, K. C. Kent Toner, Mehmet Biggers, John D. TI Further optimization of mouse spermatozoa evaporative drying techniques SO CRYOBIOLOGY LA English DT Article DE Evaporative drying; Desiccation; Mouse sperm; Glycerol; Trehalose; Intracytoplasmic injection; Mammalian cells; Preservation; Temperature; Long-term storage ID DESICCATION TOLERANCE; TREHALOSE AB It has been shown in the past that mouse spermatozoa could be dried under a stream of nitrogen gas at ambient temperature and stored at 4 degrees C or 22 degrees C for up to 3 months and was capable of generating liveborn offspring. In previous desiccation work, dried sperm were stored in a vacuum-sealed plastic bag placed in a vacuum-packed Mylar bag. However, dried specimens stored in this way often lost moisture, particularly in samples stored at higher temperatures (22 degrees C) compared to lower temperatures (4 degrees C). The present report describes a method which minimizes this water loss from the dried sperm samples. Its use is described in a preliminary study on the effect of supplementing the trehalose with glycerol. The results have demonstrated that mouse sperm can be stored at 4 degrees C over saturated NaBr without the uptake of water which occurs when they are stored in Mylar packages. In addition, we were able to get some survival of sperm (9-15%) at room temperature storage after 3 months. The addition of glycerol to trehalose had little effect on the survival of dried mouse sperm stored over NaBr for 1 and 3 months. (C) 2009 Elsevier Inc. All rights reserved. C1 [Elmoazzen, Heidi Y.; Lee, Gloria Y.; Toner, Mehmet; Biggers, John D.] Harvard Univ, Ctr Engn Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Elmoazzen, Heidi Y.; Lee, Gloria Y.; Toner, Mehmet; Biggers, John D.] Shriners Hosp Children, Boston, MA 02115 USA. [Li, Ming W.; Lloyd, K. C. Kent] Univ Calif Davis, Ctr Comparat Med, Sch Vet Med, Davis, CA 95616 USA. [McGinnis, Lynda K.] Univ Kansas, Sch Med, Ctr Reprod Sci, Kansas City, KS 66160 USA. [Biggers, John D.] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. RP Elmoazzen, HY (reprint author), Harvard Univ, Ctr Engn Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM helmoazzen@partners.org OI McGinnis, Lynda/0000-0001-7910-9655 FU National Center for Research Resources (NCRR) [R24 RR018934, U42 RR14905]; National Institutes of Health (NIH) FX The project described was supported by Grant Nos. R24 RR018934 and U42 RR14905 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). NR 9 TC 7 Z9 7 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD AUG PY 2009 VL 59 IS 1 BP 113 EP 115 DI 10.1016/j.cryobiol.2009.03.005 PG 3 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 471LK UT WOS:000268059000018 PM 19375415 ER PT J AU Silva, PS Cavallerano, JD Aiello, LM AF Silva, Paolo S. Cavallerano, Jerry D. Aiello, Lloyd M. TI Ocular Telehealth Initiatives in Diabetic Retinopathy SO CURRENT DIABETES REPORTS LA English DT Article ID RETINAL IMAGING TECHNOLOGY; MACULAR EDEMA; EYE DISEASE; OPHTHALMIC EXAMINATION; AUTOMATED DETECTION; GLUCOSE CONTROL; FOLLOW-UP; CARE; COMPLICATIONS; MELLITUS AB Diabetic retinopathy (DR) is a common complication of diabetes mellitus and a leading cause of new-onset vision loss in adults worldwide. Current medical and surgical evidence-based care, including laser photocoagulation, is effective in preserving vision. This care is most effective prior to the onset of ocular or visual symptoms, but many diabetic persons do not receive the recommended annual eye examination for the evaluation of the retina for level of DR. With diabetes incidence and prevalence increasing at epidemic rates and the prediction that 370 million people worldwide will have diabetes by the year 2030, human and fiscal resources will be unable to meet the visual needs with current acute care methods. Appropriate and validated telemedicine programs for DR hold the promise of both enrolling patients into appropriate eye care programs and, more importantly, providing more effective, high-quality diabetes eye care based on current and developing technology. C1 [Cavallerano, Jerry D.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Cavallerano, JD (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM jerry.cavallerano@joslin.harvard.edu NR 54 TC 7 Z9 8 U1 0 U2 3 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD AUG PY 2009 VL 9 IS 4 BP 265 EP 271 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 500EH UT WOS:000270280600002 PM 19640338 ER PT J AU Duh, MS Dial, E Choueiri, TK Fournier, AA Antras, L Rodermund, D Neary, MP Oh, WK AF Duh, Mei Sheng Dial, Ellison Choueiri, Toni K. Fournier, Andree-Anne Antras, Lucia Rodermund, Douglas Neary, Maureen P. Oh, William K. TI Cost implications of IV versus oral anti-angiogenesis therapies in patients with advanced renal cell carcinoma: retrospective claims database analysis SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Angiogenesis inhibitors; Cost; IV bevacizumab; Renal cell carcinoma ID CANCER; SUNITINIB; CHEMOTHERAPY; BEVACIZUMAB; SORAFENIB AB Objective: Angiogenesis inhibitors ( AI) are promising novel treatments for patients with renal cell carcinoma (RCC). However, IV therapy may impose infection risk from IV catheters, and will include increased costs due to administration and transportation costs. This study evaluated the incremental costs associated with IV administration of selected AI therapies (bevacizumab off-label) compared to oral therapies (sunitinib or sorafenib) for the treatment of RCC. Methods: Patients with >= 2 RCC claims (ICD-9: 189.0, 198.0) were identified from a US commercial health insurance claims database from 1/2004 to 12/2007. Patients receiving bevacizumab (n = 109) were matched 1: 1 to patients receiving sorafenib or sunitinib, and observed from their first AI therapy claim until the last treatment date. AI, inpatient, outpatient and pharmacy costs were calculated on a per-patient per-month (PPPM) basis over the treatment period. Costs were compared between the IV AI group and each separate oral AI group using multivariate Tobit regressions for each category separately, adjusting for demographic and baseline clinical characteristics. This study assessed costs of treatment and did not evaluate the cost-effectiveness of AIs. Results: Mean total medical costs were $13 351, $6998, and $8213 PPPM for bevacizumab, sorafenib, and sunitinib, respectively (p<0.05 for equality). Adjusted incremental total cost for the bevacizumab group was $4951 PPPM compared to sorafenib and $4610 PPPM compared to sunitinib (both p<0.05). Bevacizumab patients incurred incremental PPPM outpatient services cost compared to sorafenib and sunitinib of $2772 and $2548, respectively (both p<0.05). Conclusions: Assuming median progression-free survival of 8.5 months as shown for bevacizumab (Bukowski, et al., J Clin Oncol 2007), the incremental costs would be estimated at $39 188-42080 per patient compared to those treated with sunitinib or sorafenib. Assuming similar efficacies, oral AI therapies may result in cost savings to patients and healthcare payers over IV therapies. C1 [Duh, Mei Sheng; Dial, Ellison; Fournier, Andree-Anne; Antras, Lucia; Rodermund, Douglas] Anal Grp Inc, Boston, MA 02199 USA. [Choueiri, Toni K.; Oh, William K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neary, Maureen P.] GlaxoSmithKline Inc, Collegeville, PA USA. RP Duh, MS (reprint author), Anal Grp Inc, 111 Huntington Ave,10th Floor, Boston, MA 02199 USA. EM mduh@analysisgroup.com RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU GlaxoSmithKline, Collegeville, PA, USA FX This research was sponsored by GlaxoSmithKline, Collegeville, PA, USA. NR 24 TC 8 Z9 8 U1 0 U2 0 PU LIBRAPHARM/INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4 LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD AUG PY 2009 VL 25 IS 8 BP 2081 EP 2090 DI 10.1185/03007990903084800 PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 495YD UT WOS:000269930800025 PM 19586325 ER PT J AU London, MJ AF London, Martin J. TI Cardiovascular problems in noncardiac surgery SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE beta-adrenergic blockade; guidelines; myocardial infarction; natriuretic peptides; postoperative complications; troponins ID PERIOPERATIVE BETA-BLOCKADE; PERCUTANEOUS CORONARY INTERVENTION; MAJOR VASCULAR-SURGERY; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; HEART-RATE CONTROL; MYOCARDIAL-INFARCTION; ARTERY STENTS; CARDIAC RISK; STRESS ECHOCARDIOGRAPHY AB Purpose of review Perioperative cardiac complications remain a major area of concern as our surgical population increases in volume, age and frequency of comorbidity. A variety of strategies can be used to optimize patients and potentially reduce the incidence of these serious complications. Recent findings Recent literature suggests a trend towards less invasive testing for detection and quantification of coronary artery disease and greater interest in pharmacologic 'cardioprotection' using beta-blockers, statins and other agents targeting heart rate control and other mechanisms (e.g. reducing inflammatory responses). The recent Perioperative Ischemic Evaluation study has substantially altered this approach at least towards widespread application to lower/intermediate risk cohorts. Considerable attention has been focused on ensuring optimal standardized perioperative management of patients with a recent percutaneous coronary intervention, particularly those with an intracoronary stent. Widespread surveillance of postoperative troponin release and increasing recognition of the prognostic potential of elevated preoperative brain natriuretic peptides point towards changing strategies for long-term risk stratification. Summary The complexity of a particular patient's physiologic responses to a wide variety of surgical procedures, which are undergoing constant technological refinement generally associated with lesser degrees of invasivity and stress make calculation of patients' perioperative risk very challenging. At the present time, adequate information is available for the clinician to screen patients with high-risk preoperative predictors, delay elective surgery for patients with recent intracoronary stents and continue chronic beta-blockade in appropriate patients. New large-scale database and subanalyses of major trials (e.g. Perioperative Ischemic Evaluation and Coronary Artery Revascularization Prophylaxis) should provide additional information to minimize perioperative cardiac risk. C1 [London, Martin J.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [London, Martin J.] San Francisco VA Med Ctr, San Francisco, CA USA. RP London, MJ (reprint author), Anesthesia 129,4150 Clement St, San Francisco, CA 94121 USA. EM londonm@anesthesia.ucsf.edu NR 61 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD AUG PY 2009 VL 15 IS 4 BP 333 EP 341 DI 10.1097/MCC.0b013e32832e4795 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 480ME UT WOS:000268738100010 PM 19553809 ER PT J AU Sun, HY Singh, N AF Sun, Hsin-Yun Singh, Nina TI Immune reconstitution inflammatory syndrome in non-HIV immunocompromised patients SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE immune reconstitution inflammatory syndrome; immunocompromised hosts; non-HIV ID REGULATORY T-CELLS; ORGAN TRANSPLANT RECIPIENTS; RENAL-ALLOGRAFT REJECTION; NECROSIS-FACTOR-ALPHA; INVASIVE PULMONARY ASPERGILLOSIS; ACTIVE ANTIRETROVIRAL THERAPY; MYCOBACTERIUM-TUBERCULOSIS; CRYPTOCOCCAL MENINGITIS; PARADOXICAL RESPONSE; AUTOIMMUNE-DISEASE AB Purpose of review In the era of highly active antiretroviral therapy, immune reconstitution inflammatory syndrome has become well recognized in the HIV-infected population. However, little is known about its occurrence in non-HIV immunocompromised hosts. The present review aims to propose the pathogenesis of immune reconstitution inflammatory syndrome, summarize its occurrence in immunocompromised patients without HIV infection, and suggest potential treatment options. Recent findings Immune reconstitution inflammatory syndrome is exuberant and dysregulated inflammatory responses to invading microorganisms. It manifests when an abrupt shift of host immunity from an anti-inflammatory and immunrosuppressive status towards a pathogenic proinflammatory state occurs as a result of rapid decreases or removal of factors promoting immunosuppression or inhibiting inflammation. In addition to HIV-infected patients, immune reconstitution inflammatory syndrome has also been observed in solid organ transplant recipients, women during the postpartum period, neutropenic patients, and tumor necrosis factor antagonist recipients. Corticosteroids are the most commonly employed treatment, whereas other potential agents based on its pathogenesis deserve further investigation. Summary Non-HIV immunocompromised hosts develop immune reconstitution inflammatory syndrome when the sudden change in the dominant T helper responses to inflammation is not well balanced by anti-inflammatory responses. Judicious manipulation of host immunity and timely recognition of immune reconstitution inflammatory syndrome as we deal with the infections in these populations is critical to limit or avoid the harm by immune reconstitution inflammatory syndrome. C1 [Sun, Hsin-Yun; Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. RP Singh, N (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu OI SUN, HSIN-YUN/0000-0003-0074-7721 NR 112 TC 34 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD AUG PY 2009 VL 22 IS 4 BP 394 EP 402 DI 10.1097/QCO.0b013e32832d7aff PG 9 WC Infectious Diseases SC Infectious Diseases GA 470IS UT WOS:000267969000010 PM 19483618 ER PT J AU Dodd, ME Hatzold, J Mathias, JR Walters, KB Bennin, DA Rhodes, J Kanki, JP Look, AT Hammerschmidt, M Huttenlocher, A AF Dodd, M. Ernest Hatzold, Julia Mathias, Jonathan R. Walters, Kevin B. Bennin, David A. Rhodes, Jennifer Kanki, John P. Look, A. Thomas Hammerschmidt, Matthias Huttenlocher, Anna TI The ENTH domain protein Clint1 is required for epidermal homeostasis in zebrafish SO DEVELOPMENT LA English DT Article DE Epidermis; Zebrafish; Inflammation; Hemidesmosome ID TRANSGENIC ZEBRAFISH; DANIO-RERIO; INSERTIONAL MUTAGENESIS; HEMIDESMOSOME FORMATION; GRANULOMA-FORMATION; EXPRESSION; INFLAMMATION; PSORIASIS; EMBRYOS; FISH AB Epidermal hyperproliferation and inflammation are hallmarks of the human condition psoriasis. Here, we report that a zebrafish line with a mutation in the cargo adaptor protein Clint1 exhibits psoriasis-like phenotypes including epithelial hyperproliferation and leukocyte infiltration. Clint1 is an ENTH domain-containing protein that binds SNARE proteins and functions in vesicle trafficking; however, its in vivo function in animal models has not been reported to date. The clint1 mutants exhibit chronic inflammation characterized by increased Interleukin 1 beta expression, leukocyte infiltration, bidirectional trafficking and phagocytosis of cellular debris. The defects in clint1 mutants can be rescued by expression of zebrafish clint1 and can be phenocopied with clint1-specific morpholinos, supporting an essential role for Clint1 in epidermal development. Interaction studies suggest that Clint1 and Lethal giant larvae 2 function synergistically to regulate epidermal homeostasis. Accordingly, clint1 mutants show impaired hemidesmosome formation, loss of cell-cell contacts and increased motility suggestive of epithelial to mesenchymal transition. Taken together, our findings describe a novel function for the ENTH domain protein Clint1 in epidermal development and inflammation and suggest that its deficiency in zebrafish generates a phenotype that resembles the human condition psoriasis. C1 [Dodd, M. Ernest; Mathias, Jonathan R.; Huttenlocher, Anna] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Hatzold, Julia; Hammerschmidt, Matthias] Univ Cologne, Inst Dev Biol, Ctr Mol Med Cologne, Cologne, Germany. [Walters, Kevin B.; Huttenlocher, Anna] Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI 53706 USA. [Rhodes, Jennifer; Kanki, John P.; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bennin, David A.; Huttenlocher, Anna] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA. RP Huttenlocher, A (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. EM huttenlocher@wisc.edu FU NIH [R01 GM074827, 5KO1DK69672]; Arthritis Foundation FX We gratefully acknowledge Adam Amsterdam and Nancy Hopkins (M.I.T.) for providing hi1520 mutants, Satoshi Kinoshita for zebrafish sections, Ben August for electron microscopy, Sa Kan Yoo for thoughtful discussions and Andrea Gallagher for technical assistance. This work was supported by NIH grants to A.H. (R01 GM074827), J. R. (5KO1DK69672) and by an Arthritis Foundation fellowship (J.R.M.) and Hematology training grant (M.E.D.). M. H. and J. H. thank the Max-Planck society for initial support. Deposited in PMC for release after 12 months. NR 52 TC 21 Z9 22 U1 0 U2 2 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 AUG 1 PY 2009 VL 136 IS 15 BP 2591 EP 2600 DI 10.1242/dev.038448 PG 10 WC Developmental Biology SC Developmental Biology GA 469MZ UT WOS:000267905000011 PM 19570844 ER PT J AU Ellis, BC Gattoni-Celli, S Mancia, A Kindy, MS AF Ellis, Blake C. Gattoni-Celli, Sebastiano Mancia, Annalaura Kindy, Mark S. TI The vitamin D3 transcriptomic response in skin cells derived from the Atlantic bottlenose dolphin SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Review DE Vitamin D; Immunity; Keratinocyte; Gene expression; Transcription factors; Dolphin ID SINGLE-NUCLEOTIDE POLYMORPHISM; LYMPHOID TYROSINE PHOSPHATASE; ANTIMICROBIAL PROTEIN HCAP18; UVB-INDUCED CONVERSION; TUMOR-NECROSIS-FACTOR; BREAST-CANCER CELLS; TURSIOPS-TRUNCATUS; D-RECEPTOR; GENE-EXPRESSION; 1,25-DIHYDROXYVITAMIN D-3 AB The Atlantic bottlenose dolphin has attracted attention due to the evident impact that environmental stressors have taken on its health. In order to better understand the mechanisms linking environmental health with dolphin health, we have established cell cultures from dolphin skin as in vitro tools for molecular evaluations. The vitamin D3 pathway is one mechanism of interest because of its well established chemopreventative and immunomodulatory properties in terrestrial mammals. On the other hand, little is known of the physiological role of this molecule in aquatic animals. 1,25-dihydroxyvitamin D3 (1,25D3), the bioactive and hormonal form of vitamin D3, exerts its biological function by binding to the vitamin D receptor (VDR), a ligand-activated regulator of gene transcription. Therefore, we investigated the transcriptomic changes induced by 1,25D3 administration in dolphin skin cells. Identification of specific genes activated by 1,25D3 has provided clues to the physiological function of the vitamin D3 pathway in the dolphin. We found that exposure of the cells to 1,25D3 upregulated transactivation of a vitamin D-sensitive promoter. cDNA microarray analysis, using a novel dolphin array, identified specific gene targets within this pathway, and real-time PCR (qPCR) confirmed the enhanced expression of select genes of interest. These transcriptional changes correlated with an increase in VDR levels. This is the first report of the presence and activation of the vitamin D3 pathway in a marine mammal, and our experimental results demonstrate a number of similarities to terrestrial animals. Conservation of this pathway in the Atlantic bottlenose dolphin is consistent with the importance of nonclassic functions of vitamin D3, such as its role in innate immunity, similar to what has been demonstrated in other mammals. Published by Elsevier Ltd. C1 [Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Ellis, Blake C.; Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Mancia, Annalaura] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Ellis, Blake C.; Gattoni-Celli, Sebastiano; Mancia, Annalaura; Kindy, Mark S.] Med Univ S Carolina, Marine Biomed & Environm Sci Program, Charleston, SC 29425 USA. [Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. EM kindyms@musc.edu RI mancia, annalaura/F-9706-2013 OI mancia, annalaura/0000-0001-8680-3530 FU National Science Foundation EPSCoR grant [EPS-0132573, EPS-0447660]; Veterans Administration Merit Review (MSK); National Oceanic and Atmospheric Administration grant [MOA-2004-168/1259]; SC Sea Grant [MOA-2006-025/7182]; Marine Biomedicine and Environmental Sciences Center, Oceans and Human Health Training Program FX This work was partially supported by a National Science Foundation EPSCoR grant (MSK, EPS-0132573 and EPS-0447660), Veterans Administration Merit Review (MSK) and a National Oceanic and Atmospheric Administration grant to Center for Coastal Environmental Health and Biomolecular Research (NOAA Biotech Contract, MOA-2004-168/1259), SC Sea Grant (MOA-2006-025/7182) and the Marine Biomedicine and Environmental Sciences Center, Oceans and Human Health Training Program. NR 104 TC 9 Z9 9 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PD AUG PY 2009 VL 33 IS 8 BP 901 EP 912 DI 10.1016/j.dci.2009.02.008 PG 12 WC Immunology; Zoology SC Immunology; Zoology GA 458GW UT WOS:000267004700003 PM 19454332 ER PT J AU Zhang, Y Levin, M AF Zhang, Ying Levin, Michael TI Particle Tracking Model of Electrophoretic Morphogen Movement Reveals Stochastic Dynamics of Embryonic Gradient SO DEVELOPMENTAL DYNAMICS LA English DT Article DE left-right asymmetry; mathematical modeling; electrophoresis; Xenopus; gap junctions; laterality; gradient, serotonin ID LEFT-RIGHT ASYMMETRY; GAP-JUNCTION CHANNELS; LEFT-RIGHT AXIS; POSITIONAL INFORMATION; EARLY STEP; DEVELOPMENTAL BIOLOGY; ELECTRICAL CURRENTS; RETINOIC ACID; CELL-MEMBRANE; FROG EMBRYOS AB Some developmental events rely on an electrophoretic force to produce morphogenetic gradients. To quantitatively explore the dynamics of this process, we constructed a stochastic model of an early phase of left-right patterning: serotonin movement through the gap junction-coupled blastomeres of the Xenopus embryo. Particle-tracking simulations showed that a left-right gradient is formed rapidly, quickly reaching a final stable level. The voltage difference was critical for producing a morphogen gradient of the right steepness; gap junctional connectivity and morphogen mass determined the timing of the gradient. Endogenous electrophoresis drives similar to 50% of the particles across more than one cell width, and similar to 20% can travel across half the embryo. The stochastic behavior of the resulting gradients exhibited unexpected complexity among blastomeres' morphogen content, and showed how spatiotemporal variability within individual cells resulted in robust and consistent gradients across the embryonic left-right axis. Analysis of the distribution profile of gradient gain values made quantitative predictions about the conditions that result in the observed background level of laterality defects in unperturbed frog embryos. This work provides a general model that can be used to quantitatively analyze the unexpectedly complex dynamics of morphogens in a wide variety of systems. Developmental Dynamics 238.1923-1935, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Levin, Michael] Tufts Univ, Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Levin, Michael] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Zhang, Ying] Harvard Univ, Sch Dent Med, Ctr Regenerat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. [Zhang, Ying] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Tufts Univ, Ctr Regenerat & Dev Biol, 200 Boston Ave, Medford, MA 02155 USA. EM michael.levin@tufts.edu RI Zhang, Ying/Q-6956-2016 OI Zhang, Ying/0000-0002-8045-3821 FU American Heart Association [0740088N]; NIH [R01-GM077425] FX We thank Axel Esser and Peter Smith (of the BRC module at Woods Hole, Marine Biological Laboratory, NIH P41 RR001395) for many useful discussions. This research was conducted on two clusters: the Orchestra high-performance computer cluster supported by Research Information Technology at Harvard Medical School, and the high-performance computing research cluster supported by University Information Technology at Tufts University. We thank the OCNT group at Forsyth Institute and Lionel Zupan and Durwood Marshall at Tufts for assistance with use of computational resources. NR 84 TC 12 Z9 12 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 2009 VL 238 IS 8 BP 1923 EP 1935 DI 10.1002/dvdy.22016 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 479TZ UT WOS:000268685100006 PM 19618466 ER PT J AU Phelan, S Kanaya, AM Subak, LL Hogan, PE Espeland, MA Wing, RR Burgio, KL DiLillo, V Gorin, AA West, DS Brown, JS AF Phelan, Suzanne Kanaya, Alka M. Subak, Leslee L. Hogan, Patricia E. Espeland, Mark A. Wing, Rena R. Burgio, Kathryn L. DiLillo, Vicki Gorin, Amy A. West, Delia S. Brown, Jeanette S. CA Action Hlth Diabet Look AHEAD Res TI Prevalence and Risk Factors for Urinary Incontinence in Overweight and Obese Diabetic Women Action for Health in Diabetes (Look AHEAD) study SO DIABETES CARE LA English DT Article ID NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; EPIDEMIOLOGIC SURVEY; NATIONAL-HEALTH; WEIGHT-LOSS; COMMUNITY; STRESS; TRIAL AB OBJECTIVE - To determine the prevalence and risk factors for Urinary incontinence among different racial/ethnic groups of overweight. and obese women with type 2 diabetes. RESEARCH DESIGN AND METHODS - Cross-sectional analysis of baseline data from the Action for Health in Diabetes (Look AHEAD) study, a randomized clinical trial with 2,994 overweight/obese women with type 2 diabetes. RESULTS - Weekly Incontinence (27%) was reported more Often than other diabetes-associated complications, including retinopathy (7.5%), microalbuminuria (2.2%), and neuropathy (1.5%). The prevalence of weekly incontinence was highest among non-Hispanic whites (32%) and lowest among African Americans (18%), and Asians (12%) (P < 0,001). Asian and African American women had lower odds of weekly incontinence compared with non-Hispanic whites (75 and 55% lower, respectively; P < 0.001). Women with a BMI of >= 35 kg/m(2) had a higher odds of overall and stress incontinence (55-85% higher P < 0.03) compared with that for nonobese women. Risk factors for overall incontinence, as well as for Stress and Urgency incontinence, included prior hysterectomy (40-80% increased risks P < 0.01) and urinary tract infection in the prior year (5-90% increased risk, P < 0.001). CONCLUSIONS - Among overweight and obese women with type 2 diabetes, urinary incontinence is highly prevalent and far exceeds the prevalence of other diabetes complications. Racial/ethnic differences in incontinence prevalence are similar to those in women without diabetes, affecting non-Hispanic whites more than Asians and African Americans. Increasing obesity (BMI >= 35 kg/m(2)) was the strongest modifiable risk factor for overall incontinence and stress incontinence ill this diverse cohort. C1 [Phelan, Suzanne] Calif Polytech State Univ San Luis Obispo, Dept Kinesiol, San Luis Obispo, CA 93407 USA. [Kanaya, Alka M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Gen Internal Med, San Francisco, CA 94143 USA. [Subak, Leslee L.; Brown, Jeanette S.] Univ Calif San Francisco, Womens Hlth Clin Res Ctr, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Subak, Leslee L.; Brown, Jeanette S.] Univ Calif San Francisco, Womens Hlth Clin Res Ctr, Dept Urol, San Francisco, CA 94143 USA. [Subak, Leslee L.; Brown, Jeanette S.] Univ Calif San Francisco, Womens Hlth Clin Res Ctr, Dept Epidemiol, San Francisco, CA 94143 USA. [Hogan, Patricia E.; Espeland, Mark A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Wing, Rena R.] Miriam Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI 02906 USA. [Burgio, Kathryn L.] Univ Alabama, Birmingham, AL USA. [Burgio, Kathryn L.] Dept Vet Affairs, Birmingham, AL USA. [DiLillo, Vicki] Ohio Wesleyan Univ, Dept Psychol, Delaware, OH 43015 USA. [Gorin, Amy A.] Univ Connecticut, Dept Psychol, Ctr Hlth Intervent & Prevent, Storrs, CT USA. [West, Delia S.] Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72205 USA. RP Phelan, S (reprint author), Calif Polytech State Univ San Luis Obispo, Dept Kinesiol, San Luis Obispo, CA 93407 USA. EM sphelan@calpoly.edu FU National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; The Johns Hopkins Medical Institutions Bayview General Clinical Research [M01-RR-02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center [M01RR-01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01 RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University Award in Patient Oriented Research [(PA-98053]; NIDDK FX This study was supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Heart, Lung, and Blood Institute, National Institute of Nursing Research, National Center on Minority Health and Health Disparities, Office of Research on Women's Health, and the Centers for Disease Control and Prevention. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01-RR-02719), the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01RR-01066), the University of Colorado Health Sciences Center General Clinical Research Center (M01 RR00051) and Clinical Nutrition Research Unit (P30 DK48520), the University Award in Patient Oriented Research (PA-98053) from the NIDDK. NR 25 TC 32 Z9 37 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2009 VL 32 IS 8 BP 1391 EP 1397 DI 10.2337/dc09-0516 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479UX UT WOS:000268687800006 PM 19487639 ER PT J AU Dinh, T Rosenblum, BI Doupis, J Wang, XE Lyons, TE Giurini, JM Kuchibhotla, S Greenman, RL Julliard, W Veves, A Gnardellis, C AF Dinh, Thanh Rosenblum, Barry I. Doupis, John Wang, Xiaoen Lyons, Thomas E. Giurini, John M. Kuchibhotla, Sarada Greenman, Robert L. Julliard, Walker Veves, Aristidis Gnardellis, Charalambos TI Foot Muscle Energy Reserves in Diabetic Patients Without and With Clinical Peripheral Neuropathy SO DIABETES CARE LA English DT Article ID RARE PULSE SEQUENCE; SKELETAL-MUSCLE; METABOLISM; RISK; PHOSPHOCREATINE AB OBJECTIVE - To investigate changes in the foot muscle energy reserves in diabetic non-neuropathic and neuropathic patients. RESEARCH DESIGN AND METHODS - We measured the phosphocreatinine (PCr)/inorganic phosphate (Pi) ratio, total (31)P concentration, and the lipid/water ratio in the muscles in the metatarsal head region using MRI spectroscopy in healthy control subjects and non-neuropathic and neuropathic diabetic patients. RESULTS - The PCr/Pi ratio was higher in the control subjects (3.23 +/- 0.43) followed by the non-neuropathic group (2.61 +/- 0.36), whereas it was lowest in the neuropathic group (0.60 +/- 1.02) (P < 0.0001). There were no differences in total (31)P concentration and lipid/water ratio between the control and non-neuropathic groups, but both measurements were different in the neuropathic group (P < 0.0001). CONCLUSIONS - Resting foot muscle energy reserves are affected before the development of peripheral diabetic neuropathy and are associated with the endothelial dysfunction and inflammation. C1 [Dinh, Thanh; Rosenblum, Barry I.; Doupis, John; Lyons, Thomas E.; Giurini, John M.; Kuchibhotla, Sarada; Julliard, Walker; Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Sch Med, Boston, MA 02215 USA. [Dinh, Thanh; Rosenblum, Barry I.; Doupis, John; Lyons, Thomas E.; Giurini, John M.; Kuchibhotla, Sarada; Julliard, Walker; Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Joslin Beth Israel Deaconess Foot Ctr, Sch Med, Boston, MA 02215 USA. [Gnardellis, Charalambos] Technol Educ Inst Messolonghi, Mesolongion, Greece. [Wang, Xiaoen; Greenman, Robert L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Sch Med, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu FU National Institutes of Health [R01-HL075678, R01 DK076937] FX No potential conflicts of interest relevant to this article were reported. NR 11 TC 4 Z9 4 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 AUG PY 2009 VL 32 IS 8 BP 1521 EP 1524 DI 10.2337/dc09-0536 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479UX UT WOS:000268687800033 PM 19509013 ER PT J AU Florez, JC Price, AL Campbell, D Riba, L Parra, MV Yu, F Duque, C Saxena, R Gallego, N Tello-Ruiz, M Franco, L Rodriguez-Torres, M Villegas, A Bedoya, G Aguilar-Salinas, CA Tusie-Luna, MT Ruiz-Linares, A Reich, D AF Florez, J. C. Price, A. L. Campbell, D. Riba, L. Parra, M. V. Yu, F. Duque, C. Saxena, R. Gallego, N. Tello-Ruiz, M. Franco, L. Rodriguez-Torres, M. Villegas, A. Bedoya, G. Aguilar-Salinas, C. A. Tusie-Luna, M. T. Ruiz-Linares, A. Reich, D. TI Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes SO DIABETOLOGIA LA English DT Article DE Genetic admixture; Genetic association; Latinos; Socioeconomic status; Type 2 diabetes ID SAN-LUIS-VALLEY; MEXICAN-AMERICANS; PIMA-INDIANS; RISK-FACTORS; R230C VARIANT; MELLITUS; POPULATION; PREVALENCE; SUSCEPTIBILITY; TEXAS AB Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellin (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02-0.21], p = 2.0 x 10(-5)) and Colombians (OR 0.26 [0.08-0.78], p = 0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19-2.12], p = 0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04-0.71], p = 0.02). Adjustment for BMI did not change the results. The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects. C1 [Florez, J. C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, J. C.; Yu, F.; Saxena, R.; Reich, D.] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Florez, J. C.; Yu, F.; Saxena, R.; Reich, D.] MIT, Cambridge, MA 02139 USA. [Florez, J. C.; Saxena, R.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Price, A. L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Price, A. L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Yu, F.] Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Parra, M. V.; Duque, C.; Gallego, N.; Franco, L.; Villegas, A.; Bedoya, G.; Ruiz-Linares, A.] Univ Antioquia, Genet Mol Lab, Medellin, Colombia. [Riba, L.; Rodriguez-Torres, M.; Tusie-Luna, M. T.] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unidad Biol Mol & Med Genom, Tlalpan 14000, DF, Mexico. [Campbell, D.; Ruiz-Linares, A.] UCL, Dept Genet Evolut & Environm, Galton Lab, London NW1 2HE, England. [Tello-Ruiz, M.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Saxena, R.; Reich, D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Aguilar-Salinas, C. A.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Mexico City, DF, Mexico. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Simches Res Bldg,CPZN 5-250,185 Cambridge St, Boston, MA 02114 USA. EM jcflorez@partners.org; tusie@biomedicas.unam.mx; a.ruizlin@ucl.ac.uk RI Franco, Laercio/H-3814-2013; OI Franco, Laercio/0000-0002-9820-3425; Campbell, Desmond/0000-0003-1085-714X FU Massachusetts General Hospital Physician Scientist Development Award; Doris Duke Charitable Foundation Clinical Scientist Development Award; NIH [NS043538, DK073818]; Burroughs Wellcome Career Development Award; Harvard Medical School; Colciencias [1115-04-16451, 1115-04-012986]; Universidad de Antioqu [9889-E01321] FX We thank all the participants for their contribution of phenotype and DNA samples, and S. Jimenez-Ramirez for technical assistance. J. C. Florez is supported by a Massachusetts General Hospital Physician Scientist Development Award and a Doris Duke Charitable Foundation Clinical Scientist Development Award. A. L. Price was supported by a Ruth Kirschstein National Research Service Award from the NIH. R. Saxena is supported by a Ruth Kirschstein National Research Service Award from the NIH. D. Reich is supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences. Support for this project was provided by discretionary funding from Harvard Medical School (to D. Reich), NIH grants NS043538 (to A. Ruiz-Linares) and DK073818 (to D. Reich), Colciencias grants 1115-04-16451 and 1115-04-012986 (to G. Bedoya and A. Villegas), and a Universidad de Antioqu a grant (CODI/sostenibilidad 9889-E01321) to G. Bedoya and A. Villegas. NR 31 TC 42 Z9 43 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2009 VL 52 IS 8 BP 1528 EP 1536 DI 10.1007/s00125-009-1412-x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 470UK UT WOS:000268006200010 PM 19526211 ER PT J AU Liu, Z Habener, JF AF Liu, Z. Habener, J. F. TI Stromal cell-derived factor-1 promotes survival of pancreatic beta cells by the stabilisation of beta-catenin and activation of transcription factor 7-like 2 (TCF7L2) SO DIABETOLOGIA LA English DT Article DE Beta cells; Apoptosis; Diabetes; SDF-1; WNT signalling ID CHEMOKINE GENE VARIANT; SIGNALING PATHWAY; BONE-MARROW; STEM-CELLS; AKT; PROLIFERATION; APOPTOSIS; RECEPTOR; MIGRATION; CXCR4 AB Stromal cell-derived factor-1 (SDF-1) is a chemokine produced in stromal tissues in multiple organs. Earlier we reported on levels of SDF-1 and SDF-1 receptor (CXCR4) in the insulin-producing beta cells of the mouse pancreas and determined that the SDF-1/CXCR4 axis is important for beta cell survival through activation of the prosurvival kinase, protein kinase B (AKT). Since AKT is known to modulate the wingless-type MMTV integration site family (WNT) signalling cascade, we examined the effects of SDF-1/CXCR4 on WNT signalling in beta cells and whether this signalling is important for cell survival. Activation of downstream WNT signalling (beta-catenin and transcription factor 7-like 2, [TCF7L2]) in response to SDF-1 was examined in the islets of WNT signalling reporter (Tcf-optimal promoter beta-galactosidase) mice and in INS-1 and MIN6 beta cells. Cytoprotection of beta cells by SDF-1 in response to the induction of apoptosis was assessed by caspase 3 and TUNEL assays. SDF-1 induced WNT signalling in beta cells of isolated islets and in INS-1 cells via CXCR4-mediated activation of Galphai/o-coupled signalling and the phosphatidylinositol 3-kinase/AKT signalling cascade resulting in the inhibition of glycogen synthase kinase 3-beta. The key WNT signalling regulators, beta-catenin and AKT, were activated by SDF-1 at the transcriptional and post-translational levels. Specific inhibition of beta-catenin in the WNT signalling cascade reversed the anti-apoptotic effects of SDF-1. SDF-1 promotes pancreatic beta cell survival via activation of AKT and downstream WNT signalling via the stabilisation and activation of beta-catenin/TCF7L2 transcriptional activators. These findings suggest a mechanism for SDF-1 based glucose-lowering therapies by enhancing beta cell mass through increasing cell survival. C1 [Liu, Z.; Habener, J. F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. [Liu, Z.; Habener, J. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Thier 306,55 Fruit St, Boston, MA 02114 USA. EM jhabener@partners.org FU Juvenile Diabetes Research foundation; USPHS [DK30834] FX We thank T. Boodry and S. Avadhani for technical assistance, and V. Stanojevic and M. Thomas for helpful suggestions during the studies. This work was supported in part by a postdoctoral fellowship from the Juvenile Diabetes Research foundation (to Z. Lui) and a grant USPHS DK30834 (to J. F. Habener). NR 35 TC 25 Z9 27 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 AUG PY 2009 VL 52 IS 8 BP 1589 EP 1598 DI 10.1007/s00125-009-1384-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 470UK UT WOS:000268006200017 PM 19468708 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Hospitalization for Achalasia in the United States 1997-2006 SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Environmental risk factors; Epidemiology of achalasia; Geographic variation; Hospital statistics; Socio-economic status; Time trends ID CLINICAL-FEATURES; EPIDEMIOLOGY; POPULATION; PREVALENCE AB The Nationwide Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) was used to study the demographic characteristics of achalasia patients. HCUP data from 1997 to 2006 were stratified by categories pertaining to patient demographics, such as age, sex, race, income, residence in metropolitan area, and region of the United States, as well as categories pertaining to hospital characteristics, such teaching status, location, and bed size. The distributions of inpatients among different categories were compared between achalasia and all other diagnoses, using odds ratios and their 95% confidence intervals for comparison. The annual hospitalization rates of achalasia revealed a clear-cut age-dependent rise between the youngest age group less than 18 years old (0.25/100,000) and the oldest age group over 85 years old (37.35/100,000). Between 1997 and 2007, the rates of hospitalization remained largely unchanged for all age groups alike. Achalasia was equally distributed among men and women and among various ethnic groups. Compared with other diagnoses, achalasia was more frequent among hospitalized patients from zip codes associated with a higher average income (1.26, 1.23-1.29), living in metropolitan areas (1.12, 1.09-1.15), and living in the northeast region of the United States (1.27, 1.25-1.30). Achalasia patients were mostly seen in large hospitals (1.22, 1.19-1.26), teaching hospitals (1.73, 1.70-1.76), and hospitals located in metropolitan areas (1.15, 1.14-1.15). With exception of its striking age-dependence, the epidemiology of achalasia does not reveal any clues about its yet unsolved etiology. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 19 TC 14 Z9 17 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 AUG PY 2009 VL 54 IS 8 BP 1680 EP 1685 DI 10.1007/s10620-009-0863-8 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 464DM UT WOS:000267485400011 PM 19517232 ER PT J AU Kovacs, TO Freston, JW Haber, MM Hunt, B Atkinson, S Peura, DA AF Kovacs, Thomas O. Freston, James W. Haber, Marian M. Hunt, Barbara Atkinson, Stuart Peura, David A. TI Long-Term Efficacy of Lansoprazole in Preventing Relapse of Erosive Reflux Esophagitis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Lansoprazole; Erosive esophagitis; Gastroesophageal reflux disease; GERD; Efficacy; Long-term maintenance therapy ID PROTON PUMP INHIBITORS; ESOMEPRAZOLE 20 MG; LIFE-STYLE ADVICE; MAINTENANCE TREATMENT; DOSE LANSOPRAZOLE; CONTROLLED TRIAL; DISEASE; OMEPRAZOLE; ARTICLE; MEDICATION AB In a phase III study of lansoprazole treatment, patients with healed or unhealed erosive esophagitis entered a titrated open-label treatment period and received lansoprazole for a parts per thousand currency sign6 years to assess long-term maintenance therapy. Doses were adjusted depending on symptom response. Endoscopy was performed yearly. One hundred ninety-five subjects received lansoprazole for < 1 to 72 months; most received daily doses of a parts per thousand currency sign30 mg. Lansoprazole maintained erosive esophagitis remission in 75% of subjects receiving treatment for a parts per thousand currency sign72 months, with 39 subjects experiencing 50 recurrences. Most subjects (94-95%) had no or mild symptoms of day or night heartburn at study end, and 77% were asymptomatic at first erosive esophagitis recurrence. The most common treatment-related adverse events included diarrhea (10%), headache (8%), and abdominal pain (6%), and were mild or moderate in severity. Long-term lansoprazole is effective and well tolerated when used to maintain erosive esophagitis remission for a parts per thousand currency sign6 years. C1 [Kovacs, Thomas O.] CURE Digest Dis Res Ctr, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Freston, James W.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Haber, Marian M.] Drexel Univ, Coll Med, Dept Pathol, Philadelphia, PA 19104 USA. [Hunt, Barbara; Atkinson, Stuart] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. [Peura, David A.] Univ Virginia Hlth Syst, Charlottesville, VA USA. RP Kovacs, TO (reprint author), CURE Digest Dis Res Ctr, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM TKovacs@mednet.ucla.edu FU Takeda Global Research & Development Center, Inc. FX This study (M94-140) was funded in full by Takeda Global Research & Development Center, Inc. (TAP Pharmaceutical Products Inc. is now a part of Takeda Global Research & Development Center, Inc.) Dr. Kovacs confirms that he has no conflicts of interest or disclosures. Dr. Freston has served as a consultant for Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals North America, Inc., GlaxoSmithKline, and EnteroMedics, Inc. Dr. Haber serves as a consultant for Takeda Global Research & Development Center, Inc. Dr. Peura serves as a consultant for Takeda Global Research & Development Center, Inc. and as a member of the speaker's bureau for Takeda Pharmaceuticals North America, Inc. Ms. Hunt and Dr. Atkinson are employees of Takeda Global Research & Development Center, Inc. NR 25 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2009 VL 54 IS 8 BP 1693 EP 1701 DI 10.1007/s10620-009-0769-5 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 464DM UT WOS:000267485400013 PM 19267194 ER PT J AU Sonnenberg, A Richardson, PA Abraham, NS AF Sonnenberg, Amnon Richardson, Peter A. Abraham, Neena S. TI Hospitalizations for Inflammatory Bowel Disease Among US Military Veterans 1975-2006 SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Crohn's disease; Epidemiology; Incidence; Prevalence; Ethnicity; Time trends; Ulcerative colitis; Veterans population ID ULCERATIVE-COLITIS; CROHNS-DISEASE; UNITED-STATES; TIME TRENDS; INCIDENCE RATES; EPIDEMIOLOGY; PREVALENCE; MORTALITY AB Background The Department of Veterans Affairs (VA) is the largest healthcare system in the United States. The VA database was used to analyze patterns of hospitalization for inflammatory bowel disease (IBD) among US military veterans. Methods The study used the VA Patient Treatment File (PTF) between 1975 and 2006. Each hospital record extracted from the PTF included diagnosis, patient age, and ethnicity. Patient age was analyzed in three age groups: 0-44, 45-64, and 65+. Patient ethnicity was analyzed by two broad categories as white and nonwhite. Results Among veterans, Crohn's disease was more common than ulcerative colitis and both diseases were more common in whites than in nonwhites. During the past 30 years, the age distributions of both diseases have shifted towards older patients who have come to represent an increasingly larger fraction of patients with Crohn's disease, as well as ulcerative colitis. Hospitalization rates for inflammatory bowel disease among whites recently declined, while most rates among nonwhites continued to rise throughout the observation period. Conclusion The present study revealed a time-dependent shift towards older ages in the age distribution of IBD among hospitalized veterans. These changes, which have been observed similarly in other US statistics, may reflect a birth-cohort phenomenon underlying the long-term time trends of IBD. C1 [Sonnenberg, Amnon; Richardson, Peter A.; Abraham, Neena S.] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Richardson, Peter A.; Abraham, Neena S.] Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Richardson, Peter A.; Abraham, Neena S.] Baylor Coll Med, Houston, TX 77030 USA. [Sonnenberg, Amnon; Richardson, Peter A.; Abraham, Neena S.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 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 FU Houston VA HSR&D Center of Excellence, Houston Center for Quality of Care & Utilization Studies [HFP90-020] FX This work was supported in part by the Houston VA HSR&D Center of Excellence, Houston Center for Quality of Care & Utilization Studies [HFP90-020]. NR 17 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2009 VL 54 IS 8 BP 1740 EP 1745 DI 10.1007/s10620-009-0764-x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 464DM UT WOS:000267485400021 PM 19259815 ER PT J AU Aydin, C Aytan, N Mahon, MJ Tawfeek, HAW Kowall, NW Dedeoglu, A Bastepe, M AF Aydin, Cumhur Aytan, Nurgul Mahon, Mathew J. Tawfeek, Hesham A. W. Kowall, Neil W. Dedeoglu, Alpaslan Bastepe, Murat TI Extralarge XL alpha s (XXL alpha s), a Variant of Stimulatory G Protein alpha-Subunit (Gs alpha), Is a Distinct, Membrane-Anchored GNAS Product that Can Mimic Gs alpha SO ENDOCRINOLOGY LA English DT Article ID PROGRESSIVE OSSEOUS HETEROPLASIA; MCCUNE-ALBRIGHT-SYNDROME; ACTIVATING MUTATIONS; ADENYLYL-CYCLASE; HEREDITARY OSTEODYSTROPHY; HETEROTOPIC OSSIFICATION; HORMONE RESISTANCE; IMPRINTED LOCUS; GENE; METHYLATION AB GNAS gives rise to multiple imprinted gene products, including the alpha-subunit of the stimulatory G protein (Gs alpha) and its variant XL alpha s. Based on genomic sequence, the translation of XL alpha s begins from the middle of a long open reading frame, suggesting the existence of an N-terminally extended variant termed extralarge XL alpha s (XXL alpha s). Although XXL alpha s, like Gs alpha and XL alpha s, would be affected by most disease-causing GNAS mutations, its authenticity and biological significance remained unknown. Here we identified a mouse cDNA clone that comprises the entire open reading frame encoding XXL alpha s. Whereas XXL alpha s mRNA was readily detected in mouse heart by RT-PCR, it appeared virtually absent in insulinoma-derived INS-1 cells. By Northern blots and RT-PCR, XXL alpha s mRNA was detected primarily in the mouse brain, cerebellum, and spleen. Immunohistochemistry using a specific anti-XXL alpha s antibody demonstrated XXL alpha s protein in multiple brain areas, including dorsal hippocampus and cortex. In transfected cells, full-length human XXL alpha s was localized to the plasma membrane and mediated isoproterenol-and cholera toxin-stimulated cAMP accumulation. XXL alpha s-R844H, which bears a mutation analogous to that in the constitutively active Gs alpha mutant Gs alpha-R201H (gsp oncogene), displayed elevated basal signaling. However, unlike Gs alpha-R201H, which mostly remains in the cytoplasm, both XXL alpha s-R844H and a constitutively active XL alpha s mutant localized to the plasma membrane. Hence, XXL alpha s is a distinct GNAS product and can mimic Gs alpha,but the constitutively active XXL alpha s and Gs alpha mutants differ from each other regarding subcellular targeting. Our findings suggest that XXL alpha s deficiency or hyperactivity may contribute to the pathogenesis of diseases caused by GNAS mutations. (Endocrinology 150: 3567-3575, 2009) C1 [Aydin, Cumhur; Mahon, Mathew J.; Tawfeek, Hesham A. W.; Bastepe, Murat] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Aydin, Cumhur] Gulhane Mil Med Acad, Dept Endodont, Ctr Dent Sci, TR-06018 Ankara, Turkey. [Aytan, Nurgul; Kowall, Neil W.; Dedeoglu, Alpaslan] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Kowall, Neil W.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Aytan, Nurgul; Kowall, Neil W.; Dedeoglu, Alpaslan] Vet Affairs Boston Healthcare Syst, Res & Dev Serv, Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, 50 Blossom St,Thier 10, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Dedeoglu, Alpaslan/0000-0003-1156-0874 FU National Institute of Diabetes and Digestive and Kidney Diseases [R01DK073911]; Alzheimer's Disease Center [P30 AG13846]; Department of Veterans Affairs Merit Award; Gulhane Military Medical Academy; Turkish General Staff, Ankara, Turkey FX This work was supported by National Institutes of Health Grants R01DK073911 from the National Institute of Diabetes and Digestive and Kidney Diseases ( to M. B.); Alzheimer's Disease Center Grant P30 AG13846 ( to N.W.K.); and the Department of Veterans Affairs Merit Award ( to A. D.). C. A. received a research fellowship award from the Gulhane Military Medical Academy, Turkish General Staff, Ankara, Turkey. NR 57 TC 15 Z9 15 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2009 VL 150 IS 8 BP 3567 EP 3575 DI 10.1210/en.2009-0318 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 472UR UT WOS:000268158400018 PM 19423757 ER PT J AU Baca, CB Cheng, EM Spencer, SS Vassar, S Vickrey, BG AF Baca, Christine Bower Cheng, Eric M. Spencer, Susan S. Vassar, Stefanie Vickrey, Barbara G. CA Multictr Study Epilepsy Surg TI Racial differences in patient expectations prior to resective epilepsy surgery SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy surgery; Expectations; Race/ethnicity ID TEMPORAL-LOBE EPILEPSY; INTRACTABLE EPILEPSY; MULTICENTER AB We assessed the nature and frequency of preoperative expectations among patients with refractory epilepsy who were enrolled in a seven-center observational study of epilepsy surgery outcomes. At enrollment, patients responded to open-ended questions about expectations for surgical outcome. With the use of an iterative cutting-and-sorting technique, expectation themes were identified and rank-ordered. Associations of expectations with race/ethnicity were evaluated. Among 391 respondents, the two most frequently endorsed expectations (any rank order) were driving (62%) and job/school (43%). When only the most important (first-ranked) expectation was analyzed, driving (53%) and cognition (17%) were most frequently offered. Nonwhites endorsed job/school and cognition more frequently and driving less frequently than whites (all P <= 0.05), whether expectations of any order or only first-ranked expectations were included. Elucidating the reason for these differences can aid in the clinical decision-making process for resective surgery and potentially address disparities in its utilization. (C) 2009 Elsevier Inc. All rights reserved. C1 [Baca, Christine Bower] Univ Calif Los Angeles, Dept Neurol, Robert Wood Johnson Fdn, Clin Scholars Program, Los Angeles, CA 90024 USA. [Cheng, Eric M.; Vassar, Stefanie; Vickrey, Barbara G.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. [Spencer, Susan S.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP Baca, CB (reprint author), Univ Calif Los Angeles, Dept Neurol, Robert Wood Johnson Fdn, Clin Scholars Program, 911 Braxton Ave,3rd Floor, Los Angeles, CA 90024 USA. EM cbower@mednet.ucla.edu FU NINDS [RO1 NS 32375, K23NS058571]; Robert Wood Johnson Foundation Clinical Scholars Program [59982] FX This work was supported by RO1 NS 32375 NINDS. Dr. Bowel, Baca was supported by the Robert Wood Johnson Foundation Clinical Scholars Program (Grant 59982). Dr. Cheng was supported by a Career Development Award from NINDS (K23NS058571). NR 11 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD AUG PY 2009 VL 15 IS 4 BP 452 EP 455 DI 10.1016/j.yebeh.2009.05.010 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 484GV UT WOS:000269033000010 PM 19541545 ER PT J AU Tanaka, N Cole, AJ von Pechmann, D Wakeman, DG Hamalainen, MS Liu, HS Madsen, JR Bourgeois, BF Stufflebeam, SM AF Tanaka, Naoaki Cole, Andrew J. von Pechmann, Deidre Wakeman, Daniel G. Hamalainen, Matti S. Liu, Hesheng Madsen, Joseph R. Bourgeois, Blaise F. Stufflebeam, Steven M. TI Dynamic statistical parametric mapping for analyzing ictal magnetoencephalographic spikes in patients with intractable frontal lobe epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Magnetoencephalography; Epilepsy; Dynamic statistical parametric mapping; Ictal ID SURFACE-BASED ANALYSIS; PRESURGICAL EVALUATION; LOCALIZATION ACCURACY; CORTICAL ACTIVITY; PARTIAL SEIZURES; MEG; EEG; RECONSTRUCTION; MODELS; SINGLE AB The purpose of this study is to assess the clinical value of spatiotemporal source analysis for analyzing ictal magnetoencephalography (MEG). Ictal MEG and simultaneous scalp EEG was recorded in five patients with medically intractable frontal lobe epilepsy. Dynamic statistical parametric maps (dSPMs) were calculated at the peak of early ictal spikes for the purpose of estimating the spatiotemporal cortical source distribution. DSPM solutions were mapped onto a cortical surface, which was derived from each patient's MRI. Equivalent current dipoles (ECDs) were calculated using a single-dipole model for comparison with dSPMs. In all patients, dSPMs tended to have a localized activation, consistent with the clinically determined ictal onset zone, whereas most ECDs were considered to be inappropriate sources according to their goodness-of-fit values. Analyzing ictal MEG spikes by using dSPMs may provide useful information in presurgical evaluation of epilepsy. (C) 2009 Elsevier B.V. All rights reserved. C1 [Tanaka, Naoaki; von Pechmann, Deidre; Wakeman, Daniel G.; Hamalainen, Matti S.; Liu, Hesheng; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Cole, Andrew J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Madsen, Joseph R.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Bourgeois, Blaise F.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Tanaka, N (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM naoro@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; OI Wakeman, Daniel/0000-0002-3904-9384; Liu, Hesheng/0000-0002-7233-1509 FU National Institutes of Health [P41RR14075, RO1NS037462-07]; Mental Illness and Neuroscience Discovery Institute; NARSAD Young Investigators Award; Japan Epilepsy Research Foundation FX This work was supported by National Institutes of Health (P41RR14075, RO1NS037462-07), Mental Illness and Neuroscience Discovery Institute, NARSAD Young Investigators Award and Japan Epilepsy Research Foundation. NR 28 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD AUG PY 2009 VL 85 IS 2-3 BP 279 EP 286 DI 10.1016/j.eplepsyres.2009.03.023 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 485ET UT WOS:000269104500018 PM 19394198 ER PT J AU Hammerness, P Doyle, R Kotarski, M Georgiopoulos, A Joshi, G Zeitlin, S Biederman, J AF Hammerness, Paul Doyle, Robert Kotarski, Meghan Georgiopoulos, Anna Joshi, Gagan Zeitlin, Sarah Biederman, Joseph TI Atomoxetine in children with attention-deficit hyperactivity disorder with prior stimulant therapy: a prospective open-label study SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE ADHD; Atomoxetine; Prior stimulant ID DEFICIT/HYPERACTIVITY DISORDER; ADOLESCENTS; METHYLPHENIDATE; ADHD AB The objective of the study is to evaluate the effectiveness and tolerability of atomoxetine in youth, ages 6-17 years with ADHD, who had a prior trial of stimulant treatment. This was a 6-week prospective open-label study of atomoxetine, dosage up to 1.4 mg/kg per day in 34 children and adolescents with DSM-IV ADHD. Primary measures of response included the ADHD Rating Scale (ADHD RS) and the Clinical Global Impression (CGI) Scale. Analyses were intention-to-treat. The treatment with atomoxetine was associated with statistical and clinical significant reduction in clinician rated ADHD RS symptoms, compared with baseline. Statistical significant improvement was attained by the second week of treatment. Fifty-six percent (N = 18) met criteria for our a priori definition of response; much or very much improved on the CGI plus more than 30% reduction in ADHD RS symptoms. In conclusion, atomoxetine was generally well tolerated; 85% of subjects completed the trial. Atomoxetine was effective and well tolerated in a 6-week open study of ADHD youth with a prior history of stimulant treatment. C1 [Doyle, Robert; Kotarski, Meghan; Georgiopoulos, Anna; Joshi, Gagan; Zeitlin, Sarah; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Hammerness, Paul; Doyle, Robert; Kotarski, Meghan; Georgiopoulos, Anna; Joshi, Gagan; Zeitlin, Sarah; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Hammerness, P (reprint author), 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM phammerness@partners.org FU Eli Lilly and Company FX This study was an investigator initiated project funded by Eli Lilly and Company (with principal investigator Joseph Biederman, MD). Also, special thanks to the Pediatric Psychopharmacology Council Fund for its contributions. NR 17 TC 3 Z9 3 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD AUG PY 2009 VL 18 IS 8 BP 493 EP 498 DI 10.1007/s00787-009-0017-8 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 477IF UT WOS:000268512000004 PM 19377865 ER PT J AU Mattila, ML Jussila, K Kuusikko, S Kielinen, M Linna, SL Ebeling, H Bloigu, R Joskitt, L Pauls, D Moilanen, I AF Mattila, Marja-Leena Jussila, Katja Kuusikko, Sanna Kielinen, Marko Linna, Sirkka-Liisa Ebeling, Hanna Bloigu, Risto Joskitt, Leena Pauls, David Moilanen, Irma TI When does the Autism Spectrum Screening Questionnaire (ASSQ) predict autism spectrum disorders in primary school-aged children? SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Asperger syndrome; Pervasive developmental disorders; Autism spectrum disorders; Autism Spectrum Screening Questionnaire (ASSQ); Screening ID PERVASIVE DEVELOPMENTAL DISORDERS; CAST CHILDHOOD ASPERGER; TOTAL POPULATION; DIAGNOSTIC INTERVIEW; FUNCTIONING AUTISM; INDIVIDUALS; CRITERIA AB The aims of this study were, firstly, to study the association between parents' and teachers' ratings for the Finnish version of the Autism Spectrum Screening Questionnaire (ASSQ), secondly, to find out whether the original cut-off scores of the ASSQ identify primary school-aged children with Asperger syndrome (AS) or autism by using the Finnish ASSQ, and thirdly, to evaluate the validity of the ASSQ. Parents and/or teachers of higher-functioning (full-scale intelligence quotient a parts per thousand yen 50) 8-year-old total population school children (n = 4,408) and 7-12-year-old outpatients with AS/autism (n = 47) completed the Finnish version of the ASSQ. Agreement between informants was slight. In the whole total population, low positive correlation was found between parents' and teachers' ratings, while in the sample of high-scoring children the correlation turned out to be negative. A cut-off of 30 for parents' and teacher's summed score and 22 for teachers' single score is recommended. A valid cut-off for parents' single score could not been estimated. The clinicians are reminded that the ASSQ is a screening instrument, not a diagnosing instrument. The importance of using both parents' and teachers' ratings for screening in clinical settings is underlined. C1 [Mattila, Marja-Leena; Jussila, Katja; Kuusikko, Sanna; Ebeling, Hanna; Joskitt, Leena; Moilanen, Irma] Univ Oulu, Univ Hosp Oulu, Clin Child Psychiat, Oulu 90029, Finland. [Kielinen, Marko] Univ Oulu, Dept Educ Sci & Teacher Educ, Oulu 90014, Finland. [Linna, Sirkka-Liisa] Univ Oulu, Dept Publ Hlth & Gen Practice, Oulu 90014, Finland. [Bloigu, Risto] Univ Oulu, Med Informat Grp, Oulu 90014, Finland. [Pauls, David] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit,Med Sch, Charlestown, MA USA. RP Mattila, ML (reprint author), Univ Oulu, Univ Hosp Oulu, Clin Child Psychiat, POB 26, Oulu 90029, Finland. EM marja-leena.mattila@fimnet.fi; katja.jussila@oulu.fi; sanna.kuusikko@gmail.com; marko.kielinen@oulu.fi; sirkkaliisa.linna@oulu.fi; hanna.ebeling@oulu.fi; risto.bloigu@oulu.fi; leena.joskitt@oulu.fi; dpauls@pngu.mgh.harvard.edu; irma.moilanen@oulu.fi FU Finland's Slot Machine Association; Child Psychiatric Research Foundation, Finland; Rinnekoti Research Foundation, Espoo, Finland; Alma and K. A. Snellman Foundation, Oulu, Finland; Child Psychiatric Research Foundation, Oulu Area, Finland; Oulu Medical Research Foundation, Oulu, Finland; National Alliance for Autism Research (NAAR) FX We want to thank the children and their parents, the teachers and the entire staff of the schools for participating in this study. We thank chief psychologist Terttu Tapio and clinical psychologist Kati Wedman for their comments and help with this study. The Graduate School of Circumpolar Wellbeing, Health and Adaptation is acknowledged for their support. This study received financial support from Finland's Slot Machine Association awarded to the Finnish Association for Autism and Asperger's Syndrome and from the Child Psychiatric Research Foundation, Finland, awarded to the Eija and Veikko Lesonen Foundation, Oulu, Finland. Dr. Marja-Leena Mattila received research grants from the Rinnekoti Research Foundation, Espoo, Finland, the Alma and K. A. Snellman Foundation, Oulu, Finland, the Child Psychiatric Research Foundation, Finland, the Child Psychiatric Research Foundation, Oulu Area, Finland, and the Oulu Medical Research Foundation, Oulu, Finland. Psychologist Katja Jussila received a research grant from the Alma and K. A. Snellman Foundation, Oulu, Finland, and psychologist Sanna Kuusikko from the Alma and K. A. Snellman Foundation Oulu, Finland, and the Child Psychiatric Research Foundation, Finland. This particular study was also financially supported by a National Alliance for Autism Research (NAAR) grant awarded to professor David Pauls. NR 27 TC 17 Z9 17 U1 3 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 EI 1435-165X J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD AUG PY 2009 VL 18 IS 8 BP 499 EP 509 DI 10.1007/s00787-009-0044-5 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 477IF UT WOS:000268512000005 PM 19597920 ER PT J AU Shah, RV Chen-Tournoux, AA Picard, MH Januzzi, JL AF Shah, Ravi V. Chen-Tournoux, Annabel A. Picard, Michael H. Januzzi, James L. TI Association between troponin T and impaired left ventricular relaxation in patients with acute decompensated heart failure with preserved systolic function SO EUROPEAN JOURNAL OF ECHOCARDIOGRAPHY LA English DT Article DE Heart failure; Diastolic dysfunction; Biomarker; Echocardiography ID CARDIAC TROPONIN; DIASTOLIC DYSFUNCTION; MORTALITY; STRATIFICATION; PREVALENCE AB To examine relationships between cardiac troponin T (cTnT) and parameters of left ventricular (LV) structure and function in patients with acute destabilized heart failure (HF) with preserved LV ejection fraction. In 44 patients with acute heart failure (HF) with preserved left ventricular (LV) ejection fraction, parameters of LV structure and function were assessed via comprehensive two-dimensional Doppler echocardiography. There was no correlation between cTnT and LV wall thickness, left atrial volume index, or transmitral E wave velocity or deceleration time. There were associations between cTnT and LV end-diastolic dimension (r = -0.34, P = 0.02) and LV mass index (r = 0.32; P = .04). A lower tissue Doppler Ea wave peak velocity was associated with higher cTnT concentrations (r = -0.90, P < 0.001). In multivariate analyses, only LV end-diastolic dimension (t = 2.2; P = 0.04), LV mass index (t = 2.3; P = .03), and tissue Doppler Ea wave peak velocity (t = -4.7; P < .001) emerged as significant predictors of cTnT. In patients with HF with preserved LV ejection fraction, cTnT is strongly associated with the extent of LV relaxation abnormalities and LV mass. C1 [Chen-Tournoux, Annabel A.; Picard, Michael H.; Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, 55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org OI Picard, Michael/0000-0002-9264-3243 FU National Heart, Lung, and Blood Institute Heart Failure Research Network; Balson Scholar Fund FX R. V. S. is supported by a grant from the National Heart, Lung, and Blood Institute Heart Failure Research Network (Boston, MA, USA). J. L. J. is supported in part by the Balson Scholar Fund (Boston, MA, USA). NR 21 TC 14 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1525-2167 J9 EUR J ECHOCARDIOGR JI Eur. J. Echocardiogr. PD AUG PY 2009 VL 10 IS 6 BP 765 EP 768 DI 10.1093/ejechocard/jep063 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 484BJ UT WOS:000269017800010 PM 19483204 ER PT J AU Beer, AL Watanabe, T Ni, R Sasaki, Y Andersen, GJ AF Beer, Anton L. Watanabe, Takeo Ni, Rui Sasaki, Yuka Andersen, George J. TI 3D surface perception from motion involves a temporal-parietal network SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE functional MRI; humans; perception; temporal lobe; visual ID STRUCTURE-FROM-MOTION; HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; PRIMARY VISUAL-CORTEX; HUMAN BRAIN; OPTIC FLOW; GEOMETRICALLY ACCURATE; NEURAL RESPONSES; EXTRACTING 3D; AREA MT AB Previous research has suggested that three-dimensional (3D) structure-from-motion (SFM) perception in humans involves several motion-sensitive occipital and parietal brain areas. By contrast, SFM perception in nonhuman primates seems to involve the temporal lobe including areas MT, MST and FST. The present functional magnetic resonance imaging study compared several motion-sensitive regions of interest including the superior temporal sulcus (STS) while human observers viewed horizontally moving dots that defined either a 3D corrugated surface or a 3D random volume. Low-level stimulus features such as dot density and velocity vectors as well as attention were tightly controlled. Consistent with previous research we found that 3D corrugated surfaces elicited stronger responses than random motion in occipital and parietal brain areas including area V3A, the ventral and dorsal intraparietal sulcus, the lateral occipital sulcus and the fusiform gyrus. Additionally, 3D corrugated surfaces elicited stronger activity in area MT and the STS but not in area MST. Brain activity in the STS but not in area MT correlated with interindividual differences in 3D surface perception. Our findings suggest that area MT is involved in the analysis of optic flow patterns such as speed gradients and that the STS in humans plays a greater role in the analysis of 3D SFM than previously thought. C1 [Beer, Anton L.] Univ Regensburg, Inst Psychol, D-93053 Regensburg, Germany. [Beer, Anton L.; Watanabe, Takeo] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Ni, Rui; Andersen, George J.] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. [Sasaki, Yuka] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. RP Beer, AL (reprint author), Univ Regensburg, Inst Psychol, Univ Str 31, D-93053 Regensburg, Germany. EM anton.beer@psychologie.uni-r.de FU National Science Foundation [BCS-0345746]; National Institutes of Health [NIH-NEI R01EY015980-04A2] FX This work was supported by grant BCS-0345746 of the National Science Foundation and grant NIH-NEI R01EY015980-04A2 of the National Institutes of Health. NR 48 TC 27 Z9 27 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD AUG PY 2009 VL 30 IS 4 BP 703 EP 713 DI 10.1111/j.1460-9568.2009.06857.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 487HV UT WOS:000269263500017 PM 19674088 ER PT J AU Muellner, A Glazer, GM Reiser, MF Bradley, WG Krestin, GP Hricak, H Thrall, JH AF Muellner, Ada Glazer, Gary M. Reiser, Maximilian F. Bradley, William G., Jr. Krestin, Gabriel P. Hricak, Hedvig Thrall, James H. TI Advancing radiology through informed leadership: summary of the proceedings of the Seventh Biannual Symposium of the International Society for Strategic Studies in Radiology ((ISR)-R-3), 23-25 August 2007 SO EUROPEAN RADIOLOGY LA English DT Article DE Interventional radiology; Molecular imaging; Device approval processes; Drug approval processes; Health-care quality; Radiology; Leadership ID FOCUSED ULTRASOUND SURGERY; INTERVENTIONAL RADIOLOGY; COST-EFFECTIVENESS; CHANGING RELATIONSHIPS; UTERINE FIBROIDS; PROSTATE BIOPSY; UNITED-STATES; PART II; THERAPY; TELERADIOLOGY AB The International Society for Strategic Studies in Radiology ((ISR)-R-3) brings together thought leaders from academia and industry from around the world to share ideas, points of view and new knowledge. This article summarizes the main concepts presented at the 2007 (ISR)-R-3 symposium, providing a window onto trends shaping the future of radiology. Topics addressed include new opportunities and challenges in the field of interventional radiology; emerging techniques for evaluating and improving quality and safety in radiology; and factors impeding progress in molecular imaging and nanotechnology and possible ways to overcome them. Regulatory hurdles to technical innovation and drug development are also discussed more broadly, along with proposals for addressing regulators' concerns and streamlining the regulatory process. C1 [Muellner, Ada; Hricak, Hedvig] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Glazer, Gary M.] Stanford Univ, Dept Radiol, Sch Med, Palo Alto, CA 94304 USA. [Reiser, Maximilian F.] Univ Munich, Dept Clin Radiol, D-80336 Munich, Germany. [Bradley, William G., Jr.] Univ Calif San Diego, Dept Radiol, Med Ctr, San Diego, CA 92103 USA. [Krestin, Gabriel P.] Erasmus Univ, Dept Radiol, Med Ctr, NL-3000 CA Rotterdam, Netherlands. [Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hricak, H (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave,Room C-278, New York, NY 10065 USA. EM hricakh@mskcc.org OI Hricak, Hedvig/0000-0003-2240-9694 NR 61 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD AUG PY 2009 VL 19 IS 8 BP 1827 EP 1836 DI 10.1007/s00330-009-1370-1 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 466RR UT WOS:000267680700001 PM 19277668 ER PT J AU Chopra, MP Landes, RD Gatchalian, KM Jackson, LC Buchhalter, AR Stitzer, ML Marsch, LA Bickel, WK AF Chopra, Mohit P. Landes, Reid D. Gatchalian, Kirstin M. Jackson, Lisa C. Buchhalter, August R. Stitzer, Maxine L. Marsch, Lisa A. Bickel, Warren K. TI Buprenorphine Medication Versus Voucher Contingencies in Promoting Abstinence From Opioids and Cocaine SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE buprenorphine; cocaine; community reinforcement approach; contingency management; opiate or opioid dependence ID SUBSTANCE USE DISORDERS; METHADONE-MAINTENANCE; BEHAVIORAL TREATMENT; RANDOMIZED-TRIAL; MANAGEMENT; ADDICTION; REINFORCEMENT; DEPENDENCE; THERAPY; ABUSE AB During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030). while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies. C1 [Bickel, Warren K.] Univ Arkansas Med Sci, Dept Psychiat, Addict Res Ctr, Wilbur Mills Chair Alcoholism & Drug Abuse Preven, Little Rock, AR 72205 USA. [Chopra, Mohit P.] VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. [Landes, Reid D.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Stitzer, Maxine L.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Bickel, WK (reprint author), Univ Arkansas Med Sci, Dept Psychiat, Addict Res Ctr, Wilbur Mills Chair Alcoholism & Drug Abuse Preven, 4301 W Markham St,843, Little Rock, AR 72205 USA. EM WBickel@uams.edu RI Chopra, Mohit P/F-7250-2013 OI Chopra, Mohit P/0000-0002-9208-7224 FU National Institute on Drug Abuse (NIDA), Bethesda, MD [7R01 DA012997-06] FX The study was sponsored by Grant 7R01 DA012997-06 from the National Institute on Drug Abuse (NIDA), Bethesda, MD. The results from this study were presented in part at the 70th Annual meeting of the College on Problems of Drug Dependence (CPDD), in June 2007, San Juan, Puerto Rico. Mohit P Chopra, MD was employed by the UAMS at the time of the study. NR 37 TC 8 Z9 9 U1 3 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD AUG PY 2009 VL 17 IS 4 BP 226 EP 236 DI 10.1037/a0016597 PG 11 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 480TZ UT WOS:000268761000003 PM 19653788 ER PT J AU Fabiani, C Barabino, S Rashid, S Dana, MR AF Fabiani, Claudia Barabino, Stefano Rashid, Saadia Dana, M. Reza TI Corneal epithelial proliferation and thickness in a mouse model of dry eye SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE dry eye; animal model; corneal epithelium; cell proliferation ID PRIMARY SJOGRENS-SYNDROME; FLOW-CYTOMETRIC ANALYSIS; OCULAR SURFACE; KERATOCONJUNCTIVITIS SICCA; CONJUNCTIVAL EPITHELIUM; KERATOCYTE APOPTOSIS; INFLAMMATORY MARKERS; INTERLEUKIN-6 LEVELS; TISSUE ORGANIZATION; TEAR FLUID AB Although several studies have previously focused on the conjunctival epithelial response to surface dryness, little is known about the effect of a dry environment on corneal epithelium, which is the most clinically significant tissue affected in dry eye. The aim of this study was to quantitatively evaluate the effect of desiccating stress on the number of proliferating corneal epithelial cells and corneal epithelial thickness in mice placed in a controlled-environment chamber (CEC) that induces dry eye. Corneal epithelial cell proliferation and thickness were studied in 8- to 12-week-old female BALB/c mice placed in the CEC (temperature: 22.3 +/- 0.7 degrees C; relative humidity: 22.5 +/- 4.5%; airflow: 15 L/min) for 7 days and compared to a control group of mice with no dry eye. Actively proliferating cells were identified by immunofluorescence using a FITC-conjugated antibody against the Ki-67 protein, a cell proliferation marker expressed during active phases of the cell cycle. To detect the spatial distribution of proliferative cells, Ki-67(+) cells were counted in three areas of the epithelium: center, periphery, and limbus. Corneal epithelial thickness was evaluated in the central cornea after staining with hematoxylin-eosin. Results from each experimental group were compared using the Mann-Whitney test. The number of Ki-67(+) cells observed in the corneal epithelium of mice exposed to the CEC was significantly higher in each area (center: 32.1 +/- 1.1; periphery: 94.2 +/- 5.3; limbus: 4.0 +/- 1.5) than in the control group (center: 13.2 +/- 1.0, p = 0.02: periphery: 42.9 +/- 2.3, p = 0.02; limbus: 0.0, p = 0.01). In mice subjected to desiccating stress, a significant number of Ki-67(+) positive cells were detected in the basal and suprabasal cell layers (central area 46%; periphery 30.8%: limbus 0%), whereas in the control group the cells were exclusively distributed through the basal cell layer. Ki-67(+) cells were not found in the corneal stroma or endothelium in any group. The corneal epithelium was found to be significantly thicker in dry eye mice (54.94 +/- 6.09 mu m) as compared to the controls (43.9 +/- 6.23 mu m, p < 0.0001) by a mean of 25%. These results demonstrate that desiccating stress increases corneal epithelial turnover and thickness, similar to what is observed in other chronic inflammatory states of other epithelialized surfaces. The CEC can facilitate the study of the regulation of epithelial cell function and turnover at the molecular and cellular levels under desiccating stress conditions. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Dana, M. Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Cornea Serv, Boston, MA 02114 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu OI Fabiani, Claudia/0000-0003-4515-7741 FU NEI NIH HHS [R01 EY020889] NR 35 TC 29 Z9 34 U1 1 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 2009 VL 89 IS 2 BP 166 EP 171 DI 10.1016/j.exer.2009.03.003 PG 6 WC Ophthalmology SC Ophthalmology GA 480BQ UT WOS:000268707200007 PM 19298814 ER PT J AU Vosler, PS Sun, DD Wang, SP Gao, YQ Kintner, DB Signore, AP Cao, GD Chen, J AF Vosler, Peter S. Sun, Dandan Wang, Suping Gao, Yanqin Kintner, Douglas B. Signore, Armando P. Cao, Guodong Chen, Jun TI Calcium dysregulation induces apoptosis-inducing factor release: Cross-talk between PARP-1-and calpain- signaling pathways SO EXPERIMENTAL NEUROLOGY LA English DT Article DE NMDA toxicity; Calpain; PARP-1; Apoptosis-inducing factor; Ischemia; Mitochondria; Calcium homeostasis ID MEDIATED PROGRAMMED NECROSIS; POLY(ADP-RIBOSE) PAR POLYMER; TRANSIENT CEREBRAL-ISCHEMIA; OXYGEN-GLUCOSE DEPRIVATION; NEURONAL CELL-DEATH; NITRIC-OXIDE; CORTICAL CULTURES; MU-CALPAIN; GLUTAMATE; ACTIVATION AB Recent discoveries show that caspase-independent cell death pathways are a pervasive mechanism in neurodegenerative diseases, and apoprosis-inducing factor (AIF) is an important effector of this mode of neuronal death. There are currently two known mechanisms underlying AIF release following excitotoxic stress, PARP-1 and calpain. To test whether there is an interaction between PARP-1 and calpain in triggering AIF release, we used the NMDA toxicity model in rat primary cortical neurons. Exposure to NMIDA resulted in AIF truncation and nuclear translocation, and shRNA-mediated knockdown of AIF resulted in neuroprotection. Both calpain and PARM are involved with AIF processing as AIF truncation, nuclear translocation and neuronal death were attenuated by calpain inhibition using adeno-associated virus-mediated overexpression of the endogenous calpain inhibitor, calpastatin, or treatment with the PARP-1 inhibitor 3-ABA. Activation of PARP-1 is necessary for calpain activation as PARP-1 inhibition blocked mitochondrial calpain activation. Finally, NMDA toxicity induces mitochondrial Ca(2+) dysregulation in a PARP-1 dependent manner. Thus, PARP-1 and mitochondrial calpain activation are linked via PARP-1-induced alterations in mitochondrial Ca(2+) homeostasis. Collectively, these findings link the two seemingly independent mechanisms triggering AIF-induced neuronal death. (C) 2009 Elsevier Inc. All rights reserved. C1 [Vosler, Peter S.; Wang, Suping; Signore, Armando P.; Cao, Guodong; Chen, Jun] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15213 USA. [Vosler, Peter S.; Wang, Suping; Signore, Armando P.; Cao, Guodong; Chen, Jun] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Sch Med, Pittsburgh, PA 15213 USA. [Gao, Yanqin; Cao, Guodong; Chen, Jun] Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Sun, Dandan; Kintner, Douglas B.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol Surg, Madison, WI 53792 USA. [Wang, Suping; Cao, Guodong; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst Pittsburgh, Geriatr Res, Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Chen, J (reprint author), Univ Pittsburgh, Dept Neurol, 507 S Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15261 USA. EM chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU National Institutes of Health/NINDS [NS43802, NS45048, NS36736, NS 56118, NS38118, NS48216]; NIH NRSA [1F30NS057886]; Chinese Natural Science Foundation [30470592, 30670642] FX This project was supported by the National Institutes of Health/NINDS grants NS43802, NS45048, NS36736, and NS 56118 (to J.C.) and NS38118 and NS48216 (to D.S.), and VA Merit Review grant (to J.C.). P. S.V. is supported by an NIH NRSA pre-doctoral fellowship (1F30NS057886). YG was supported by the Chinese Natural Science Foundation (grants 30470592 and 30670642). NR 36 TC 47 Z9 52 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 2009 VL 218 IS 2 BP 213 EP 220 DI 10.1016/j.expneurol.2009.04.032 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 472GE UT WOS:000268117400006 PM 19427306 ER PT J AU Hisatomi, T Ishibashi, T Miller, JW Kroemer, G AF Hisatomi, Toshio Ishibashi, Tatsuro Miller, Joan W. Kroemer, Guido TI Pharmacological inhibition of mitochondrial membrane permeabilization for neuroprotection SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Apoptosis; Mitochondria membrane permeabilization; Caspase; AIF; Apaf-1; Cytochrome c; Retina ID APOPTOSIS-INDUCING FACTOR; HIV PROTEASE INHIBITORS; ISCHEMIC BRAIN-INJURY; ADENINE-NUCLEOTIDE TRANSLOCATOR; NEURONAL CELL-DEATH; IN-VIVO; NEUROTROPHIC FACTOR; INNER MEMBRANE; 1-METHYL-4-PHENYLPYRIDINIUM TOXICITY; PHOTORECEPTOR APOPTOSIS AB Recent data have provided important clues about the molecular mechanisms underlying certain neurodegenerative diseases. Most cell death in vertebrates proceeds via the mitochondrial pathway of apoptosis. Mitochondria contain proapoptotic factors such as cytochrome c and AIF in their intermembrane space. Furthermore, mitochondrial membrane permeabilization (MMP) is a critical event during apoptosis, representing the "point of no return" of the lethal process. Modern medicine is developing an increasing number of drugs for neurodegenerative disease, but no neuroprotective treatment has yet been established. While current treatments temporarily alleviate symptoms, they do not halt disease progression. This paper briefly reviews the pharmacological inhibition of mitochondrial membrane permeabilization for neuroprotection. (C) 2009 Elsevier Inc. All rights reserved. C1 [Hisatomi, Toshio] Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Higashi Ku, Fukuoka 8128582, Japan. [Hisatomi, Toshio; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, Boston, MA USA. [Kroemer, Guido] INSERM, U848, Villejuif, France. [Kroemer, Guido] Inst Gustave Roussy, Villejuif, France. [Kroemer, Guido] Univ Paris 11, Villejuif, France. RP Hisatomi, T (reprint author), Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM hisatomi@med.kyushu-u.ac.jp; kroemer@igr.fr RI Kroemer, Guido/B-4263-2013; OI Hisatomi, Toshio/0000-0003-2552-9595 FU Ligue Nationale contre le Cancer (Equipe labellisee); European Commission; Canceropole Ile-de-France; Fondation de France; Fondation pour la Recherche Medicale FX GK is supported by the Ligue Nationale contre le Cancer (Equipe labellisee), European Commission (Active p53, Apo-Sys, RIGHT, TransDeath, ChemoRes, DeathTrain), Canceropole Ile-de-France, Fondation de France, and Fondation pour la Recherche Medicale. NR 81 TC 13 Z9 15 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 2009 VL 218 IS 2 BP 347 EP 352 DI 10.1016/j.expneurol.2009.03.007 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 472GE UT WOS:000268117400021 PM 19303007 ER PT J AU Lima, XT Abuabara, K Kimball, AB Lima, HC AF Lima, Xinaida Taligare Abuabara, Katrina Kimball, Alexandra Boer Lima, Hermenio Cavalcante TI Briakinumab SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Article DE ABT-874; biologics; IL-12; IL-23; psoriasis; therapy ID INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY; FULLY HUMAN; PSORIATIC-ARTHRITIS; DOUBLE-BLIND; EFFICACY; SAFETY; ABT-874; TRIAL; USTEKINUMAB; SALMONELLA AB Background: Psoriasis is a chronic, autoimmune, T-cell mediated, inflammatory disease. An improved understanding of the pathogenesis of the autoimmune response has led to the development of targeted biologic therapies. Briakinumab is a human monocolonal antibody that blocks the activity of the cytokines IL-12 and IL-23. Immune dysregulation has been implicated in multiple inflammatory disorders and briakinumab has been investigated for the treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. Objectives: This review focuses on briakinumab and its use in chronic plaque-type psoriasis. Methods: A literature review was performed, searching Medline and the clinicaltrials.gov database for all articles with the keywords ABT-874, IL-12/IL-23 and psoriasis. Conclusions: Although limited by small sample sizes, length of follow-up, and a lack of direct comparisons with other psoriasis treatments, initial data regarding the safety and efficacy of briakinumab for the treatment of psoriasis is promising. Ongoing Phase III trials may provide additional information regarding the relative efficacy and safety of briakinumab. C1 [Lima, Xinaida Taligare; Kimball, Alexandra Boer; Lima, Hermenio Cavalcante] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Abuabara, Katrina] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Lima, XT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM xlima@partners.org RI Lima, Hermenio/G-5379-2010 OI Lima, Hermenio/0000-0003-0950-3731 FU Massachusetts General Hospital; Harvard Medical School; Centocor FX The paper was supported by the Massachusetts General Hospital and the Department of Dermatology, Harvard Medical School. XT Lima has a fellowship partially sponsored by Centocor. AB Kimball is a consultant and investigator for Abbott (the originator of briakinumab) and Centocor. K Abuabara has no conflicts of interest. NR 32 TC 24 Z9 25 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD AUG PY 2009 VL 9 IS 8 BP 1107 EP 1113 DI 10.1517/14712590903092188 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 479LF UT WOS:000268660100014 PM 19569977 ER PT J AU Richardson, P Linden, E Revta, C Ho, V AF Richardson, Paul Linden, Erica Revta, Carolyn Ho, Vincent TI Use of defibrotide in the treatment and prevention of veno-occlusive disease SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review DE defibrotide; SCT; sinusoidal obstruction syndrome; veno occlusive disease ID BONE-MARROW-TRANSPLANTATION; STEM-CELL-TRANSPLANTATION; TISSUE-PLASMINOGEN ACTIVATOR; VENO-OCCLUSIVE DISEASE; HIGH-DOSE CHEMOTHERAPY; POLYDEOXYRIBONUCLEOTIDE-DERIVED DRUG; GEMTUZUMAB OZOGAMICIN EXPOSURE; GLUTATHIONE-S-TRANSFERASE; MESENTERIC VASCULAR BED; TOTAL-BODY IRRADIATION AB Hepatic veno-occlusive disease (VOD) is one of the most important complication, of high-dose chemotherapy and stem cell transplantation VOD is a clinical syndrome characterized by jaundice, hepatic enlargement and fluid retention typically SE en by day +30 after transplantation Severe VOD is complicated by multiorgan failure and a high mortality rate approaching 100% Defibrotide (DF) is a novel agent with both antithrombotic and fibrinolytic properties that has emerged as an effective therapy for severe VOD In Phase II studies treatment of severe VOD has resulted in complete responses of 30-60% and survival past day 100 ranging between 32-50% A Phase III historically controlled study of DF for treatment of severe VOD has recently been completed and results are awaited with interest In addition DF may be effective prophylaxis for VOD in high-risk patients This review will focus on a summary of the pharmacology of DF and the clinical evidence for its use in VOD. C1 [Richardson, Paul; Linden, Erica; Revta, Carolyn; Ho, Vincent] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, P (reprint author), Dana Farber Canc Inst, Dana 1B58 44 Binney St, Boston, MA 02115 USA. NR 125 TC 7 Z9 7 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD AUG PY 2009 VL 2 IS 4 BP 365 EP 376 DI 10.1586/ehm.09.30 PG 12 WC Hematology SC Hematology GA 687TP UT WOS:000284801100009 PM 21082942 ER PT J AU Kieval, JZ Walsh, M Legutko, PA Daly, MK AF Kieval, J. Z. Walsh, M. Legutko, P. A. Daly, M. K. TI Efficacy of portable X-ray in identifying retained suture needles in ophthalmologic cases SO EYE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 06-10, 2007 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol DE radiograph; ocular foreign body; screening procedure ID INTRAOCULAR FOREIGN-BODIES; PLAIN FILM; ULTRASOUND; RADIOGRAPHY; TRAUMA; ORBIT; EYE; CT AB Aims To evaluate the role and efficacy of portable X-ray in reliably identifying retained suture needles in ophthalmologic surgical cases. Methods Ophthalmologic 10-0 nylon suture needles were placed into 10 of 20 porcine eyes positioned within the orbit of a human skull. Portable, plain film radiographs were taken of all eyes with a C-arm fluoroscopy machine. The films were reviewed by six ophthalmologists and six radiologists who were blinded to the presence or absence of needles, as well as the number of needles used in the protocol. The sensitivity and specificity of identifying retained suture needles by plain film radiographs were then analysed based on the results of the physicians' interpretations of the films. Results The overall sensitivity and specificity for physicians reviewing radiographs with suspected intraoperative suture needles were 54 and 77%, respectively. When looking separately at radiologists reviewing the films, the sensitivity was 57% and the specificity was 87%. Ophthalmologists reviewing the films identified retained needles less reliably with a sensitivity of 51% and a specificity of 67%. Conclusions Significant controversy exists regarding the reliability and utility of plain film radiography in identifying intraocular foreign bodies. This study demonstrates that the use of plain film radiographs to rule-out the presence of an intraocular surgical needle is neither a sensitive nor specific imaging modality. Eye ( 2009) 23, 1731-1734; doi: 10.1038/eye.2008.320; published online 17 October 2008 C1 [Kieval, J. Z.; Daly, M. K.] VA Boston Healthcare Syst, Dept Ophthalmol, Boston, MA 02130 USA. [Kieval, J. Z.; Daly, M. K.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Walsh, M.] VA Boston Healthcare Syst, Dept Radiol, Boston, MA 02130 USA. [Legutko, P. A.] Semphonic, Novato, CA USA. RP Daly, MK (reprint author), VA Boston Healthcare Syst, Dept Ophthalmol, 150 S Huntington Ave, Boston, MA 02130 USA. EM Mary.Daly2@va.gov NR 11 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD AUG PY 2009 VL 23 IS 8 BP 1731 EP 1734 DI 10.1038/eye.2008.320 PG 4 WC Ophthalmology SC Ophthalmology GA 482VB UT WOS:000268915900019 PM 18927595 ER PT J AU Zhang, HM Astrof, NS Liu, JH Wang, JH Shimaoka, M AF Zhang, Hongmin Astrof, Nathan S. Liu, Jin-Huan Wang, Jia-Huai Shimaoka, Motomu TI Crystal structure of isoflurane bound to integrin LFA-1 supports a unified mechanism of volatile anesthetic action in the immune and central nervous systems SO FASEB JOURNAL LA English DT Article DE allosteric modulation; conformational change; ferritin; halogen bond; stereoisomer ID I-DOMAIN; GABA(A) RECEPTOR; OPTICAL ISOMERS; SERUM-ALBUMIN; BINDING; INHIBITION; PROTEINS; INFLAMMATION; REFINEMENT; ACTIVATION AB Volatile anesthetics (VAs), such as isoflurane, induce a general anesthetic state by binding to specific targets (i.e., ion channels) in the central nervous system (CNS). Simultaneously, VAs modulate immune functions, possibly via direct interaction with alternative targets on leukocytes. One such target, the integrin lymphocyte function-associated antigen-1 (LFA-1), has been shown previously to be inhibited by isoflurane. A better understanding of the mechanism by which isoflurane alters protein function requires the detailed information about the drug-protein interaction at an atomic level. Here, we describe the crystal structure of the LFA-1 ligand-binding domain (I domain) in complex with isoflurane at 1.6 angstrom. We discovered that isoflurane binds to an allosteric cavity previously implicated as critical for the transition of LFA-1 from the low-to the high-affinity state. The isoflurane binding site in the I domain involves an array of amphiphilic interactions, thereby resembling a "common anesthetic binding motif" previously predicted for authentic VA binding sites. These results suggest that the allosteric modulation of protein function by isoflurane, as demonstrated for the integrin LFA-1, might represent a unified mechanism shared by the interactions of volatile anesthetics with targets in the CNS.-Zhang, H., Astrof, N. S., Liu, J.-H., Wang, J.-H., Shimaoka, M. Crystal structure of isoflurane bound to integrin LFA-1 supports a unified mechanism of volatile anesthetic action in the immune and central nervous systems. FASEB J. 23, 2735-2740 ( 2009) C1 [Astrof, Nathan S.; Shimaoka, Motomu] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Zhang, Hongmin; Liu, Jin-Huan; Wang, Jia-Huai] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, Hongmin; Liu, Jin-Huan; Wang, Jia-Huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Zhang, Hongmin; Liu, Jin-Huan; Wang, Jia-Huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Astrof, Nathan S.; Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Shimaoka, M (reprint author), Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, 3 Blackfan Circle, Boston, MA 02115 USA. EM shimaoka@idi.harvard.edu RI Zhang, Hongmin/C-4503-2009 OI Zhang, Hongmin/0000-0001-6357-4106 FU National Institutes of Health, [AI063421, HL048675] FX We thank Koichi Yuki and Sulpicio G. Soriano ( Children's Hospital Boston and Harvard Medical School, Boston, MA, USA) for providing reagents and advice. This work was supported by grants from the National Institutes of Health, AI063421 ( M. S.) and HL048675 ( M. S., J. H. W.). NR 34 TC 25 Z9 26 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 AUG PY 2009 VL 23 IS 8 BP 2735 EP 2740 DI 10.1096/fj.09-129908 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 481UE UT WOS:000268836700041 PM 19332643 ER PT J AU Johnston, RK Balasubramanian, S Kasiganesan, H Baicu, CF Zile, MR Kuppuswamy, D AF Johnston, Rebecca K. Balasubramanian, Sundaravadivel Kasiganesan, Harinath Baicu, Catalin F. Zile, Michael R. Kuppuswamy, Dhandapani TI beta(3) Integrin-mediated ubiquitination activates survival signaling during myocardial hypertrophy SO FASEB JOURNAL LA English DT Article DE NF-kappa B; cIAP1; pressure overload ID NF-KAPPA-B; RAT VENTRICULAR MYOCYTES; FOCAL COMPLEX-FORMATION; CARDIAC-MUSCLE-CELLS; HEART-FAILURE; DILATED CARDIOMYOPATHY; PRESSURE-OVERLOAD; E3 LIGASES; IN-VIVO; C-SRC AB Identifying the molecular mechanisms activated in compensatory hypertrophy and absent during decompensation will provide molecular targets for prevention of heart failure. We have previously shown enhanced ubiquitination (Ub) during the early growth period of pressure overload (PO) hypertrophy near intercalated discs of cardiomyocytes, where integrins are important for mechanotransduction. In this study, we tested the role of integrins upstream of Ub, whether enhanced Ub contributes to survival signaling in early PO, and if loss of this mechanism could lead to decreased ventricular function. The study used a beta(3) integrin (-/-) mouse and a wild-type mouse as a control for in vivo PO by transverse aortic constriction (TAC) and for cultured cardiomyocytes in vitro, stimulated with the integrin-activating peptide RGD. We demonstrate beta(3) integrin mediates transient Ub of targeted proteins during PO hypertrophy, which is necessary for cardiomyocyte survival and to maintain ventricular function. Prosurvival signaling proceeds by initiation of NF-kappa B transcription of the E3 ligase, cIAP1. In PO beta(-/-)(3) mice, absence of this mechanism correlates with increased TUNEL staining and decreased ventricular mass and function by 4 wk. This is the first study to show that a beta(3) integrin/Ub/NF-kappa B pathway contributes to compensatory hypertrophic growth.-Johnston, R. K., Balasubramanian, S., Kasiganesan, H., Baicu, C. F., Zile, M. R., Kuppuswamy, D. beta(3) Integrin-mediated ubiquitination activates survival signaling during myocardial hypertrophy. FASEB J. 23, 2759-2771 ( 2009) C1 [Johnston, Rebecca K.; Balasubramanian, Sundaravadivel; Kasiganesan, Harinath; Baicu, Catalin F.; Zile, Michael R.; Kuppuswamy, Dhandapani] Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, Charleston, SC 29425 USA. [Zile, Michael R.; Kuppuswamy, Dhandapani] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, 114 Doughty St, Charleston, SC 29425 USA. EM kuppusd@musc.edu FU National Institutes of Health (NIH) [HL-48788, RO1 HL-092124, T32HL07260]; American Heart Association predoctoral fellowship [0615468U] FX This study was supported by National Institutes of Health (NIH) grant PPG HL-48788, by a Merit Award from the Research Service of the Department of Veterans Affairs, by NIH grant RO1 HL-092124 ( to D. K.), by American Heart Association predoctoral fellowship 0615468U ( to R. K. J.), and by NIH predoctoral fellowship NIH T32HL07260 ( to R. K. J.). We thank An Van Laer for proficiency with the TAC model. We also thank Dr. Robin Muise-Helmericks, Dr. Amy Bradshaw, and Phillip Moschella for thoughtful comments and useful discussions, and Dr. Francis G. Spinale for help with the measurement of myocyte cross-sectional area. NR 49 TC 25 Z9 28 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 AUG PY 2009 VL 23 IS 8 BP 2759 EP 2771 DI 10.1096/fj.08-127480 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 481UE UT WOS:000268836700044 PM 19364763 ER PT J AU Kozanek, M Rubash, HE Li, GA de Asla, RJ AF Kozanek, Michal Rubash, Harry E. Li, Guoan de Asla, Richard J. TI Effect of Post-traumatic Tibiotalar Osteoarthritis on Kinematics of the Ankle Joint Complex SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Kinematics; Ankle Joint; Post-traumatic Osteoarthritis ID TERM FOLLOW-UP; GAIT ANALYSIS; FOOT COMPLEX; STANCE PHASE; ARTHRODESIS; ARTHRITIS; ARTHROPLASTY; ARTHROSIS; SUBTALAR; REPLACEMENT AB Background: Knowledge of joint kinematics in the healthy and diseased joint may be useful if surgical techniques and joint replacement designs are to be improved. To date, little is known about the kinematics of the arthritic tibiotalar joint and its effect on the kinematics of the subtalar joint. Materials and Methods: Kinematics of the ankle joint complex (AJC) were measured in six patients with unilateral post-traumatic tibiotalar osteoarthritis in simulated heel strike, midstance and toe off weight bearing positions using magnetic resonance and dual fluoroscopic imaging techniques. The kinematic data obtained was compared to a normal cohort from a previous study. Results: From heel strike to midstance, the arthritic tibiotalar joint demonstrated 2.2 +/- 5.0 degrees of dorsiflexion while in the healthy controls the tibiotalar joint plantarflexed 9.1 +/- 5.3 degrees (p < 0.01). From midstance to toe off, the subtalar joint in the arthritic group dorsiflexed 3.3 +/- 4.1 degrees whereas in the control group the subtalar joint plantarflexed 8.5 +/- 2.9 degrees (p < 0.01). The subtalar joint in the arthritic group rotated externally 1.2 +/- 1.0 degrees and everted 3.3 +/- 6.1 degrees from midstance to toe off while in the control group 12.3 +/- 8.3 degrees of internal rotation and 10.7 +/- 3.8 degrees eversion (p < 0.01 and p < 0.01, respectively) was measured. Conclusion: The current study suggests that during the stance phase of gait, subtalar joint motion in the sagittal, coronal, and transverse rotational planes tends to occur in an opposite direction in subjects with tibiotalar osteoarthritis when compared to normal ankle controls. This effectively represents a breakdown in the normal motion coupling seen in healthy ankle joints. Clinical Relevance: Knowledge of ankle kinematics of arthritic joints may be helpful when designing prostheses or in assessing the results of treatment interventions. C1 [Li, Guoan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 45 TC 13 Z9 14 U1 2 U2 14 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD AUG PY 2009 VL 30 IS 8 BP 734 EP 740 DI 10.3113/FAI.2009.0734 PG 7 WC Orthopedics SC Orthopedics GA 479II UT WOS:000268652500003 PM 19735628 ER PT J AU Rubio, N Rajadurai, A Held, KD Prise, KM Liber, HL Redmond, RW AF Rubio, Noemi Rajadurai, Anpuchchelvi Held, Kathryn D. Prise, Kevin M. Liber, Howard L. Redmond, Robert W. TI Real-time imaging of novel spatial and temporal responses to photodynamic stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 18-22, 2009 CL San Francisco, CA SP Soc Free Rad Biol & Med ID MEDIATED INTERCELLULAR COMMUNICATION; SISTER-CHROMATID EXCHANGES; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; ALPHA-PARTICLES; NADPH OXIDASE; BYSTANDER RESPONSES; IRRADIATED-CELLS; CHROMOSOMAL-ABERRATIONS; HUMAN KERATINOCYTES AB Cells subjected to various forms of stress have been shown to induce bystander responses in nontargeted cells, thus extending the Stress response to a larger population. However, the mechanism(s) of bystander responses remains to be clearly identified, particularly for photodynamic stress. Oxidative stress and cell viability were studied on the spatial and temporal levels after photodynamic targeting of a subpopulation of EMT6 routine mammary cancer cells in a multiwell plate by computerized time-lapse fluorescence microscopy. In the targeted population a dose-dependent loss of cell viability was observed in accordance with increased oxidative stress. This was accompanied by increased oxidative stress in bystander Populations but oil different time scales, reaching a maximum more rapidly in targeted cells. Treatment with extracellular catalase, or the NADPH oxidase inhibitor diphenyleneiodinium, decreased production of reactive oxygen species (ROS) in both populations. These effects are ascribed to photodynamic activation of NADPH-oxidase in the targeted cells, resulting in a rapid burst of ROS formation with hydrogen peroxide acting as the signaling molecule responsible for initiation of these photodynamic bystander responses. The consequences of increased oxidative stress in bystander cells should be considered in the overall framework of photodynamic stress. (C) 2009 Elsevier Inc. All rights reserved. C1 [Rubio, Noemi; Rajadurai, Anpuchchelvi; Redmond, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Held, Kathryn D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Prise, Kevin M.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland. [Liber, Howard L.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM Redmond@helix.mgh.harvard.edu RI Prise, Kevin/N-7872-2015 OI Prise, Kevin/0000-0001-6134-7946 FU NCI NIH HHS [P01 CA095227] NR 73 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2009 VL 47 IS 3 BP 283 EP 290 DI 10.1016/j.freeradbiomed.2009.04.024 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 464UI UT WOS:000267532800010 PM 19409981 ER PT J AU Liang, HY Ran, QT Jang, YC Holstein, D Lechleiter, J McDonald-Marsh, T Musatov, A Song, W Van Remmen, H Richardson, A AF Liang, Hanyu Ran, Qitao Jang, Youngmok Charles Holstein, Deborah Lechleiter, James McDonald-Marsh, Tiffany Musatov, Andrej Song, Wook Van Remmen, Holly Richardson, Arlan TI Glutathione peroxidase 4 differentially regulates the release of apoptogenic proteins from mitochondria SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 18-22, 2009 CL San Francisco, CA SP Soc Free Rad Biol & Med DE Gpx4; Phospholipid hydroperoxide glutathione peroxidase 4; Apoptosis; Cardiolipin; Lipid peroxidation; Oxidative stress; Free radicals ID RAT-LIVER MITOCHONDRIA; CYTOCHROME-C RELEASE; NF-KAPPA-B; CELL-DEATH; OXIDATIVE STRESS; INDUCED APOPTOSIS; CARDIOLIPIN; INJURY; OXYGEN; MEMBRANES AB Glutathione peroxidase 4 (Gpx4) is a unique antioxidant enzyme that repairs oxidative damage to biomembranes. In this study, we examined the effects of Gpx4 on the release of various apoptogenic proteins from mitochondria using transgenic mice overexpressing Gpx4 [Tg(GPX(+/0))] and mice deficient in Gpx4 (Gpx4(+/-) mice). Diquat exposure triggered apoptosis that occurred through an intrinsic pathway and resulted in the mitochondrial release of cytochrome c (Cyt c), Smac/DIABLO, and Omi/HtrA2 in the liver of wild-type (Wt) mice. Liver apoptosis and Cyt c release were Suppressed in Tg(GPX(+/0)) mice but exacerbated in Gpx4(+/-) mice: however, neither the Tg(GPX4(+/0)) nor the Gpx4(+/-) mice showed any alterations in the levels of Smac/DIABLO or Omi/HtrA2 released from mitochondria. Submitochondrial fractionation data showed that Smac/DIABLO and Omi/HtrA2 existed primarily in the intermembrane space and matrix, whereas Cyt c and Gpx4 were both associated with the inner membrane. In addition, diquat exposure induced cardiolipin peroxidation in the liver of Wt mice; the levels of cardiolipin peroxidation were reduced in Tg(GPX4(+/0)) mice but elevated in Gpx4(+/-) mice. These data suggest that Gpx4 differentially regulates apoptogenic protein release owing to its inner membrane location in mitochondria and its ability to repair cardiolipin peroxidation. Published by Elsevier Inc. C1 [Liang, Hanyu; Ran, Qitao; Jang, Youngmok Charles; Holstein, Deborah; Lechleiter, James; Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Ran, Qitao; Lechleiter, James; Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Ran, Qitao; Van Remmen, Holly; Richardson, Arlan] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [McDonald-Marsh, Tiffany; Musatov, Andrej] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78245 USA. [Song, Wook] Seoul Natl Univ, Dept Phys Educ, Seoul 151742, South Korea. RP Richardson, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. EM richardsona@uthscsa.edu RI Liang, Hanyu/A-1066-2010; Musatov, Andrej/K-8963-2012 FU NIA NIH HHS [P01 AG020591-079004, P01 AG019316-080008, P01AG19316, P01AG020591, P01 AG019316, P01 AG020591, R37 AG026557-04, R37 AG026557, P30 AG013319-15, 1P30-AG13319, P30 AG013319] NR 53 TC 31 Z9 33 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2009 VL 47 IS 3 BP 312 EP 320 DI 10.1016/j.freeradbiomed.2009.05.012 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 464UI UT WOS:000267532800014 PM 19447173 ER PT J AU Kim, BM Choi, MY AF Kim, Byeong-Moo Choi, Michael Y. TI New Insights into the Role of Hedgehog Signaling in Gastrointestinal Development and Cancer SO GASTROENTEROLOGY LA English DT Editorial Material ID SONIC-HEDGEHOG; PATHWAY; ACTIVATION; POLARITY C1 [Choi, Michael Y.] Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Choi, MY (reprint author), Massachusetts Gen Hosp, Dept Med, GI Unit, Jackson 822,55 Fruit St, Boston, MA 02114 USA. EM mchoi@partners.org NR 18 TC 4 Z9 4 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2009 VL 137 IS 2 BP 422 EP 424 DI 10.1053/j.gastro.2009.06.021 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 477WZ UT WOS:000268551000010 PM 19563845 ER PT J AU Everhart, JE Lok, AS Kim, HY Morgan, TR Lindsay, KL Chung, RT Bonkovsky, HL Ghany, MG AF Everhart, James E. Lok, Anna S. Kim, Hae-Young Morgan, Timothy R. Lindsay, Karen L. Chung, Raymond T. Bonkovsky, Herbert L. Ghany, Marc G. CA HALT-C Trial Grp TI Weight-Related Effects on Disease Progression in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial SO GASTROENTEROLOGY LA English DT Article ID NUTRITION EXAMINATION SURVEY; FATTY LIVER-DISEASE; UNTREATED PATIENTS; NATIONAL-HEALTH; UNITED-STATES; STEATOSIS; FIBROSIS; OBESITY; INSULIN; OVERWEIGHT AB BACKGROUND & AIMS: With the limited efficacy of current therapy for chronic hepatitis C, modifiable risk factors for liver disease progression are important to identify. Because obesity is associated with liver disease, we examined the effects of weight-related conditions on disease outcomes in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. METHODS: Of 1050 patients, 985 could be evaluated for predefined progression of liver disease not related to hepatocellular carcinoma. Clinical outcomes were determined over 3.5 years for all patients and progression to cirrhosis on protocol biopsy among patients who had bridging fibrosis (56.5% of cohort) at entry. RESULTS: At study entry, median body mass index was high (29.2 kg/m(2)) and accompanied by other weight-related conditions, including diabetes (24.9%), high median waist circumference, and insulin resistance (by updated homeostasis model assessment of insulin resistance; HOMA2-IR). Among noninvasive measures, HOMA2-IR was most strongly associated with outcomes with hazard ratio (HR) of 1.26 per quartile increase (95% CI, 1.09-1.45). Presence of steatosis on baseline biopsy was associated with an increased outcome rate among patients with bridging fibrosis (P < .0001) and a decreased rate among patients with cirrhosis (P = .006). Presence of Mallory bodies was associated with outcomes (HR, 1.59; 95% CI, 1.10-2.31) as was significant weight change of >= 5% in the first year after randomization (HR, 1.25 per category increase in weight, 95% Cl, 1.01-1.55). CONCLUSIONS: Insulin resistance, histologic features of fatty liver disease, and weight change were associated with outcomes of chronic hepatitis C. Improvement in these weight-related factors might modify disease progression. C1 [Everhart, James E.] NIDDKD, NIH, Div Digest Dis & Nutr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Ghany, Marc G.] NIDDKD, NIH, Liver Dis Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Everhart, JE (reprint author), NIDDKD, NIH, Div Digest Dis & Nutr, Dept Hlth & Human Serv, 2 Democracy Plaza,Room 655,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM JE17g@nih.gov OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institutes of Health FX This study was supported by the National Institute of Diabetes, Digestive, and Kidney Diseases (contract numbers are listed with the acknowledgments). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 24 TC 60 Z9 62 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2009 VL 137 IS 2 BP 549 EP 557 DI 10.1053/j.gastro.2009.05.007 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 477WZ UT WOS:000268551000030 PM 19445938 ER PT J AU Nevzorova, YA Tschaharganeh, D Gassler, N Geng, Y Weiskirchen, R Sicinski, P Trautwein, C Liedtke, C AF Nevzorova, Yulia A. Tschaharganeh, Darjus Gassler, Nikolaus Geng, Yan Weiskirchen, Ralf Sicinski, Piotr Trautwein, Christian Liedtke, Christian TI Aberrant Cell Cycle Progression and Endoreplication in Regenerating Livers of Mice That Lack a Single E-Type Cyclin SO GASTROENTEROLOGY LA English DT Article ID PARTIAL-HEPATECTOMY; HEPATIC-FAILURE; IN-VIVO; E GENE; CDK2; GROWTH; BINUCLEATION; HEPATOCYTES; POLYPLOIDY; MOUSE AB BACKGROUND & AIMS: E-cyclins control the transition of quiescent cells into the cell cycle. Two E-cyclins, CcnE1 and CcnE2, have been described, but their specific contributions to cell cycle reentry in vivo are poorly understood. Liver regeneration following partial heparectomy is an excellent in vivo model for the study of cell cycle reentry of quiescent cells. We investigated the relevance of E-cyclins in directing resting hepatocytes into the cell cycle after partial hepatectomy using CcnE1 and CcnE2 knockout mice. METHODS: Partial hepatectomy (70%) was performed in CcnE1 (E1(-/-)) and CcnE2 (E2(-/-)) knockout and wild-type mice. Liver regeneration was monitored by cell cycle markers For G(1)/S phase, S phase, and M phase as well as by determining the liver/body weight ratio after partial hepatectomy. Ploidy of hepatocytes was determined by fluorescence-activated cell sorting and fluorescent in situ hybridization. RESULTS: CcnE1 deletion resulted in normal liver regeneration with a slight delay of the G(1)/S-phase transition and a defect in endoreplication of otherwise polyploid hepatocytes. Surprisingly, E2(-/-) mice displayed accelerated and sustained DNA synthesis after partial hepatectomy, excessive endoreplication in hepatocytes, and a liver mass that was 45% greater than that of wild-type mice after termination of the regeneration process. CcnE2 depletion induced overexpression of CcnE1 and prolonged cdk2 kinase activity after partial hepatectomy. CONCLUSIONS: CcnE2 has an unexpected role in repressing CcnE1; the phenotype of E2(-/-) mice appears to result from CcnE1 overexpression and cdk2 hyperactivation. CcnE1 and CcnE2 therefore have nonredundant functions for S-phase entry and endoreplication during liver regeneration. C1 [Nevzorova, Yulia A.; Tschaharganeh, Darjus; Trautwein, Christian; Liedtke, Christian] Rhein Westfal TH Aachen, Univ Hosp Aachen, Dept Med 3, D-52074 Aachen, Germany. [Gassler, Nikolaus] Rhein Westfal TH Aachen, Univ Hosp Aachen, Inst Pathol, D-52074 Aachen, Germany. [Weiskirchen, Ralf] Rhein Westfal TH Aachen, Univ Hosp Aachen, Inst Clin Chem & Pathobiochem, D-52074 Aachen, Germany. [Geng, Yan; Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Geng, Yan; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Liedtke, C (reprint author), Rhein Westfal TH Aachen, Univ Hosp Aachen, Dept Med 3, Pauwelsstr 30, D-52074 Aachen, Germany. EM cliedtke@ukaachen.de FU Deutsche Forschungsgerneinschaft [L11045/2-1, L11045/2-2]; National Cancer Institute [R01 CA108950] FX Supported by Deutsche Forschungsgerneinschaft grants L11045/2-1. and L11045/2-2 (to C.L. and C.T.) and National Cancer Institute grant R01 CA108950 (to P.S.). NR 32 TC 25 Z9 25 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2009 VL 137 IS 2 BP 691 EP 703 DI 10.1053/j.gastro.2009.05.003 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 477WZ UT WOS:000268551000044 PM 19445941 ER PT J AU Spiegel, BMR AF Spiegel, Brennan M. R. TI Endoscopy for acute upper GI tract hemorrhage: sooner is better SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID UPPER GASTROINTESTINAL HEMORRHAGE; CONTROLLED-TRIAL; THERAPY; QUALITY; LENGTH; OXYGEN; STAY; CARE C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr,VA Ctr Outcomes Res & Edu, Los Angeles, CA 90095 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr,VA Ctr Outcomes Res & Edu, Los Angeles, CA 90095 USA. NR 25 TC 10 Z9 12 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 AUG PY 2009 VL 70 IS 2 BP 236 EP 239 DI 10.1016/j.gie.2008.12.053 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 480OJ UT WOS:000268745200007 PM 19631802 ER PT J AU Sepe, PS Moparty, B Pitman, MB Saltzman, JR Brugge, WR AF Sepe, Paul S. Moparty, Bhavani Pitman, Martha B. Saltzman, John R. Brugge, William R. TI EUS-guided FNA for the diagnosis of GI stromal cell tumors: sensitivity and cytologic yield SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/108th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2007 CL Washington, DC SP Amer Gastroenterol Assoc, Amer Assoc Study Liver Dis, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract ID FINE-NEEDLE-ASPIRATION; ENDOSCOPIC ULTRASOUND; COMPLICATION ASSESSMENT; GASTROINTESTINAL-TRACT; SUBMUCOSAL TUMORS; CENTER EXPERIENCE; BIOPSY; LESIONS; ENDOSONOGRAPHY; MANAGEMENT AB Background: EUS-guided FNA has been well documented to aid in the diagnosis of subepithelial lesions by providing cytologic material. Studies to date evaluating the sensitivity of EUS-FNA for the diagnosis of GI stromal cell tumors (GIST) have been small, and few have relied on surgical histologic diagnosis as the reference standard. Objective: Our purpose was to determine the diagnostic yield and sensitivity of EUS-FNA for the diagnosis of GIST and to identify EUS features of GIST that are predictive of the ability to obtain adequate tissue by EUS-FNA. Design: All patients with histologically confirmed, c-kit-positive GIST who underwent EUS-FNA from 1998 to 2006 were reviewed. EUS images were examined for mass size, shape, location, wall layer, heterogeneity, echogenicity, cystic spaces, lobulation, ulceration, and central Umbilication. Needle gauge, number of needle passes, and presence of a cytologist during the EUS-FNA were recorded. Results: A total of 37 patients (29 with diagnostic FNA cytology; 8 with nondiagnostic cytology) met the inclusion criteria. The diagnostic yield and sensitivity of EUS-FNA cytology for the diagnosis of GIST was 78.4% (29/37). The sensitivity was 84.4% (27/32) for GISTs located in the stomach, but poor for lesions located in the duodenum because none of these tumors yielded diagnostic cytology (n = 3). An increase in size up to 10 cm, round/oval shape, and identification of the origin of GIST within a specific sonographic wall layer were statistically significant in their ability to predict adequate tissue yield. Conclusions: The sensitivity of EUS-FNA cytology for the diagnosis of GIST is 78.4% and is influenced by size, location, shape, and layer of origin. (Gastrointest Endosc 2009;70:254-61.) C1 [Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. [Sepe, Paul S.] Massachusetts Gen Hosp, Div Gastroenterol, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. [Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Saltzman, John R.] Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. [Moparty, Bhavani] Baylor Univ, Med Ctr, Texas Digest Dis Consultants, Dallas, TX USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org NR 26 TC 84 Z9 92 U1 0 U2 2 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 AUG PY 2009 VL 70 IS 2 BP 254 EP 261 DI 10.1016/j.gie.2008.11.038 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 480OJ UT WOS:000268745200010 PM 19482280 ER PT J AU Artifon, ELA Couto, D Sakai, P da Silveira, EB AF Artifon, Everson L. A. Couto, Decio, Jr. Sakai, Paulo da Silveira, Eduardo B. TI Prospective evaluation of EUS versus CT scan for staging of ampullary cancer SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ENDOSCOPIC ULTRASOUND; COMPUTED-TOMOGRAPHY; PANCREATIC TUMORS; ANGIOGRAPHY; SONOGRAPHY; CARCINOMA AB Background: Malignancies of the biliary and pancreatic systems are associated with a poor prognosis. However, ampullary cancer carries a better prognosis and is often diagnosed when curative treatment is still possible. Accurate staging is important for the determination of the most appropriate treatment option. Objectives: (1) To determine the test performance characteristics of EUS and CT in loco-regional staging of ampullary neoplasms, and (2) to determine the impact of CT scan results on the test performance characteristics of EUS. Design and Setting: Prospective single-arm intervention study performed in 2 academic hospitals. Results and Main Outcome Measurements: Thirty-seven patients were screened and 33 staged with EUS and CT A total of 27 patients (13 men; mean age, 69.5 years; mean serum bilirubin level, 12.6 mg/dL) with locally advanced disease completed the protocol with EUS and CT and underwent surgical resection. Tumor classifications were as follows: 2 patients (7.4%), T1 tumors; 13 patients (48.1%), T2 tumors; and 12 patients (44.4%), T3 tumors, as per surgical pathology. Seventeen tumors (62.9%) were classified as NO and 10 (37.1%) as NI. The difference in proportion of correct tumor (74.1% vs 51.8%; P =.15, 95% CI, -0.06-0-50) and lymph node (81.4% vs; 55.5%; P =.07, 95% Cl, -0.01-0.53) staging by EUS and CT, respectively, was not statistically significantly different. However, the strength of tumor (kappa 0.51 vs 0.11) and nodal (kappa 0.59 vs 0.05) agreement with pathology was statistically significantly higher for EUS than for CT (P <.05). EUS was more sensitive and specific than CT for tumor and nodal staging, and the association of CT to EUS data did not improve the final test accuracy Limitation: Low number of T1 tumors. Conclusions: EUS is in accurate diagnostic test and exhibits a high level of agreement with surgical pathology. CT findings do not improve the test performance characteristics of EUS. Therefore, the evaluation for metastatic disease should not be compromised by CT protocols that aim to perform tumor and nodal staging. Further studies to determine the role of specialized CT protocols in patients with ampullary malignancies are needed. (Gastrointest Endosc 2009;70:290-6.) C1 [Artifon, Everson L. A.; Couto, Decio, Jr.; Sakai, Paulo] Univ Sao Paulo, Sch Med, Dept Gastroenterol, Sao Paulo, Brazil. [da Silveira, Eduardo B.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97201 USA. RP da Silveira, EB (reprint author), 3710 SW US Vet Hosp Rd,MC P3GI, Portland, OR 97239 USA. EM eda_silveira@hotmail.com NR 18 TC 26 Z9 26 U1 0 U2 2 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 AUG PY 2009 VL 70 IS 2 BP 290 EP 296 DI 10.1016/j.gie.2008.11.045 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 480OJ UT WOS:000268745200016 PM 19523619 ER PT J AU Yu, M Smolen, GA Zhang, JM Wittner, B Schott, BJ Brachtel, E Ramaswamy, S Maheswaran, S Haber, DA AF Yu, Min Smolen, Gromoslaw A. Zhang, Jianmin Wittner, Ben Schott, Benjamin J. Brachtel, Elena Ramaswamy, Sridhar Maheswaran, Shyamala Haber, Daniel A. TI A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression SO GENES & DEVELOPMENT LA English DT Article DE EMT; LBX1; breast cancer; cancer stem cell ID EPITHELIAL-MESENCHYMAL TRANSITION; DORSAL SPINAL-CORD; PRECURSOR CELLS; STEM-CELLS; METASTASIS; PHENOTYPE; EXPRESSION; SIGNATURE; CARCINOMA; MIGRATION AB Epithelial-to-mesenchymal transition (EMT) plays an important role during normal embryogenesis, and it has been implicated in cancer invasion and metastasis. Here, we report that Ladybird homeobox 1 (LBX1), a developmentally regulated homeobox gene, directs expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor beta 2 (TGFB2). In mammary epithelial cells, overexpression of LBX1 leads to morphological transformation, expression of mesenchymal markers, enhanced cell migration, increased CD44(high)/CD24(low) progenitor cell population, and tumorigenic cooperation with known oncogenes. In human breast cancer, LBX1 is up-regulated in the unfavorable estrogen receptor (ER)/progesterone (PR)/HER2 triple-negative basal-like subtype. Thus, aberrant expression of LBX1 may lead to the activation of a developmentally regulated EMT pathway in human breast cancer. C1 [Yu, Min; Smolen, Gromoslaw A.; Zhang, Jianmin; Wittner, Ben; Schott, Benjamin J.; Ramaswamy, Sridhar; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Yu, Min; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Charlestown, MA 02129 USA. [Brachtel, Elena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu FU NIH [CA-129933]; Howard Hughes Medical Institute FX This work was supported by grants from the NIH (CA-129933) and the Howard Hughes Medical Institute. NR 28 TC 59 Z9 62 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG PY 2009 VL 23 IS 15 BP 1737 EP 1742 DI 10.1101/gad.1809309 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 478OW UT WOS:000268598600005 PM 19651985 ER PT J AU Ni, JQ Liu, LP Binari, R Hardy, R Shim, HS Cavallaro, A Booker, M Pfeiffer, BD Markstein, M Wang, H Villalta, C Laverty, TR Perkins, LA Perrimon, N AF Ni, Jian-Quan Liu, Lu-Ping Binari, Richard Hardy, Robert Shim, Hye-Seok Cavallaro, Amanda Booker, Matthew Pfeiffer, Barret D. Markstein, Michele Wang, Hui Villalta, Christians Laverty, Todd R. Perkins, Lizabeth A. Perrimon, Norbert TI A Drosophila Resource of Transgenic RNAi Lines for Neurogenetics SO GENETICS LA English DT Article ID SITE-SPECIFIC RECOMBINATION; DOUBLE-STRANDED-RNA; GENETIC INTERFERENCE; INVERTED REPEATS; MELANOGASTER; EXPRESSION; VECTOR; TRANSFORMATION; SYSTEM; CONSTRUCTION AB Conditional expression of hairpin constructs in Drosophila is a powerful method to disrupt the activity of single genes with a spatial and temporal resolution that. is impossible, or exceedingly difficult, using classical genetic methods. We previously described a method (Ni et al. 2008) whereby RNAi constructs are targeted into the genome by the phic31-mediated integration approach using Vermilion-AttB-Loxp-Intron-UAS-MCS (VALIUM), a vector that contains vermilion as a selectable marker, an attB sequence to allow for phiC31-targeted integration at genomic attP landing sites, two pentamers of UAS, the h,51)70 core promoter, a multiple cloning site, and two introns. As the level of gene activity knockdown associated with transgenic RNAi depends on the level of expression Of the hairpin constructs, we generate a number of derivatives of our initial vector, called the "VALIUM" series, to improve the efficiency of the method. Here, we report the results from the systematic analysis of these derivatives and characterize VALIUM10 as the most. optimal vector of this series. A critical feature of VALIUM10 is the presence of gypsy insulator sequences that boost dramatically the level of knockdown. We document the efficacy of VALIUM as a vector to analyze the phenotype of genes expressed in the nervous system and have generated a library of 2282 constructs targeting 2043 genes that, will be particularly useful for Studies of the nervous system as they target, in particular, transcription factors, ion channels, and transporters. C1 [Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02175 USA. [Ni, Jian-Quan; Liu, Lu-Ping; Cavallaro, Amanda; Pfeiffer, Barret D.; Laverty, Todd R.; Perkins, Lizabeth A.; Perrimon, Norbert] Howard Hughes Med Inst, Ashburn, VA 20147 USA. [Perkins, Lizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. [Hardy, Robert] Univ Calif San Diego, Howard Hughes Med Inst, George Palade Ctr Mol Med, La Jolla, CA 92093 USA. RP Perrimon, N (reprint author), Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, 77 Ave Louis Pasteur, Boston, MA 02175 USA. EM perrimon@receptor.med.harvard.edu OI Markstein, Michele/0000-0003-2635-8118 FU Howard Hughes Medical Institute; NIGMS NIH HHS [GM067761, GM084947, R01 GM067761, R01 GM084947] NR 27 TC 137 Z9 139 U1 2 U2 16 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 2009 VL 182 IS 4 BP 1089 EP 1100 DI 10.1534/genetics.109.103630 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 499IZ UT WOS:000270214000013 PM 19487563 ER PT J AU Phillips, LL Paukert, AL Stanley, MA Kunik, ME AF Phillips, Laura L. Paukert, Amber L. Stanley, Melinda A. Kunik, Mark E. TI Incorporating religion and spirituality to improve care for anxiety and depression in older adults SO GERIATRICS LA English DT Article DE anxiety; depression; religion; spirituality ID ILL ELDERLY-PATIENTS; HEALTH; INVOLVEMENT; PREDICTOR; SYMPTOMS; MEDICINE; OUTCOMES AB Recent research has suggested that religion/spirituality may be linked to improved physical and emotional health, although the patients motivation and method of using religious/spiritual beliefs appear to be a key factor in obtaining benefit. Studies have shown that there is a high level of religion/spirituality among older adults in the United States and significant patient-reported desire to include such beliefs in health care settings. This article provides a brief overview of the support for considering religion/spirituality in the health care of older adults and reviews potential drawbacks and methods for providers to assess and use patient beliefs to improve anxiety/depression. Phillips LL, Paukert AL, Stanley MA, Kunik ME. Incorporating religion and spirituality to improve care for anxiety and depression in older adults. Geriatrics. 2009;64(8):15-18. C1 [Phillips, Laura L.] Olin E Teague VA Med Ctr, Temple, TX USA. [Paukert, Amber L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Stanley, Melinda A.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Stanley, Melinda A.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Stanley, Melinda A.; Kunik, Mark E.] VA S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Kunik, Mark E.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Phillips, LL (reprint author), Olin E Teague VA Med Ctr, Temple, TX USA. NR 20 TC 9 Z9 9 U1 1 U2 8 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD AUG PY 2009 VL 64 IS 8 BP 15 EP + PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 483LX UT WOS:000268969400003 PM 20722312 ER PT J AU Mirabeau-Beale, KL Kornblith, AB Penson, RT Lee, H Goodman, A Campos, SM Duska, L Pereira, L Bryan, J Matulonis, UA AF Mirabeau-Beale, Kristina L. Kornblith, Alice B. Penson, Richard T. Lee, Hang Goodman, Annekathryn Campos, Susana M. Duska, Linda Pereira, Lauren Bryan, Jessica Matulonis, Ursula A. TI Comparison of the quality of life of early and advanced stage ovarian cancer survivors SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2008 CL Chicago, IL SP Amer Soc Clin Oncol DE Ovarian cancer; Quality of life; Survivorship; Fear of recurrence ID FUNCTIONAL ASSESSMENT; CLINICAL-TRIALS; FATIGUE; SCALE; ONCOLOGY; HOPELESSNESS; PREDICTORS; DISTRESS; OUTCOMES AB Objective. The objective of this study was to compare the long-term adjustment and QOL of early and advanced stage ovarian cancer survivors (OCS). Methods. Early and advanced OCS >3 years from diagnosis with no evidence of recurrent cancer were interviewed. The following Surveys were administered: EORTC QLQ-C30 (overall QOL) and QLQ-OV28 (ovarian specific issues), MHI-17 (anxiety, depression and global well-being), CALGB sexual functioning, FACT Fatigue, Beck's Hopelessness Scale, Fear of Recurrence (FOR), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy (CAM use), and MOS Social Support Survey (MOS). The results of the surveys were compared between the early and advanced stage groups. Results. 42 advanced and 58 early stage patients were interviewed. The majority of survivors scored above the medical outpatient norm for emotional status (71% of early stage and 64% of advanced stage survivors). Overall QOL, fatigue, hopelessness, spirituality, social support, degree to which unmet needs were met and use of complementary therapy, did not differ between the two groups. No advanced stage OCS had diagnosable PTSD scores, while 6.9% of early stage survivors had scores indicative of PTSD. Decreased sexual interest attributed to cancer and anxiety when getting CA-125 testing were of concern for both groups. OCS used oil average 5 CAM to improve their QOL. Conclusion. Regardless of staging, OCS experience similarly overall positive QOL and adjustment, though PTSD, sexual problems and fear of recurrence are still important for some survivors. (C) 2009 Elsevier Inc. All rights reserved. C1 [Mirabeau-Beale, Kristina L.; Lee, Hang] Harvard Univ, Sch Med, Boston, MA USA. [Kornblith, Alice B.] Dana Farber Canc Inst, Div Womens Canc, Boston, MA 02115 USA. [Penson, Richard T.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Goodman, Annekathryn] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Campos, Susana M.; Pereira, Lauren; Bryan, Jessica; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Duska, Linda] Univ Virginia Hlth Syst, Div Gynecol Oncol, Charlottesville, VA 22908 USA. RP Mirabeau-Beale, KL (reprint author), 170 Brookline Ave,Unit 829, Boston, MA 02115 USA. EM Klm17@hms.harvard.edu NR 34 TC 49 Z9 50 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2009 VL 114 IS 2 BP 353 EP 359 DI 10.1016/j.ygyno.2009.05.009 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 470JQ UT WOS:000267971400039 PM 19481244 ER PT J AU Primack, BA Fine, D Yang, CK Wickett, D Zickmund, S AF Primack, Brian A. Fine, Danielle Yang, Christopher K. Wickett, Dustin Zickmund, Susan TI Adolescents' impressions of antismoking media literacy education: qualitative results from a randomized controlled trial SO HEALTH EDUCATION RESEARCH LA English DT Article ID MASTER SETTLEMENT AGREEMENT; SMOKING-CESSATION METHODS; 6-YEAR FOLLOW-UP; TOBACCO USE; NORMATIVE BELIEFS; CIGARETTE-SMOKING; UNITED-STATES; YOUTH SMOKING; PREVENTION; INITIATION AB Although media literacy represents an innovative venue for school-based antismoking programming, studies have not systematically compared student impressions of these and traditional programs. This study utilized data from a randomized trial comparing these two types of programs. After each program, students responded to three open-ended questions related to their assigned curriculum. Two coders, blinded to student assignments, independently coded these data. Coders had strong inter-rater agreement (kappa = 0.77). Our primary measures were spontaneously noted overall assessment, enjoyment/interest and the likelihood of changing smoking behavior. Of the 531 participants, 255 (48.0%) were randomized to the intervention (media literacy) group. Intervention participants had more net positive responses [rate ratio (RR) = 1.27, 95% confidence interval (CI) = 1.05, 1.54], more responses rating the program as compelling (RR = 1.63, 95% CI = 1.16, 2.29) and fewer responses rating the program as non-compelling (RR = 0.62, 95% CI = 0.39, 0.97). However, the intervention group was not more likely to suggest that the curriculum was likely to change behavior positively (RR = 0.57, 95% CI = 0.30, 1.06). Findings suggest that although media literacy provides a compelling format for the delivery of antitobacco programming, integration of components of traditional programming may help media literacy programs achieve maximal efficacy. C1 [Primack, Brian A.; Yang, Christopher K.; Wickett, Dustin] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15213 USA. [Primack, Brian A.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15213 USA. [Fine, Danielle] Univ Colorado, Boulder, CO 80302 USA. [Zickmund, Susan] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15213 USA. RP Primack, BA (reprint author), Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU NCI NIH HHS [K07 CA114315, K07-CA114315] NR 72 TC 16 Z9 16 U1 5 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD AUG PY 2009 VL 24 IS 4 BP 608 EP 621 DI 10.1093/her/cyn062 PG 14 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 469IA UT WOS:000267888500006 PM 19052155 ER PT J AU Werner, RM Konetzka, RT Stuart, EA Norton, EC Polsky, D Park, J AF Werner, Rachel M. Konetzka, R. Tamara Stuart, Elizabeth A. Norton, Edward C. Polsky, Daniel Park, Jeongyoung TI Impact of Public Reporting on Quality of Postacute Care SO HEALTH SERVICES RESEARCH LA English DT Article; Proceedings Paper CT Annual Research Meeting of the Academy-Health CT Academy Health Annual Research Meeting CY JUN 09-10, 2008 CY JUN 08-10, 2008 CL Washington, DC CL Washington, DC SP Acad Hlth SP Acad Hlth DE Quality of care; postacute care; nursing home quality; public reporting ID NEW-YORK-STATE; RESIDENT ASSESSMENT INSTRUMENT; ARTERY-BYPASS-SURGERY; PROPENSITY SCORE; OF-CARE; CARDIAC-SURGERY; NURSING-HOMES; MARKET SHARE; INFORMATION; MORTALITY AB Objective Evidence supporting the use of public reporting of quality information to improve health care quality is mixed. While public reporting may improve reported quality, its effect on quality of care more broadly is uncertain. This study tests whether public reporting in the setting of nursing homes resulted in improvement of reported and broader but unreported quality of postacute care. Data Sources/Study Setting 1999-2005 nursing home Minimum Data Set and inpatient Medicare claims. Study Design We examined changes in postacute care quality in U.S. nursing homes in response to the initiation of public reporting on the Centers for Medicare and Medicaid Services website, Nursing Home Compare. We used small nursing homes that were not subject to public reporting as a contemporaneous control and also controlled for patient selection into nursing homes. Postacute care quality was measured using three publicly reported clinical quality measures and 30-day potentially preventable rehospitalization rates, an unreported measure of quality. Principal Findings Reported quality of postacute care improved after the initiation of public reporting for two of the three reported quality measures used in Nursing Home Compare. However, rates of potentially preventable rehospitalization did not significantly improve and, in some cases, worsened. Conclusions Public reporting of nursing home quality was associated with an improvement in most postacute care performance measures but not in the broader measure of rehospitalization. C1 [Werner, Rachel M.] Univ Penn, Sch Med, Div Gen Internal Med, Ctr Hlth Equ Res & Promot,Philadelphia VAMC, Philadelphia, PA 19104 USA. [Werner, Rachel M.; Polsky, Daniel] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Konetzka, R. Tamara] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Stuart, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Norton, Edward C.] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA. [Norton, Edward C.] Univ Michigan, Dept Econ, Ann Arbor, MI 48109 USA. RP Werner, RM (reprint author), 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@mail.med.upenn.edu RI Norton, Edward/B-2211-2009; OI Norton, Edward/0000-0003-4555-0631; Stuart, Elizabeth/0000-0002-9042-8611 FU AHRQ HHS [R01 HS016478, R01 HS016478-01] NR 49 TC 59 Z9 59 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2009 VL 44 IS 4 BP 1169 EP 1187 DI 10.1111/j.1475-6773.2009.00967.x PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 469FX UT WOS:000267882400005 PM 19490160 ER PT J AU Das, S Makino, S Melman, YF Shea, MA Goyal, SB Rosenzweig, A MacRae, CA Ellinor, PT AF Das, Saumya Makino, Seiko Melman, Yonathan F. Shea, Marisa A. Goyal, Sanjeev B. Rosenzweig, Anthony MacRae, Calum A. Ellinor, Patrick T. TI Mutation in the S3 segment of KCNQ1 results in familial lone atrial fibrillation SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Genetics; Mutation ID POTASSIUM CHANNEL; GENETIC-LOCUS; RISK; K(V)LQT1; PROTEINS; DOMAIN; FORM AB BACKGROUND Mutations in several ion channel genes have been reported to cause rare cases of familial atrial fibrillation (AF). OBJECTIVE The purpose of this study was to determine the genetic basis for AF in a family with autosomal dominant AF. METHODS Family members were evaluated by 12-lead ECG, echocardiogram, signal-averaged P-wave analysis, and laboratory studies. Fourteen family members in AF-324 were studied. Six individuals had AF, with a mean age at onset of 32 years (range 16-59 years). RESULTS Compared with unaffected family members, those with AF had a Longer mean QRS duration (100 vs 86 ms, P = .015) but no difference in the corrected QT interval (423 +/- 15 ms vs 421 +/- 21 ms). The known loci for AF and other cardiovascular diseases were evaluated. Evidence of Linkage was obtained with marker D11S4088 located within KCNQ1, and a highly conserved serine in the third transmembrane region was found to be mutated to a proline (S209P). Compared to the wild-type channel, the S209P mutant activates more rapidly, deactivates more slowly, and has a hyperpolarizing shift in the voltage activation curve. A fraction of the mutant channels are constitutively open at all voltages, resulting in a net increase in I(Ks) current. CONCLUSION We identified a family with Lone AF due to a mutation in the highly conserved S3 domain of KCNQ1, a region of the channel not previously implicated in the pathogenesis of AF. C1 [Das, Saumya; Makino, Seiko; Melman, Yonathan F.; MacRae, Calum A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Das, Saumya; Shea, Marisa A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Goyal, Sanjeev B.] St Vincent Hosp, Worcester, MA 01604 USA. [Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. EM pellinor@partners.org FU National Institutes of Health [HL75431, HL71632]; ACC-Pfizer; Deane Institute for Integrative Research FX The first three authors contributed equally to this manuscript. This project is supported by National Institutes of Health Award HL75431 to Dr. MacRae and Award HL71632 to Dr. Ellinor: an ACC-Pfizer award to Dr. Das and an award from the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke to Dr. Ellinor. Address reprint requests and correspondence: Dr. Patrick T. Ellinor, Massachusetts General Hospital, 149 13th Street, Fourth Floor, Charlestown, Massachusetts 02129. E-mail address: pellinor@partners.org. (Received January 8, 2009; accepted April 8, 2009.) NR 21 TC 38 Z9 41 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2009 VL 6 IS 8 BP 1146 EP 1153 DI 10.1016/j.hrthm.2009.04.015 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482ER UT WOS:000268867700007 PM 19632626 ER PT J AU de Leval, L Hasserjian, RP AF de Leval, Laurence Hasserjian, Robert Paul TI Diffuse Large B-Cell Lymphomas and Burkitt Lymphoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review DE WHO 2008 classification; Diffuse large B-cell lymphoma; Burkitt; Burkitt-like; High-grade; Pathology; Genetics; Diagnosis ID EPSTEIN-BARR-VIRUS; PYOTHORAX-ASSOCIATED LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; PRIMARY CNS LYMPHOMA; ANTHRACYCLINE-BASED CHEMOTHERAPY; GERMINAL CENTER PHENOTYPE; BCL-2 PROTEIN EXPRESSION; GENE-EXPRESSION AB Diffuse large B-cell lymphomas (DLBCLs) and Burkitt lymphoma (BL) account for the majority of aggressive lymphomas in adults and children. DLBCLs exhibit marked biological heterogeneity and variable clinical presentation and clinical course. Conversely, BL is genetically relatively homogeneous but associated with variable clinicopathological features. In this article, the authors summarize the recent advances pertaining to these B-cell neoplasms, following the latest World Health Organization classification and focusing on changes introduced since the previous edition. These changes include the addition of variants and subgroups of DLBCLs and "borderline" categories for high-grade B-cell neoplasms that show features intermediate between DLBCL and classical Hodgkin lymphoma, or between DLBCL and BL. In particular, the diagnostic and therapeutic problems related to neoplasms with features intermediate between DLBCL and BL will be discussed. C1 [de Leval, Laurence] CHU Sart Tilman, Dept Pathol, Inst Pathol, B-4000 Liege, Belgium. [Hasserjian, Robert Paul] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM l.deleval@ulg.ac.be NR 162 TC 17 Z9 20 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2009 VL 23 IS 4 BP 791 EP + DI 10.1016/j.hoc.2009.04.004 PG 38 WC Oncology; Hematology SC Oncology; Hematology GA 483WX UT WOS:000269004500010 PM 19577170 ER PT J AU Weinstein, RS Graham, AR Richter, LC Barker, GP Krupinski, EA Lopez, AM Erps, KA Bhattacharyya, AK Yagi, Y Gilbertson, JR AF Weinstein, Ronald S. Graham, Anna R. Richter, Lynne C. Barker, Gail P. Krupinski, Elizabeth A. Lopez, Ana Maria Erps, Kristine A. Bhattacharyya, Achyut K. Yagi, Yukako Gilbertson, John R. TI Overview of telepathology, virtual microscopy, and whole slide imaging: prospects for the future SO HUMAN PATHOLOGY LA English DT Article DE Telepathology Telemedicine; Virtual slides; Virtual microscopy; Surgical pathology; Telehealth; Medical education; Breast cancer; Cancer; Interprofessional training; Medicolegal ID OF-VETERANS-AFFAIRS; ROBOTIC TELEPATHOLOGY; PATHOLOGY; CONSULTATION; PERFORMANCE; EXPERIENCE; EDUCATION; SERVICES AB Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. Today, fourth-generation telepathology systems, so-called virtual slide telepathology systems, are being used for education applications. Both conventional and innovative surgical pathology diagnostic services are being designed and implemented as well. The technology has been commercialized by more than 30 companies in Asia, the United States, and Europe. Early adopters of telepathology have been laboratories with special challenges in providing anatomic pathology services, ranging from the need to provide anatomic pathology services at great distances to the use of the technology to increase efficiency of services between hospitals less than a mile apart. As to what often happens in medicine, early adopters of new technologies are professionals who create model programs that are successful and then stimulate the creation of infrastructure (ie, reimbursement, telecommunications, information technologies, and so on) that forms the platforms for entry of later, mainstream, adopters. The trend at medical schools, in the United States, is to go entirely digital for their pathology courses, discarding their student light microscopes, and building virtual slide laboratories. This may create a generation of pathology trainees who prefer digital pathology imaging over the traditional hands-on light microscopy. The creation of standards for virtual slide telepathology is early in its development but accelerating. The field of telepathology has now reached a tipping point at which major corporations now investing in the technology will insist that standards be created for pathology digital imaging as a value added business proposition. A key to success in teleradiology, already a growth industry, has been the implementation of standards for digital radiology imaging. Telepathology is already the enabling technology for new, innovative laboratory services. Examples include STAT QA surgical pathology second opinions at a distance and a telehealth-enabled rapid breast care service. The innovative bundling of telemammography, telepathology, and teleoncology services may represent a new paradigm in breast care that helps address the serious issue of fragmentation of breast cancer care in the United States and elsewhere. Legal and regulatory issues in telepathology are being addressed and are regarded as a potential catalyst for the next wave of telepathology advances, applications, and implementations. (C) 2009 Elsevier Inc. All rights reserved. C1 [Weinstein, Ronald S.] Univ Arizona, Dept Pathol, Coll Med, Univ Med Ctr,Arizona Telemed Program, Tucson, AZ 85724 USA. [Krupinski, Elizabeth A.; Lopez, Ana Maria] Univ Arizona, Dept Med, Coll Med, Tucson, AZ 85724 USA. [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Coll Med, Tucson, AZ 85724 USA. [Weinstein, Ronald S.; Barker, Gail P.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA. [Weinstein, Ronald S.; Barker, Gail P.] T Hlth Inst, Phoenix, AZ 85004 USA. [Yagi, Yukako; Gilbertson, John R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yagi, Yukako; Gilbertson, John R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weinstein, RS (reprint author), Univ Arizona, Dept Pathol, Coll Med, Univ Med Ctr,Arizona Telemed Program, 1501 N Campbell Ave, Tucson, AZ 85724 USA. EM ronaldw@u.arizona.edu OI Lopez, Ana Maria/0000-0002-2759-5353 NR 49 TC 119 Z9 120 U1 3 U2 36 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 2009 VL 40 IS 8 BP 1057 EP 1069 DI 10.1016/j.humpath.2009.04.006 PG 13 WC Pathology SC Pathology GA 481EQ UT WOS:000268790600001 PM 19552937 ER PT J AU Goodworth, AD Wall, C Peterka, RJ AF Goodworth, Adam D. Wall, Conrad, III Peterka, Robert J. TI Influence of Feedback Parameters on Performance of a Vibrotactile Balance Prosthesis SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Balance prosthesis; feedback control model; posture control; sensorimotor integration ID HUMAN POSTURAL CONTROL; MODEL AB We investigated the influence of feedback conditions on the effectiveness of a balance prosthesis. The balance prosthesis used an array of 12 tactile vibrators (tactors) placed on the anterior and posterior surfaces of the torso to provide body orientation feedback related to several different combinations of angular position and velocity of body sway in the sagittal plane. Control tests were performed with no tactor activation. Body sway was evoked in subjects with normal sensory function by rotating the support surface upon which subjects stood with eyes closed. Body sway was analyzed by computing root mean square sway measures and by a frequency-response function analysis that characterized the amplitude (gain) and timing (phase) of body sway over a frequency range of 0.017-2.2 Hz. Root mean square sway measures showed a reduction of surface stimulus evoked body sway for most vibrotactile feedback settings compared to control conditions. However, frequency-response function analysis showed that the sway reduction was due primarily to a reduction in sway below about 0.5 Hz, whereas there was actually an enhancement of sway above 0.6 Hz. Finally, we created a postural model that accounted for the experimental results and gave insight into how vibrotactile information was incorporated into the postural control system. C1 [Goodworth, Adam D.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. [Wall, Conrad, III] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Peterka, Robert J.] Oregon Hlth & Sci Univ, Inst Neurol Sci, Beaverton, OR 97006 USA. RP Goodworth, AD (reprint author), Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. EM goodwora@ohsu.edu; cwall@mit.edu; peterkar@ohsu.edu FU National Institutes of Health [DC6201, T32DC005945, AG17960] FX This work was supported by the National Institutes of Health Grant DC6201, Grant T32DC005945, and Grant AG17960. NR 25 TC 18 Z9 18 U1 4 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD AUG PY 2009 VL 17 IS 4 BP 397 EP 408 DI 10.1109/TNSRE.2009.2023309 PG 12 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 482PD UT WOS:000268900300012 PM 19497820 ER PT J AU Mitchell, J Sullam, PM AF Mitchell, Jennifer Sullam, Paul M. TI Streptococcus mitis Phage-Encoded Adhesins Mediate Attachment to alpha 2-8-Linked Sialic Acid Residues on Platelet Membrane Gangliosides SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE GLYCOPROTEINS GSPB; CLUMPING FACTOR-A; HAEMOPHILUS-INFLUENZAE; INFECTIVE ENDOCARDITIS; STAPHYLOCOCCUS-AUREUS; NEISSERIA-MENINGITIDIS; PROTEINS PBLA; IB-ALPHA; BINDING; GORDONII AB The direct binding of bacteria to human platelets contributes to the pathogenesis of infective endocarditis. Platelet binding by Streptococcus mitis strain SF100 is mediated in part by two bacteriophage-encoded proteins, PblA and PblB. However, the platelet membrane receptor for these adhesins has been unknown. In this study, we demonstrate that these proteins mediate attachment of bacterial cells to sialylated gangliosides on the platelet cell surface. Desialylation of human platelet monolayers reduced adherence of SF100, whereas treatment of the platelets with N- or O-glycanases did not affect platelet binding. Treatment of platelets with sialidases having different linkage specificities showed that removal of alpha 2-8-linked sialic acids resulted in a marked reduction in bacterial binding. Preincubation of SF100 with ganglioside GD3, a glycolipid containing alpha 2-8-linked sialic acids that is present on platelet membranes, blocked subsequent binding of this strain to these cells. In contrast, GD3 had no effect on the residual binding of platelets by strain PS344, an isogenic Delta pblA Delta pblB mutant. Preincubating platelets with specific monoclonal antibodies to ganglioside GD3 also inhibited binding of SF100 to platelets, but again, they had no effect on binding by PS344. When the direct binding of S. mitis strains SF100 and PS344 to immobilized gangliosides was tested, binding of PS344 to GD3 was reduced by 70% compared to the parent strain. These results indicated that platelet binding by SF100 is mediated by the interaction of PblA and PblB with alpha 2-8-linked sialic acids on ganglioside GD3. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Sullam, PM (reprint author), VA Med Ctr 111W, Div Infect Dis, 4150 Clement St, San Francisco, CA 94121 USA. EM paul.sullam@ucsf.edu FU Department of Veterans Affairs; National Institutes of Health [R01 AI041513, R01 AI057433] FX This study was supported by the Department of Veterans Affairs and by grants R01 AI041513 and R01 AI057433 from the National Institutes of Health. NR 29 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2009 VL 77 IS 8 BP 3485 EP 3490 DI 10.1128/IAI.01573-08 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 471ZX UT WOS:000268098400040 PM 19506011 ER PT J AU Sahani, DV Kambadakone, AR AF Sahani, Dushyant V. Kambadakone, Avinash R. TI Crohn's Disease and Radiation Exposure: It's Time We Got Our Act Together? SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID BOWEL FOLLOW-THROUGH; CT; ENTEROGRAPHY; MDCT C1 [Sahani, Dushyant V.; Kambadakone, Avinash R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD AUG PY 2009 VL 15 IS 8 BP 1278 EP 1280 DI 10.1002/ibd.20836 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 482FD UT WOS:000268869000025 PM 19107775 ER PT J AU Sheu, CC Zhai, RH Wang, ZX Gong, MN Tejera, P Chen, F Su, L Thompson, BT Christiani, DC AF Sheu, Chau-Chyun Zhai, Rihong Wang, Zhaoxi Gong, Michelle N. Tejera, Paula Chen, Feng Su, Li Thompson, B. Taylor Christiani, David C. TI Heme Oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome SO INTENSIVE CARE MEDICINE LA English DT Article DE Acute respiratory distress syndrome; Genetic susceptibility; Haplotypes; Heme oxygenase-1; Microsatellite polymorphism; Molecular epidemiology ID ACUTE LUNG INJURY; GENE PROMOTER POLYMORPHISM; CARBON-MONOXIDE; PROVIDES PROTECTION; SUSCEPTIBILITY; DISEASE; EXPRESSION; OUTCOMES; HEME-OXYGENASE-1; TRANSPLANTATION AB Heme oxygenase-1 (HO-1) acts in cytoprotection against acute lung injury. The polymorphic (GT) (n) repeat in the HO-1 gene (HMOX1) promoter regulates HMOX1 expression. We investigated the associations of HMOX1 polymorphisms with acute respiratory distress syndrome (ARDS) risk and plasma HO-1 levels. Unmatched, nested case-control study. Academic medical center. Consecutive patients with ARDS risk factors upon ICU admission were prospectively enrolled. Cases were 437 Caucasians who developed ARDS and controls were 1,014 Caucasians who did not. We genotyped the (GT) (n) polymorphism and three tagging single nucleotide polymorphisms (tSNPs) in 1,451 patients, and measured the plasma HO-1 levels in 106 ARDS patients. We clustered the (GT) (n) repeats into: S-allele (< 24 repeats), M-allele (24-30 repeats) and L-allele (a parts per thousand yen31 repeats). We found that longer (GT) (n) repeats were associated with reduced ARDS risk (P (trend) = 0.004 for both alleles and genotypes), but no individual tSNP was associated with ARDS risk. HMOX1 haplotypes were significantly associated with ARDS risk (global test, P = 0.016), and the haplotype S-TAG was associated with increased ARDS risk (OR, 1.75; 95% CI, 1.15-2.68; P = 0.010). Intermediate-phenotype analysis showed longer (GT) (n) repeats were associated with higher plasma HO-1 levels (P (trend) = 0.019 for alleles and 0.027 for genotypes). Longer (GT) (n) repeats in the HMOX1 promoter are associated with higher plasma HO-1 levels and reduced ARDS risk. The common haplotype S-TAG is associated with increased ARDS risk. Our results suggest that HMOX1 variation may modulate ARDS risk through the promoter microsatellite polymorphism. C1 [Sheu, Chau-Chyun; Zhai, Rihong; Wang, Zhaoxi; Tejera, Paula; Chen, Feng; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Thompson, B. Taylor; Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. [Gong, Michelle N.] Mt Sinai Sch Med, Div Pulm & Crit Care Med, New York, NY 10029 USA. [Sheu, Chau-Chyun] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Kaohsiung 807, Taiwan. [Sheu, Chau-Chyun] Kaohsiung Med Univ, Coll Med, Fac Resp Therapy, Kaohsiung 807, Taiwan. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institutes of Health, USA [HL60710, ES00002] FX This study was supported by grants HL60710 and ES00002 from National Institutes of Health, USA. The authors would like to thank Weiling Zhang, Kelly McCoy, Thomas McCabe, Julia Shin, and Hanae Fujii-Rios for patient recruitment; Andrea Shafer and Starr Sumpter for research support; Maureen Convery for laboratory expertise; Janna Frelich for data management; and the patients and staff of ICUs at Massachusetts General Hospital. NR 40 TC 40 Z9 43 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD AUG PY 2009 VL 35 IS 8 BP 1343 EP 1351 DI 10.1007/s00134-009-1504-6 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 473ZE UT WOS:000268251100005 PM 19526221 ER PT J AU Blankstein, R Okada, DR Rocha-Filho, JA Rybicki, FJ Brady, TJ Cury, RC AF Blankstein, Ron Okada, David R. Rocha-Filho, Jose A. Rybicki, Frank J. Brady, Thomas J. Cury, Ricardo C. TI Cardiac myocardial perfusion imaging using dual source computed tomography SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Ischemia; Myocardial perfusion imaging; Coronary artery disease; Computed tomography ID CORONARY-ARTERY-DISEASE; COMPREHENSIVE ASSESSMENT; ANGIOGRAPHY; QUANTIFICATION; CT AB The ability to simultaneously visualize both coronary atherosclerosis and myocardial perfusion may enable the assessment of the anatomical burden and physiological significance of coronary lesions in a single exam. In this paper we introduce a novel use of the dual source CT: pharmacologically induced stress myocardial perfusion imaging, (SP-DSCT). We describe an experimental protocol by which we used the DSCT to assess both stress and rest myocardial perfusion in order to identify areas of infarcted and ischemic myocardium. Based on our initial investigations, this protocol is feasible and can be used to identify hemodynamically significant stenosis. Nevertheless, further studies are required to determine the incremental value of this technique to traditional coronary CT angiography and/or nuclear stress myocardial perfusion imaging. C1 [Blankstein, Ron; Rybicki, Frank J.] Brigham & Womens Hosp, Dept Med & Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Blankstein, Ron; Okada, David R.; Rocha-Filho, Jose A.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Blankstein, Ron; Okada, David R.; Rocha-Filho, Jose A.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Miami, FL USA. RP Blankstein, R (reprint author), Brigham & Womens Hosp, Dept Med & Radiol, Noninvas Cardiovasc Imaging Program, 75 Francis St,ASB1-L1, Boston, MA 02115 USA. EM rblankstein@partners.org NR 15 TC 13 Z9 14 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD AUG PY 2009 VL 25 BP 209 EP 216 DI 10.1007/s10554-009-9438-1 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 468OD UT WOS:000267828000007 ER PT J AU Melrose, RJ Campa, OM Harwood, DG Osato, S Mandelkern, MA Sultzer, DL AF Melrose, Rebecca J. Campa, Olivia M. Harwood, Dylan G. Osato, Sheryl Mandelkern, Mark A. Sultzer, David L. TI The neural correlates of naming and fluency deficits in Alzheimer's disease: an FDG-PET study SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 12th Biennial Cognitive Aging Conference CY APR, 2008 CL Atlanta, GA DE Alzheimer's disease; language; naming; temporal lobe; inferior frontal gyrus; PET imaging ID SEMANTIC MEMORY LOSS; GLUCOSE-UTILIZATION; VERBAL FLUENCY; DEMENTIA; LANGUAGE; IMPAIRMENT; RETRIEVAL; KNOWLEDGE; BATTERY; SYSTEMS AB Objective To examine the neural processes associated with language deficits in Alzheimer's disease (AD), and in particular to elucidate the correlates of confrontation naming and word retrieval impairments. Methods Sixty patients with probable AD were included. Confrontation naming was assessed using the number of words spontaneously named correctly on the Boston Naming Test. We recorded the number of additional words stated following phonemic cuing. We also assessed phonemic (FAS) and semantic (supermarket items) fluency. We then correlated performance on each measure with resting cortical metabolic activity using FDG-PET images. Results We found that poorer ability to spontaneously name an object was associated with hypometabolism of bilateral inferior temporal lobes. In contrast, when a phonemic cue was provided, successful naming under this condition was associated with higher metabolic activity in bilateral inferior frontal gyrus (IFG), right superior frontal gyrus (SFG), left temporal, and occipital regions. Consistent with these findings, we found that poorer semantic fluency was associated with hypometabolism in regions including both IFG and temporal regions, and poorer phonemic fluency was associated with hypometabolism in only left IFG. Across analyses, measures that required cued retrieval were associated with metabolism in the left IFG, whereas measures taxing semantic knowledge were associated with metabolic rate of left temporal cortex. Conclusions Naming deficits in AD reflect compromise to temporal regions involved in the semantic knowledge network, and frontal regions involved in the controlled retrieval of information from that network. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Melrose, Rebecca J.; Campa, Olivia M.; Harwood, Dylan G.; Osato, Sheryl; Sultzer, David L.] VA Greater Angeles Healthcare Syst, Clin Neurosci Res Lab, Los Angeles, CA USA. [Melrose, Rebecca J.; Harwood, Dylan G.; Osato, Sheryl; Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mandelkern, Mark A.] VA Greater Angeles Healthcare Syst, Nucl Med Serv, Irvine, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Melrose, RJ (reprint author), 11301 Wilshire Blvd,116AE, Los Angeles, CA 90073 USA. EM rjmelrose@ucla.edu FU NIMH NIH HHS [R01 MH056031-03, MH56301] NR 39 TC 32 Z9 32 U1 2 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD AUG PY 2009 VL 24 IS 8 BP 885 EP 893 DI 10.1002/gps.2229 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 477XM UT WOS:000268552300012 PM 19296551 ER PT J AU Mathalon, DH Jorgensen, KW Roach, BJ Ford, JM AF Mathalon, Daniel H. Jorgensen, Kasper W. Roach, Brian J. Ford, Judith M. TI Error detection failures in schizophrenia: ERPs and FMRI SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article; Proceedings Paper CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol DE Error detection; Schizophrenia; NoGo task; ERN; ERPs; FMRI ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; MEDIAL FRONTAL-CORTEX; BRAIN POTENTIALS; NEURAL SYSTEM; CORRECTING BEHAVIOR; RESPONSE SELECTION; PERFORMANCE; DOPAMINE; TASK AB Self-monitoring of actions, critical for guiding goal-directed behavior, is deficient in schizophrenia. Defective error-monitoring may reflect more general self-monitoring deficiencies. Prior studies have shown that the error-related negativity (ERN) component of the event-related potential (ERP) is smaller in patients with schizophrenia. Other studies using functional magnetic resonance imaging (FMRI) have shown the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), both critical for error detection, to be less responsive to errors in patients with schizophrenia. In the present study, both ERP and FMRI data were collected while 11 patients with schizophrenia and 10 healthy controls performed a Go-NoGo task requiring a button press to Xs (p = .88) while withholding responses to Ks (p = .12). We measured the ERN and ACC and DLPFC activations to false alarms. The task elicited a robust ERN and modest activations in ACC and DLPFC to false alarms. As expected, ERN was larger in controls than patients. However, ACC and DLPFC activations were not greater in controls than patients. Surprisingly, DLPFC was more activated by errors in patients than controls. ERPs may be superior to fMRI for assessing error processing abnormalities in schizophrenia because (1) ERNs can be measured precisely without needing to control for the multiple comparisons of FMRI, and (2) ERPs have the temporal precision to detect transient activity necessary for error detection and on-the-fly behavioral adjustments. Published by Elsevier B.V. C1 San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM daniel.mathalon@ucsf.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974 FU NIMH NIH HHS [K02 MH067967, K02 MH067967-08, MH 40052, MH 58262, R01 MH040052, R01 MH058262, R01 MH058262-08A1] NR 79 TC 29 Z9 31 U1 8 U2 10 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 AUG PY 2009 VL 73 IS 2 BP 109 EP 117 DI 10.1016/j.ijpsycho.2009.02.005 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 478YW UT WOS:000268625700009 PM 19414043 ER PT J AU Nanda, A Chen, MH Renshaw, AA D'Amico, AV AF Nanda, Akash Chen, Ming-Hui Renshaw, Andrew A. D'Amico, Anthony V. TI GLEASON PATTERN 5 PROSTATE CANCER: FURTHER STRATIFICATION OF PATIENTS WITH HIGH-RISK DISEASE AND IMPLICATIONS FOR FUTURE RANDOMIZED TRIALS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol DE Prostate cancer; Prostate-specific antigen (PSA); Gleason score; Tertiary Grade 5; Stratification ID SMALL-CELL CARCINOMA; RADICAL PROSTATECTOMY; CONSENSUS CONFERENCE; BIOCHEMICAL FAILURE; RADIATION-THERAPY; OUTCOMES; SCORE; RECOMMENDATIONS; PREDICT; UPDATE AB Purpose: To compare prostate-specific antigen (PSA) outcomes in a cohort of men with high-risk prostate cancer based on the presence or absence of any Gleason Grade 5 component (primary, secondary, or tertiary). Methods and Materials: Our study cohort consisted of 312 men with T1c-T3N0M0 prostate cancer with Gleason Scores of 7 with tertiary Grade 5, 8, or 9-10 who underwent radical prostatectomy or external beam radiotherapy with or without androgen suppression therapy. Cox regression multivariable analysis was used to assess whether a difference existed in risk of PSA recurrence in men with Gleason Score of 9-10 compared with those with Gleason Score of 8 and 7 with tertiary Grade 5, adjusting for treatment, age, and known prostate cancer prognostic factors. Results: After a median follow-up of 5.7 years, men with a Gleason Score of 8 had a lower risk of PSA recurrence than those with a Gleason Score of 9-10 (hazard ratio, 0.74; 95% confidence interval, 0.52-1.05; p = 0.09). Conversely, men with a Gleason Score of 7 with tertiary Grade 5 had a similar risk of PSA recurrence compared with men with a Gleason Score of 9-10 (hazard ratio, 1.08; 95% confidence interval, 0.60-1.94; p = 0.81). Median times to PSA failure for men with Gleason Scores of 9-10,7 with tertiary Grade 5, and 8 were 4.5, 5.0, and 5.4 years, respectively. Conclusions: Our results highlight the importance of further substratification of the high-risk Gleason Score category of 8-10 into 8 vs. 9, 10, and 7 with tertiary Grade 5. (C) 2009 Elsevier Inc. C1 [Nanda, Akash] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Renshaw, Andrew A.] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Nanda, A (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM ananda@partners.org NR 28 TC 34 Z9 36 U1 0 U2 4 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 AUG 1 PY 2009 VL 74 IS 5 BP 1419 EP 1423 DI 10.1016/j.ijrobp.2008.10.027 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 475GH UT WOS:000268346100017 PM 19131185 ER PT J AU Woodward, WA Bristow, RG Clarke, MF Coppes, RP Cristofanilli, M Duda, DG Fike, JR Hambardzumyan, D Hill, RP Jordan, CT Milas, L Pajonk, F Curran, WJ Dicker, AP Chen, Y AF Woodward, Wendy A. Bristow, Robert G. Clarke, Michael F. Coppes, Robert P. Cristofanilli, Massimo Duda, Dan G. Fike, John R. Hambardzumyan, Dolores Hill, Richard P. Jordan, Craig T. Milas, Luka Pajonk, Frank Curran, Walter J. Dicker, Adam P. Chen, Yuhchyau TI RADIATION THERAPY ONCOLOGY GROUP TRANSLATIONAL RESEARCH PROGRAM STEM CELL SYMPOSIUM: INCORPORATING STEM CELL HYPOTHESES INTO CLINICAL TRIALS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Stem cell; Radiation therapy; Cancer; Radiobiology; Clonogens ID ENDOTHELIAL PROGENITOR CELLS; NEURAL PRECURSOR CELLS; BONE-MARROW; BREAST-CANCER; IN-VIVO; HIPPOCAMPAL NEUROGENESIS; TUMOR ANGIOGENESIS; SALIVARY-GLANDS; ADULT NEUROGENESIS; PERIVASCULAR NICHE AB At a meeting of the Translation Research Program of the Radiation Therapy Oncology Group held in early 2008, attendees focused on updating the current state of knowledge in cancer stem cell research and discussing ways in which this knowledge can be translated into clinical use across all disease sites. This report summarizes the major topics discussed and the future directions that research should take. Major conclusions of the symposium were that the flow cytometry of multiple markers in fresh tissue would remain the standard technique of evaluating cancer-initiating cells and that surrogates need to be developed for both experimental and clinical use. (C) 2009 Elsevier Inc. C1 [Woodward, Wendy A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Bristow, Robert G.; Hambardzumyan, Dolores; Hill, Richard P.] Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada. [Clarke, Michael F.] Stanford Univ, Palo Alto, CA 94304 USA. [Coppes, Robert P.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Duda, Dan G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fike, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hambardzumyan, Dolores] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Jordan, Craig T.; Chen, Yuhchyau] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Pajonk, Frank] Univ Calif Los Angeles, Los Angeles, CA USA. [Curran, Walter J.; Dicker, Adam P.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Woodward, WA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM wwoodward@mdanderson.org RI Pajonk, Frank/E-4247-2010; Coppes, Robert P/B-4089-2008; OI Coppes, Robert P/0000-0001-5503-1064; Dicker, Adam/0000-0003-0733-3337 FU RTOG [U10CA21661, U24 CA114734] FX Supported by The RTOG grants # U10CA21661 and #U24 CA114734. NR 62 TC 9 Z9 9 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 AUG 1 PY 2009 VL 74 IS 5 BP 1580 EP 1591 DI 10.1016/j.ijrobp.2009.03.047 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 475GH UT WOS:000268346100041 PM 19540073 ER PT J AU Lewis, DR Clegg, LX Johnson, NJ AF Lewis, D. R. Clegg, L. X. Johnson, N. J. TI Lung disease mortality in the United States: the Nationa Longitudinal Mortality Study SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE cancer; mortality; lung diseases; health disparities; income; education ID OBSTRUCTIVE PULMONARY-DISEASE; GLOBAL BURDEN; CANCER; SMOKING; RACE/ETHNICITY; EPIDEMIOLOGY; DEATHS; TRENDS; AREA AB SETTING: The National Longitudinal Mortality Study (NLMS) offers the advantage of assessing mortality in a representative population of the United States. OBJECTIVE: To evaluate health disparities associated with lung cancer and chronic obstructive pulmonary disease (COPD) mortality in the United States and whether these associations are similar between these outcomes. DESIGN: The NLMS is a prospective study. Data from NLMS cohort years 1985, 1992, 1993, 1995 and 1.996 were included, representing nearly 1.5 million person-years. Lung cancer and COPD mortality relative risks (RRs) from Cox regression analysis, including residential characteristics, marital status, education, health insurance and family income, were evaluated. RESULTS: By 1998, 1273 lung cancer deaths and 772 COPD deaths occurred. Lung cancer mortality rates were approximately two times higher than COPD mortality rates among race and ethnic groups. Cox regression analysis revealed that low education (RR = 1.77, significant, P = 0.01) and low family income (RR = 1.50, significant, P = 0.01) are associated with lung cancer and COPD mortality, controlling for age, race/ethnicity, sex and smoking status. CONCLUSIONS: COPD and lung cancer mortality have similar associations with health disparity indicators in the NLMS data, with some differences in the magnitude of the effect. C1 [Lewis, D. R.] NCI, Surveillance Res Program, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Clegg, L. X.] US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, Washington, DC USA. [Johnson, N. J.] US Bur Census, Suitland, MD USA. RP Lewis, DR (reprint author), NCI, Surveillance Res Program, NIH, US Dept Hlth & Human Serv, 6116 Execut Blvd,Room 504,MSC 8316, Bethesda, MD 20892 USA. EM lewisde@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 35 TC 13 Z9 13 U1 1 U2 5 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 EI 1815-7920 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD AUG PY 2009 VL 13 IS 8 BP 1008 EP 1014 PG 7 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 477JW UT WOS:000268516300014 PM 19723382 ER PT J AU Seon, JK Park, SJ Lee, KB Li, G Kozanek, M Song, EK AF Seon, Jong Keun Park, Sang Jin Lee, Keun Bae Li, Gang Kozanek, Michal Song, Eun Kyoo TI Functional comparison of total knee arthroplasty performed with and without a navigation system SO INTERNATIONAL ORTHOPAEDICS LA English DT Article ID COMPUTER-ASSISTED NAVIGATION; CONVENTIONAL TECHNIQUE; CORONAL ALIGNMENT; REPLACEMENT; EXPERIENCE; PLACEMENT; SUPPORT; TRIAL AB This study was undertaken to compare the clinical and radiological outcomes achieved using total knee arthroplasty (TKA) with and without a navigation system. This study included 43 TKAs performed with a navigation system and 42 TKAs without a navigation system with a minimum two-year follow-up. We compared clinical outcomes including range of motion, Hospital for Special Surgery (HSS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at the final follow-up. For radiological comparisons, we evaluated radiological alignment on standing radiographs of knees. HSS and WOMAC scores showed significant improvements at final follow-ups in both groups, but showed no significant inter-group differences (p > 0.05). Similarly, no significant differences were observed in range of motion (p = 0.962). TKAs performed with navigation showed significantly better outcomes in terms of mechanical angle and prosthetic alignment outliers than TKAs performed without navigation. However, we could not find any differences in functional outcomes between TKAs performed with or without a navigation system. C1 [Seon, Jong Keun; Park, Sang Jin; Song, Eun Kyoo] Chonnam Natl Univ, Hwasun Hosp, Ctr Joint Dis, Hwasungun 501757, Cheollamando, South Korea. [Li, Gang; Kozanek, Michal] Massachusetts Gen Hosp, Dept Orthoped, Bioengn Labs, Boston, MA 02114 USA. [Lee, Keun Bae] Chonnam Natl Univ Hosp, Dept Orthoped, Kwangju, South Korea. RP Song, EK (reprint author), Chonnam Natl Univ, Hwasun Hosp, Ctr Joint Dis, 160 Ilsimri Hwasuneup, Hwasungun 501757, Cheollamando, South Korea. EM seonbell@yahoo.co.kr NR 20 TC 33 Z9 36 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD AUG PY 2009 VL 33 IS 4 BP 987 EP 990 DI 10.1007/s00264-008-0594-z PG 4 WC Orthopedics SC Orthopedics GA 475AK UT WOS:000268326900017 PM 18587573 ER PT J AU Haddadin, RI Oh, DJ Kang, MH Filippopoulos, T Gupta, M Hart, L Sage, EH Rhee, DJ AF Haddadin, Ramez I. Oh, Dong-Jin Kang, Min Hyung Filippopoulos, Theodoros Gupta, Meenakashi Hart, Lois Sage, E. Helene Rhee, Douglas J. TI SPARC-null Mice Exhibit Lower Intraocular Pressures SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HUMAN TRABECULAR MESHWORK; OPEN-ANGLE GLAUCOMA; MATRIX METALLOPROTEINASES; NONINVASIVE MEASUREMENT; SECRETED PROTEIN; GENE-EXPRESSION; NORMAL-EYES; HUMAN LENS; RAT EYE; MOUSE AB PURPOSE. SPARC is a matricellular protein that is highly expressed in remodeling tissues, including the trabecular meshwork and ciliary body. The hypothesis for the study was that SPARC contributes to the regulation of intraocular pressure (IOP). The IOPs of SPARC-null mice, their corresponding wildtype (WT), and heterozygous animals were compared. METHODS. Diurnal and nocturnal IOPs of C57Bl/6x129SvJ WT, SPARC-null, and heterozygous mice were measured. Fluoro-photometric measurements were made to assess aqueous turnover. Central corneal thickness (CCT) was measured using histology, ultrasound biomicroscopy, and optical coherence tomography. Iridocorneal angles were examined using light microscopy (LM). RESULTS. During the day, the mean IOP of SPARC-null mice (n = 142, 16.9 +/- 2.4 mm Hg) was lower than that of both WT mice (n = 104, 19.9 +/- 2.9 mm Hg; P < 10(-12)), and heterozygotes (n = 38, 19.3 +/- 2.5 mm Hg; P < 10(-4)). At night, SPARC-null mice also exhibited a blunted increase in IOP in comparison to WT and heterozygous mice. CCTs were not significantly different between WT and SPARC-null mice. Heterozygous mice tended to have thicker corneas (3.4%). Fluoro-photometric measurements suggest that aqueous turnover rates in SPARC-null mice are equal to if not greater than rates in WT mice. LM of the SPARC-null iridocorneal angle revealed morphology that is indistinguishable from WT. CONCLUSIONS. SPARC-null mice have lower IOPs than do their WT counterparts with equal CCTs. The rate of aqueous turnover suggests that the mechanism is enhanced outflow resistance. (Invest Ophthalmol Vis Sci. 2009; 50: 3771-3777) DOI: 10.1167/iovs.08-2489 C1 [Haddadin, Ramez I.; Oh, Dong-Jin; Kang, Min Hyung; Filippopoulos, Theodoros; Gupta, Meenakashi; Hart, Lois; Rhee, Douglas J.] Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Sage, E. Helene] Benaroya Res Inst Virginia Mason, Hope Heart Program, Seattle, WA USA. RP Rhee, DJ (reprint author), Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com FU Fight for Sight, National Eye Institute Core [EY 014104]; Massachusetts Lions Eye Research Foundation; Research to Prevent Blindness FX Supported by Fight for Sight, National Eye Institute Core Grant EY 014104 to the Massachusetts Eye and Ear Infirmary, Massachusetts Lions Eye Research Foundation, and Research to Prevent Blindness. NR 53 TC 44 Z9 44 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2009 VL 50 IS 8 BP 3771 EP 3777 DI 10.1167/iovs.08-2489 PG 7 WC Ophthalmology SC Ophthalmology GA 475XA UT WOS:000268398000031 PM 19168904 ER PT J AU El Annan, J Chauhan, SK Ecoiffier, T Zhang, Q Saban, DR Dana, R AF El Annan, Jaafar Chauhan, Sunil K. Ecoiffier, Tatiana Zhang, Qiang Saban, Daniel R. Dana, Reza TI Characterization of Effector T Cells in Dry Eye Disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SJOGRENS-SYNDROME; CD40 LIGAND; KERATOCONJUNCTIVITIS SICCA; ALLOGRAFT-REJECTION; CHEMOKINE RECEPTORS; MULTIPLE-SCLEROSIS; DESICCATING STRESS; OCULAR SURFACE; LYMPH-NODES; TEAR FLUID AB PURPOSE. Dry eye disease (DED) is associated with ocular surface inflammation that is thought to be mediated primarily by CD4 T cells. The purpose of this study was to investigate whether this T cell-mediated immune response is generated in the lymphoid compartment and to characterize the functional phenotype of the T cells activated in DED. METHODS. DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled environment chamber and to systemic scopolamine. T cells from regional draining lymph nodes (LNs) of DED mice and normally sighted mice were analyzed for surface activation markers (CD69 and CD154), chemokine and cytokine receptors, and proliferation potential. RESULTS. Draining LNs of DED mice showed increased frequencies of CD69- and CD154-expressing T cells with higher proliferative capacity. In addition, these LN T cells primarily showed a helper T-cell (Th)1 phenotype, expressing significantly higher levels of IFN-gamma and IL-12R beta 2 but not IL-4R. Similarly, the LNs of DED mice showed significantly increased frequencies of T cells expressing CXCR3 and CCR5, but not CCR4, suggesting a bias toward a Th1 phenotype. CONCLUSIONS. These data demonstrate that a Th1-type immune response is induced in the regional LNs of DED mice. The identification of specific cytokine/chemokine receptors over-expressed by these T cells may signify potential novel targets/strategies for the treatment of DED. (Invest Ophthalmol Vis Sci. 2009; 50: 3802-3807) DOI: 10.1167/iovs.08-2417 C1 [El Annan, Jaafar; Chauhan, Sunil K.; Ecoiffier, Tatiana; Zhang, Qiang; Saban, Daniel R.; Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [El Annan, Jaafar; Chauhan, Sunil K.; Ecoiffier, Tatiana; Zhang, Qiang; Saban, Daniel R.; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU Allergan Inc. FX Supported in part by a research grant from Allergan Inc. NR 38 TC 45 Z9 46 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2009 VL 50 IS 8 BP 3802 EP 3807 DI 10.1167/iovs.08-2417 PG 6 WC Ophthalmology SC Ophthalmology GA 475XA UT WOS:000268398000035 PM 19339740 ER PT J AU Hwang, AS Gall, V Liang, MH AF Hwang, Andrew S. Gall, Victoria Liang, Matthew H. TI Evaluation of the Internet for Finding Persons With Undiagnosed Rheumatoid Arthritis and Systemic Lupus Erythematosus SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE screening; case finding; internet; rheumatoid arthritis; systemic lupus erythematosus; early diagnosis ID INFORMATION-SEEKING; HEALTH INFORMATION; MEDICAL-CARE; DISEASE; ONSET; INFLIXIMAB; ECOLOGY; BENEFIT; TRIAL AB Background: The internet is used by many new rheumatology patients before visiting a health care provider, and is also used for health education, for recruiting study participants, administering surveys, conducting clinical trials, data entry and management of multicenter trials, and providing a forum for patients to share experiences in chat rooms. The internet has not been used for nor evaluated for public health applications. Objectives: We evaluated the internet for early detection and referral of individuals with "typical" early symptoms of undiagnosed rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods: The websites and selected links identified by search terms of typical symptoms were evaluated for health information quality, readability, and whether or not the sites prioritized possibilities and suggested actions. Results: None of the websites examined were completely suitable for finding undiagnosed persons with early RA or SLE. Although the websites had accurate information, their reading levels were too high for the average reader, and were generally poor in terms of giving a differential diagnosis, prioritizing the possibilities and none provided an algorithm for action. Conclusions: Internet sites could be enhanced for early detection and referral. The internet has become an important factor in clinical practice and physicians are increasingly explaining or responding to the information that their patients find on the internet. Our study shows that the information available to individuals with undiagnosed RA and SLE is likely to be of little help to them and could delay their seeking appropriate attention. C1 [Liang, Matthew H.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med, Boston, MA 02115 USA. [Hwang, Andrew S.] Brown Univ, Providence, RI 02912 USA. [Gall, Victoria] Boston VA Healthcare Syst, Rheumatol Sect, Boston, MA USA. RP Liang, MH (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM mliang@partners.org FU NIH [P60 AR47782]; Rheuminations; Molson Family Foundation; Arthritis Foundation; Lupus Foundation FX Mr Hwang was the recipient of the Gina Finzi Memorial Student Summer Fellowship from the Lupus Foundation. NR 26 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD AUG PY 2009 VL 15 IS 5 BP 218 EP 222 DI 10.1097/RHU.0b013e3181b126d3 PG 5 WC Rheumatology SC Rheumatology GA 481QP UT WOS:000268826800002 PM 19590439 ER PT J AU Lee, JE Kim, KH Park, HJ Lee, SJ Jea, SY AF Lee, Joo Eun Kim, Kyeong Hwan Park, Hong Jae Lee, Soo Jung Jea, Seung Youn TI Morning glory disk anomaly: A computerized analysis of contractile movements with implications for pathogenesis SO JOURNAL OF AAPOS LA English DT Article ID SMOOTH-MUSCLE; OPTIC-NERVE; ASSOCIATION; CELLS AB Excavated optic disk anomalies, such as morning glory disk anomaly, peripapillary staphyloma, and optic disk coloboma, are rare.(1) Contractile movement of a given lesion is even rarer. Only 4 patients with morning glory disk anomalies accompanied by contractile movement have been reported.(2,5) We offer a computerized analysis of the contraction, observable on a video recording of a patient with this disorder, with an explanation of the possible pathogenesis of the disorder. C1 [Lee, Joo Eun; Kim, Kyeong Hwan; Park, Hong Jae; Lee, Soo Jung] Maryknoll Med Ctr, Dept Ophthalmol, Pusan 600730, South Korea. [Lee, Joo Eun; Jea, Seung Youn] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Lee, JE (reprint author), Maryknoll Med Ctr, Dept Ophthalmol, 4-12 Daecheong Dong, Pusan 600730, South Korea. EM jooeun2@korea.com RI Kim, Kyeong Hwan/C-5036-2012 OI Kim, Kyeong Hwan/0000-0002-7359-663X NR 9 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD AUG PY 2009 VL 13 IS 4 BP 403 EP 405 DI 10.1016/j.jaapos.2009.02.006 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 484ZB UT WOS:000269088600018 PM 19683194 ER PT J AU Biederman, J Monuteaux, MC Faraone, SV Mick, E AF Biederman, Joseph Monuteaux, Michael C. Faraone, Stephen V. Mick, Eric TI Parsing the Associations Between Prenatal Exposure to Nicotine and Offspring Psychopathology in a Nonreferred Sample SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; MATERNAL SMOKING; CONDUCT DISORDER; OPPOSITIONAL DEFIANT; ANTISOCIAL-BEHAVIOR; FAMILIAL SUBTYPE; PREGNANCY; RISK; BOYS; CHILDREN AB Purpose: Several studies have suggested an association between maternal smoking during pregnancy and both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) in the offspring of women who smoke during pregnancy. However, it is unclear whether one or both of the documented links are spurious, given the considerable comorbidity between these disorders. The main aim of this study was to disentangle the association between maternal smoking during pregnancy with psychopathological outcomes, adjusting for possible confounders. Methods: Two large, identically designed, longitudinal, case-control family studies of male and female probands with and without ADHD were combined. We used data from the nonreferred siblings of the probands from both studies (n = 536). All subjects were blindly assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of exposure to maternal smoking during pregnancy. Results: Among all siblings, maternal smoking during pregnancy was significantly associated with ADHD, independent of CD and other covariates. In contrast, maternal smoking during pregnancy was a risk factor for CD only in siblings of control probands, after adjusting for covariates. Conclusions: These results support the hypothesis that maternal smoking during pregnancy is a risk factor for both ADHD and CD, independently of each other. However, the risk for CD appears to be conditional on family risk status. (c) 2009 Society for Adolescent Medicine. All rights reserved. C1 [Biederman, Joseph; Monuteaux, Michael C.; Mick, Eric] Massachusetts Gen Hosp, Dept Psychiat, Clin Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Monuteaux, Michael C.; Mick, Eric] Massachusetts Gen Hosp, Dept Psychiat, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, SUNY Genet Res Program, Syracuse, NY USA. RP Monuteaux, MC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Clin Program Pediat Psychopharmacol & Adult ADHD, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM mmonuteaux@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU USPHS (NICHD) [5RO1 HD-36317-07] FX This work was supported in part by a grant from USPHS (NICHD), grant 5RO1 HD-36317-07 (to J.B.), and a grant from USPHS (NICHD), 5RO1 HD-36317-07 (to J.B.). NR 35 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD AUG PY 2009 VL 45 IS 2 BP 142 EP 148 DI 10.1016/j.jadohealth.2008.12.003 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 477YZ UT WOS:000268556200007 PM 19628140 ER PT J AU Simons, FER Clark, S Camargo, CA AF Simons, F. Estelle R. Clark, Sunday Camargo, Carlos A., Jr. TI Anaphylaxis in the community: Learning from the survivors SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Epinephrine; adrenaline; autoinjector; anaphylaxis; acute allergic reaction; food allergy; insect sting allergy ID EMERGENCY-DEPARTMENT VISITS; FOOD-INDUCED ANAPHYLAXIS; LONG-TERM MANAGEMENT; ALLERGIC REACTIONS; EPINEPHRINE; CHILDREN; MULTICENTER AB Background: Most studies of anaphylaxis in the community focus on persons at risk who might, or might not, have experienced anaphylaxis. Objective: We sought to focus on survivors of anaphylaxis in the community and their experiences in using, or not using, an epinephrine autoinjector for first-aid treatment. Methods: An e-mail survey was conducted. Responses were anonymous and could not be traced to any person or location. Anaphylaxis was defined as the most severe sudden-onset allergic reaction ever experienced by the participants or a person for whom they were responsible (eg, a child). There were 17 core multiple-choice questions for all participants, with 16 additional questions for users who injected epinephrine either into themselves or someone else, and I additional question for nonusers. Results: Of the 1885 participants, 500 (27%) were epinephrine users, and 1385 (73%) were nonusers. The groups were similar with regard to multisystem organ involvement (82% vs 78%, P = .07) and many other aspects of anaphylaxis; however, epinephrine users were more likely (all P < .05) to report respiratory or shock symptoms; to report peanut, fish, or insect sting triggers; to be asthmatic; and to have taken or been given asthma medication on the day of the episode. Epinephrine users reported problems in deciding whether to give the injection, repeat the dose, and/or go to an emergency department. Nonusers reported not injecting epinephrine for various reasons, including use of an H(1)-antihistamine (38%), no prescription for epinephrine (28%), and/or a mild anaphylaxis episode (13%). Conclusions: In a unique population composed of 1885 survivors of anaphylaxis in the community, users of epinephrine autoinjectors for first-aid treatment were outnumbered by nonusers. The insights reported by epinephrine users and the reasons why nonusers did not inject epinephrine are documented. (J Allergy Clin Immunol 2009;124:301-6.) C1 [Simons, F. Estelle R.] Univ Manitoba, Dept Pediat & Child Hlth, CHIR Natl Training Program Allergy & Asthma, Fac Med, Winnipeg, MB, Canada. [Simons, F. Estelle R.] Univ Manitoba, Dept Immunol, CHIR Natl Training Program Allergy & Asthma, Fac Med, Winnipeg, MB, Canada. [Clark, Sunday] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15260 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Simons, FER (reprint author), 820 Sherbrook St, Winnipeg, MB R3A 1R9, Canada. EM lmcniven@hsc.mb.ca NR 30 TC 63 Z9 64 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2009 VL 124 IS 2 BP 301 EP 306 DI 10.1016/j.jaci.2009.03.050 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 482CD UT WOS:000268860400017 PM 19540575 ER PT J AU Camargo, CA Rachelefsky, G Schatz, M AF Camargo, Carlos A., Jr. Rachelefsky, Gary Schatz, Michael TI Managing asthma exacerbations in the emergency department: Summary of the National Asthma Education and Prevention Program Expert Panel Report 3 guidelines for the management of asthma exacerbations SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma exacerbation; emergency department; Expert Panel Report 3; acute asthma; respiratory failure ID INTRAVENOUS MAGNESIUM-SULFATE; RANDOMIZED CONTROLLED-TRIAL; PULSE OXIMETRY; SEVERITY SCORE; CHILDREN; ALBUTEROL; ADMISSION; HYDROCORTISONE; METAANALYSIS; TERBUTALINE C1 [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02114 USA. [Rachelefsky, Gary] Univ Calif Los Angeles, David Geffen Sch Med, Execut Care Ctr Asthma Allergy & Resp Dis, Los Angeles, CA 90095 USA. [Schatz, Michael] Kaiser Permanente Med Ctr, Dept Allergy, San Diego, CA USA. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. NR 49 TC 11 Z9 11 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2009 VL 124 IS 2 SU S BP S5 EP S14 DI 10.1016/j.jaci.2009.05.010 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 482CE UT WOS:000268860500002 PM 19647135 ER PT J AU Schatz, M Kazzi, AAN Brenner, B Camargo, CA Corbridge, T Krishnan, JA Nowak, R Rachelefsky, G AF Schatz, Michael Kazzi, Amin Antoine Nabih Brenner, Barry Camargo, Carlos A., Jr. Corbridge, Thomas Krishnan, Jerry A. Nowak, Richard Rachelefsky, Gary TI Joint Task Force Report: Supplemental Recommendations for the Management and Follow-Up of Asthma Exacerbations Introduction SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material DE Asthma exacerbation; acute asthma; emergency department; Expert Panel Report 3; noninvasive positive pressure ventilation; continuous positive airway pressure ventilation; bilevel positive airway pressure ventilation; respiratory failure; intubation; mechanical ventilation; discharge medications; corticosteroids; follow-up care; asthma specialist care C1 [Schatz, Michael] Kaiser Permanente Med Ctr, Dept Allergy, San Diego, CA 92111 USA. [Kazzi, Amin Antoine Nabih] Amer Univ Beirut, Dept Emergency Med, Beirut, Lebanon. [Brenner, Barry] Univ Hosp, Case Med Ctr, Case Western Reserve Sch Med, Dept Emergency Med, Cleveland, OH USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Corbridge, Thomas] Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 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. [Nowak, Richard] Henry Ford Hlth Syst, Dept Emergency Med, Detroit, MI USA. [Rachelefsky, Gary] Univ Calif Los Angeles, David Geffen Sch Med, Execut Care Ctr Asthma Allergy & Resp Dis, Los Angeles, CA 90095 USA. RP Schatz, M (reprint author), Kaiser Permanente Med Ctr, Dept Allergy, 7060 Clairemont Mesa Blvd, San Diego, CA 92111 USA. NR 5 TC 6 Z9 6 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2009 VL 124 IS 2 BP S1 EP S4 DI 10.1016/j.jaci.2009.05.001 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 482CE UT WOS:000268860500001 PM 19647130 ER PT J AU Finlay, CG Forsyth, JP AF Finlay, Carlos G. Forsyth, John P. TI Context and renewal of conditioned fear: An experimental evaluation using 20% carbon dioxide-enriched air as an unconditioned stimulus SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Anxiety; Fear renewal; Context; Fear conditioning; Exposure therapy ID LEARNING-THEORY PERSPECTIVE; CO2-ENRICHED AIR; PANIC DISORDER; SPIDER PHOBIA; RETRIEVAL CUE; EXTINCTION; RETURN; ACQUISITION; RELAPSE; STATES AB This analogue experiment used fear conditioning and extinction procedures to establish and reduce fearful responding and then test for fear renewal following a context change. Healthy undergraduates (N = 61) underwent a differential fear conditioning procedure using geometric shapes as conditioned stimuli (CS) and inhalations of 20% CO(2)-enriched air as an aversive unconditioned stimulus (US). Across phases (i.e., habituation, acquisition, extinction, and test), red and green ambient lighting served as contextual stimuli, and electrodermal and evaluative ratings were assessed as indices of conditioned fear. The control group underwent extinction and test phases under identical conditions (i.e., no context changes). The experimental groups either underwent acquisition and test phases in one context and the intervening extinction phase in a different context (A-B-A), or underwent acquisition and extinction phases in one context and the test phase in a novel context (A-A-B). Consistent with expectation, fear renewal was observed when the test context matched the acquisition context. This effect was modest for electrodermal responses, but reasonably robust for evaluative responses. The role of context in the subsequent renewal of fear following exposure-based treatment is discussed. Published by Elsevier Ltd. C1 [Finlay, Carlos G.; Forsyth, John P.] SUNY Albany, Albany, NY 12222 USA. RP Finlay, CG (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116-B,150 S Huntington Ave, Boston, MA 02130 USA. EM carlos.finlay@va.gov NR 49 TC 5 Z9 5 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD AUG PY 2009 VL 23 IS 6 BP 737 EP 745 DI 10.1016/j.janxdis.2009.02.014 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 452XL UT WOS:000266574400002 PM 19342193 ER PT J AU Lilly, MM Pole, N Best, SR Metzler, T Marmar, CR AF Lilly, Michelle M. Pole, Nnamdi Best, Suzanne R. Metzler, Thomas Marmar, Charles R. TI Gender and PTSD: What can we learn from female police officers? SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Gender; PTSD; Peritraumatic distress; Police; Somatization ID POSTTRAUMATIC-STRESS-DISORDER; SOCIAL DESIRABILITY SCALE; SEX-DIFFERENCES; PSYCHOMETRIC PROPERTIES; TRAUMATIC EVENTS; RISK-FACTORS; SYMPTOMS; ADULTS; METAANALYSIS; PREDICTORS AB Studies of civilians typically find that female gender is a risk factor for posttraurnatic stress disorder (PTSD). Police and military studies often find no gender differences in PTSD. We compared 157 female police officers and 124 female civilians on several variables including trauma exposure, peritraumatic emotional distress, current somatization, and cumulative PTSD symptoms. We found that despite greater exposure to assaultive violence in the officer group, female civilians reported significantly more severe PTSD symptoms. Elevated PTSD symptoms in female civilians were explained by significantly more intense peritraurnatic emotional distress among female civilians. We also found that female officers showed a stronger direct relationship between peritraurnatic emotional distress and current somatization. Our findings suggest that apparent gender differences in PTSD may result from differences in peritraurnatic emotionality, which influence subsequent PTSD and somatization symptoms. Emotionality may be more important than biological sex in understanding gender differences in PTSD. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Lilly, Michelle M.; Pole, Nnamdi] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. [Best, Suzanne R.; Metzler, Thomas; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Best, Suzanne R.; Metzler, Thomas; Marmar, Charles R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Pole, N (reprint author), Smith Coll, Dept Psychol, Bass Hall, Northampton, MA 01060 USA. EM npole@email.smith.edu FU NIMH NIH HHS [R01 MH056350-03, R01 MH056350, R01-MH056350-01A1] NR 68 TC 29 Z9 32 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD AUG PY 2009 VL 23 IS 6 BP 767 EP 774 DI 10.1016/j.janxdis.2009.02.015 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 452XL UT WOS:000266574400006 PM 19345556 ER PT J AU Kaufman, DR Pevzner, J Rodriguez, M Cimino, JJ Ebner, S Fields, L Moreno, V McGuiness, C Weinstock, RS Shea, S Starren, J AF Kaufman, David R. Pevzner, Jenia Rodriguez, Martha Cimino, James J. Ebner, Susana Fields, Lesley Moreno, Vilma McGuiness, Christina Weinstock, Ruth S. Shea, Steven Starren, Justin TI Understanding workflow in telehealth video visits: Observations from the IDEATel project SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Telemedicine; Workflow; Distributed cognition; Nurse case manager; Video analysis; Communication modalities; Diabetes; Interaction design ID COLUMBIA-UNIVERSITY INFORMATICS; DISTRIBUTED COGNITION; DIABETES MANAGEMENT; ETHNICALLY DIVERSE; TELEMEDICINE; CARE; USABILITY; EDUCATION; MELLITUS AB Home telemedicine is an emerging healthcare paradigm that has the potential to transform the treatment of chronic illness. The purpose of this paper is to: (I) develop a theoretical and methodological framework for studying workflow in telemediated clinician-patient encounters drawing on a distributed cognition approach and (2) employ the framework in an in-depth analysis of workflow in the IDEATel project, a telemedicine program for older adults with diabetes. The methods employed in this research included (a) videotaped observations of 27 nurse-patient encounters and (b) semi-structured interviews with participants. The analyses were used to provide a descriptive analysis of video visits, understand the mediating role of different technologies and to characterize the ways in which artifacts and representations are used to understand the state of the patient. The study revealed barriers to productive use of telehealth technology as well as adaptations that circumvented such limitations. This research has design implications for: (a) improving the coordination of communication and (b) developing tools that better integrate and display information. Although home telemedicine programs will differ in important respects. there are invariant properties across such systems. Explicating these properties can serve as a needs requirement analysis to develop more effective systems and implementation plans. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kaufman, David R.; Pevzner, Jenia; Rodriguez, Martha; Cimino, James J.] Columbia Univ, Dept Biomed Informat, New York, NY 10027 USA. [Cimino, James J.] NIH, Ctr Clin, Lab Informat Dev, Bethesda, MD 20892 USA. [Ebner, Susana] Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Vet Affairs Med Ctr, Joslin Diabet Ctr, Dept Med, Syracuse, NY USA. [Shea, Steven] Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Med, New York, NY USA. [Shea, Steven] Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Publ Hlth, New York, NY USA. [Starren, Justin] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI USA. RP Kaufman, DR (reprint author), Columbia Univ, Dept Biomed Informat, New York, NY 10027 USA. EM davek@dbmi.columbia.edu OI Cimino, James/0000-0003-4101-1622 FU National Library of Medicine [LM007663-OIA2]; Centers for Medicare and Medicaid Services [95-C-90998] FX The research described in this paper was partially supported by a grant from the National Library of Medicine to Justin Starren (LM007663-OIA2) and a Cooperative Agreement from Centers for Medicare and Medicaid Services to Steven Shea (95-C-90998). In addition, we acknowledge the IDEATel consortium (www.ideatel.org/acknowledgei-nent.html). We thank Jessica Ancker, Connie Chan, Albert Lai, Lisa Matthews, Yalini Senathirajah and anonymous reviewers for constructive comments on earlier versions of the manuscript. NR 29 TC 7 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD AUG PY 2009 VL 42 IS 4 BP 581 EP 592 DI 10.1016/j.jbi.2009.03.012 PG 12 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 468UB UT WOS:000267846800001 PM 19358897 ER PT J AU Oral, E Godleski-Beckos, C Ghali, BW Lozynsky, AJ Muratoglu, OK AF Oral, Ebru Godleski-Beckos, Christine Ghali, Bassem W. Lozynsky, Andrew J. Muratoglu, Orhun K. TI Effect of Cross-link Density on the High Pressure Crystallization of UHMWPE SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE joint arthroplasty; polyethylene; crystalline; wear; radiation; implant ID MOLECULAR-WEIGHT POLYETHYLENE; VITAMIN-E; PROPAGATION RESISTANCE; MECHANICAL-PROPERTIES; ALPHA-TOCOPHEROL; WEAR; OSTEOLYSIS; OXIDATION; PHASE; MODEL AB Ultrahigh molecular weight polyethylene (UHMWPE) is a bearing surface material for total joint implants. It is radiation cross-linked for high wear resistance and is melted or treated with vitamin E for oxidative stability. We investigated high pressure crystallization (HPC) of irradiated UHMWPE as an alternative method to improve the mechanical strength while stabilizing the residual free radicals from radiation cross-linking. HPC of uncross-linked UHMWPE has resulted in the formation of extended chain crystals and increased crystallinity, leading to improved strength. We hypothesized that increased cross-link density would hinder crystallization during HPC due to decreased chain mobility. Therefore, we investigated the crystalline structure and tensile mechanical properties of high pressure crystallized 25-, 65- and 100-kGy irradiated UHMWPE. We also determined free radical content and wear. The strength of 25- and 65-kGy irradiated UHMWPEs was improved by HPC with increased crystallinity and crystal size. 100-kGy irradiated UHMWPE did not show improved strength, supporting our hypothesis that decreased chain mobility would hinder crystal formation and strength improvement. None of the HPC irradiated UHMWPEs contained detectable free radicals and their wear properties were maintained, suggesting oxidative and mechanical stability in the long term. Therefore, HPC can be used effectively for imparting oxidative stability while strength improvement can be achieved for irradiated UHMWPE with low to moderate cross-link density. (C) 2009 Wiley Periodicals. Inc. J Biomed Mater Res Part B: Appl Biomater 90B: 720-729. 2009 C1 [Oral, Ebru; Godleski-Beckos, Christine; Ghali, Bassem W.; Lozynsky, Andrew J.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM omuratoglu@partners.org FU NIAMS NIH HHS [AR110542, R01 AR051142, R01 AR051142-02, R01 AR051142-03] NR 23 TC 8 Z9 9 U1 1 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD AUG PY 2009 VL 90B IS 2 BP 720 EP 729 DI 10.1002/jbm.b.31340 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 472FD UT WOS:000268114200029 PM 19213055 ER PT J AU Mani, G Chandrasekar, B Feldman, MD Patel, D Agrawal, CM AF Mani, Gopinath Chandrasekar, Bysani Feldman, Marc D. Patel, Devang Agrawal, C. Mauli TI Interaction of Endothelial Cells with Self-Assembled Monolayers for Potential Use in Drug-Eluting Coronary Stents SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE stents; endothelial cells; cell-material interactions ID TITANIUM-OXIDE SURFACES; 316L STAINLESS-STEEL; BALLOON ANGIOPLASTY; PROTEIN ADSORPTION; ARTERY DISEASE; GOLD; FLUORESCENCE; ORIENTATION; THROMBOSIS; BINDING AB Drug-eluting stents (DES) are implanted in patients to treat in-stent restenosis. Commercially available DES use polymers for coating and releasing drugs. Several studies have showed that polymer coatings cause adverse reactions. Delayed endothelialization of polymer-coated DES leads to late stent thrombosis. Recently, the potential for using self-assembled monolayers (self-assembled monolayers (SAMs)-organic constructs composed of (a) chemical groups which attach to metal surfaces, (b) long hydrocarbon chains, and (c) terminal functional groups) as an alternate drug delivery system for coronary stents has been demonstrated. In this study, the interaction of human aortic endothelial cells (HAECs) with SAMs and therapeutic SAMs (therapeutic self-assembled monolayers (TSAMs)-SAMs derivatized with the drug, flufenamic acid) was investigated. HAECs were cultured on plain glass, control, SAW, and TSAMs-coated titanium (Ti) and gold (Au) specimens. The viability and proliferation of HAECs were investigated using MTT colorimetric assay. The adhesion of HAECs on SAMs and TSAMs was equivalent to that of control metal surfaces and superior to that of plain glass surfaces. The cells continued to proliferate on both SAMs and TSAMs even though the rate of proliferation was slower than plain glass or control-Ti. The spreading of HAECs on TSAMs with typical polygonal shape indicated that these surfaces are conducive to endothelialization. The expression of surface adhesion protein, platelet endothelial cell adhesion molecule-1, on TSAMs indicated that the endothelial cells preserved their phenotype on these surfaces. Thus, this study demonstrated that SAMs and TSAMs do not elicit an adverse response from endothelial cells in in vitro conditions. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 90B: 789-801, 2009 C1 [Mani, Gopinath; Feldman, Marc D.; Agrawal, C. Mauli] Univ Texas San Antonio, Coll Engn, Dept Biomed Engn, San Antonio, TX 78249 USA. [Chandrasekar, Bysani; Feldman, Marc D.; Patel, Devang] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. [Feldman, Marc D.] Dept Vet Affairs S Texas Hlth Care Syst, San Antonio, TX 78229 USA. RP Agrawal, CM (reprint author), Univ Texas San Antonio, Coll Engn, Dept Biomed Engn, San Antonio, TX 78249 USA. EM Mauli.Agrawal@utsa.edu NR 62 TC 20 Z9 20 U1 2 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD AUG PY 2009 VL 90B IS 2 BP 789 EP 801 DI 10.1002/jbm.b.31348 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 472FD UT WOS:000268114200037 PM 19274726 ER PT J AU Vranceanu, AM Barsky, A Ring, D AF Vranceanu, Ana-Maria Barsky, Arthur Ring, David TI Psychosocial Aspects of Disabling Musculoskeletal Pain SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID LOW-BACK-PAIN; COGNITIVE-BEHAVIOR THERAPY; EVIDENCE-BASED ORTHOPEDICS; SELF-EFFICACY; RHEUMATOID-ARTHRITIS; HEALTH-STATUS; DEPRESSION; PREVALENCE; MANAGEMENT; DETERMINANTS C1 [Vranceanu, Ana-Maria; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. [Barsky, Arthur] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Vranceanu, AM (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 58 TC 77 Z9 78 U1 0 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 2009 VL 91A IS 8 BP 2014 EP 2018 DI 10.2106/JBJS.H.01512 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 479GG UT WOS:000268647100027 PM 19651964 ER PT J AU Schipani, E Maes, C Carmeliet, G Semenza, GL AF Schipani, Ernestina Maes, Christa Carmeliet, Geert Semenza, Gregg L. TI Regulation of Osteogenesis-Angiogenesis Coupling by HIFs and VEGF SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE hypoxia inducible factor; vascular endothelial growth factor; osteoblast; angiogenesis ID HYPOXIA-INDUCIBLE FACTOR; ENDOTHELIAL GROWTH-FACTOR; VHL TUMOR-SUPPRESSOR; ENDOCHONDRAL BONE-FORMATION; GENE-EXPRESSION; FACTOR 1-ALPHA; EMBRYONIC-DEVELOPMENT; DISTRACTION OSTEOGENESIS; TRANSCRIPTIONAL ACTIVITY; PROLYL HYDROXYLATION AB Bone is a highly vascularized tissue, but the function of angiogenesis in bone modeling and remodeling is still poorly defined, and the molecular mechanisms that regulate angiogenesis in bone are only partially elucidated. Genetic manipulations in mice have recently highlighted the critical role of the hypoxia-inducible-factor/vascular endothelial growth factor pathway in coupling angiogenesis and osteogenesis. In this brief perspective, we review the current understanding of the mechanisms responsible for this coupling. Elucidation of such mechanisms will expand our knowledge of bone development and homeostasis, and it may aid in the design of new therapies for accelerating bone regeneration and repair. J Bone Miner Res 2009;24:1347-1353. Published online on June 29, 2009; doi: 10.1359/JBMR.090602 C1 [Schipani, Ernestina] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Schipani, Ernestina] Harvard Univ, Sch Med, Boston, MA USA. [Maes, Christa; Carmeliet, Geert] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, Leuven, Belgium. [Semenza, Gregg L.] McKusick Nathans Inst Genet Med, Inst Cell Engn, Vasc Program, Baltimore, MD USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 5,Fruit St, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu FU NIAMS NIH HHS [R01 AR048191] NR 95 TC 111 Z9 114 U1 3 U2 20 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 2009 VL 24 IS 8 BP 1347 EP 1353 DI 10.1359/JBMR.090602 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 482CK UT WOS:000268861300001 PM 19558314 ER PT J AU Miyamoto, SD Brown, RD Robinson, BA Tyler, KL Long, CS Debiasi, RL AF Miyamoto, Shelley D. Brown, R. D. Robinson, Bridget A. Tyler, Kenneth L. Long, Carlin S. Debiasi, Roberta L. TI Cardiac Cell-specific Apoptotic and Cytokine Responses to Reovirus Infection: Determinants of Myocarditic Phenotype SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Viral myocarditis; myocytes; fibroblasts ID LEFT-VENTRICULAR FUNCTION; VIRAL CORE PROTEINS; DILATED CARDIOMYOPATHY; GENE-EXPRESSION; BETA-INTERFERON; IMMUNOSUPPRESSIVE THERAPY; INHIBITION PROTECTS; MYOCYTE CULTURES; CLINICAL-TRIAL; MICE AB Background: The pathophysiologic mechanisms underlying viral myocarditis are not well defined. As a result, effective treatments do not exist and viral myocarditis remains a potentially lethal infection of the heart. Methods and Results: We used Cultured rat cardiac myocytes and fibroblasts to investigate apoptosis and cytokine production in response to infection by myocarditic vs. non-myocarditic strains Of reovirus. Myocarditic reovirus strain 8B and non-myocarditic strain DB188 replicate comparably ill each cardiac cell type. However, strain 8B and related myocarditic reoviruses preferentially increase apoptosis of myocytes relative to fibroblasts, whereas DB188 and nonmyocarditic strains preferentially increase fibroblast apoptosis. Infection of cardiac fibroblasts with the nonmyocarditic strain DB188 elicits, substantial increases ill a panel of cytokines compared to fibroblasts infected with strain 8B or mock-infected controls. Analysis of culture supernatants using cytometric bead arrays revealed that DB188 enhanced release of interleukin (IL)-1 beta, IL-4, IL-6, IL-10, IL-12(p70), GRO-KC, tumor necrosis factor-alpha, and MCP-1 relative to 8B or mock-infected controls (all P < .05). Conclusion: We hypothesize that differential cytokine production and cell-specific apoptosis are important determinants of myocarditic potential of reoviral strains. Therapies that target the beneficial effects of cytokines in limiting cytopathic damage may offer an effective and novel treatment approach to viral myocarditis. (J Cardiac Fail 2009;15;529-539) C1 [Miyamoto, Shelley D.; Robinson, Bridget A.; Debiasi, Roberta L.] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. [Brown, R. D.; Tyler, Kenneth L.; Long, Carlin S.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. [Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO USA. [Debiasi, Roberta L.] George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA. [Debiasi, Roberta L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. RP Miyamoto, SD (reprint author), Childrens Hosp, 13123 E l6th Ave,B100, Aurora, CO 80045 USA. EM Miyamoto.shelley@tchden.org OI Tyler, Kenneth/0000-0003-3294-5888 FU Children's Hospital. Denver, CO; VA MERIT; NIH [R01 NS051403, NS050139, HL59428, HL79160, K08 A1052261-05] FX Supported by the Research Scholar Award. The Children's Hospital. Denver, CO (S.M.) VA MERIT and NIH R01 NS051403 and NS050139 (K.T.) NIH HL59428 and HL79160 (C.L.): NIH K08 A1052261-05 (R.D.). NR 71 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 BP 529 EP 539 DI 10.1016/j.cardfail.2009.01.004 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OA UT WOS:000268897300010 PM 19643365 ER PT J AU Ajijola, OA Makovey, I Barantke, M Heist, EK Harrell, T Upadhyay, G Blandea, D McCarty, D Macklin, EA Orencole, M Semigran, M Ruskin, JN Picard, M Singh, JP AF Ajijola, Olujimi A. Makovey, Iryna Barantke, Melanie Heist, E. Kevin Harrell, Tanya Upadhyay, Gaurav Blandea, Dan McCarty, David Macklin, Eric A. Orencole, Mary Semigran, Marc Ruskin, Jeremy N. Picard, Michael Singh, Jagmeet P. TI The Degree of Clinical and Anatomic Response to Cardiac Resynchronization Therapy Correlates Significantly with Clinical Outcomes SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Ajijola, Olujimi A.; Makovey, Iryna; Barantke, Melanie; Heist, E. Kevin; Harrell, Tanya; Upadhyay, Gaurav; Blandea, Dan; Orencole, Mary; Ruskin, Jeremy N.; Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [McCarty, David; Picard, Michael] Massachusetts Gen Hosp, Div Echocardiog, Boston, MA 02114 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Semigran, Marc] Massachusetts Gen Hosp, Heart Failure Serv, Boston, MA 02114 USA. RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 187 BP S58 EP S58 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500186 ER PT J AU Bhardwaj, A Shah, R Januzzi, JL AF Bhardwaj, Anju Shah, Ravi Januzzi, James L. TI Clinical Results for the New Presage (TM) Soluble ST2 Assay in Acutely Destabilized Heart Failure: Results from the PRIDE Study SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Bhardwaj, Anju; Shah, Ravi; Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 095 BP S32 EP S32 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500095 ER PT J AU Boehmer, JP Starling, RC Cooper, LT Torre-Amione, G Wittstein, I Dee, GW Markham, DW Zucker, MJ McNamara, DM AF Boehmer, John P. Starling, Randall C. Cooper, Leslie T. Torre-Amione, Guillermo Wittstein, Ilan Dee, G. William Markham, David W. Zucker, Mark J. McNamara, Dennis M. TI A High Incidence of Ventricular Recovery in Acute Cardiomyopathy Patients Supported with a Left Ventricular Assist Device: Results of the IMAC 2 Trial SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Boehmer, John P.] Penn State Univ, Coll Med, Inst Heart & Vasc, Hershey, PA USA. [Starling, Randall C.] Cleveland Clin, Kaufman Ctr Heart Failure, Cleveland, OH 44106 USA. [Cooper, Leslie T.] Mayo Clin, Rochester, MN USA. [Torre-Amione, Guillermo] Methodist Hosp, Houston, TX 77030 USA. [Wittstein, Ilan] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Dee, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Markham, David W.] UT SW Med Ctr, Dallas, TX USA. [Zucker, Mark J.] Newark Beth Israel Med Ctr, Newark, NJ USA. [McNamara, Dennis M.] Univ Pittsburgh, UPMC, Cardiovasc Inst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 201 BP S62 EP S62 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500200 ER PT J AU Choi, JH Ke, QE Bae, S Bodyak, N Kajunski, C Strugnell, S Arbeeny, C Thadhani, R Kang, PM AF Choi, Jun H. Ke, Qingen Bae, Soochan Bodyak, Natalya Kajunski, Christine Strugnell, Steve Arbeeny, Cynthia Thadhani, Ravi Kang, Peter M. TI Activated Vitamin D Compound Doxercalciferol Prevents the Development of Cardiac Hypertrophy in Dahl Salt Sensitive Rats SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Choi, Jun H.; Ke, Qingen; Bae, Soochan; Bodyak, Natalya; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kajunski, Christine; Strugnell, Steve; Arbeeny, Cynthia] Genzyme Corp, Cambridge, MA USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 256 BP S78 EP S78 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500254 ER PT J AU Cooper, LT Dec, GW Mather, P Alexis, J Torre-Amione, G Wittstein, I Zucker, M Narula, J McNamara, DM AF Cooper, Leslie T. Dec, G. William Mather, Paul Alexis, Jeffrey Torre-Amione, Guillermo Wittstein, Ilan Zucker, Mark Narula, Jagat McNamara, Dennis M. CA IMAC Investigators TI Recovery and Outcomes of Peripartum Cardiomyopathy: Results of IMAC 2 Registry SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Cooper, Leslie T.] Mayo Clin, Div Cardiovasc, Rochester, MN USA. [Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mather, Paul] Thomas Jefferson Univ Hosp, Div Cardiovasc, Philadelphia, PA 19107 USA. [Alexis, Jeffrey] Univ Rochester, Div Cardiol, Rochester, NY USA. [Torre-Amione, Guillermo] Methodist Hosp, Div Cardiol, Houston, TX 77030 USA. [Wittstein, Ilan] Div Cardiol, Baltimore, MD USA. [Zucker, Mark] Beth Israel Hosp, Cardiovasc Inst, Newark, NJ USA. [Narula, Jagat] Univ Calif Irvine, Irvine, CA USA. [McNamara, Dennis M.] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 310 BP S94 EP S94 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500308 ER PT J AU Filippi, RD Christenson, R Shah, R Bhardwaj, A Januzzi, JL AF Filippi, R. de Christopher Christenson, Robert Shah, Ravi Bhardwaj, Anju Januzzi, James L. TI Clinical Validation of a Novel Assay for Galectin-3 for Risk Assessment in Acutely Destabilized Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Filippi, R. de Christopher; Christenson, Robert] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Shah, Ravi; Bhardwaj, Anju; Januzzi, James L.] Massachusetts Gen Hosp Harvard, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 020 BP S9 EP S9 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500021 ER PT J AU Kapuku, GK Davis, HC Thomas, P Januzzi, J Harshield, G AF Kapuku, Gaston K. Davis, Harry C. Thomas, Patrick Januzzi, James Harshield, Gregory TI Does the Relationship between Natriuretic Hormones and Diastolic Function Differ by Race? SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Kapuku, Gaston K.; Davis, Harry C.; Harshield, Gregory] Med Coll GA, Augusta, GA USA. [Thomas, Patrick; Januzzi, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 082 BP S28 EP S28 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500083 ER PT J AU Metra, M Teerlink, JR Weatherley, BD Greenberg, BH Felker, GM Ponikowski, P Voors, AA Filippatos, G Feaganes, J Unemori, E Teichman, SL Cotter, G AF Metra, Marco Teerlink, John R. Weatherley, Beth D. Greenberg, Barry H. Felker, G. Michael Ponikowski, Piotr Voors, Adrian A. Filippatos, Gerasimos Feaganes, John Unemori, Elaine Teichman, Sam L. Cotter, Gad TI Changes in Dyspnea during Treatment of Acute Heart Failure Are Correlated with Clinical Signs. Rehospitalizations and Mortality. Results from the Pre-RELAX-AHF Trial SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Metra, Marco] Univ Brescia, Brescia, BS, Italy. [Teerlink, John R.] UCSF, San Francisco VAMC, San Francisco, CA USA. [Felker, G. Michael] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Weatherley, Beth D.; Feaganes, John; Cotter, Gad] Momentum Res Inc, Durham, NC USA. [Greenberg, Barry H.] Univ Calif San Diego, UCSD Med Ctr, Adv Heart Failure Program, San Diego, CA 92103 USA. [Ponikowski, Piotr] Med Univ, Mil Hosp, Dept Hlth Sci, Wroclaw, Poland. [Voors, Adrian A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Unemori, Elaine; Teichman, Sam L.] Corthera Inc, San Mateo, CA USA. [Filippatos, Gerasimos] Univ Athens, Hosp Attikon, Athens, Greece. RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064 NR 0 TC 1 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 SU 1 MA 203 BP S62 EP S63 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500202 ER PT J AU Parks, KA Semigran, MJ Stone, JR AF Parks, Kimberly A. Semigran, Marc J. Stone, James R. TI Myocardial Upregulation of hnRNP-C Predicts Short Term Recovery in Patients with Acute Systolic Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Parks, Kimberly A.; Semigran, Marc J.; Stone, James R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 129 BP S41 EP S41 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500128 ER PT J AU Ryu, K d'Avila, A Heist, EK Rosenberg, SP Chou, J Yang, M Singh, JP AF Ryu, Kyungmoo d'Avila, Andre Heist, E. Kevin Rosenberg, Stuart P. Chou, Jessie Yang, Michael Singh, Jagmeet P. TI Simultaneous Electrical and Mechanical Mapping Using 3D Cardiac Mapping System: Novel Approach for Optimal Cardiac Resynchronization Therapy SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Ryu, Kyungmoo; Rosenberg, Stuart P.; Chou, Jessie; Yang, Michael] St Jude Med Inc, Sylmar, CA USA. [d'Avila, Andre; Heist, E. Kevin; Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 042 BP S16 EP S17 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500043 ER PT J AU Semigran, HL MacRae, CA Shin, JT AF Semigran, Hannah L. MacRae, Calum A. Shin, Jordan T. TI Developmental Inotropic Sensitivity to Isoproterenol in Developing Zebrafish Hearts In Vivo SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Semigran, Hannah L.; MacRae, Calum A.; Shin, Jordan T.] Massachusetts Gen Hosp, CVRC, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 048 BP S18 EP S19 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500049 ER PT J AU Shah, RV Desai, AS Givertz, MM AF Shah, Ravi V. Desai, Akshay S. Givertz, Michael M. TI The Effect of Renin-Angiotensin System Inhibitors on Mortality and Heart Failure Hospitalization in Diastolic Heart Failure: A Pooled Analysis of Randomized Controlled Trials SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Shah, Ravi V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Desai, Akshay S.; Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 237 BP S72 EP S72 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500235 ER PT J AU Shah, RV Richards, AM Bayes-Genis, A Pinto, Y Lainchbury, J Ordonez, J van Kimmenade, R Januzzi, JL AF Shah, Ravi V. Richards, A. Mark Bayes-Genis, Antoni Pinto, Yigal Lainchbury, John Ordonez, Jordi van Kimmenade, Roland Januzzi, James L. TI Predictors and Ramifications of Worsening Renal Function in Acutely Destabilized Heart Failure: Results from the ICON Study SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Shah, Ravi V.; Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Richards, A. Mark; Lainchbury, John] Univ Otago, Dept Med, Cardioendocrine Res Grp, Christchurch, New Zealand. [Bayes-Genis, Antoni; Ordonez, Jordi] Hosp Santa Creu & Sant Pau, Dept Med, Barcelona, Spain. [Bayes-Genis, Antoni; Ordonez, Jordi] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Pinto, Yigal] Univ Amsterdam, Heart Failure Res Ctr, Amsterdam, Netherlands. [van Kimmenade, Roland] Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. RI Ordonez-Llanos, Jorge/A-9335-2010; Ordonez-Llanos, Jordi/B-4961-2011; Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; Bayes-Genis, Antoni/0000-0002-3044-197X; NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 054 BP S20 EP S21 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500055 ER PT J AU Shah, RV Richards, AM Bayes-Genis, A Pinto, Y Lainchbury, J Ordonez, J van Kimmenade, R Januzzi, JL AF Shah, Ravi V. Richards, A. Mark Bayes-Genis, Antoni Pinto, Yigal Lainchbury, John Ordonez, Jordi van Kimmenade, Roland Januzzi, James L. TI What Predicts Troponin Release in Acutely Decompensated Heart Failure? SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Shah, Ravi V.; Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richards, A. Mark; Lainchbury, John] Univ Otago, Dept Med, Cardioendocrine Res Grp, Christchurch, New Zealand. [Bayes-Genis, Antoni; Ordonez, Jordi] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Bayes-Genis, Antoni; Ordonez, Jordi] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Pinto, Yigal] Univ Amsterdam, Heart Failure Res Ctr, Amsterdam, Netherlands. [van Kimmenade, Roland] Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. RI Ordonez-Llanos, Jorge/A-9335-2010; Ordonez-Llanos, Jordi/B-4961-2011; Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; Bayes-Genis, Antoni/0000-0002-3044-197X; NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 055 BP S21 EP S21 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500056 ER PT J AU Sharma, GVRK Woods, P O'Connell, C Connolly, L Joseph, J McIntyre, K AF Sharma, G. V. R. K. Woods, Patricia O'Connell, Carol Connolly, Louise Joseph, Jacob McIntyre, Kevin TI Left Ventricular End-Diastolic Pressure Guided Treatment of Patients Hospitalized for Heart Failure Reduces Rehospitalization Rate SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Sharma, G. V. R. K.; Woods, Patricia; Connolly, Louise; Joseph, Jacob] VA Boston Healthcare Syst, Dept Cardiol, W Roxbury, MA USA. [Sharma, G. V. R. K.] Harvard Univ, Sch Med, Boston, MA USA. [Joseph, Jacob] Boston Univ, Sch Med, Boston, MA 02118 USA. [O'Connell, Carol; McIntyre, Kevin] CVP Diagnost, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 289 BP S88 EP S88 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500287 ER PT J AU Teerlink, JR Metra, M Felker, GM Voors, AA Greenberg, BH Ponikowski, P Teichman, SL Cotter, G AF Teerlink, John R. Metra, Marco Felker, G. Michael Voors, Adriaan A. Greenberg, Barry H. Ponikowski, Piotr Teichman, Sam L. Cotter, Gad TI Vasodilators in Acute Heart Failure (AHF): Does Blood Pressure Matter? Results from Pre-Relax-AHF SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Metra, Marco] Univ Brescia, Brescia, BS, Italy. [Felker, G. Michael] Duke Clin Res Inst, Durham, NC USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Ponikowski, Piotr] Med Univ, Dept Hlth Sci, Mil Hosp, Wroclaw, Poland. [Teichman, Sam L.] Corthera Inc, San Mateo, CA USA. [Cotter, Gad] Momentum Res Inc, Durham, NC USA. RI Teerlink, John/D-2986-2012; Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 SU 1 MA 243 BP S74 EP S74 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500241 ER PT J AU Uthamalingam, S Kandala, J Daley, M Capodilupo, R Januzzi, JL AF Uthamalingam, Shanmugam Kandala, Jagdesh Daley, Marilyn Capodilupo, Robert Januzzi, James L. TI Serum Albumin Levels Predicts Both In-Hospital and Mid-Term Mortality among Patients Admitted to Hospital with Acute Decompensated Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Uthamalingam, Shanmugam; Kandala, Jagdesh; Daley, Marilyn; Capodilupo, Robert] Catholic Med Ctr, Manchester, NH USA. [Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 332 BP S100 EP S100 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500330 ER PT J AU Washko, D MacRae, CA Shin, JT AF Washko, Daniel MacRae, Calum A. Shin, Jordan T. TI Loss of BMPR2B in Zebrafish Causes Augmented BMP-Signaling through Recruitment of an Alternative Type 2 Receptor SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 13th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 13-16, 2009 CL Boston, MA SP Heart Failure Soc Amer C1 [Washko, Daniel; MacRae, Calum A.; Shin, Jordan T.] Massachusetts Gen Hosp, CVRC, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2009 VL 15 IS 6 MA 132 BP S42 EP S42 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 482OC UT WOS:000268897500131 ER PT J AU Rahman, MM Bhattacharya, A Banu, J Kang, JX Fernandes, G AF Rahman, Md Mizanur Bhattacharya, Arunabh Banu, Jameela Kang, Jing X. Fernandes, Gabriel TI Endogenous n-3 fatty acids protect ovariectomy induced bone loss by attenuating osteoclastogenesis SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE n-3 fatty acids; bone mineral density; inflammation; osteoporosis; osteoclasts ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; C57BL/6 FEMALE MICE; EICOSAPENTAENOIC ACID; TRANSGENIC MICE; IN-VIVO; FAT-1 MICE; POSTMENOPAUSAL OSTEOPOROSIS; DOCOSAHEXAENOIC ACID AB Beneficial effects of n-3 fatty acids (FA) on bone mineral density (BMD) have been reported in mice, rats and human beings, but the precise mechanisms involved have not been described. This study used the Fat-1 mouse, a transgenic model that synthesizes n-3 FA from n-6 FA to directly determine if outcome of bone health were correlated with n-3 FA. Ovariectomized (Ovx) and sham operated wild-type (WT) and Fat-1 mice were fed an AIN-93M diet containing 10% corn oil for 24 weeks. BMD was analysed by dual energy x-ray absorptiometry. Fat-1 Ovx mice exhibited significantly lower level of osteotropic factors like receptor activator of NF-kappa B ligand and tartrate-resistant acid phosphatase (TRAP)5b in serum and higher BMD in distal femoral metaphysis, proximal tibial metaphysis, femoral diaphysis and lumbar vertebra as compared to WT Ovx mice. LPS-stimulated bone marrow (BM) cells from Fat-1 Ovx mice produced significantly lower level of pro-inflammatory cytokines like tumour necrosis factor-alpha, interleukin (IL)-1-beta, IL-6 and higher level of anti-inflammatory cytokines like IL-10, IFN-gamma and higher level of nitric oxide as compared to BM cells from WT Ovx mice. LPS-stimulated COX-II activity as well as NF-kappa B activation in BM cells from Fat-1 Ovx mice was significantly less as compared to BM cells from WT Ovx mice. Furthermore, Fat-1 BM cells generated significantly less number of TRAP osteoclast-like cells as compared to WT BM cells. In conclusion, we offer further insight into the mechanisms involved in preventing the BMD loss in Ovx mice by n-3 FA using a Fat-1 transgenic mouse model. C1 [Rahman, Md Mizanur; Bhattacharya, Arunabh; Banu, Jameela; Fernandes, Gabriel] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Immunol & Rheumatol, San Antonio, TX 78229 USA. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Fernandes, G (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Immunol & Rheumatol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM fernandes@uthscsa.edu FU [RO1 AG023648] FX We thank Kazi Nishu for her technical help. This study was supported by RO1 AG023648. NR 82 TC 37 Z9 38 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD AUG PY 2009 VL 13 IS 8B BP 1833 EP 1844 DI 10.1111/j.1582-4934.2009.00649.x PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 525CN UT WOS:000272190800020 PM 20141608 ER PT J AU Barletta, JA Perner, S Iafrate, AJ Yeap, BY Weir, BA Johnson, LA Johnson, BE Meyerson, M Rubin, MA Travis, WD Loda, M Chirieac, LR AF Barletta, Justine A. Perner, Sven Iafrate, A. John Yeap, Beow Y. Weir, Barbara A. Johnson, Laura A. Johnson, Bruce E. Meyerson, Matthew Rubin, Mark A. Travis, William D. Loda, Massimo Chirieac, Lucian R. TI Clinical significance of TTF-1 protein expression and TTF-1 gene amplification in lung adenocarcinoma SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE lung adenocarcinoma; TTF-1; survival ID TRANSCRIPTION FACTOR-I; TISSUE MICROARRAY; CELL CARCINOMAS; CANCER; SURVIVAL; FACTOR-1; MORPHOGENESIS; EMBRYOS AB The majority of lung adenocarcinomas express the lineage-specific thyroid transcription factor-1 (TTF-1). We recently reported that in a subset of lung adenocarcinomas the TTF-1 gene is amplified. Although the prognostic significance of TTF-1 expression has been previously investigated, the significance of TTF-1 amplification has not been established. We studied 89 consecutive patients with lung adenocarcinomas treated by surgery at Brigham and Women's Hospital between 1997 and 1999 and performed immunohistochemical analysis for TTF-1 expression and fluorescence in situ hybridization for TTF-1 amplification. We investigated associations between clinical-pathological characteristics, TTF-1 expression, TTF-1 amplification and overall survival. TTF-1 expression was categorized as high (48%), low (24%) or absent (28%). TTF-1 was amplified in 7% of cases. Patients with adenocarcinomas with low or high TTF-1 expression had a significantly better outcome than those with absent TTF-1 expression (median overall survival times of 72.4, 77.8 and 30.5 months, respectively, P = 0.002). In contrast, patients with adenocarcinomas with TTF-1 expression had a worse outcome if TTF-1 was amplified (median overall survival time 39.5 versus 87.5 months). In multivariate analysis, improved overall survival was independently predicted by TTF-1 expression in combination with no TTF-1 amplification (P < 0.001). In patients with lung adenocarcinoma, TTF-1 expression is a predictor of good outcome. Patients with no TTF-1 expression or TTF-1 expression and TTF-1 gene amplification tend to have a significantly worse prognosis than patients with TTF-1 expression and no TTF-1 gene amplification. C1 [Barletta, Justine A.; Perner, Sven; Johnson, Laura A.; Rubin, Mark A.; Loda, Massimo; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Barletta, Justine A.; Perner, Sven; Iafrate, A. John; Yeap, Beow Y.; Johnson, Laura A.; Rubin, Mark A.; Loda, Massimo; Chirieac, Lucian R.] Harvard Univ, Sch Med, Boston, MA USA. [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Weir, Barbara A.; Meyerson, Matthew; Loda, Massimo] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Travis, William D.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Chirieac, LR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lchirieac@partners.org RI Meyerson, Matthew/E-7123-2012; OI Rubin, Mark/0000-0002-8321-9950 FU National Institutes of Health [CA90578, CA074386, CA092824] FX This study was supported by CA90578, CA074386 and CA092824 from the National Institutes of Health. We are indebted to Ms. Laura Kwan for secretarial support. NR 31 TC 49 Z9 50 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD AUG PY 2009 VL 13 IS 8B BP 1977 EP 1986 DI 10.1111/j.1582-4934.2008.00594.x PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 525CN UT WOS:000272190800033 PM 19040416 ER PT J AU Huang, H Cantor, AB AF Huang, Hui Cantor, Alan B. TI Common Features of Megakaryocytes and Hematopoietic Stem Cells: What's the Connection? SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE MEGAKARYOCYTES; HEMATOPOIETIC STEM CELLS; HEMATOPOIESIS; STEM CELL NICHE; ENDOTHELIAL CELLS ID DEFINITIVE HEMATOPOIESIS; TRANSCRIPTION FACTOR; HAEMOGENIC ENDOTHELIUM; ADULT HEMATOPOIESIS; LEUKEMIC-CELLS; MOUSE EMBRYO; MICE LACKING; BONE-MARROW; C-MPL; PROGENITORS AB Megakaryocytes (Mks) are rare polyploid bone marrow cells whose function is to produce blood platelets. Since the purification and cloning of the major Mk cytokine, thrombopoietin, in 1994, considerable progress has been made in understanding the biology of Mk development. Remarkably, these advances have revealed a number of key features of Mks that are shared with hernatopoietic stem cells (HSCs), such as common surface receptors, lineage-specific transcription factors, and specialized signaling pathways. Why there should be such a close connection between these two cell types remains unclear. In this Prospect article, we summarize the data supporting these shared features and speculate on possible teleological bases. In particular, we focus on common links involving developmental hierarchy, endothelial cells, and bone marrow niche interactions. This discussion highlights new data showing close ontologic relationship between HSCs and specialized "hemogenic" endothelial cells during development, and functional overlap between Mks/platelets and endothelial cells. Overall, these findings may he of relevance in the development of techniques for FISC ex vivo culture and/or possible generation of HSCs via somatic cell reprogramming. J. Cell. Biochem. 107: 857-864, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Huang, Hui; Cantor, Alan B.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dana Farber Canc Inst,Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Cantor, AB (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dana Farber Canc Inst,Div Pediat Hematol Oncol, 300 Longwood Ave,Karp 7, Boston, MA 02115 USA. EM alan.cantor@childrens.harvard.edu FU NIH [R01 HL082952] FX Grant sponsor: NIH; Grant number: R01 HL082952. NR 62 TC 19 Z9 19 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD AUG 1 PY 2009 VL 107 IS 5 BP 857 EP 864 DI 10.1002/jcb.22184 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 477TT UT WOS:000268542500003 PM 19492306 ER PT J AU Eyman, D Damodarasamy, M Plymate, SR Reed, MJ AF Eyman, D. Damodarasamy, M. Plymate, S. R. Reed, M. J. TI CCL5 Secreted by Senescent Aged Fibroblasts Induces Proliferation of Prostate Epithelial Cells and Expression of Genes that Modulate Angiogenesis SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR; TUMOR ANGIOGENESIS; PATHOLOGICAL ANGIOGENESIS; PARACRINE INDUCER; CHEMOKINE RANTES; HYPERPLASIA; CANCER; PLEIOTROPHIN; CCL5/RANTES; PROGRESSION AB There is increased interest in the effects of secretory products from aged cells on promoting both benign and malignant cell growth. We identified a human fibroblast line, AG04382, from an aged donor that naturally demonstrated senescence-associated features and whose conditioned media significantly induced proliferation of benign prostatic hyperplasia (BPHI) cells. Candidate cytokines mediating this effect were identified with protein arrays and validated by ELISA. We found that the AG04382 fibroblast line secreted high levels of CXCL5, CCL5, and CCL2, but relative to the other lines, its conditioned media was unique in its increased expression of CCL5. Blocking studies using specific antibodies against CXCL5, CCL5, and CCL2 in the conditioned media of AG04382 showed that only CCL5 contributed significantly to BPHI proliferation. Stimulation of BPHI cells with rhuCCL5 resulted in increased proliferation and migration, as well as significant changes in the expression of genes that influence angiogenesis. These data suggest that CCL5 is a candidate chemokine secreted by aged cells that promotes prostate growth and regulates angiogenesis. J. Cell. Physiol. 220: 376-381, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Eyman, D.; Damodarasamy, M.; Reed, M. J.] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. [Plymate, S. R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Reed, MJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Harborview Res & Training Bldg 325,9th Ave, Seattle, WA 98104 USA. EM mjr@u.washington.edu FU NIH [U54 CA12654C, R0 AG 15887] FX Contract grant numbers: U54 CA12654C, R0 AG 15887 NR 55 TC 16 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 2009 VL 220 IS 2 BP 376 EP 381 DI 10.1002/jcp.21776 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 465BG UT WOS:000267555000013 PM 19360811 ER PT J AU Childress, AC Spencer, T Lopez, F Gerstner, O Thulasiraman, A Muniz, R Post, A AF Childress, Ann C. Spencer, Thomas Lopez, Frank Gerstner, Ortrud Thulasiraman, Anuradha Muniz, Rafael Post, Anke TI Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules Administered Once Daily to Children with Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; D,L-THREO-METHYLPHENIDATE HYDROCHLORIDE; DOUBLE-BLIND; METHYLPHENIDATE; ADHD; PREVALENCE; PLACEBO; SCHOOL AB Objective: This 5-week, multicenter, double-blind, placebo-controlled, parallel-group investigation is the first fixed-dose study to evaluate efficacy and tolerability of three doses of (10, 20, or 30 mg, once daily [o.d.]) dexmethylphenidate hydrochloride (HCl) extended-release (d-MPH XR; Focalin (R) XR) across multiple settings to treat pediatric attention-deficit/hyperactivity disorder (ADHD). Results: ADHD pediatric outpatients (n = 253) diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition, criteria were randomized (1: 1: 1: 1) to receive d-MPH XR (10, 20, or 30 mg o.d.) or placebo. Treatment with d-MPH XR significantly (p<0.001) reduced the mean score (change from baseline) on Conners'-ADHD/DSM-IV Scales (CADS) as assessed by the teacher CADS-T (dose [mean]; 10 mg [18], 20 mg [16.9], 30 mg [20.7]) and parents, CADS-P (dose [mean]; 10 mg [15.8]; 20 mg [17.8]; 30 mg [20.5]) compared to placebo (mean CADS-T [5.7]; CADS-P [4.6]). A significant (p<0.001) proportion of patients in the three d-MPH XR treatment groups showed improvement on the clinician-rated, Clinical Global Impressions-Improvement (CGI-I) scales (10 mg [73.8%]; 20 mg [71.2%]; 30 mg [77.2%]) and severity ratings (CGI-S) compared to the placebo group (CGI-I, 22.2%). Adverse events were mild to moderate in severity and similar to previous observations for this class of neurostimulants. Conclusion: All three doses of d-MPH XR (10, 20, or 30 mg o.d), were significantly more effective than placebo in improving ADHD symptoms as confirmed by the teacher, parent and clinician. Additionally, d-MPH XR was well tolerated and demonstrated a consistent safety profile. C1 [Childress, Ann C.] Ctr Psychiat & Behav Med Inc, Las Vegas, NV 89128 USA. [Spencer, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lopez, Frank] Childrens Dev Ctr, Winter Pk, FL USA. [Gerstner, Ortrud; Thulasiraman, Anuradha; Muniz, Rafael; Post, Anke] Nova Pharmaceut Corp, E Hanover, NJ USA. RP Childress, AC (reprint author), Ctr Psychiat & Behav Med Inc, 7351 Prairie Falcon Rd,Suite 160, Las Vegas, NV 89128 USA. EM drann87@aol.com FU Novartis Pharmaceuticals Corporation FX This study was funded by Novartis Pharmaceuticals Corporation. NR 35 TC 8 Z9 8 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2009 VL 19 IS 4 BP 351 EP 361 DI 10.1089/cap.2009.0007 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 486WJ UT WOS:000269231100003 PM 19702487 ER PT J AU Yuen, KCJ Biller, BMK Molitch, ME Cook, DM AF Yuen, Kevin C. J. Biller, Beverly M. K. Molitch, Mark E. Cook, David M. TI Is Lack of Recombinant Growth Hormone (GH)-Releasing Hormone in the United States a Setback or Time to Consider Glucagon Testing for Adult GH Deficiency? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID INSULIN TOLERANCE-TEST; BODY-MASS INDEX; STIMULATION TEST; PLUS ARGININE; PROVOCATIVE TESTS; CONSENSUS GUIDELINES; CORTISOL RESPONSES; ENDOCRINE-SOCIETY; CUTOFF LIMITS; DIAGNOSIS AB Context: The use of the combined GHRH and arginine (GHRH-ARG) test has gained increasing acceptance in the United States as a reliable alternative test to the insulin tolerance test (ITT) for diagnosing adult GH deficiency (GHD). In July 2008, the only manufacturer of recombinant GHRH in the United States, EMD Serono, Inc., announced the discontinuation of Geref, thus raising the question of which reliable alternative GH stimulation test should practicing endocrinologists be considering in place of the GHRH-ARG test. In this article, we review the existing published data and consensus guidelines and provide recommendations for alternative stimulation tests to the GHRH-ARG test. Evidence Acquisition: The major source of data acquisition included PubMed search strategies and personal experience of the authors from clinical experience. Evidence Synthesis: Previous consensus guidelines and previous data assessing the reliability and discriminatory value of the GHRH-ARG, glucagon, ARG, and GH secretagogues on assessing GH reserve are discussed. Our recommendations for performing the glucagon stimulation test, potential drawbacks in conducting this test, and caveats in interpreting this test are also discussed. Conclusions: The ITT should remain the test of choice in diagnosing adult GHD. However, when the ITT is not desirable and recombinant GHRH remains unavailable in the United States, we recommend the alternative to the GHRH-ARG test to be the glucagon stimulation test, based on its reliability and availability. Nevertheless, further studies into alternative GH stimulation tests that are available in the United States, comparable, and simpler to perform than the ITT in diagnosing adult GHD are still needed. (J Clin Endocrinol Metab 94: 2702-2707, 2009) C1 [Yuen, Kevin C. J.; Cook, David M.] Oregon Hlth & Sci Univ, Dept Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. RP Yuen, KCJ (reprint author), Oregon Hlth & Sci Univ, Dept Endocrinol Diabet & Clin Nutr, 3181 SW Sam Jackson Pk Rd,Mailcode L607, Portland, OR 97239 USA. EM yuenk@ohsu.edu NR 45 TC 42 Z9 44 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2009 VL 94 IS 8 BP 2702 EP 2707 DI 10.1210/jc.2009-0299 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479UW UT WOS:000268687700005 PM 19509104 ER PT J AU Marcocci, C Chanson, P Shoback, D Bilezikian, J Fernandez-Cruz, L Orgiazzi, J Henzen, C Cheng, SF Sterling, LR Lu, J Peacock, M AF Marcocci, Claudio Chanson, Philippe Shoback, Dolores Bilezikian, John Fernandez-Cruz, Laureano Orgiazzi, Jacques Henzen, Christoph Cheng, Sunfa Sterling, Lulu Ren Lu, John Peacock, Munro TI Cinacalcet Reduces Serum Calcium Concentrations in Patients with Intractable Primary Hyperparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID QUALITY-OF-LIFE; ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; SF-36 HEALTH SURVEY; SECONDARY HYPERPARATHYROIDISM; POSTMENOPAUSAL WOMEN; PARATHYROIDECTOMY FAILURES; CALCIMIMETIC AGENT; CONTROLLED-TRIAL; DOUBLE-BLIND; FOLLOW-UP AB Context: Patients with persistent primary hyperparathyroidism (PHPT) after parathyroidectomy or with contraindications to parathyroidectomy often require chronic treatment for hypercalcemia. Objective: The objective of the study was to assess the ability of the calcimimetic, cinacalcet, to reduce serum calcium in patients with intractable PHPT. Design: This was an open-label, single-arm study comprising a titration phase of variable duration (2-16 wk) and a maintenance phase of up to 136 wk. Setting: The study was conducted at 23 centers in Europe, the United States, and Canada. Patients: The study included 17 patients with intractable PHPT and serum calcium greater than 12.5 mg/dl (3.1 mmol/liter). Intervention: During the titration phase, cinacalcet dosages were titrated every 2 wk (30 mg twice daily to 90 mg four times daily) for 16 wk until serum calcium was 10 mg/dl or less (2.5 mmol/liter). If serum calcium increased during the maintenance phase, additional increases in the cinacalcet dose were permitted. Main Outcome Measure: The primary end point was the proportion of patients experiencing a reduction in serum calcium of 1 mg/dl or greater (0.25 mmol/liter) at the end of the titration phase. Results: Mean +/- SD baseline serum calcium was 12.7 +/- 0.8 mg/dl (3.2 +/- 0.2 mmol/liter). At the end of titration, a 1 mg/dl or greater reduction in serum calcium was achieved in 15 patients (88%). Fifteen patients (88%) experienced treatment-related adverse events, none of which were serious. The most common adverse events were nausea, vomiting, and paresthesias. Conclusions: In patients with intractable PHPT, cinacalcet reduces serum calcium, is generally well tolerated, and has the potential to fulfill an unmet medical need. (J Clin Endocrinol Metab 94: 2766-2772, 2009) C1 [Marcocci, Claudio] Univ Pisa, Dept Endocrinol & Metab, I-56124 Pisa, Italy. [Chanson, Philippe] Univ Paris 11, F-94275 Le Kremlin Bicetre, France. [Chanson, Philippe] Hop Bicetre, APHP, Dept Endocrinol & Reprod Dis, F-94275 Le Kremlin Bicetre, France. [Shoback, Dolores] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shoback, Dolores] San Francisco VA Med Ctr, Endocrine Res Unit, San Francisco, CA 94143 USA. [Bilezikian, John] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. [Fernandez-Cruz, Laureano] Univ Barcelona, E-08028 Barcelona, Spain. [Orgiazzi, Jacques] Univ Lyon 1, Ctr Hosp Lyon Sud, Serv Endocrinol Diabetol, F-69495 Pierre Benite, France. [Henzen, Christoph] Endokrinol Diabetol Kantonsspital, Luzern, Switzerland. [Cheng, Sunfa; Sterling, Lulu Ren; Lu, John] Amgen Inc, Thousand Oaks, CA 91320 USA. [Peacock, Munro] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Marcocci, C (reprint author), Univ Pisa, Dept Endocrinol & Metab, Via Paradisa 2, I-56124 Pisa, Italy. EM c.marcocci@endoc.med.unipi.it RI Chanson, Philippe/F-8511-2013 FU Amgen Inc; Amgen Europe; Antonia Panayi FX Disclosure Summary: C. M., J. B., L. F.-C., J. O., and C. H. have nothing to declare. P. C. has received a research grant from and consults for Amgen. D. S. is a consultant for Amgen and a speaker for Novartis, and has received honoraria from both. S. C., L. R. S., and J. L. are employed by Amgen. M. P. is a consultant for Amgen, Deltanoid, Genzyme, and Kirin. NR 33 TC 61 Z9 63 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2009 VL 94 IS 8 BP 2766 EP 2772 DI 10.1210/jc.2008-2640 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479UW UT WOS:000268687700014 PM 19470620 ER PT J AU Russell, M Bredella, M Tsai, P Mendes, N Miller, KK Klibanski, A Misra, M AF Russell, M. Bredella, M. Tsai, P. Mendes, N. Miller, K. K. Klibanski, A. Misra, M. TI Relative Growth Hormone Deficiency and Cortisol Excess Are Associated with Increased Cardiovascular Risk Markers in Obese Adolescent Girls SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID METABOLIC SYNDROME; BODY-COMPOSITION; FACTOR-I; IGF-I; FAT DISTRIBUTION; MEDIA THICKNESS; BINDING PROTEIN; GH DEFICIENCY; VISCERAL FAT; INSULIN AB Context: Obesity in adolescents is increasingly prevalent and its impact on cardiovascular risk important to determine. Hormonal predictors of cardiovascular risk markers in obese adolescents are not known. Objective: Our objective was to examine whether relative GH deficiency and cortisol excess are determinants of increased cardiovascular risk markers in obese teenage girls. Design and Setting: A cross-sectional study was conducted at a clinical research center. Study participants: Thirty girls (15 obese girls and 15 normal-weight controls) 12-18 years old matched for maturity and race. Main Outcome Measures: Inflammatory markers of cardiovascular risk including high-sensitivity C-reactive protein (hsCRP), TNF-alpha receptors 1 and 2, E-selectin, soluble intercellular adhesion molecule-1, and IL-6 were analyzed. Leptin, adiponectin, and 24-h urine free cortisol (UFC) were also measured. A GHRH-arginine stimulation test was performed. Results: The hsCRP levels were higher in obese girls than controls (4.63 +/- 4.81 vs. 0.67 +/- 0.72 mg/liter; P = 0.002 after log conversion), as were other markers of cardiovascular risk. Eight of the 15 obese girls but no normal-weight girl had hsCRP higher than 3 mg/liter (P = 0.002). Body mass index SD score was higher than 4.0 in 87.5% of girls with hsCRP higher than 3 mg/liter and no girls with hsCRP less than 3 mg/liter. Girls with hsCRP higher than 3 mg/liter had higher UFC and lower peak GH compared with those with hsCRP less than 3 mg/liter. Peak GH was an important negative predictor of most markers of increased cardiovascular risk. In addition to peak GH, UFC and adiponectin independently predicted hsCRP. Conclusion: Relative GH deficiency and cortisol excess are significant contributors to increased levels of markers of cardiovascular risk in obese adolescent girls.(J Clin Endocrinol Metab 94: 2864-2871, 2009) C1 [Russell, M.; Tsai, P.; Mendes, N.; Miller, K. K.; Klibanski, A.; Misra, M.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Bredella, M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Russell, M.; Misra, M.] MassGeneral Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/A-1469-2015 FU NCRR NIH HHS [K23 RR018851, M01 RR001066, UL1 RR025758, M01-RR-01066, 1UL1 RR025758-01]; NIDDK NIH HHS [P30 DK46200, F32-DK072816, F32 DK072816, P30 DK040561, P30 DK040561-14, P30 DK046200] NR 39 TC 14 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2009 VL 94 IS 8 BP 2864 EP 2871 DI 10.1210/jc.2009-0380 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479UW UT WOS:000268687700028 PM 19435823 ER PT J AU Leder, BZ Neer, RM Wyland, JJ Lee, HW Burnett-Bowie, SAM Finkelstein, JS AF Leder, Benjamin Z. Neer, Robert M. Wyland, Jason J. Lee, Hang W. Burnett-Bowie, Sherri-Ann M. Finkelstein, Joel S. TI Effects of Teriparatide Treatment and Discontinuation in Postmenopausal Women and Eugonadal Men with Osteoporosis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-I; FRACTURE RISK REDUCTION; BONE-MINERAL DENSITY; LONG-TERM EXTENSION; PARATHYROID-HORMONE; SKELETAL SENSITIVITY; LONGITUDINAL CHANGES; RANDOMIZED-TRIAL; ALENDRONATE; RESPONSIVENESS AB Context: In postmenopausal women, bone mineral density (BMD) declines after teriparatide therapy is stopped. The pattern of BMD loss after teriparatide therapy is stopped in men is less clear. Objective: The aim of the study was to determine whether the pattern of teriparatide-induced bone accrual and post-teriparatide bone loss differs between postmenopausal women and eugonadal men. Design: We conducted a prospective cohort substudy. Patients: The study included 14 postmenopausal women and 17 eugonadal men, ages 46-85 yr, with lumbar spine or femoral neck BMD T-scores below -2. Intervention: Teriparatide (37 mu g sc daily) was administered for 24 months, followed by 12 months off therapy. Main Outcome Measures: We measured BMD at various anatomic sites by dual-energy x-ray absorptiometry, trabecular spine BMD by quantitative computed tomography, and bone turnover markers during the treatment and observation periods. The response to teriparatide administration and discontinuation was compared between females and males. Results: BMD of the spine, femoral neck, total hip, and trabecular spine increased similarly during the treatment period in men and women, whereas BMD at the radius was stable in men but decreased by 8.1 +/- 3.3% in women (P < 0.0001). After teriparatide was stopped, BMD at the posterior-anterior spine decreased by 7.1 +/- 3.8% in women and by 4.1 +/- 3.5% in men (P = 0.036). BMD at the total hip and femoral neck decreased by 3.8 +/- 3.9 and 3.1 +/- 4.3%, respectively, in women but remained stable in men (P < 0.05 for both sites). BMD at the distal radius remained stable in men but increased in women by 1.6 +/- 3.1% (P = 0.069). Conclusions: Teriparatide appears to increase BMD similarly in postmenopausal women and eugonadal men with osteoporosis. After teriparatide is stopped, the decline in BMD is greater in women than in men. If confirmed in larger cohorts, these findings would suggest that the indication for immediate antiresorptive therapy after teriparatide may not be as urgent in men as in women. (J Clin Endocrinol Metab 94: 2915-2921, 2009) C1 [Leder, Benjamin Z.; Neer, Robert M.; Wyland, Jason J.; Burnett-Bowie, Sherri-Ann M.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Lee, Hang W.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, THR 1047,50 Blossom St, Boston, MA 02114 USA. EM bzleder@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU NCRR NIH HHS [RR-1066, M01 RR001066]; NIAMS NIH HHS [P50 AR044855, P50 AR44855]; NIDDK NIH HHS [K24 DK 02759, K24 DK002759] NR 30 TC 29 Z9 30 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2009 VL 94 IS 8 BP 2915 EP 2921 DI 10.1210/jc.2008-2630 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479UW UT WOS:000268687700035 PM 19435827 ER PT J AU Frystyk, J Brick, DJ Gerweck, AV Utz, AL Miller, KK AF Frystyk, J. Brick, D. J. Gerweck, A. V. Utz, A. L. Miller, K. K. TI Bioactive Insulin-Like Growth Factor-I in Obesity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; HORMONE-DEFICIENT ADULTS; FACTOR-BINDING PROTEIN-1; IGF-I; SERUM-LEVELS; WEIGHT-LOSS; WOMEN; IGFBP-2; GH; OVERWEIGHT AB Context: In obesity, total IGF-I is not reduced to the degree predicted by low GH levels, and free IGF-I levels are normal to high. Total and free IGF-I may not reflect IGF-I biological activity because immunoassays cannot account for the modifying effects of IGF binding proteins on interactions between IGF-I and its receptor. Objective: The aim of the study was to investigate the biological activity of IGF-I in obesity. Design and Setting: We conducted a cross-sectional study at a General Clinical Research Center. Study Participants: Thirty-four healthy women (11 lean, 12 overweight, and 11 obese) of comparable age (overall mean, 30.7 +/- 1.3 yr) participated in the study. Intervention: There were no interventions. Main Outcome Measures: We measured bioactive IGF-I (as measured by a kinase receptor activation assay), IGFBP-1, and GH using 6-h pools of serum collected every 10 min for 24 h, and fasting IGF-I and IGFBP-3. Results: Mean 24-h GH (R = -0.76; P < 0.0001), total IGF-I (R = -0.36; P = 0.040), and IGFBP-1 (R = -0.41; P = 0.017) levels were inversely associated with BMI, whereas bioactive IGF-I and IGFBP-3 levels were not. Mean bioactive IGF-I was similar in the groups [0.96 +/- 0.09 (lean), 1.08 +/- 0.09 (overweight), and 0.84 +/- 0.11 (obese) mu g/liter; overall P = 0.22]. Percentage bioactive IGF-I [(bioactive/total IGF-I) x 100] was higher in obese subjects than both lean and overweight subjects (P = 0.039). Conclusions: Despite low GH secretion in obesity and decreasing IGFBP-1 with increasing BMI, 24-h mean bioactive IGF-I levels are not reduced in obese women and do not correlate with BMI or IGFBP-1 levels. This argues against elevated bioactive IGF-I as the etiology of reduced GH secretion through a feedback mechanism in obesity. (J Clin Endocrinol Metab 94: 3093-3097, 2009) C1 [Brick, D. J.; Gerweck, A. V.; Miller, K. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. [Brick, D. J.; Gerweck, A. V.; Miller, K. K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Frystyk, J.] Aarhus Univ Hosp, Med Res Labs, DK-8000 Aarhus, Denmark. [Frystyk, J.] Aarhus Univ Hosp, Med Dept M, DK-8000 Aarhus, Denmark. [Utz, A. L.] Vanderbilt Univ, Dept Endocrinol, Nashville, TN 37232 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org FU National Institutes of Health [HL077674, MO1 RR01066, UL1 RR025758]; Danish Research Council for Health and Disease FX This work was supported by National Institutes of Health Grants HL077674, MO1 RR01066, and UL1 RR025758 and the Danish Research Council for Health and Disease. NR 46 TC 37 Z9 37 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2009 VL 94 IS 8 BP 3093 EP 3097 DI 10.1210/jc.2009-0614 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479UW UT WOS:000268687700063 PM 19470623 ER PT J AU Kim, WY Perera, S Zhou, B Carretero, J Yeh, JJ Heathcote, SA Jackson, AL Nikolinakos, P Ospina, B Naumov, G Brandstetter, KA Weigman, VJ Zaghlul, S Hayes, DN Padera, RF Heymach, JV Kung, AL Sharpless, NE Kaelin, WG Wong, KK AF Kim, William Y. Perera, Samanthi Zhou, Bing Carretero, Julian Yeh, Jen Jen Heathcote, Samuel A. Jackson, Autumn L. Nikolinakos, Petros Ospina, Beatriz Naumov, George Brandstetter, Kathleyn A. Weigman, Victor J. Zaghlul, Sara Hayes, D. Neil Padera, Robert F. Heymach, John V. Kung, Andrew L. Sharpless, Norman E. Kaelin, William G., Jr. Wong, Kwok-Kin TI HIF2 alpha cooperates with RAS to promote lung tumorigenesis in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR; ENDOTHELIAL PROGENITOR CELLS; LINDAU TUMOR-SUPPRESSOR; COLON-CANCER CELLS; ONCOGENIC K-RAS; GENE-EXPRESSION; E-CADHERIN; FACTOR 1-ALPHA; BONE-MARROW; CONDITIONAL INACTIVATION AB Members of the hypoxia-inducible factor (HIF) family of transcription factors regulate the cellular response to hypoxia. In non-small cell lung cancer (NSCLC), high HIF2 alpha levels correlate with decreased overall survival, and inhibition of either the protein encoded by the canonical HIF target gene VEGF or VEGFR2 improves clinical outcomes. However, whether HIF2 alpha is causal in imparting this poor prognosis is unknown. Here, we generated mice that conditionally express both a nondegradable variant of HIF2 alpha and a mutant form of Kras (Kras(G12)) that induces lung tumors. Mice expressing both Hij2 alpha and Kras(G12D) in the lungs developed larger tumors and had an increased tumor burden and decreased survival compared with mice expressing only Kras(G12D). Additionally, tumors expressing both Kras(G12D) and Hij2 alpha were more invasive, demonstrated features of epithelial-mesenchymal transition (EMT), and exhibited increased angiogenesis associated with mobilization of circulating endothelial progenitor cells. These results implicate HIF2 alpha causally in the pathogenesis of lung cancer in mice, demonstrate in vivo that HIF2 alpha can promote expression of markers of EMT, and define HIF2 alpha as a promoter of tumor growth and progression in a solid tumor other than renal cell carcinoma. They further suggest a possible causal relationship between HIF2 alpha and prognosis in patients with NSCLC. C1 [Kim, William Y.; Zhou, Bing; Yeh, Jen Jen; Heathcote, Samuel A.; Jackson, Autumn L.; Weigman, Victor J.; Hayes, D. Neil; Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Perera, Samanthi; Carretero, Julian; Brandstetter, Kathleyn A.; Zaghlul, Sara; Kaelin, William G., Jr.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Perera, Samanthi; Carretero, Julian; Brandstetter, Kathleyn A.; Zaghlul, Sara; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Yeh, Jen Jen] Univ N Carolina, Dept Surg, Chapel Hill, NC 27599 USA. [Nikolinakos, Petros; Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Ospina, Beatriz; Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hayes, D. Neil] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sharpless, Norman E.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kim, WY (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, 450 West Dr,CB 7295, Chapel Hill, NC 27599 USA. EM wykim@med.unc.edu RI zhou, bing/C-2150-2011; Carretero, Julian/N-5214-2014; OI Carretero, Julian/0000-0001-7269-8506; wong, kwok kin/0000-0001-6323-235X FU Cecily and Robert Harris Foundation; Joan Sca.rangello Foundation to Conquer Lung Cancer; Flight Attendant Medical Research Institute; Melanoma Research Foundation; Department of Defense; NIH [K08 AG024004, R01 AG2400401, R01 CA122794, K08 CA097203] FX We thank K. Rathmell and N. Bardeesy for useful discussions. This work was supported by the Cecily and Robert Harris Foundation (K.-K. Wong); the Joan Sca.rangello Foundation to Conquer Lung Cancer (K.-K. Wong and W.Y. Kim); the Flight Attendant Medical Research Institute (K.-K. Wong); the Melanoma Research Foundation (W.Y. Kim); the Department of Defense (W.Y. Kim), and NIH grants K08 AG024004 (to K.-K. Wong), R01 AG2400401 (to K.-K. Wong), R01 CA122794 (to K.-K. Wong), and K08 CA097203 (W.Y. Kim). We also acknowledge the assistance of the UNC Lineberger Genomics and Bioinformatics Core Facility. NR 87 TC 75 Z9 79 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2009 VL 119 IS 8 BP 2160 EP 2170 DI 10.1172/JCI38443 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 478NW UT WOS:000268596000010 PM 19662677 ER PT J AU Mitra, J Glover, JR Ktonas, PY Kumar, AT Mukherjee, A Karayiannis, NB Frost, JD Hrachovy, RA Mizrahi, EM AF Mitra, Joyeeta Glover, John R. Ktonas, Periklis Y. Kumar, Arun Thitai Mukherjee, Amit Karayiannis, Nicolaos B. Frost, James D., Jr. Hrachovy, Richard A. Mizrahi, Eli M. TI A Multistage System for the Automated Detection of Epileptic Seizures in Neonatal Electroencephalography SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; Neonatal; Epileptic; Seizure; Detection; Automated ID WAVELET TRANSFORM; EEG; ALGORITHM; INFANTS AB This paper describes the design and test results of it three-stage automated system for neonatal EEG seizure detection. Stage I of the system is the initial detection stage and identifies overlapping 5-second segments of suspected seizure activity in each EEG channel. In stage II, the detected segments from stage I are spatiotemporally clustered to produce multichannel candidate Seizures. In stage III, the candidate seizures are processed further using measures of quality and context-based rules to eliminate false candidates. False candidates because of artifacts and commonly Occurring EEG background patterns such as bifrontal delta activity are also rejected. Seizures at least 10 seconds in duration are considered for reporting results. The testing data consisted of recordings of 28 seizure Subjects (34 hours of data) and 48 nonseizure subjects (87 hours of data) obtained in the neonatal intensive care unit. The data were not edited to remove artifacts and were identical in every way to data normally processed visually. The system was able to detect seizures Of widely varying morphology with an average detection sensitivity of almost 80% and a subject sensitivity of 96%, in comparison with a team of clinical neurophysiologists who had scored the same recordings. The average false detection rate obtained in nonseizure subjects was 0.74 per hour. C1 [Glover, John R.; Ktonas, Periklis Y.; Karayiannis, Nicolaos B.] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. [Mitra, Joyeeta] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. [Kumar, Arun Thitai] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA. [Mukherjee, Amit] Rensselaer Polytech Inst, ECSE Dept, Troy, NY USA. [Frost, James D., Jr.] Baylor Coll Med, Dept Neurol, Peter Kellaway Sect Neurophysiol, Houston, TX 77030 USA. [Hrachovy, Richard A.; Mizrahi, Eli M.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Hrachovy, Richard A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Glover, JR (reprint author), Univ Houston, Dept Elect & Comp Engn, N308 Engn Bldg 1, Houston, TX 77204 USA. EM glover@uh.edu FU National Institutes of Health [R01-NS40577] FX Supported by National Institutes of Health grant R01-NS40577. NR 16 TC 36 Z9 36 U1 0 U2 0 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 AUG PY 2009 VL 26 IS 4 BP 218 EP 226 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 480OQ UT WOS:000268746000002 PM 19602985 ER PT J AU Fox, BD Smitherman, SM Amhaz, H Ruiz, MI Rouah, E Radaideh, M Ehni, BL AF Fox, Benjamin D. Smitherman, Sheila M. Amhaz, Hassan Ruiz, Monica I. Rouah, Emilie Radaideh, Majdi Ehni, Bruce L. TI A supratentorial, hemorrhagic, intraparenchymal epidermoid cyst SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Epidermoid cyst; Hemorrhage; Intraparenchymal; Supratentorial; Tumor ID CENTRAL-NERVOUS-SYSTEM; TUMORS CHOLESTEATOMAS; POSTERIOR-FOSSA; PATHOGENESIS AB Epidermoid cysts are Slow growing benign tumors that represent < 1-2% of all intracranial tumors and rarely present as supratentorial, intraparenchymal masses. We present the first report of a supratentorial, hemorrhagic, intraparenchymal epidermoid cyst with its presentation. our operative approach, postoperative course, radiographic features, and a literature review. Published by Elsevier Ltd. C1 [Fox, Benjamin D.; Smitherman, Sheila M.; Ehni, Bruce L.] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. [Amhaz, Hassan] Baylor Coll Med, Off Student Affairs, Houston, TX 77030 USA. [Rouah, Emilie; Radaideh, Majdi; Ehni, Bruce L.] Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. [Ruiz, Monica I.; Rouah, Emilie] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Radaideh, Majdi] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. RP Ehni, BL (reprint author), Baylor Coll Med, Dept Neurosurg, 1709 Dryden Rd,Suite 750, Houston, TX 77030 USA. EM bruce.ehni@va.gov NR 28 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD AUG PY 2009 VL 16 IS 8 BP 1101 EP 1105 DI 10.1016/j.jocn.2008.04.033 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 478SG UT WOS:000268608000033 PM 19428259 ER PT J AU D'Amico, AV Chen, MH AF D'Amico, Anthony V. Chen, Ming-Hui TI Pretreatment Prostate-Specific Antigen Velocity and the Risk of Death From Prostate Cancer in the Individual With Low-Risk Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BEAM RADIATION-THERAPY; RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; ANDROGEN SUPPRESSION; PERINEURAL INVASION; RADIOTHERAPY; MORTALITY; MEN; DEPRIVATION; ADJUVANT C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 16 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2009 VL 27 IS 22 BP 3575 EP 3576 DI 10.1200/JCO.2009.22.6068 PG 2 WC Oncology SC Oncology GA 477EX UT WOS:000268502500003 PM 19506151 ER PT J AU Chan, JM Oh, WK Xie, WL Regan, MM Stampfer, MJ King, IB Abe, M Kantoff, PW AF Chan, June M. Oh, William K. Xie, Wanling Regan, Meredith M. Stampfer, Meir J. King, Irena B. Abe, Miyako Kantoff, Philip W. TI Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate- or High-Risk Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2008 CL Chicago, IL SP Amer Soc Clin Oncol ID STRESS-RELATED GENES; BREAST-CANCER; SERUM SELENIUM; ALA-9VAL POLYMORPHISM; OXIDATIVE STRESS; NUTRITIONAL PREVENTION; ALPHA-TOCOPHEROL; SUBSEQUENT RISK; DNA-DAMAGE; SUPPLEMENTATION AB Purpose In vitro, in vivo, and epidemiologic studies support a role for selenium in reducing the risk of prostate cancer. Our group previously demonstrated a strong interaction between plasma selenium and the manganese superoxide dismutase (SOD2) gene and incident prostate cancer risk. We now hypothesized that SOD2 modifies the association between selenium level and risk of aggressive prostate cancer at diagnosis. Patients and Methods We assessed SOD2 variants and plasma selenium in 489 patients with localized/locally advanced prostate cancer from an ongoing retrospective cohort. Cross-sectional associations with aggressive prostate cancer (ie, stage T2b-3, prostate-specific antigen > 10 ng/mL, or biopsy Gleason score >= 7) were evaluated using the chi(2) test, Cochran-Armitage test for trend, and estimations of relative risk (RR) and 95% CIs. Results SOD2 genotype alone was not associated with disease aggressiveness, whereas higher versus lower selenium levels were associated with a slightly increased likelihood of presenting with aggressive disease (RR = 1.35; 95% CI, 0.99 to 1.84). There was evidence of an interaction between SOD2 and selenium levels such that among men with the AA genotype, higher selenium levels were associated with a reduced risk of presenting with aggressive disease (RR = 0.60; 95% CI, 0.32 to 1.12), whereas among men with a V allele, higher selenium levels were associated with an increased risk of aggressive disease (for VV or VA men, RR = 1.82; 95% CI, 1.27 to 2.61; P for interaction = .007). Conclusion These data suggest that the relationship between circulating selenium levels at diagnosis and prognostic risk of prostate cancer is modified by SOD2 genotype and indicate caution against broad use of selenium supplementation for men with prostate cancer. J Clin Oncol 27: 3577-3583. (C) 2009 by American Society of Clinical Oncology C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Chan, JM (reprint author), Helen Diller Family Canc Res Bldg,1450 3rd St,MC, San Francisco, CA 94158 USA. EM june.chan@ucsf.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [P50CA89520, P50 CA089520, P50 CA090381, P50CA90381, R01 CA106947] NR 52 TC 42 Z9 42 U1 0 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 AUG 1 PY 2009 VL 27 IS 22 BP 3577 EP 3583 DI 10.1200/JCO.2008.18.8938 PG 7 WC Oncology SC Oncology GA 477EX UT WOS:000268502500004 PM 19528373 ER PT J AU Motzer, RJ Hutson, TE Tomczak, P Michaelson, MD Bukowski, RM Oudard, S Negrier, S Szczylik, C Pili, R Bjarnason, GA Garcia-del-Muro, X Sosman, JA Solska, E Wilding, G Thompson, JA Kim, ST Chen, I Huang, X Figlin, RA AF Motzer, Robert J. Hutson, Thomas E. Tomczak, Piotr Michaelson, M. Dror Bukowski, Ronald M. Oudard, Stephane Negrier, Sylvie Szczylik, Cezary Pili, Roberto Bjarnason, Georg A. Garcia-del-Muro, Xavier Sosman, Jeffrey A. Solska, Ewa Wilding, George Thompson, John A. Kim, Sindy T. Chen, Isan Huang, Xin Figlin, Robert A. TI Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2008 CL Chicago, IL SP Amer Soc Clin Oncol ID HYPOTHYROIDISM; EFFICACY; TUMORS AB Purpose A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-alpha) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. Patients and Methods Seven hundred fifty treatment-nave patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-alpha 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up. Results Median overall survival was greater in the sunitinib group than in the IFN-alpha group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-alpha group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor-signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-alpha (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-alpha (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%). Conclusion Sunitinib demonstrates longer overall survival compared with IFN-alpha plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy. J Clin Oncol 27: 3584-3590. (C) 2009 by American Society of Clinical Oncology C1 [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Baylor Sammons Canc Ctr Texas Oncol, Dallas, TX USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. Johns Hopkins Univ, Baltimore, MD USA. Vanderbilt Univ, Nashville, TN USA. Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. Seattle Canc Care Alliance, Seattle, WA USA. Pfizer Global Res & Dev, La Jolla, CA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Klin Onkol Oddzial Chemioterapii, Poznan, Poland. Mil Inst Med, Warsaw, Poland. Wojewodzka Przychodnia Onkolog, Gdansk, Poland. Hop Europeen Georges Pompidou, Paris, France. Ctr Leon Berard, F-69373 Lyon, France. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Inst Catala Oncol, Barcelona, Spain. RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM motzerr@mskcc.org RI Gonzalez Larriba, Jose Luis/G-6177-2016; OI Gonzalez Larriba, Jose Luis/0000-0003-2631-0309; Michaelson, Dror/0000-0001-9249-6338; Bjarnason, Georg Arnold/0000-0001-6903-5357 NR 12 TC 1110 Z9 1163 U1 2 U2 38 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2009 VL 27 IS 22 BP 3584 EP 3590 DI 10.1200/JCO.2008.20.1293 PG 7 WC Oncology SC Oncology GA 477EX UT WOS:000268502500005 PM 19487381 ER PT J AU Grant, CS Ingle, JN Suman, VJ Dumesic, DA Wickerham, DL Gelber, RD Flynn, PJ Weir, LM Intra, M Jones, WO Perez, EA Hartmann, LC AF Grant, Clive S. Ingle, James N. Suman, Vera J. Dumesic, Daniel A. Wickerham, D. Lawrence Gelber, Richard D. Flynn, Patrick J. Weir, Lorna M. Intra, Mattia Jones, Wayne O. Perez, Edith A. Hartmann, Lynn C. TI Menstrual Cycle and Surgical Treatment of Breast Cancer: Findings From the NCCTG N9431 Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DISEASE-FREE SURVIVAL; PREMENOPAUSAL WOMEN; SERUM PROGESTERONE; 5-YEAR ANALYSIS; RECEPTOR STATUS; SURGERY; PHASE; PROGNOSIS; CARCINOMA; CURE AB Purpose For nearly two decades, multiple retrospective reports, small prospective studies, and meta-analyses have arrived at conflicting results regarding the value of timing surgical intervention for breast cancer on the basis of menstrual cycle phase. We present the results of a multicooperative group, prospective, observational trial of menstrual cycle phase and outcome after breast cancer surgery, led by the North Central Cancer Treatment Group (NCCTG) in collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the International Breast Cancer Study Group (IBCSG). Patients and Methods Premenopausal women age 18 to 55 years, who were interviewed for menstrual history and who were surgically treated for stages I to II breast cancer, had serum drawn within 1 day of surgery for estradiol, progesterone, and luteinizing hormone levels. Menstrual history and hormone levels were used to determine menstrual phase: luteal, follicular, and other. Disease-free survival (DFS) and overall survival (OS) rates were determined by Kaplan-Meier method and were compared by using the log-rank test and Cox proportional hazard modeling. Results Of 1,118 women initially enrolled, 834 women comprised the study cohort: 230 (28%) in luteal phase; 363 (44%) in follicular phase; and 241 grouped as other. During a median follow-up of 6.6 years, and in analysis that accounted for nodal disease, estrogen receptor status, adjuvant radiation therapy or chemotherapy, neither DFS nor OS differed with respect to menstrual phase. The 5-year DFS rates were 82.7%, 82.1%, and 79.2% for follicular, luteal, or other phases, respectively. Corresponding OS survival rates were 91.9%, 92.2%, and 91.8%, respectively. Conclusion When menstrual cycle phases were strictly defined, neither DFS nor OS differed between women who underwent surgery during the follicular phase versus the luteal phase. Nearly 30% of the patients did not meet criteria for either follicular-or luteal-phase categories. J Clin Oncol 27: 3620-3626. (C) 2009 by American Society of Clinical Oncology C1 [Grant, Clive S.] Mayo Clin, Div Gen Surg, N Cent Canc Treatment Grp, Dept Surg,Div Med Oncol,Canc Ctr Stat, Rochester, MN 55905 USA. Reprod Med & Infertil Associates, N Cent Canc Treatment Grp, Woodbury, MN USA. Allegheny Canc Ctr, N Cent Canc Treatment Grp, Pittsburgh, PA USA. Dana Farber Canc Inst, Natl Surg Adjuvant Breast & Bowel Project, Boston, MA 02115 USA. Community Clin Oncol Program Metrominnesota, Int Breast Canc Study Grp, Natl Surg Adjuvant Breast & Bowel Project, St Louis Pk, MN USA. British Columbia Canc Agcy, Vancouver Canc Ctr, Natl Surg Adjuvant Breast & Bowel Project, Vancouver, BC V5Z 4E6, Canada. European Inst Oncol, Div Breast Surg, Milan, Italy. Auckland City Hosp, Dept Surg, Int Breast Canc Study Grp, Auckland, New Zealand. Mayo Clin, Int Breast Canc Study Grp, N Cent Canc Treatment Grp, Jacksonville, FL 32224 USA. Mayo Clin, Div Hematol Oncol, Australian New Zealand Breast Canc Trials Grp, Jacksonville, FL 32224 USA. RP Grant, CS (reprint author), Mayo Clin, Div Gen Surg, N Cent Canc Treatment Grp, Dept Surg,Div Med Oncol,Canc Ctr Stat, 200 1st St SW, Rochester, MN 55905 USA. EM cgrant@mayo.edu FU NCI NIH HHS [U10 CA025224-26, U10 CA025224, U10 CA012027, U10 CA069974, U10-CA-69651, CA25224, CA075364, U10 CA069651, U10-CA-12027, U10 CA037377, U10-CA-69974, U10-CA-37377] NR 34 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2009 VL 27 IS 22 BP 3620 EP 3626 DI 10.1200/JCO.2008.21.3603 PG 7 WC Oncology SC Oncology GA 477EX UT WOS:000268502500010 PM 19487378 ER PT J AU Haffajee, AD Yaskell, T Torresyap, G Teles, R Socransky, SS AF Haffajee, Anne D. Yaskell, Tina Torresyap, Gay Teles, Ricardo Socransky, Sigmund S. TI Comparison between polymerase chain reaction-based and checkerboard DNA hybridization techniques for microbial assessment of subgingival plaque samples SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE bacteria; checkerboard; DNA probes; PCR; subgingival biofilm ID REAL-TIME PCR; PORPHYROMONAS-GINGIVALIS; PERIODONTAL PATHOGENS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; CULTURE; QUANTIFICATION; INFECTIONS AB P>Aim To compare polymerase chain reaction (PCR) with subsequent reverse hybridization (micro-IDent test) and checkerboard DNA-DNA hybridization for the identification of 13 bacterial species in subgingival plaque samples. Material and Methods Subgingival plaque samples were taken using paper points and curettes from two sites each with pocket depth < 4, 4-6 and > 6 mm at baseline and 3 months in 25 periodontitis subjects and two sites in 25 periodontally healthy subjects. Samples were analysed for their content of 13 bacterial species using both assays. Similarities for each species between techniques were determined using regression analysis. Differences between health and periodontitis were determined using the Mann-Whitney test. Results Three hundred and fifty samples were evaluated using both techniques. Regression analysis indicated that 10/13 test species showed significant positive correlations between the counts determined by checkerboard analysis and levels determined by the PCR-based test after adjusting for 13 comparisons. The highest rank correlations of 0.58, 0.49 and 0.46 were seen for Treponema denticola, Fusobacterium nucleatum and Eubacterium nodatum, respectively (p < 0.0001). Both tests could distinguish samples from healthy and periodontitis subjects. Conclusion Detection patterns of 10/13 test species in subgingival plaque samples from periodontitis and healthy subjects were similar using the two molecular techniques. C1 [Haffajee, Anne D.; Yaskell, Tina; Torresyap, Gay; Teles, Ricardo; Socransky, Sigmund S.] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM ahaffajee@forsyth.org FU Hain Life-science GmbH, Nehren, Germany FX This study was supported by Hain Life-science GmbH, Nehren, Germany. NR 25 TC 16 Z9 17 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD AUG PY 2009 VL 36 IS 8 BP 642 EP 649 DI 10.1111/j.1600-051X.2009.01434.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 469FJ UT WOS:000267880900004 PM 19563330 ER PT J AU Wrishko, RE Ernest, CS Small, DS Li, YG Weerakkody, GJ Riesmeyer, JR Macias, WL Rohatagi, S Salazar, DE Antman, EM Wiviott, SD Braunwald, E Ni, L AF Wrishko, Rebecca E. Ernest, C. Steven, II Small, David S. Li, Ying G. Weerakkody, Govinda J. Riesmeyer, Jeffrey R. Macias, William L. Rohatagi, Shashank Salazar, Daniel E. Antman, Elliott M. Wiviott, Stephen D. Braunwald, Eugene Ni, Lan TI Population Pharmacokinetic Analyses to Evaluate the Influence of Intrinsic and Extrinsic Factors on Exposure of Prasugrel Active Metabolite in TRITON-TIMI 38 SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Population pharmacokinetics; maximal platelet aggregation; prasugrel; TRITON-TIMI 38 ID PERCUTANEOUS CORONARY INTERVENTION; ST-SEGMENT ELEVATION; THIENOPYRIDINE ANTIPLATELET AGENT; ASPIRIN-TREATED PATIENTS; ASSOCIATION TASK-FORCE; MYOCARDIAL-INFARCTION; PLATELET-AGGREGATION; AMERICAN-COLLEGE; GUIDELINE UPDATE; ACHIEVES GREATER AB Serial pharmacokinetic (PK) sampling in 1159 patients from TRITON-TIMI 38 was undertaken. A multilinear regression model was used to quantitatively predict prasugrel's active metabolite (Pras-AM) concentrations from its 2 downstream inactive metabolites. Population-based methods were then applied to Pras-AM concentration data to characterize the PK. The potential influence of body weight, body mass index, age, sex, renal function, diabetes, tobacco use, and other disease status on Bayesian estimates of Pras-AM exposures was assessed. The PK of Pras-AM was adequately described by a multicompartmental model and consistent with results from previous studies. The systemic exposure of prasugrel was not appreciably affected by body mass index, gender, diabetes, smoking, and renal impairment. Pras-AM mean exposure in patients weighing <60 kg (4.1%) was 30% (90% confidence interval [CI] 1.16-1.45) higher than exposure in patients >= 60 kg. Mean Pras-AM exposures for patients >= 75 years (10.5%) were 19% (90% CI: 1.11-1.28) higher compared with patients <75 years. C1 [Wrishko, Rebecca E.] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Rohatagi, Shashank; Salazar, Daniel E.] Daiichi Sankyo Inc, Parsippany, NJ USA. [Antman, Elliott M.; Wiviott, Stephen D.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Antman, Elliott M.; Wiviott, Stephen D.; Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. RP Wrishko, RE (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM wrishkore@lilly.com FU Daiichi Sankyo Company, Ltd; Eli Lilly and Company; Sanofi-Aventis FX This work was supported by Daiichi Sankyo Company, Ltd and Eli Lilly and Company. Drs Wrishko, Small, Weerakkody, Riesmeyer, Macias, and Ni and Mr Ernest and Ms Li are employees and stockholders of Eli Lilly and Company. Drs Rohatagi and Salazar are employees of Daiichi Sankyo, Inc. Dr Braunwald is the chairman of the TIMI Study Group at the Brigham and Women's Hospital. The Brigham and Women's Hospital receives (or has received within the past 24 months) grant support from Eli Lilly and Daiichi Sankyo for the TIMI Study Group where Dr Braunwald's salary is derived. Drs Wiviott and Antman received research grants from Eli Lilly, Daiichi Sankyo, and Sanofi-Aventis. In addition, Dr Wiviott reports receiving consulting fees or paid advisory board fees from Sanofi-Aventis and lecture fees from Eli Lilly and Daiichi Sankyo; Dr Antman received consulting fees or paid advisory board fees from Sanofi-Aventis and lecture fees from Eli Lilly and Sanofi-Aventis. NR 28 TC 47 Z9 47 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD AUG PY 2009 VL 49 IS 8 BP 984 EP 998 DI 10.1177/0091270009337942 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 470IH UT WOS:000267967900011 PM 19546250 ER PT J AU Henin, A Mick, E Biederman, J Fried, R Hirshfeld-Becker, DR Micco, JA Miller, KG Rycyna, CC Wozniak, J AF Henin, Aude Mick, Eric Biederman, Joseph Fried, Ronna Hirshfeld-Becker, Dina R. Micco, Jamie A. Miller, Katherine G. Rycyna, Caroline C. Wozniak, Janet TI Is Psychopharmacologic Treatment Associated With Neuropsychological Deficits in Bipolar Youth? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OPEN-LABEL TRIAL; MANIA RATING-SCALE; PROCESSING SPEED; HEALTHY-SUBJECTS; DOUBLE-BLIND; ANTIEPILEPTIC DRUGS; DISORDER; CHILDREN; ADOLESCENTS; MONOTHERAPY AB Objective: To evaluate the impact of psychopharmacologic treatments on neuropsychological functioning in bipolar youth. Method: Participants were 173 children (aged 6-17 years) with DSM-IV bipolar disorder. Participants were comprehensively assessed using structured diagnostic interviews (Schedule for Affective Disorders and Schizophrenia for School-Age Children) and neuropsychological measures (eg, subtests of the Wechsler Intelligence Scale for Children-III and Wechsler Adult Intelligence Scale-III) during the years 2001-2006. Comparisons were made in neuropsychological functioning between medicated and unmedicated youth with bipolar disorder. Results: Children who were treated with mood stabilizers performed significantly (P<.05) more poorly than untreated children on measures of processing speed and working memory. Treatment with other classes of medication, including second-generation antipsychotics, was not significantly associated with neuropsychological impairments. Conclusions: Treatment with mood stabilizers may be associated with specific neuropsychological impairments. Cognitive side effects may,need to be considered in selecting particular psychopharmacologic treatments for children with bipolar disorder. J Clin Psychiatry 2009;70(8):1178-1185 (C) Copyright 2009 physicians postgraduate Press, Inc. C1 [Henin, Aude] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Cambridge, MA 02138 USA. [Henin, Aude; Mick, Eric; Biederman, Joseph; Fried, Ronna; Hirshfeld-Becker, Dina R.; Micco, Jamie A.; Miller, Katherine G.; Rycyna, Caroline C.; Wozniak, Janet] Pediat Psychopharmacol Clin & Res Program, Boston, MA USA. RP Henin, A (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, 185 Alewife Brook Pkwy Suite 2000, Cambridge, MA 02138 USA. EM ahenin@partners.org OI Mick, Eric/0000-0001-8505-8145 FU Janssen; Pfizer; Bristol-Myers Squibb; Ortho-McNeil Janssen Scientific Affairs; Stanley Medical Research Institute; NARSAD junior Investigator Award; NIMH [K01MH065523]; Neal-Kimmerly Fund; Study of Cognition, Boston, Massachusetts FX Clinical trials were supported by Janssen, Pfizer, Bristol-Myers Squibb, Ortho-McNeil Janssen Scientific Affairs, and the Stanley Medical Research Institute. Analyses of these data were supported by a NARSAD junior Investigator Award (Dr Henin) and by a research grant from the NIMH (K01MH065523; Dr Mick). Support also came, in part, from the Neal-Kimmerly Fund for the Study of Cognition, Boston, Massachusetts. NR 55 TC 16 Z9 16 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2009 VL 70 IS 8 BP 1178 EP 1185 DI 10.4088/JCP.08m04696 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 487JX UT WOS:000269270600014 PM 19573494 ER PT J AU Perivoliotis, D Cather, C AF Perivoliotis, Dimitri Cather, Corinne TI Cognitive Behavioral Therapy of Negative Symptoms SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE schizophrenia; psychotherapy; cognitive behavioral therapy; negative symptoms ID SCHIZOPHRENIA; DEFICIT; TRIAL AB Negative symptoms account for much of the functional disability associated with schizophrenia and often persist despite pharmacological treatment. Cognitive behavioral therapy (CBT) is a promising adjunctive psychotherapy for negative symptoms, The treatment is based on a cognitive formulation in which negative symptoms arise and are maintained by dysfunctional beliefs that are a reaction to the neurocognitive impairment and discouraging life events frequently experienced by individuals with schizophrenia. This article outlines recent innovations in tailoring CBT for negative symptoms and functioning, including the use of a strong goal-oriented recovery approach, in-session exercises designed to disconfirm dysfunctional beliefs, and adaptations to circumvent neurocognitive and engagement difficulties. A case illustration is provided, (C) 2009 Wiley Periodicals, Inc. J Clin Psychol: In Session 65:815-830, 2009. C1 [Perivoliotis, Dimitri] Univ Penn, Philadelphia, PA 19104 USA. [Cather, Corinne] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Perivoliotis, D (reprint author), Univ Penn, 3535 Market St,Room 2032, Philadelphia, PA 19104 USA. EM dimitrip@mail.med.upenn.edu NR 25 TC 14 Z9 16 U1 2 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD AUG PY 2009 VL 65 IS 8 BP 815 EP 830 DI 10.1002/jclp.20614 PG 16 WC Psychology, Clinical SC Psychology GA 477IY UT WOS:000268513900003 PM 19572278 ER PT J AU Friedman-Yakoobian, MS Mueser, KT Giuliano, A Goff, DC Seidman, LJ AF Friedman-Yakoobian, Michelle S. Mueser, Kim T. Giuliano, Anthony Goff, Donald C. Seidman, Larry J. TI Family-Directed Cognitive Adaptation for Schizophrenia SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE schizophrenia; family treatment; cognitive adaptation; cognitive remediation; psychotherapy ID INTERVENTION; METAANALYSIS; ILLNESS; BURDEN; SCALE AB Cognitive impairment is pervasive in schizophrenia and is a major cause of poor functioning and caregiver burden. However, there are few treatments specifically aimed at helping families cope with a relative's cognitive difficulties and reducing the effects of cognitive impairments on the client's daily functioning. Family-directed cognitive adaptation (FCA) is a 16-session treatment developed to address this need. In this article, we provide a rationale for the development of FCA, describe the program itself, and summarize a pilot study aimed at evaluating the acceptability and feasibility of the treatment. We conclude with a case example of a family who participated in the program. (C) 2009 Wiley Periodicals, Inc. J Clin Psychol: In Session 65: 854-867,2009. C1 [Friedman-Yakoobian, Michelle S.; Giuliano, Anthony; Seidman, Larry J.] Harvard Univ, Dept Psychiat,Sch Med, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Beth Israel Deaconess Med Ctr, Jamaica Plain, MA 02130 USA. [Mueser, Kim T.] Dartmouth Med Sch, Dept Psychiat, Dartmouth, NS, Canada. [Goff, Donald C.] Harvard Univ, Sch Med, Dept Psychiat,Schizophrenia Program, Massachusetts Gen Hosp, Jamaica Plain, MA 02130 USA. RP Friedman-Yakoobian, MS (reprint author), Harvard Univ, Dept Psychiat,Sch Med, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Beth Israel Deaconess Med Ctr, 180 Morton St, Jamaica Plain, MA 02130 USA. EM Mfriedm3@bidmc.harvard.edu NR 21 TC 8 Z9 8 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD AUG PY 2009 VL 65 IS 8 BP 854 EP 867 DI 10.1002/jclp.20611 PG 14 WC Psychology, Clinical SC Psychology GA 477IY UT WOS:000268513900006 PM 19536868 ER PT J AU Anton, RF Myrick, H Baros, AM Latham, PK Randall, PK Wright, TM Stewart, SH Waid, R Malcolm, R AF Anton, Raymond F. Myrick, Hugh Baros, Alicia M. Latham, Patricia K. Randall, Patrick K. Wright, Tara M. Stewart, Scott H. Waid, Randy Malcolm, Robert TI Efficacy of a Combination of Flumazenil and Gabapentin in the Treatment of Alcohol Dependence Relationship to Alcohol Withdrawal Symptoms SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE alcoholism; treatment; flumazenil; gabapentin; alcohol withdrawal ID CHRONIC INTERMITTENT ETHANOL; GAMMA-AMINOBUTYRIC-ACID; DOUBLE-BLIND; GABA(A) RECEPTORS; CONTROLLED-TRIAL; GENE-EXPRESSION; OPEN-LABEL; PLACEBO; SCALE; PHARMACOLOGY AB Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials. C1 [Anton, Raymond F.; Myrick, Hugh; Baros, Alicia M.; Latham, Patricia K.; Randall, Patrick K.; Wright, Tara M.; Stewart, Scott H.; Waid, Randy; Malcolm, Robert] Med Univ S Carolina, Charleston, SC 29425 USA. [Myrick, Hugh; Wright, Tara M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Anton, RF (reprint author), Med Univ S Carolina, MSC 861,67 President St, Charleston, SC 29425 USA. EM antonr@musc.edu FU Hythiam, Inc. FX This study was conducted under air unrestricted grant from Hythiam, Inc. NR 48 TC 31 Z9 31 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2009 VL 29 IS 4 BP 334 EP 342 DI 10.1097/JCP.0b013e3181aba6a4 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 470QX UT WOS:000267995200004 PM 19593171 ER PT J AU Fava, M Wisniewski, SR Thase, ME Baker, RA Tran, QV Pikalov, A Yang, HY Marcus, RN Berman, RM AF Fava, Maurizio Wisniewski, Stephen R. Thase, Michael E. Baker, Ross A. Tran, Quynh-Van Pikalov, Andrei Yang, Huyuan Marcus, Ronald N. Berman, Robert M. TI Metabolic Assessment of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder A Pooled Analysis of 2 Studies SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE adjunctive aripiprazole; antidepressant therapy; major depressive disorder; weight; metabolic profile ID TREATMENT-RESISTANT DEPRESSION; DOUBLE-BLIND; OPEN-LABEL; OLANZAPINE/FLUOXETINE COMBINATION; BIPOLAR MANIA; WEIGHT-GAIN; EFFICACY; SAFETY; AUGMENTATION; ANTIDEPRESSANTS AB In 2 identical multicenter, double-blind, placebo-controlled trials, an 8-week prospective treatment phase to ensure inadequate response to standard antidepressants was followed with 6 weeks of aripiprazole (2-20 mg/d) or placebo, plus a standard antidepressant. This pooled analysis involving 737 patients across the 2 studies evaluated the metabolic effects of adjunctive aripiprazole in patients with major depressive disorder. Outcomes included mean change from end of prospective treatment phase to endpoint in body weight, waist circumference, fasting levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG), fasting plasma glucose, and glycosylated hemoglobin (hemoglobin A(1C)). Logistic regression determined whether baseline variables were associated with weight gain or whether weight change was associated with clinical outcome. Statistically significant increases occurred in mean body weight (adjunctive aripiprazole, +1.73 kg, vs adjunctive placebo, +0.38 kg; P < 0.001). Significantly more subjects receiving adjunctive aripiprazole had clinically relevant (>= 7%) weight gain versus placebo (5.2% vs 0.6%; P < 0.001). More patients treated with adjunctive aripiprazole shifted body mass index category group from normal to overweight and from overweight to obese than those treated with adjunctive placebo. Body mass index, sex, age, Montgomery-Asberg Depression Rating Scale score, fasting TG, fasting glucose, and standard antidepressants were not clinically meaningful predictors of weight gain with adjunctive aripiprazole, and change in weight had no correlation with clinical outcome. Adjunctive aripiprazole produced no significant changes versus placebo in mean waist circumference, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TG, fasting plasma glucose, or hemoglobin A(1C). Also, there was no apparent change in the incidence of National Cholesterol Education Program-defined abnormal metabolic measures after treatment with aripiprazole. C1 [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Baker, Ross A.; Yang, Huyuan] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Tran, Quynh-Van; Pikalov, Andrei] Otsuka Amer Pharmaceut Inc, Rockville, MD USA. [Marcus, Ronald N.; Berman, Robert M.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 55 Fruit St BUL 351, Boston, MA 02114 USA. EM mfava@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860 FU Bristol-Myers Squibb (Princeton, NJ); Otsuka Pharmaceutical Co, Ltd (Tokyo, Japan) FX This study was supported by Bristol-Myers Squibb (Princeton, NJ) and Otsuka Pharmaceutical Co, Ltd (Tokyo, Japan). NR 20 TC 14 Z9 14 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2009 VL 29 IS 4 BP 362 EP 367 DI 10.1097/JCP.0b013e3181ac9b0b PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 470QX UT WOS:000267995200008 PM 19593176 ER PT J AU Leuchter, AF McCracken, JT Hunter, AM Cook, IA Alpert, JE AF Leuchter, Andrew F. McCracken, James T. Hunter, Aimee M. Cook, Ian A. Alpert, Jonathan E. TI Monoamine Oxidase A and Catechol-O-Methyltransferase Functional Polymorphisms and the Placebo Response in Major Depressive Disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE major depressive disorder; placebo response; genetic polymorphisms; catechol-O-methyltransferase (COMT); monoamine oxidase A (MAO-A); dopamine; norepinephrine ID A GENE PROMOTER; PREFRONTAL CORTEX; DOPAMINE RELEASE; ANTIDEPRESSANT RESPONSE; OPTIMAL PERFORMANCE; PARKINSONS-DISEASE; INDUCED REWARD; ADAPTIVE GAIN; MAO ACTIVITY; NOREPINEPHRINE AB The placebo response shows pronounced interindividual variability. Placebos are postulated to act through central reward pathways that are modulated by monoamines. Because monoaminergic signaling is under strong genetic control, we hypothesized that common functional polymorphisms modulating monoaminergic tone would be related to degree of improvement during placebo treatment of subjects with major depressive disorder. We examined polymorphisms in genes encoding the catabolic enzymes catechol-O-methyltransferase and monoamine oxidase A. Subjects with monoamine oxidase A G/T polymorphisms (rs6323) coding for the highest activity form of the enzyme (G or G/G) had a significantly lower magnitude of placebo response than those with other genotypes. Subjects with Val(158)Met catechol-O-methyltransferase polymorphisms coding for a lower-activity form of the enzyme (2 Met alleles) showed a statistical trend toward a lower magnitude of placebo response. These findings support the hypothesis that genetic polymorphisms modulating monoaminergic tone are related to degree of placebo responsiveness in major depressive disorder. C1 [Leuchter, Andrew F.; McCracken, James T.; Hunter, Aimee M.; Cook, Ian A.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Leuchter, Andrew F.; Hunter, Aimee M.; Cook, Ian A.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Lab Brain Behav & Pharmacol, Los Angeles, CA 90024 USA. [Alpert, Jonathan E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Alpert, Jonathan E.] Harvard Univ, Sch Med, Boston, MA USA. RP Leuchter, AF (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, 760 Westwood Plaza,Rm 37-452, Los Angeles, CA 90024 USA. EM afl@ucla.edu OI Alpert, Jonathan/0000-0002-4332-908X FU NIH [R01 AT002479]; Eli Lilly Company; Pfizer, Inc. FX This work was supported by R01 AT002479 from the National Center for Complementary and Alternative Medicine of the NIH. Grant support was also received from Eli Lilly & Company and Pfizer, Inc. NR 40 TC 48 Z9 50 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2009 VL 29 IS 4 BP 372 EP 377 DI 10.1097/JCP.0b013e3181ac4aaf PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 470QX UT WOS:000267995200010 PM 19593178 ER PT J AU Baran, JL Hoang, MP AF Baran, Johanna L. Hoang, Mai P. TI Apocrine mixed tumor of the skin with a prominent pilomatricomal component SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID HAIR MATRIX DIFFERENTIATION; BASAL-CELL CARCINOMA; FOLLICULAR DIFFERENTIATION; SEBACEOUS DIFFERENTIATION; CHONDROID SYRINGOMA; ADNEXAL NEOPLASMS; CYTOKERATINS; ECCRINE; MARKERS; COMPLEX AB Pilomatrical differentiation within an apocrine mixed tumor (AMT) when present is only focal and has not been reported to be extensive. We herein report an AMT with prominent pilomatrical differentiation. A 47-year-old male presented with a 0.7 cm lesion on the right eyebrow. Histologic sections revealed, underneath a neurofibroma, a well-circumscribed tumor composed of nodules of branching epithelial elements and occasional keratinous cysts within a myxoid and lipomatous stroma. The ductal structures appeared to be composed of two layers of basophilic cuboidal cells and exhibited decapitation secretion. In approximately 50% of the tumor, eosinophilic ghost/shadow cells associated with a foreign body giant cell reaction formed a nodule resembling a pilomatricoma. Focally, columns of matrical cells were seen giving rise to shadow cells. Cytokeratin (CK) 5/6 and CK14 labeled the epithelial component. CK7, CK19 and Ber-EP4 labeled the ductal structures. Carcinoembryonic antigen and epithelial membrane antigen highlighted the luminal surface. S100 stained the stromal cells within the myxoid matrix, adipocytes and spindle cells within the overlying neurofibroma. CK10 highlighted the corneocytes within the keratinous cysts. CK17 labeled the epithelial lining of the keratinous cyst. The presence of follicular and apocrine differentiation within our tumor reinforces the common embryologic derivation of these elements. C1 [Hoang, Mai P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Dermatopathol Unit, Boston, MA 02114 USA. RP Hoang, MP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Dermatopathol Unit, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org NR 22 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD AUG PY 2009 VL 36 IS 8 BP 882 EP 886 DI 10.1111/j.1600-0560.2008.01137.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 461PZ UT WOS:000267282100010 PM 19586498 ER PT J AU LeMaster, CH Brown, DFM Nadel, ES AF LeMaster, Christopher H. Brown, David F. M. Nadel, Eric S. TI PROGRESSIVE RASH AFTER RECENT ANTIBIOTIC EXPOSURE SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID PENICILLIN-ALLERGIC PATIENTS; CEPHALOSPORINS; CEPHALOTHIN; ANAPHYLAXIS C1 [Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [LeMaster, Christopher H.; Brown, David F. M.; Nadel, Eric S.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 114,55 Fruit St, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2009 VL 37 IS 2 BP 160 EP 162 PG 3 WC Emergency Medicine SC Emergency Medicine GA 494LF UT WOS:000269813600009 PM 19564090 ER PT J AU Camargo, CA Rachelefsky, G Schatz, M AF Camargo, Carlos A., Jr. Rachelefsky, Gary Schatz, Michael TI MANAGING ASTHMA EXACERBATIONS IN THE EMERGENCY DEPARTMENT: SUMMARY OF THE NATIONAL ASTHMA EDUCATION AND PREVENTION PROGRAM EXPERT PANEL REPORT 3 GUIDELINES FOR THE MANAGEMENT OF ASTHMA EXACERBATIONS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID INTRAVENOUS MAGNESIUM-SULFATE; RANDOMIZED CONTROLLED-TRIAL; PULSE OXIMETRY; SEVERITY SCORE; CHILDREN; ALBUTEROL; ADMISSION; HYDROCORTISONE; METAANALYSIS; TERBUTALINE C1 [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp,Dept Med, Boston, MA USA. [Rachelefsky, Gary] Univ Calif Los Angeles, Geffen Sch Med, Execut Care Ctr Asthma Allergy & Resp Dis, Los Angeles, CA 90024 USA. [Schatz, Michael] Kaiser Permanente Med Ctr, Dept Allergy, San Diego, CA USA. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. NR 49 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2009 VL 37 IS 2 SU S BP S6 EP S17 DI 10.1016/j.jemermed.2009.06.105 PG 12 WC Emergency Medicine SC Emergency Medicine GA 494LH UT WOS:000269813800002 PM 19683665 ER PT J AU Schatz, M Kazzi, AAN Brenner, B Camargo, CA Corbridge, T Krishnan, JA Nowak, R Rachelefsky, G AF Schatz, Michael Kazzi, Amin Antoine Nabih Brenner, Barry Camargo, Carlos A., Jr. Corbridge, Thomas Krishnan, Jerry A. Nowak, Richard Rachelefsky, Gary TI INTRODUCTION SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material C1 [Schatz, Michael] Kaiser Permanente Med Ctr, Dept Allergy, San Diego, CA 92111 USA. [Kazzi, Amin Antoine Nabih] Amer Univ Beirut, Dept Emergency Med, Beirut, Lebanon. [Brenner, Barry] Univ Hosp, Dept Emergency Med, Case Western Reserve Sch Med, Case Med Ctr, Cleveland, OH USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Boston, MA USA. [Corbridge, Thomas] Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 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. [Nowak, Richard] Henry Ford Hlth Syst, Dept Emergency Med, Detroit, MI USA. [Rachelefsky, Gary] Univ Calif Los Angeles, Geffen Sch Med, Execut Care Ctr Asthma Allergy & Resp Dis, Los Angeles, CA 90024 USA. RP Schatz, M (reprint author), Kaiser Permanente Med Ctr, Dept Allergy, 7060 Clairemont Mesa Blvd, San Diego, CA 92111 USA. EM Michael.X.Schatz@kp.org NR 6 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2009 VL 37 IS 2 BP S1 EP S5 DI 10.1016/j.jemermed.2009.06.104 PG 5 WC Emergency Medicine SC Emergency Medicine GA 494LH UT WOS:000269813800001 PM 19683660 ER PT J AU Tyson, MD Lerner, LB AF Tyson, Mark D. Lerner, Lori B. TI Safety of Holmium Laser Enucleation of the Prostate in Anticoagulated Patients SO JOURNAL OF ENDOUROLOGY LA English DT Article ID BLADDER OUTLET OBSTRUCTION; TRANSURETHRAL RESECTION; RANDOMIZED-TRIAL; HYPERPLASIA; THERAPY AB Purpose: Oral anticoagulation ( OA) is considered a strict contraindication to transurethral resection of the prostate ( TURP). In recent years, however, safe and effective surgical alternatives such as holmium laser enucleation of the prostate ( HoLEP) have emerged. Evidence from randomized trials has revealed that HoLEP has fewer bleeding complications than TURP, suggesting that HoLEP in anticoagulated patients is safer than TURP. However, published data evaluating bleeding complications in anticoagulated patients undergoing HoLEP are incomplete. Using a retrospective design, this is the first study to compare the bleeding complication rates of anticoagulated patients undergoing HoLEP to patients not on OA. Materials and Methods: We reviewed the electronic medical records of the first 76 HoLEP patients treated by a single urologist in two New England hospitals from May 2002 to September 2007. Results: Thirty-nine were on OA, and 37 were controls. Thirteen patients were on coumadin ( mean international normalized ratio [ INR] 1.5), and 25 were on aspirin at the time of their surgery. Among the patients on OA, 8% ( n = 2) had intraoperative hematuria compared to 14% ( n = 5) of controls ( p = 0.25). No patients in either group required blood transfusions. Stratifying the OA population revealed no statistical differences in bleeding complication rates between the coumadin, aspirin, and control groups ( p = 0.34). Additionally, there were no differences in standard postoperative outcomes. Conclusion: These findings suggest that HoLEP has excellent hemostatic properties in high-risk patients and is a safe surgical alternative to TURP in patients on OA. C1 [Tyson, Mark D.; Lerner, Lori B.] Dartmouth Med Sch, Hanover, NH 03755 USA. [Lerner, Lori B.] VA Boston Healthcare Syst, Urol Sect, Boston, MA USA. RP Tyson, MD (reprint author), Dartmouth Med Sch, 5 Rope Ferry Rd 6112, Hanover, NH 03755 USA. EM mark.tyson@dartmouth.edu NR 15 TC 24 Z9 26 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 AUG PY 2009 VL 23 IS 8 BP 1343 EP 1346 DI 10.1089/end.2009.0013 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 479ZC UT WOS:000268700000021 PM 19575692 ER PT J AU Taft, CT Monson, CM Schumm, JA Watkins, LE Panuzio, J Resick, PA AF Taft, Casey T. Monson, Candice M. Schumm, Jeremiah A. Watkins, Laura E. Panuzio, Jillian Resick, Patricia A. TI Posttraumatic Stress Disorder Symptoms, Relationship Adjustment, and Relationship Aggression in a Sample of Female Flood Victims SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Posttraumatic stress disorder; Relationship adjustment; Relationship aggression; Flood; Natural disaster ID NATIONAL-COMORBIDITY-SURVEY; PSYCHIATRIC-DISORDERS; VIETNAM VETERANS; COMBAT VETERANS; VIOLENCE; METAANALYSIS; PREVALENCE; SURVIVORS; TRAUMA; ADULTS AB This study tested a model examining the interrelationships among posttraumatic stress disorder (PTSD) symptoms, intimate relationship adjustment, and intimate relationship aggression in a sample of 205 adult female flood victims. At the bivariate level, higher PTSD symptoms were associated with higher physical and psychological aggression victimization, poorer relationship adjustment, and higher physical and psychological aggression perpetration. Results from structural equation modeling (SEM) analyses indicated that relationship aggression victimization influenced aggression perpetration directly, and in the case of physical aggression, indirectly through its relationship with PTSD symptoms and relationship adjustment. The influence of PTSD symptoms on physical aggression perpetration was fully explained by poorer relationship adjustment. These findings extend prior work from other traumatized populations documenting associations between variables reflecting PTSD symptomatology and indices of relationship functioning, and indicate a need for further investigation in this area of inquiry. C1 [Taft, Casey T.; Monson, Candice M.; Watkins, Laura E.; Panuzio, Jillian; Resick, Patricia A.] VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, Boston, MA 02130 USA. [Taft, Casey T.; Monson, Candice M.; Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Schumm, Jeremiah A.] Harvard Univ, Sch Med, Boston, MA USA. [Schumm, Jeremiah A.] VA Boston Healthcare Syst, Brockton, MA USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@med.va.gov FU NIMH NIH HHS [R01 MH055542, R03 MH052513, R03 MH052513-01] NR 36 TC 16 Z9 17 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD AUG PY 2009 VL 24 IS 6 BP 389 EP 396 DI 10.1007/s10896-009-9241-8 PG 8 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 451US UT WOS:000266497000005 PM 21057584 ER PT J AU Taft, CT Resick, PA Watkins, LE Panuzio, J AF Taft, Casey T. Resick, Patricia A. Watkins, Laura E. Panuzio, Jillian TI An Investigation of Posttraumatic Stress Disorder and Depressive Symptomatology among Female Victimsof Interpersonal Trauma SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Posttraumatic stress disorder; Depression; Comorbidity; Violence; Abuse ID COGNITIVE PROCESSING THERAPY; INTIMATE PARTNER VIOLENCE; ADMINISTERED PTSD SCALE; CHILDHOOD SEXUAL-ABUSE; PERITRAUMATIC DISSOCIATION; MAJOR DEPRESSION; COMORBID DEPRESSION; BATTERED WOMEN; SELF-REPORT; DISTORTIONS AB This study examined factors associated with PTSD-depression comorbidity among a sample of 162 adult female rape or assault victims with PTSD, as well as potential differential predictors of PTSD and depression severity. PTSD-only participants reported higher levels of childhood sexual abuse than those with comorbid PTSD and depression, and the PTSD/MDD group reported relatively more distorted trauma-related beliefs, dissociation, PTSD severity, and depression severity. Distorted trauma-related beliefs and dissociation were the strongest unique predictors of higher PTSD and depressive symptoms. Rates of PTSD and depression comorbidity did not appear to be a function of symptom overlap. Study findings suggest possible explanations for the high PTSD and depression comorbidity rates commonly found among victims of interpersonal violence. C1 [Taft, Casey T.; Resick, Patricia A.; Watkins, Laura E.; Panuzio, Jillian] VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, Boston, MA 02130 USA. [Taft, Casey T.; Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02118 USA. [Panuzio, Jillian] Univ Nebraska, Lincoln, NE USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@med.va.gov FU NIMH NIH HHS [R01 MH051509, R01 MH051509-10] NR 52 TC 30 Z9 31 U1 2 U2 20 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD AUG PY 2009 VL 24 IS 6 BP 407 EP 415 DI 10.1007/s10896-009-9243-6 PG 9 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 451US UT WOS:000266497000007 PM 21052546 ER PT J AU Hall, YN Rodriguez, RA Boyko, EJ Chertow, GM O'Hare, AM AF Hall, Yoshio N. Rodriguez, Rudolph A. Boyko, Edward J. Chertow, Glenn M. O'Hare, Ann M. TI Characteristics of Uninsured Americans with Chronic Kidney Disease SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic kidney disease; uninsured; risk factors; end-stage renal disease; race-ethnicity ID STAGE RENAL-DISEASE; JOINT NATIONAL COMMITTEE; HIGH BLOOD-PRESSURE; 7TH REPORT; OUTCOMES; PROGRESSION; RISK; MEN; POPULATION; PREVENTION AB In the United States, public health insurance is available for nearly all persons with end-stage renal disease (ESRD). Little is known about the extent of health insurance coverage for persons with non-dialysis dependent chronic kidney disease (CKD). To describe patterns of health insurance coverage for adults with non-dialysis dependent CKD and to examine risk factors for progression of CKD to ESRD and management of hypertension among those lacking insurance. Cross-sectional analysis of data from a nationally representative sample of 16,148 US adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey 1999-2006. National prevalence estimates of health insurance coverage, ESRD risk factors, and treatment of hypertension. An estimated 10.0% (95% CI, 8.3%-12.0%) of US adults with non-dialysis dependent CKD were uninsured, 60.9% (95% CI, 58.2%-63.7%) had private insurance and 28.7% (95% CI, 26.4%-31.1%) had public insurance alone. Uninsured persons with non-dialysis dependent CKD were more likely to be under the age of 50 (62.8% vs. 23.0%, P < 0.001) and nonwhite (58.7%, vs. 21.8%, P < 0.001) compared with their insured counterparts. Approximately two-thirds of uninsured adults with non-dialysis dependent CKD had at least one modifiable risk factor for CKD progression, including 57% with hypertension, 40% who were obese, 22% with diabetes, and 13% with overt albuminuria. In adjusted analyses, uninsured persons with non-dialysis dependent CKD were less likely to be treated for their hypertension (OR, 0.59; 95% CI, 0.40-0.85) and less likely to be receiving recommended therapy with angiotensin inhibitors (OR, 0.45; 95% CI, 0.26-0.77) compared with those with insurance coverage. Uninsured persons with non-dialysis dependent CKD are at higher risk for progression to ESRD than their insured counterparts but are less likely to receive recommended interventions to slow disease progression. Lack of public health insurance for patients with non-dialysis dependent CKD may result in missed opportunities to slow disease progression and thereby reduce the public burden of ESRD. C1 [Hall, Yoshio N.; Rodriguez, Rudolph A.; Boyko, Edward J.; O'Hare, Ann M.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Hall, Yoshio N.; Rodriguez, Rudolph A.; Boyko, Edward J.; O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA USA. [Chertow, Glenn M.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. RP Hall, YN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM ynhall@u.washington.edu FU Satellite Healthcare's Norman S. Coplon [N01-DK-75007-01, U01-DK066481-05]; [K23-AG-028980-02] FX Dr. Hall received support from Satellite Healthcare's Norman S. Coplon extramural grant program. Dr. Chertow received support from N01-DK-75007-01 and U01-DK066481-05. Dr. O'Hare received support from K23-AG-028980-02. The findings and conclusions in this report are those of the authors and do not represent the views of the US government. NR 33 TC 20 Z9 22 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 AUG PY 2009 VL 24 IS 8 BP 917 EP 922 DI 10.1007/s11606-009-1028-3 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 471PC UT WOS:000268069500005 PM 19506974 ER PT J AU Pasquale, LR Kang, JH AF Pasquale, Louis R. Kang, Jae Hee TI Lifestyle, Nutrition, and Glaucoma SO JOURNAL OF GLAUCOMA LA English DT Review DE primary open-angle glaucoma; lifestyle factors; diet; semiquantitative food frequency questionnaire ID OPEN-ANGLE GLAUCOMA; HORMONE REPLACEMENT THERAPY; BLUE MOUNTAINS EYE; BEAVER DAM EYE; INTRAOCULAR-PRESSURE; RISK-FACTORS; OCULAR HYPERTENSION; CIGARETTE-SMOKING; BLOOD-PRESSURE; BARBADOS EYE AB The only proven strategy to prevent primary open-angle glaucoma (POAG) is the use of ocular hypotensive therapy among people diagnosed with ocular hypertension. In this review, various modifiable lifestyle factors, Such as exercise, diet, and cigarette smoking, that may influence intraocular pressure and that have been studied in relation to the risk of developing POAG are discussed. Epidemiologic Studies oil lifestyle factors are few, and the current evidence suggests that there are no environmental factors that are clearly associated with POAG; however, a few factors merit further study. This review also Outlines future directions for research into the primary prevention of POAG. C1 [Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Kang, Jae Hee] Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP Pasquale, LR (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu FU National Institutes of Health [EY015473] FX Financial support: Supported by grant EY015473 from the National Institutes of Health. NR 96 TC 20 Z9 21 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD AUG PY 2009 VL 18 IS 6 BP 423 EP 428 DI 10.1097/IJG.0b013e31818d3899 PG 6 WC Ophthalmology SC Ophthalmology GA 485WY UT WOS:000269157100001 PM 19680048 ER PT J AU Odedina, FT Yu, DH Akinremi, TO Reams, RR Freedman, ML Kumar, N AF Odedina, Folakemi T. Yu, Daohai Akinremi, Titilola O. Reams, R. Renee Freedman, Matthew L. Kumar, Nagi TI Prostate Cancer Cognitive-Behavioral Factors in a West African Population SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Prostate cancer; Nigerian men; Prostate cancer knowledge; West African men ID BLACK-WHITE DIFFERENCES; ANDROGEN RECEPTOR GENE; AGE-SPECIFIC INCIDENCE; AMERICAN MEN; SCREENING BEHAVIOR; RACIAL-DIFFERENCES; HEALTH MAINTENANCE; CLINICAL STAGE; CAUCASIAN MEN; UNITED-STATES AB Background Similar to African American men, several published studies indicate high incidence of prostate cancer among Nigerian men. However, there is no published study on personal factors that influence prostate cancer detection in this population. We explored prostate cognitive-behavioral factors among indigenous Nigerian men and Nigerian immigrants residing in the US. Methods A cross-sectional survey methodology was employed to collect data from Nigerian men residing in Abeokuta (Nigeria) and Houston (US). Study participants were men between 35 and 79 years. Results The demographic characteristics of both study groups were similar. Based on two-sample comparison results, indigenous Nigerian men demonstrated significant differences from US Nigerian men on several prostate cancer personal cognitive-behavioral factors, including perceived susceptibility to prostate cancer, attitude towards prostate cancer screening and prostate cancer knowledge. Conclusion Emigration of Nigerian men from Nigeria to the US has a significant impact on prostate cancer knowledge and beliefs. C1 [Odedina, Folakemi T.; Reams, R. Renee] Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. [Odedina, Folakemi T.; Yu, Daohai; Kumar, Nagi] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Oncol Sci, Tampa, FL 33682 USA. [Akinremi, Titilola O.] Fed Med Ctr, Dept Pathol, Abeokuta, Nigeria. [Freedman, Matthew L.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Odedina, FT (reprint author), Florida A&M Univ, Coll Pharm & Pharmaceut Sci, 1520 Martin Luther King Blvd, Tallahassee, FL 32307 USA. EM Folakemi.odedina@famu.edu NR 89 TC 5 Z9 5 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD AUG PY 2009 VL 11 IS 4 BP 258 EP 267 DI 10.1007/s10903-008-9212-9 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 645ZQ UT WOS:000281505100003 PM 19051034 ER PT J AU Niu, N Laufer, T Homer, RJ Cohn, L AF Niu, Naiqian Laufer, Terri Homer, Robert J. Cohn, Lauren TI Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2-Dependent Allergic Airway Inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; IN-VIVO; MICE; RESPONSES; CYTOKINE; ANTIGEN; HYPERRESPONSIVENESS; BASOPHILS; IMMUNITY; DISEASE AB In allergic airway inflammation, dendritic cells (DCs) are required for Th2 generation, recruitment, and activation in the respiratory tract. DCs have been shown to be necessary and sufficient for the induction of Th1 immune responses. In Th2 immunity and allergic airway inflammation, the ability of a DC to function as the sole APC has not been tested. We show that CD11c/A(beta)(b) mice with MHC class II expression restricted to CD11c-expressing DCs develop airway neutrophilia rather than allergic airway inflammation. Although CD11c/A(beta)(b) mice are capable of Th2 recruitment and activation in the lung, Th2 priming in CD11c/A(beta)(b) mice results in IFN-gamma production. Effective Th2 generation and allergic airway inflammation was achieved in CD11c/A(beta)(b) mice after treatment with anti-IFN-gamma. These studies show that DCs alone cannot drive the development of Th2 cells but require an additional MHC class II signal to stimulate effective Th2 immunity. The Journal of Immunology, 2009, 183: 1523-1527. C1 [Niu, Naiqian; Cohn, Lauren] Yale Univ, Sch Med, Pulm & Crit Care Med Sect, New Haven, CT 06520 USA. [Homer, Robert J.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. [Laufer, Terri] Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Laufer, Terri] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA. RP Cohn, L (reprint author), Yale Univ, Sch Med, Pulm & Crit Care Med Sect, 333 Cedar St,POB 208057, New Haven, CT 06520 USA. EM lauren.cohn@yale.edu FU National Institutes of Health [ROI-64040] FX This work was supported by National Institutes of Health Grant ROI-64040 (to L.C.) and the Seltzer Family Translational Research Fund (to L.C.). NR 25 TC 12 Z9 12 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2009 VL 183 IS 3 BP 1523 EP 1527 DI 10.4049/jimmunol.0901349 PG 5 WC Immunology SC Immunology GA 477LB UT WOS:000268519500006 PM 19596982 ER PT J AU Podgrabinska, S Kamalu, O Mayer, L Shimaoka, M Snoeck, H Randolph, GJ Skobe, M AF Podgrabinska, Simona Kamalu, Okebugwu Mayer, Lloyd Shimaoka, Motomu Snoeck, Hans Randolph, Gwendalyn J. Skobe, Mihaela TI Inflamed Lymphatic Endothelium Suppresses Dendritic Cell Maturation and Function via Mac-1/ICAM-1-Dependent Mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VITRO MODEL; MAC-1 CD11B/CD18; LANGERHANS CELLS; PERIPHERAL LYMPH; E-CADHERIN; T-CELLS; VEGF-C; LYMPHANGIOGENESIS; TOLERANCE; ADHESION AB The lymphatic system is essential for the generation of immune responses by facilitating immune cell trafficking to lymph nodes. Dendritic cells (DCs), the most potent APCs, exit tissues via lymphatic vessels, but the mechanisms of interaction between DCs and the lymphatic endothelium and the potential implications of these interactions for immune responses are poorly understood. In this study, we demonstrate that lymphatic endothelial cells (LECs) modulate the maturation and function of DCs. Direct contact of human monocyte-derived DCs with an inflamed, TNF-alpha-stimulated lymphatic endothelium reduced expression of the costimulatory molecule CD86 by DCs and suppressed the ability of DCs to induce T cell proliferation. These effects were dependent on adhesive interactions between DCs and LECs that were mediated by the binding of Mac-1 on DCs to ICAM-1 on LECs. Importantly, the suppressive effects of the lymphatic endothelium on DCs were observed only in the absence of pathogen-derived signals. In vivo, DCs that migrated to the draining lymph nodes upon inflammatory stimuli, but in the absence of a pathogen, showed increased levels of CD86 expression in ICAM-1-deficient mice. Together, these data demonstrate a direct role of LECs in the modulation of immune response and suggest a function of the lymphatic endothelium in preventing undesired immune reactions in inflammatory conditions. The Journal of Immunology, 2009, 183: 1767-1779. C1 [Podgrabinska, Simona; Skobe, Mihaela] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Kamalu, Okebugwu; Mayer, Lloyd; Randolph, Gwendalyn J.] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA. [Snoeck, Hans; Randolph, Gwendalyn J.] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA. [Shimaoka, Motomu] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Skobe, M (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. EM mihaele.skobe@mssm.edu FU Emerald Foundation; U.S. Department of Defense [BC044819]; National Institutes of Health-National Cancer Institute Shared Resources [5R24 CA095823-04]; National Science Foundation Major Research Instrumentation [DBI-9724504]; National Institutes of Health Shared Instrumentation [1 S10 RR0 9145-01] FX This work was supported by funds from the Emerald Foundation (to M.S.) and by U.S. Department of Defense Grant BC044819 (to M.S.). Confocal laser scanning microscopy was performed at the Mount Sinai School of Medicine-Microscopy Shared Resource Facility supported with funding from National Institutes of Health-National Cancer Institute Shared Resources Grant 5R24 CA095823-04, National Science Foundation Major Research Instrumentation Grant DBI-9724504, and National Institutes of Health Shared Instrumentation Grant 1 S10 RR0 9145-01. NR 64 TC 76 Z9 76 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2009 VL 183 IS 3 BP 1767 EP 1779 DI 10.4049/jimmunol.0802167 PG 13 WC Immunology SC Immunology GA 477LB UT WOS:000268519500033 PM 19587009 ER PT J AU Butler, LM Dorsey, G Hladik, W Rosenthal, PJ Brander, C Neilands, TB Mbisa, G Whitby, D Kiepiela, P Mosam, A Mzolo, S Dollard, SC Martin, JN AF Butler, Lisa M. Dorsey, Grant Hladik, Wolfgang Rosenthal, Philip J. Brander, Christian Neilands, Torsten B. Mbisa, Georgina Whitby, Denise Kiepiela, Photini Mosam, Anisa Mzolo, Similo Dollard, Sheila C. Martin, Jeffrey N. TI Kaposi Sarcoma-Associated Herpesvirus (KSHV) Seroprevalence in Population-Based Samples of African Children: Evidence for At Least 2 Patterns of KSHV Transmission SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIGHLY ENDEMIC AREA; HUMAN-HERPESVIRUS-8 INFECTION; BLOOD-TRANSFUSION; UGANDAN CHILDREN; RISK-FACTORS; VERTICAL TRANSMISSION; SEXUAL TRANSMISSION; SEROLOGIC EVIDENCE; HHV-8 INFECTION AB Background. Kaposi sarcoma-associated herpesvirus ( KSHV) infection is endemic among adult populations in Africa. A prevailing view is that childhood transmission is primarily responsible for the high seroprevalence of KSHV among adults that is observed throughout the continent. However, few studies have directly examined children, particularly in locations where KS is not commonly endemic. Methods. Participants were children aged 1.5-8.9 years, including 427 children from a population-based sample in South Africa, 422 from a population-based sample in Uganda, and 567 from a clinic-based sample in Uganda. All serum specimens were tested by the same laboratory for KSHV antibodies with use of 2 enzyme immunoassays (against K8.1 and ORF65) and 1 immunofluorescence assay. Results. KSHV seroprevalence was 7.5%-9.0% among South African children and was not associated with age. In contrast, in the Ugandan population-based sample, KSHV seroprevalence increased from 10% among 2-year-old children to 30.6% among 8-year-old children (P(trend) <.001). In the Ugandan clinic-based sample, sero-prevalence increased from 9.3% among 2-year-old children to 36.4% among 8-year-old children (P(trend) <.001). trend Conclusion. Two distinct relationships between age and KSHV infection among children imply that KSHV transmission among children is not uniform throughout Africa and is therefore not always responsible for the high seroprevalence observed in adults. There are at least 2 patterns of KSHV transmission in Africa. C1 [Butler, Lisa M.; Dorsey, Grant; Rosenthal, Philip J.; Neilands, Torsten B.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94105 USA. [Hladik, Wolfgang; Dollard, Sheila C.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Brander, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Cambridge, MA 02138 USA. [Brander, Christian] Inst Catalana Recerca & Estudis Avancats, Barcalona, Spain. [Brander, Christian] Hosp Univ Germans Trias & Pujol, Inst Recerca Sida, Badalona, Catalonia, Spain. [Mbisa, Georgina; Whitby, Denise] Natl Canc Inst Frederick, Frederick, MD USA. [Kiepiela, Photini] MRC, HIV Prevent & Res Unit, Durban, South Africa. [Mosam, Anisa; Mzolo, Similo] Univ KwaZulu Natal, Durban, South Africa. RP Butler, LM (reprint author), Univ Calif San Francisco, 50 Beale St,Suite 120, San Francisco, CA 94105 USA. EM lbutler@psg.ucsf.edu OI Brander, Christian/0000-0002-0548-5778 FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E, R01 CA119903]; NIAID NIH HHS [P30 AI027763, U01 AI052142]; NICHD NIH HHS [K01 HD052020, K01 HD052020-03]; NIMH NIH HHS [T32 MH019105] NR 51 TC 33 Z9 33 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2009 VL 200 IS 3 BP 430 EP 438 DI 10.1086/600103 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 465RH UT WOS:000267604000015 PM 19534596 ER PT J AU Kiernan, TJ Yan, BP Ruggiero, N Bernal, JDEJ Cubeddu, RJ Witzke, C Don, C Cruz-Gonzalez, I Rosenfield, K Pomersantev, E Palacios, I AF Kiernan, T. J. Yan, B. P. Ruggiero, N. Bernal, J. D. Eisenberg J. Cubeddu, R. J. Witzke, C. Don, C. Cruz-Gonzalez, I. Rosenfield, K. Pomersantev, E. Palacios, I. TI Coronary Artery Perforations in the Contemporary Interventional Era SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID COVERED STENT; MANAGEMENT; IMPLANTATION; OUTCOMES; REPAIR AB Methods: We performed a retrospective analysis of documented coronary perforations at Massachusetts General Hospital from 2000 to 2008. Medical records review and detailed angiographic analysis were performed in all patients. Results: Sixty-eight cases of coronary perforation were identified from a total of 14,281 PCIs from March 2000 to March 2008 representing an overall incidence of 0.48%. The study cohort was predominantly male (61.8%), mean age 71 +/- 11 years with 78% representing acute cases (unstable angina: 36.8%, NSTEMI: 30.9%, STEMI: 10.3%). Coronary artery perforation occurred as a complication of wire manipulation in 45 patients (66.2%) with 88.9% of this group being hydrophilic wires, of coronary stenting in 11 (16.2%), of angioplasty alone in 6 (8.8%), and of rotational atherectomy in 8 (11.8%). The perforation was sealed with an angioplasty balloon alone in 16 patients (23.5%), and with stents in 14 patients (20.6%) (covered stents: 11.8% and noncovered stents: 8.8%). Emergency CABG was performed in 2 patients (2.9%). Five patients (7.4%) developed periprocedural MI. The in-hospital mortality rate was 5.9% in the study cohort. Conclusion: Coronary artery perforation as a complication of PCI is still rare as demonstrated in our series with an incidence of 0.48%. The predominant cause of coronary perforations in the current era of PCI is wire injury. (J Interven Cardiol 2009;22:350-353). C1 [Kiernan, T. J.; Yan, B. P.; Ruggiero, N.; Bernal, J. D. Eisenberg J.; Cubeddu, R. J.; Witzke, C.; Don, C.; Cruz-Gonzalez, I.; Rosenfield, K.; Pomersantev, E.; Palacios, I.] Massachusetts Gen Hosp, Div Intervent Cardiol, Boston, MA 02114 USA. RP Palacios, I (reprint author), Massachusetts Gen Hosp, Div Intervent Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM ipalacios@partners.org RI Yan, Bryan/P-5928-2015 NR 14 TC 18 Z9 22 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD AUG PY 2009 VL 22 IS 4 BP 350 EP 353 DI 10.1111/j.1540-8183.2009.00469.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 479MO UT WOS:000268663800006 PM 19453819 ER PT J AU Guan, SX Fan, JH Han, A Chen, M Woodley, DT Li, W AF Guan, Shengxi Fan, Jianhua Han, Arum Chen, Mei Woodley, David T. Li, Wei TI Non-Compensating Roles between Nck alpha and Nck beta in PDGF-BB Signaling to Promote Human Dermal Fibroblast Migration SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; SMOOTH-MUSCLE CELLS; SH2/SH3 ADAPTERS; ACTIN POLYMERIZATION; KINASE ACTIVATION; KIDNEY PODOCYTES; PROTEIN; PHOSPHORYLATION; INTERACTS; MECHANISM AB Platelet-derived growth factor BB (PDGF-BB) is a Food and Drug Administration (FDA)-approved growth factor, acting as a mitogen and motogen of dermal fibroblasts (DFs), for skin wound healing. The two closely related SH2/SH3 adapter proteins, Nck alpha and Nck beta, connect PDGF-BB signaling to the actin cytoskeleton and cell motility. The mechanism has not been fully understood. In this study, we investigated, side by side, the roles of Nck alpha and Nck beta in PDGF-BB-stimulated DF migration. We found that cells expressing the PDGFR beta-Y751F mutant (preventing Ncka binding) or PDGFR beta-Y1009F mutant (preventing Nckb binding), DF cells isolated from Nck alpha- or Nck beta-knockout mice, and primary human DF cells with RNA interference (RNAi) knockdown of the endogenous Nck alpha or Nck beta all failed to migrate in response to PDGF-BB. Overexpression of the middle SH3 domain of Nck alpha or Nck beta alone in human DFs also blocked PDGF-BB-induced cell migration. However, neither Ncka nor Nck beta was required for the activation of the PDGF receptor, p21-activated protein kinase (Pak1), AKT, extracellular signal-regulated kinase (ERK) 1/2, or p38MAP by PDGF-BB. Although PDGF-BB stimulated the membrane translocation of both Nck alpha and Nck beta, Nck alpha appeared to mediate Cdc42 signaling for filopodium formation, whereas Nck beta mediated Rho signaling to induce stress fibers. Thus, this study has elucidated the independent roles and mechanisms of action of Nck alpha and Nck beta in DF migration, which is critical for wound healing. C1 [Li, Wei] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Dermatol, Los Angeles, CA 90033 USA. [Fan, Jianhua; Chen, Mei; Woodley, David T.; Li, Wei] Greater Los Angles Vet Adm Hlth Syst, Los Angeles, CA USA. RP Li, W (reprint author), Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Dermatol, 1441 Eastlake Ave Rd, Los Angeles, CA 90033 USA. EM wli@usc.edu FU National Institutes of Health [GM/AR67100-01] FX We thank Tony Pawson for Nck alpha+/- and Nck beta+/- mice and Jonathon Cooper for TRUMP cells expressing the PDGFR mutants. This study was supported by the National Institutes of Health Grant GM/AR67100-01 (to W. L.). NR 57 TC 8 Z9 8 U1 1 U2 1 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 AUG PY 2009 VL 129 IS 8 BP 1909 EP 1920 DI 10.1038/jid.2008.457 PG 12 WC Dermatology SC Dermatology GA 479FC UT WOS:000268644100011 PM 19242519 ER PT J AU Warren, HS AF Warren, H. Shaw TI Mouse models to study sepsis syndrome in humans SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material DE innate immunity; cell death; apoptosis ID MULTIPLE-ORGAN DYSFUNCTION; CELL-DEATH; MICE; ENDOTOXIN; LIPOPOLYSACCHARIDE; SHOCK C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Warren, HS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. EM swarren1@partners.org FU NIAID NIH HHS [AI059010]; NIGMS NIH HHS [GM59694] NR 18 TC 17 Z9 17 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 2009 VL 86 IS 2 BP 199 EP 201 DI 10.1189/jlb.0309210 PG 3 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 476PP UT WOS:000268454900002 PM 19643738 ER PT J AU Liang, XY Lin, T Sun, GJ Beasley-Topliffe, L Cavaillon, JM Warren, HS AF Liang, Xueya Lin, Tian Sun, Guangjie Beasley-Topliffe, Laura Cavaillon, Jean-Marc Warren, H. Shaw TI Hemopexin down-regulates LPS-induced proinflammatory cytokines from macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE TLR; agonist; serum; Pam3Cys; innate immunity ID LIPOPOLYSACCHARIDE-BINDING-PROTEIN; BACTERIAL-ENDOTOXIN; CARBON-MONOXIDE; INNATE IMMUNITY; HOST-DEFENSE; SEPSIS; MICE; HEME; HEMOGLOBIN; NECROSIS AB Detection of LPS in tissues is an integral component of innate immunity that acts to protect against invasion by Gram-negative bacteria. Plasma down-regulates LPS-induced cytokine production from macrophages, thereby limiting systemic inflammation in blood and distant tissues. To identify the protein(s) involved in this process, we used classical biochemical chromatographic techniques to identify fractions of mouse sera that suppress LPS-induced TNF from bone marrow-derived macrophages (BMDMs). Fractionation yielded microgram quantities of a protein that was identified by MS to be hemopexin (Hx). Mouse Hx purified on hemin-agarose beads and rhHx decreased the production of cytokines from BMDMs and peritoneal macrophages induced by LPS. Preincubation of LPS with Hx did not affect the activity of LPS on LAL, whereas preincubation of Hx with macrophages followed by washing resulted in decreased activity of these cells in response to LPS, suggesting that Hx acts on macrophages rather than LPS. Heme-free Hx did not stimulate HO-1 in the macrophages. Purified Hx also decreased TNF and IL-6 from macrophages induced by the synthetic TLR2 agonist Pam3Cys. Our data suggest that Hx, which is an acute-phase protein that increases during inflammation, limits TLR4 and TLR2 agonist-induced macrophage cytokine production directly through a mechanism distinct from HO-1. J. Leukoc. Biol. 86: 229-235; 2009. C1 [Liang, Xueya; Lin, Tian; Sun, Guangjie; Beasley-Topliffe, Laura; Warren, H. Shaw] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Liang, Xueya; Lin, Tian; Sun, Guangjie; Beasley-Topliffe, Laura; Warren, H. Shaw] Harvard Univ, Sch Med, Boston, MA USA. [Cavaillon, Jean-Marc] Inst Pasteur, Unit Cytokines & Inflammat, Paris, France. RP Warren, HS (reprint author), Massachusetts Gen Hosp East, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. EM swarren1@partners.org FU National Institutes of Health [AI059010, GM59694]; Shriners Hospital for Crippled Children [8720]; Institute Pasteur FX This work was funded by the National Institutes of Health (AI059010, GM59694), Shriners Hospital for Crippled Children (8720), and institutional funding from the Institute Pasteur. X. L., J.-M. C., and H. S. W. have submitted information contained in this article for patent protection in accordance with institutional policies. NR 41 TC 55 Z9 55 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 2009 VL 86 IS 2 BP 229 EP 235 DI 10.1189/jlb.1208742 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 476PP UT WOS:000268454900006 PM 19395472 ER PT J AU Opel, DJ Wilfond, BS Brownstein, D Diekema, DS Pearlman, RA AF Opel, D. J. Wilfond, B. S. Brownstein, D. Diekema, D. S. Pearlman, R. A. TI Characterisation of organisational issues in paediatric clinical ethics consultation: a qualitative study SO JOURNAL OF MEDICAL ETHICS LA English DT Article; Proceedings Paper CT 10th Annual Meeting of the American-Society-for-Bioethics-and-Humanities CY 2008 CL Cleveland, OH SP Amer Soc Bioethics & Humanities AB Background: The traditional approach to resolving ethics concerns may not address underlying organisational issues involved in the evolution of these concerns. This represents a missed opportunity to improve quality of care "upstream''. The purpose of this study was to understand better which organisational issues may contribute to ethics concerns. Methods: Directed content analysis was used to review ethics consultation notes from an academic children's hospital from 1996 to 2006 (N = 71). The analysis utilised 18 categories of organisational issues derived and modified from published quality improvement protocols. Results: Organisational issues were identified in 68 of the 71 (96%) ethics consult notes across a range of patient settings and reasons for consultation. Thirteen of the 18 categories of organisational issues were identified and there was a median of two organisational issues per consult note. The most frequently identified organisational issues were informal organisational culture (eg, collective practices and approaches to situations with ethical dimensions that are not guided by policy), policies and procedures (eg, staff knows policy and/or procedural guidelines for an ethical concern but do not follow it) and communication (eg, communication about critical information, orders, or hand-offs repeatedly does not occur among services). Conclusions: Organisational issues contribute to ethical concerns that result in clinical ethics consults. Identifying and addressing organisational issues such as informal culture and communication may help decrease the recurrence of future similar ethics concerns. C1 [Opel, D. J.; Wilfond, B. S.; Diekema, D. S.] Seattle Childrens Hosp, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. [Pearlman, R. A.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Opel, D. J.; Wilfond, B. S.; Brownstein, D.; Diekema, D. S.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Pearlman, R. A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Opel, DJ (reprint author), Metropolitan Pk W,M-S MPW 8-2,1100 Olive Way,Suit, Seattle, WA 98101 USA. EM djopel@u.washington.edu NR 32 TC 3 Z9 3 U1 1 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD AUG PY 2009 VL 35 IS 8 BP 477 EP 482 DI 10.1136/jme.2008.027896 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 477HB UT WOS:000268508700007 PM 19644005 ER PT J AU Taniguchi, L Faria, BD Rosa, RT Carvalho, ADE Gursky, LC Elifio-Esposito, SL Parahitiyawa, N Samaranayake, LP Rosa, EAR AF Taniguchi, Lisa Faria, Berenice de Fatima Rosa, Rosimeire Takaki de Paula e Carvalho, Alessandra Gursky, Lauren Christine Elifio-Esposito, Selene Lobo Parahitiyawa, Nipuna Samaranayake, Lakshman Perera Ribeiro Rosa, Edvaldo Antonio TI Proposal of a low-cost protocol for colorimetric semi-quantification of secretory phospholipase by Candida albicans grown in planktonic and biofilm phases SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Biofilm; Candida albicans; Colorimetry; Phospholipase; Planktonic ID HUMAN ORAL EPITHELIUM; EXPRESSION; VIRULENCE; PURIFICATION AB Biofilms are aggregates of microorganisms living in multilayered structures inside polymeric matrices onto surfaces. These biofilms may subvert the physiological properties of adjacent tissues causing morphofunctional failure. Many studies have shown that the expression of virulence attributes is maximized when microbes form such communities. This study evaluated the differential phospholipasic activity of Candida albicans SC5314 grown in planktonic phase and in biofilm. We propose two distinct protocols for the colorimetric evaluation of phosphatidylcholine hydrolysis in neutral and acidic conditions. The results showed that both protocols are suitable for the proposed intention and that 72 h-old planktonic cultures of C. albicans SC5314 secrete higher quantities of neutral (6.42-fold) and acidic (3.85-fold) phospholipases than biofilms. (c) 2009 Elsevier B.V. All rights reserved. C1 [Ribeiro Rosa, Edvaldo Antonio] Pontificia Univ Catolica Parana, Ctr Ciencias Biol & Saude, Lab Estomatol, Fac Dent, BR-80215900 Curitiba, Parana, Brazil. [Faria, Berenice de Fatima] Formed Pharm Co, Curitiba, Parana, Brazil. [Gursky, Lauren Christine] Forsyth Inst, Dept Periodontol, Boston, MA USA. [Elifio-Esposito, Selene Lobo] Pontificia Univ Catolica Parana, Fac Biol Sci, Lab Physiol & Biophys, BR-80215901 Curitiba, Parana, Brazil. [Parahitiyawa, Nipuna] Univ Peradeniya, Fac Dent Sci, Div Microbiol, Peradeniya 20400, Sri Lanka. [Parahitiyawa, Nipuna; Samaranayake, Lakshman Perera] Univ Hong Kong, Prince Philip Dent Hosp, Sai Ying Pun, Hong Kong, Peoples R China. RP Rosa, EAR (reprint author), Pontificia Univ Catolica Parana, Ctr Ciencias Biol & Saude, Lab Estomatol, Fac Dent, Rua Imaculada Conceicao 1155, BR-80215900 Curitiba, Parana, Brazil. EM edvaldo.rosa@pucpr.br RI Samaranayake, Lakshman/B-2171-2009; Rosa, Edvaldo/B-1228-2008; Elifio-Esposito, Selene/N-6411-2014; OI Rosa, Edvaldo/0000-0001-6087-4365; /0000-0002-9122-336X FU PUCPR FX This study was part of the activities of LT. and B.F.F. to receive their Advanced Diplomas in Microbiology. The study was carried out with intramural funds of PUCPR. NR 13 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD AUG PY 2009 VL 78 IS 2 BP 171 EP 174 DI 10.1016/j.mimet.2009.05.012 PG 4 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 481OI UT WOS:000268820700011 PM 19464327 ER PT J AU Andersson, KB Birkeland, JAK Finsen, AV Louch, WE Sjaastad, I Wang, YB Chen, J Molkentin, JD Chien, KR Sejersted, OM Christensen, G AF Andersson, Kristin Brevik Birkeland, Jon Arne Kro Finsen, Alexandra Vanessa Louch, William E. Sjaastad, Ivar Wang, Yibin Chen, Ju Molkentin, Jeffery D. Chien, Kenneth R. Sejersted, Ole M. Christensen, Geir TI Moderate heart dysfunction in mice with inducible cardiomyocyte-specific excision of the Serca2 gene SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE SR Ca2+ ATPase; Serca2; Sarcoplasmic reticulum; Conditional gene excision; LoxP; Ca2+ membrane fluxes; Heart failure ID SARCOPLASMIC-RETICULUM; NA+-CA2+ EXCHANGE; CA2+; PHOSPHOLAMBAN; RELEASE; TRANSPORT; MEMBRANE; KNOCKOUT; FAILURE; PROTEIN AB The sarco(endo)plasmic reticulum calcium ATPase 2 (SERCA2) transports Ca2+ from cytosol into the sarcoplasmic reticulum (SR) of cardiomyocytes, thereby maintaining the store of releasable Ca2+ necessary for contraction. Reduced SERCA function has been linked to heart failure, and loss of SERCA2 in the adult mammalian heart would be expected to cause immediate severe myocardial contractile dysfunction and death. We investigated heart function in adult mice with an inducible cardiomyocyte-specific excision of the Atp2a2 (Serca2) gene (SERCA2 KO). Seven weeks after induction of Serca2 gene excision, the mice displayed a substantial reduction in diastolic function with a 5-fold increase in the time constant of isovolumetric pressure decay (tau). However, already at 4 weeks following gene excision less than 5% SERCA2 protein was found in myocardial tissue. Surprisingly, heart function was only moderately impaired at this time point. Tissue Doppler imaging showed slightly reduced peak systolic tissue velocity and a less than 2-fold increase in tau was observed. The SR Ca2+ content was dramatically reduced in cardiomyocytes from 4-week SERCA2 KO mice, and Ca2+ transients were predominantly generated by enhanced Ca2+ flux through L-type Ca2+ channels and the Na+-Ca2+ exchanger. Moreover, equivalent increases in cytosolic [Ca2+] in control and SERCA2 KO myocytes induced greater cell shortening in SERCA2 KO, suggesting enhanced myofilament responsiveness. Our data demonstrate that SR-independent Ca2+ transport mechanisms temporarily can prevent major cardiac dysfunction despite a major reduction of SERCA2 in cardiomyocytes. (C) 2009 Elsevier Inc. All rights reserved. C1 [Andersson, Kristin Brevik; Birkeland, Jon Arne Kro; Finsen, Alexandra Vanessa; Louch, William E.; Sjaastad, Ivar; Sejersted, Ole M.; Christensen, Geir] Ullevaal Univ Hosp, Expt Med Res Inst, NO-0407 Oslo, Norway. [Andersson, Kristin Brevik; Birkeland, Jon Arne Kro; Finsen, Alexandra Vanessa; Louch, William E.; Sjaastad, Ivar; Sejersted, Ole M.; Christensen, Geir] Univ Oslo, Ctr Heart Failure Res, N-0407 Oslo, Norway. [Sjaastad, Ivar] Ullevaal Univ Hosp, Dept Cardiol, NO-0407 Oslo, Norway. [Wang, Yibin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA. [Wang, Yibin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol & Med, Los Angeles, CA 90095 USA. [Chen, Ju] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Molkentin, Jeffery D.] Univ Cincinnati, Childrens Hosp Med Ctr, Dept Pediat, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA. [Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Andersson, KB (reprint author), Ullevaal Univ Hosp, Expt Med Res Inst, Kirkeveien 166, NO-0407 Oslo, Norway. EM k.b.andersson@medisin.uio.no RI Sejersted, Ole/D-5601-2009; Chen, Ju/E-5579-2011; OI Sejersted, Ole/0000-0001-8817-3296; Wang, Yibin/0000-0003-0852-0767 FU Eastern Norway Regional Health Authority; The Research Council of Norway; The Norwegian Council for Cardiovascular Diseases; Anders Jahre's Fund for the Promotion of Science; University of Oslo EMBIO fellowship FX We thank Mrs. Essy Booltink (Labor Diagnostika Nord, Germany) for excellent work.; This work was supported by the Eastern Norway Regional Health Authority, The Research Council of Norway, The Norwegian Council for Cardiovascular Diseases, Anders Jahre's Fund for the Promotion of Science and a University of Oslo EMBIO fellowship (K.B.A.). NR 23 TC 81 Z9 82 U1 0 U2 4 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 AUG PY 2009 VL 47 IS 2 BP 180 EP 187 DI 10.1016/j.yjmcc.2009.03.013 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 471FQ UT WOS:000268041800005 PM 19328205 ER PT J AU Alarcon, RD Becker, AE Lewis-Fernandez, R Like, RC Desai, P Foulks, E Gonzales, J Hansen, H Kopelowicz, A Lu, FG Oquendo, MA Primm, A AF Alarcon, Renato D. Becker, Anne E. Lewis-Fernandez, Roberto Like, Robert C. Desai, Prakash Foulks, Edward Gonzales, Junius Hansen, Helena Kopelowicz, Alex Lu, Francis G. Oquendo, Maria A. Primm, Annelle CA Grp Advancement Psychiat TI Issues for DSM-V The Role of Culture in Psychiatric Diagnosis SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Editorial Material ID PSYCHOSIS; RACE C1 [Lewis-Fernandez, Roberto] Columbia Univ, Dept Psychiat, NYSPI, New York, NY 10032 USA. [Alarcon, Renato D.] Mayo Clin, Dept Psychiat & Psychol, Coll Med, Rochester, MN USA. [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Becker, Anne E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lewis-Fernandez, Roberto] New York State Psychiat Inst & Hosp, New York State Ctr Excellence Cultural Competence, New York, NY 10032 USA. [Lewis-Fernandez, Roberto] New York State Psychiat Inst & Hosp, Hispan Treatment Program, New York, NY 10032 USA. [Like, Robert C.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Family Med, New Brunswick, NJ USA. [Desai, Prakash] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Foulks, Edward] Tulane Univ, Dept Psychiat, New Orleans, LA 70118 USA. [Gonzales, Junius] Univ S Florida, Coll Behav & Community Sci, Louis de la Porte Florida Mental Hlth Inst, Tampa, FL USA. [Hansen, Helena] NYU, Dept Psychiat, New York, NY 10016 USA. [Kopelowicz, Alex] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Lu, Francis G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Primm, Annelle] Amer Psychiat Assoc, Off Minor & Natl Affairs, Arlington, VA USA. [Primm, Annelle] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Lewis-Fernandez, R (reprint author), Columbia Univ, Dept Psychiat, NYSPI, Rm 3200,Unit 69,1051 Riverside Dr, New York, NY 10032 USA. OI kopelowicz, alex/0000-0002-1728-4105 NR 18 TC 24 Z9 24 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD AUG PY 2009 VL 197 IS 8 BP 559 EP 560 DI 10.1097/NMD.0b013e3181b0cbff PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 485ZF UT WOS:000269164300001 PM 19684490 ER PT J AU Perron, BE Zeber, JE Kilbourne, AM Bauer, MS AF Perron, Brian E. Zeber, John E. Kilbourne, Amy M. Bauer, Mark S. TI A Brief Measure of Perceived Clinician Support by Patients With Bipolar Spectrum Disorders SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Provider support; therapeutic alliance; factor analysis; mood disorders-bipolar; veterans ID THERAPEUTIC ALLIANCE; MEDICATION ADHERENCE; PREDICTIVE-VALIDITY; NONADHERENCE; MAINTENANCE; QUALITY; SCALES; MANIA; LIFE; CARE AB The quality of the patient-provider relationship is regarded as an essential ingredient in the treatment of serious mental illnesses, and is associated with favorable outcomes including improved treatment adherence. However, monitoring the strength and influence of provider support in clinical settings is challenged by the absence of brief, psychometrically sound, and easily administered assessments. The purpose of this study was to test the factor structure and examine the clinical and psychosocial correlates of a brief measure of provider support. Participants were recruited from the continuous improvement for veterans in care-Mood Disorders study (N = 429). The hypothesized factor structure exhibited a good fit with the data. At baseline, provider support was associated with higher levels of service access and medication compliance and lower levels of alcohol use and suicidality. Regular monitoring of provider support may provide useful when tailoring psychosocial treatment strategies, especially in routine care settings. C1 [Perron, Brian E.] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. [Perron, Brian E.; Kilbourne, Amy M.] VA Ann Arbor Healthcare Syst, Serious Mental Illness Treatment Res & Evaluat Ct, Ann Arbor, MI USA. [Zeber, John E.] S Texas Vet Hlth Care Syst VERDICT, Vet Affairs HSR&D, San Antonio, TX USA. [Zeber, John E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Kilbourne, Amy M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Harvard S Shore Psychiat Residency Training Progr, Boston, MA USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. RP Perron, BE (reprint author), Univ Michigan, Sch Social Work, 1080 S Univ Ave, Ann Arbor, MI 48109 USA. EM beperron@umich.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service; Office of Mental Health Services FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service and Office of Mental Health Services. A Brief Measure of Perceived Clinician is support by Patients with Bipolar Spectrum Disorders. NR 42 TC 4 Z9 4 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD AUG PY 2009 VL 197 IS 8 BP 574 EP 579 DI 10.1097/NMD.0b013e3181b08bc6 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 485ZF UT WOS:000269164300004 PM 19684493 ER PT J AU Gerstner, ER McNamara, MB Norden, AD LaFrankie, D Wen, PY AF Gerstner, Elizabeth R. McNamara, Margaret B. Norden, Andrew D. LaFrankie, Debra Wen, Patrick Y. TI Effect of adding temozolomide to radiation therapy on the incidence of pseudo-progression SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Pseudo-progression; Glioma; Radiation; Chemotherapy ID MALIGNANT GLIOMAS; GLIOBLASTOMA; RADIOTHERAPY; PSEUDOPROGRESSION; CONCOMITANT; MECHANISMS; SURVIVAL; NECROSIS AB Recently, there has been greater awareness that combination radiation and temozolomide used to treat glioblastomas may cause increased contrast enhancement on the first post radiation MRI scan. However, this increased enhancement may stabilize or decrease over time and represent pseudo-progression (psPD) rather than true progressive disease. It has never been shown that this phenomenon is greater with combination therapy than radiation alone. To address this question, we reviewed MRI scans in glioblastoma patients treated with radiation alone versus patients treated with radiation and concomitant temozolomide and compared the frequency of psPD in the two groups. Eighteen of 47 patients (38%) treated with radiation alone demonstrated enlargement on their first post-radiation MRI scan and 11 of these 18 (61%) proved to have psPD as defined by no further enlargement on stable therapy for 3 months following radiation. Twenty-four of 45 patients (53%) treated with radiation and temozolomide had enlargement on their first post-radiation MRI scan and 13 of these 24 (54%) had psPD. Median overall survival (OS) in patients with psPD treated with radiation alone was 15.6 versus 12.8 months in those without psPD. Median OS in patients treated with radiation and concomitant temozolomide who had psPD was 24.4 versus 15.9 months in those who did not have psPD. We were unable to detect a difference in OS between the four groups. Presence of psPD, independent of treatment, was associated with prolonged progression-free survival (P = 0.05) but not OS. psPD may be more common in combination therapy but most likely by a small margin. C1 [Gerstner, Elizabeth R.] Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02114 USA. [McNamara, Margaret B.; Norden, Andrew D.; LaFrankie, Debra; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Inst Canc, Ctr Neurooncol, Boston, MA 02115 USA. [Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM egerstner@partners.org NR 12 TC 56 Z9 56 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD AUG PY 2009 VL 94 IS 1 BP 97 EP 101 DI 10.1007/s11060-009-9809-4 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 466SS UT WOS:000267683600011 PM 19221865 ER PT J AU Chen, ZQ Peppi, M Kujawa, SG Sewell, WF AF Chen, Zhiqiang Peppi, Marcello Kujawa, Sharon G. Sewell, William F. TI Regulated Expression of Surface AMPA Receptors Reduces Excitotoxicity in Auditory Neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EXCITATORY AMINO-ACIDS; GUINEA-PIG COCHLEA; SYNAPTIC PLASTICITY; MAMMALIAN COCHLEA; BRAIN-INJURY; GLUTAMATE; TRAFFICKING; MOUSE; CELLS; RAT AB Chen Z, Peppi M, Kujawa SG, Sewell WF. Regulated expression of surface AMPA receptors reduces excitotoxicity in auditory neurons. J Neurophysiol 102: 1152-1159, 2009. First published June 10, 2009; doi: 10.1152/jn. 00288.2009. Dynamic regulation of the expression of surface AMPA receptors (AMPARs) is a key mechanism to modulate synaptic strength and efficacy in the CNS and also to regulate auditory sensitivity. Here we address the role of surface AMPAR expression in excitotoxicity by blocking clathrin-mediated AMPAR endocytosis in auditory neurons. We used a membrane-permeable, dynamin-derived, myristoylated peptide (myr-Dyn) to inhibit surface AMPAR endocytosis induced by glutamate receptor agonists in culture and by noise exposure in vivo. Myr-Dyn infused into the mouse cochlea induced excitotoxic responses to acoustic stimuli that were normally not excitotoxic. These included vacuolization in the nerve terminals and spiral ganglion as well as irreversible auditory brain stem response threshold shifts. In cultured spiral ganglion neuronal cells, blockade of the reduction of surface AMPARs exacerbated neuronal death by incubation with N-methyl-D-aspartate and AMPA. This excitotoxic neuronal death could be prevented by calpeptin, a calpain-specific inhibitor. These results suggest that the reduction of surface AMPAR by endocytosis during excitatory stimulation plays an important role in limiting the excitotoxic damage to the neuron. C1 [Chen, Zhiqiang; Peppi, Marcello; Kujawa, Sharon G.; Sewell, William F.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. [Chen, Zhiqiang; Peppi, Marcello; Kujawa, Sharon G.; Sewell, William F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kujawa, Sharon G.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Sewell, William F.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. EM wfs@epl.meei.harvard.edu FU National Institutes of Deafness and Other Communication Disorders [DC-000767, DC-008577] FX The work was supported by National Institutes of Deafness and Other Communication Disorders Grants DC-000767 to W. F. Sewell and DC-008577 to S. G. Kujawa. NR 39 TC 23 Z9 23 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2009 VL 102 IS 2 BP 1152 EP 1159 DI 10.1152/jn.00288.2009 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 490KS UT WOS:000269500400046 PM 19515954 ER PT J AU Whitney, ER Kemper, TL Rosene, DL Bauman, ML Blatt, GJ AF Whitney, Elizabeth R. Kemper, Thomas L. Rosene, Douglas L. Bauman, Margaret L. Blatt, Gene J. TI Density of Cerebellar Basket and Stellate Cells in Autism: Evidence for a Late Developmental Loss of Purkinje Cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE cerebellum; basket cells; stellate cells; autism ID POSTERIOR-FOSSA STRUCTURES; RECEPTOR SUBUNIT GENES; INFANTILE-AUTISM; CLIMBING FIBERS; MUTANT MICE; BRAIN; DISORDER; TWIN; SIZE; RAT AB Alterations in the cerebellum have been described as a neuropathological feature of autism. Although numerous studies have focused on the Purkinje cell (PC), the projection neuron of the cerebellar cortex, PC function is critically dependent on their innervation by the GABAergic basket cells (BCs) and stellate cells (SCs) in the cerebellar molecular layer. The present study was designed to determine whether there are differences in the packing density of these inhibitory interneurons or whether the ratio of these interneurons to PCs differs in autistic and age-matched control brains. The GABAergic interneurons were identified by using immunohistochemistry for parvalbumin (PV) in serial sections from the posterior cerebellar lobe of six autistic and four control brains and counted using stereological principles. Prior PC counts in the same area on adjacent sections (Whitney et al., 2008) were available and were used to calculate the number of BCs and SCs per PC. In this sample of brains, no statistically significant difference was detected between the autistic and the control groups in the density of BCs or SCs (P = 0.44 and P = 0.84, respectively) or in the number of BCs or SCs per PC (P = 0.47 and P = 0.44, respectively). The preservation of BCs and SCs, in the presence of the reduced PC numbers as found in at least two, and possibly three, of these six autistic cases (Whitney et al., 2008) suggests that PCs were generated, migrated to their proper location in the PC layer, and subsequently died in the autistic cases that showed a reduction in PCs. (C) 2009 Wiley-Liss, Inc. C1 [Whitney, Elizabeth R.; Kemper, Thomas L.; Rosene, Douglas L.; Bauman, Margaret L.; Blatt, Gene J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02218 USA. [Bauman, Margaret L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Whitney, ER (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, L 1006,715 Albany St, Boston, MA 02218 USA. EM ewhitney@bu.edu RI Rosene, Douglas/G-1973-2015; OI Rosene, Douglas/0000-0001-8719-1441 FU NIH-NICHD [HD39459]; National Alliance for Autism Research (NAAR); Nancy Lauric Marks Foundation; John and Lisa Hussman Foundation FX Contract grant sponsor: NIH-NICHD; Contract grant number: HD39459; Contract grant sponsor: National Alliance for Autism Research (NAAR); Contract grant sponsor: Nancy Lauric Marks Foundation; Contract grant sponsor: John and Lisa Hussman Foundation. NR 67 TC 43 Z9 43 U1 10 U2 20 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 1 PY 2009 VL 87 IS 10 BP 2245 EP 2254 DI 10.1002/jnr.22056 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 463RW UT WOS:000267450700006 PM 19301429 ER PT J AU Walcott, BP Sivarajan, G Bashinskaya, B Anderson, DE Leonetti, JP Origitano, TC AF Walcott, Brian P. Sivarajan, Ganesh Bashinskaya, Bronislava Anderson, Douglas E. Leonetti, John P. Origitano, Thomas C. TI Sporadic unilateral vestibular schwannoma in the pediatric population SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE facial nerve; neurofibromatosis; pediatric neurosurgery; retrosigmoid approach; translabyrinthine approach; vestibular schwannoma ID ACOUSTIC NEUROMAS; FACIAL-NERVE; TYPE-2 NEUROFIBROMATOSIS; RETROSIGMOID APPROACH; MANAGEMENT; REMOVAL; RADIOSURGERY; RESECTION; MICROSURGERY; PRESERVATION AB Object. Vestibular schwannomas (VSs) are rare in the pediatric population. Most often, these lesions manifest as a bilateral disease process in the setting of neurofibromatosis Type 2. Even in the absence of additional clinical diagnostic criteria, the presentation of a unilateral VS in a young patient may be a harbinger of future penetrance for this hereditary tumor syndrome. Methods. The authors retrospectively reviewed the charts of a cohort of 7 patients who presented with apparently sporadic, unilateral VSs. These patients had previously undergone surgery via translabyrinthine, retrosigmoid, or combined approaches. Clinical outcomes were reviewed with emphasis on facial nerve function and follow-up for signs and symptoms of a heritable disorder. Results. All patients underwent microsurgical resection in a multidisciplinary effort by the senior authors. The average tumor size was 4.57 cm, with an average duration of symptoms prior to definitive diagnosis of 31.2 months. The tumor size at the time of presentation followed a trend different from reports in adults, while the duration of symptoms did not. At a follow-up average of 6.3 years (range 1-12 years), 100% of patients demonstrated good facial function (House-Brackmann Grade I or II). No patient in this cohort demonstrated symptoms, objective signs, or genetic analysis indicating the presence of neurofibromatosis Type 2. Conclusions. Diagnosis and management of sporadic, unilateral VSs in children is complicated by clinical presentations and surgical challenges unique from their adult counterparts. Careful consideration should be given to a heritable genetic basis for sporadic unilateral VS in the pediatric population. Results of genetic testing do not preclude the necessity for long-term follow-up and systemic investigation. In patients who present with large tumors, preliminary experience leads the authors to suggest that a combined retrosigmoid-translabyrinthine approach offers the greatest opportunity for preservation of facial nerve function. (DOI: 10.3171/2009.3.PEDS08434) C1 [Sivarajan, Ganesh; Anderson, Douglas E.; Leonetti, John P.; Origitano, Thomas C.] Loyola Univ, Med Ctr, Stritch Sch Med, Maywood, IL 60153 USA. [Sivarajan, Ganesh; Anderson, Douglas E.; Origitano, Thomas C.] Loyola Univ, Med Ctr, Dept Neurol Surg, Maywood, IL 60153 USA. [Leonetti, John P.] Loyola Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Loyola Ctr Cranial Base Surg,Loyola Univ Chicago, Maywood, IL 60153 USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Walcott, Brian P.; Bashinskaya, Bronislava] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. RP Anderson, DE (reprint author), Loyola Univ, Med Ctr, Stritch Sch Med, 2160 S 1st Ave, Maywood, IL 60153 USA. EM dander1@lumc.edu NR 42 TC 5 Z9 6 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROS-PEDIATR JI J. Neurosurg.-Pediatr. PD AUG PY 2009 VL 4 IS 2 BP 125 EP 129 DI 10.3171/2009.3.PEDS08434 PG 5 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 475EO UT WOS:000268341400007 PM 19645545 ER PT J AU Khuman, J Bilal, K Koppula, R Zhang, X Mbye, L Whalen, M AF Khuman, Jugta Bilal, Kiran Koppula, Rajani Zhang, Xuan Mbye, Lamin Whalen, Michael TI TNF ALPHA AND FAS RECEPTOR MEDIATE COGNITIVE DEFICITS INDEPENDENT OF CELL DEATH AFTER CLOSED HEAD INJURY IN MICE SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 2nd Joint Symposium of the National-and-International-Neurotrauma-Societies CY SEP 07-11, 2009 CL Santa Barbara, CA SP Natl & Int Neurotrauma Soc C1 [Khuman, Jugta; Bilal, Kiran; Koppula, Rajani; Zhang, Xuan; Mbye, Lamin; Whalen, Michael] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 2009 VL 26 IS 8 MA P206 BP A53 EP A53 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 479AF UT WOS:000268629900228 ER PT J AU Levin, H Wilde, E Troyanskaya, M Petersen, N Scheibel, R AF Levin, Harvey Wilde, Elisabeth Troyanskaya, Maya Petersen, Nancy Scheibel, Randall TI DIFFUSION TENSOR IMAGING OF MILD TO MODERATE BLAST RELATED TBI IN RELATION TO POST-CONCUSSION AND POSTTRAUMATIC STRESS DISORDER SYMPTOMS SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 2nd Joint Symposium of the National-and-International-Neurotrauma-Societies CY SEP 07-11, 2009 CL Santa Barbara, CA SP Natl & Int Neurotrauma Soc C1 [Levin, Harvey; Wilde, Elisabeth; Troyanskaya, Maya; Scheibel, Randall] Baylor Coll Med, Houston, TX 77030 USA. [Petersen, Nancy] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 AUG PY 2009 VL 26 IS 8 MA P267 BP A69 EP A69 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 479AF UT WOS:000268629900287 ER PT J AU Mbye, LHAN Whalen, MJ AF Mbye, Lamin H. A. N. Whalen, Michael J. TI STUDENT COMPETITION FINALIST POLOXAMER P188 ATTENUATES CELL MEMBRANE PERMEABILITY, AND IMPROVES HISTOPATHOLOGICAL AND FUNCTIONAL OUTCOME FOLLOWING TRAUMATIC BRAIN INJURY IN MICE SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 2nd Joint Symposium of the National-and-International-Neurotrauma-Societies CY SEP 07-11, 2009 CL Santa Barbara, CA SP Natl & Int Neurotrauma Soc C1 [Mbye, Lamin H. A. N.] Massachusetts Gen Hosp, Charlestown, MA USA. [Whalen, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 2009 VL 26 IS 8 MA P362 BP A93 EP A93 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 479AF UT WOS:000268629900379 ER PT J AU Wallis, RA Panizzon, K AF Wallis, Roi Ann Panizzon, Kimberly TI TREATMENT WITH BCL-2(20-34) PROVIDES LONG-TERM PROTECTION AGAINST THE DECREASED SEIZURE THRESHOLD OF CA1 HIPPOCAMPAL NEURONS AFTER CONTROLLED CORTICAL IMPACT SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 2nd Joint Symposium of the National-and-International-Neurotrauma-Societies CY SEP 07-11, 2009 CL Santa Barbara, CA SP Natl & Int Neurotrauma Soc C1 [Panizzon, Kimberly] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Wallis, Roi Ann] Univ Calif Los Angeles, Sch Med, 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 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 2009 VL 26 IS 8 MA P243 BP A63 EP A63 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 479AF UT WOS:000268629900263 ER PT J AU Wood, GJ Akiyama, T Carstens, E Oaklander, AL Yosipovitch, G AF Wood, Gordon J. Akiyama, Tasuku Carstens, E. Oaklander, Anne Louise Yosipovitch, Gil TI An Insatiable Itch SO JOURNAL OF PAIN LA English DT Review ID HERPES-ZOSTER; POSTHERPETIC NEURALGIA; NOTALGIA PARESTHETICA; ATOPIC-DERMATITIS; NEUROPATHIC PAIN; PRURITUS; NEURONS; NOCICEPTORS; MECHANISMS; RECEPTORS C1 [Akiyama, Tasuku; Carstens, E.] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Davis, CA 95616 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yosipovitch, Gil] Wake Forest Univ Hlth Sci, Dept Dermatol Neurobiol & Anat, Winston Salem, NC USA. RP Wood, GJ (reprint author), Care Of Paice JA, Northwestern Univ, Sch Med, 676 N St Claire St,Suite 850, Chicago, IL 60611 USA. EM j-paice@northwestern.edu NR 43 TC 9 Z9 9 U1 0 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 1526-5900 J9 J PAIN JI J. Pain PD AUG PY 2009 VL 10 IS 8 BP 792 EP 797 DI 10.1016/j.jpain.2009.04.002 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 485CK UT WOS:000269098100002 PM 19638326 ER PT J AU Fromme, EK Rosenfeld, KE Brokaw, FC Hughes, MT Arnold, RM AF Fromme, Erik K. Rosenfeld, Kenneth E. Brokaw, Francis C. Hughes, Mark T. Arnold, Robert M. TI Update in Palliative Medicine SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID PAIN CLINICAL-TRIALS; IMMPACT RECOMMENDATIONS C1 [Fromme, Erik K.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Rosenfeld, Kenneth E.] VA Greater Angeles Healthcare Syst, Palliat Care Sect, Div Gen Med, Los Angeles, CA USA. [Brokaw, Francis C.] Dartmouth Hitchcock Med Ctr, Div Gen Internal Med, Lebanon, NH 03766 USA. [Hughes, Mark T.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Arnold, Robert M.] Univ Pittsburgh, Sect Palliat Care & Med Eth, Div Gen Internal Med, Pittsburgh, PA USA. RP Fromme, EK (reprint author), Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, L586 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM frommee@ohsu.edu FU National Cancer Institute [K07CA109511] FX Dr. Fromme is supported by a Career Development Award from the National Cancer Institute K07CA109511. Six of these papers were presented at the Society of General Internal Medicine 31st Annual Meeting on April 12, 2008 in Pittsburgh, Pennsylvania. NR 5 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG PY 2009 VL 12 IS 8 BP 731 EP 736 DI 10.1089/jpm.2009.0019 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 480XG UT WOS:000268770000016 ER PT J AU Mieli-Vergani, G Heller, S Jara, P Vergani, D Chang, MH Fujisawa, T Gonzalez-Peralta, RP Kelly, D Mohan, N Shah, U Murray, KF AF Mieli-Vergani, Giorgina Heller, Solange Jara, Paloma Vergani, Diego Chang, Mei-Hwei Fujisawa, Tomoo Gonzalez-Peralta, Regino P. Kelly, Deirdre Mohan, Neelam Shah, Uzma Murray, Karen F. TI Autoimmune Hepatitis SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review DE Autoimmune hepatitis; hepatitis; Immunosuppression; Liver disease; Pediatrics ID SOLUBLE LIVER ANTIGEN; AUTOANTIBODY PREVALENCE; ANTINUCLEAR ANTIBODIES; FOLLOW-UP; CHILDREN; DISEASE; TRANSPLANTATION; CHILDHOOD; REMISSION; CYCLOSPORINE AB Autoimmune hepatitis is characterized by inflammatory liver histology, circulating nonorgan-specific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of juvenile autoimmune hepatitis (AIH) are recognized according to seropositivity for smooth muscle and/or anti-nuclear antibody (AIH type 1) or liver kidney microsomal antibody (AIH type 2). There is a female predominance in both. AIH type 2 presents more acutely, at a younger age and commonly with immunoglobulin A deficiency, whereas duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the 2 groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to non-adherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AM type I patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. Differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. In this article we review the state of the art of diagnosis, monitoring, and treatment for children with AIH. JPGN 49:158-164, 2009. C1 [Murray, Karen F.] Seattle Childrens Hosp, Hepatobiliary Program, Seattle, WA 98105 USA. [Mieli-Vergani, Giorgina] Kings Coll Hosp London, Sch Med, Univ London Kings Coll, London SE5 8RX, England. [Heller, Solange] Hosp Infantil Mexico Feder Gomez, Dept Gastroenterol & Nutr, Mexico City, DF, Mexico. [Jara, Paloma] Pediat Univ Hosp La Paz, Pediat Hepatol & Transplantat Serv, Madrid, Spain. [Vergani, Diego] Kings Coll Hosp London, Inst Liver Studies, London SE5 8RX, England. [Chang, Mei-Hwei] Natl Taiwan Univ Hosp, Dept Pediat, Taipei 10016, Taiwan. [Fujisawa, Tomoo] Yokohama E Hosp, Childrens Ctr Hlth & Dev, Yokohama, Kanagawa, Japan. [Gonzalez-Peralta, Regino P.] Univ Florida, Coll Med, Div Pediat Gastroenterol Hepatol & Nutr, Gainesville, FL USA. [Kelly, Deirdre] Birmingham Childrens Hosp NHS Trust, Liver Unit, Birmingham, W Midlands, England. [Kelly, Deirdre] Univ Birmingham, Birmingham, W Midlands, England. [Mohan, Neelam] Sir Ganga Ram Hosp, Ctr Child Hlth, Dept Pediat, New Delhi, India. [Shah, Uzma] MassGen Hosp Children, Boston, MA USA. RP Murray, KF (reprint author), Seattle Childrens Hosp, Hepatobiliary Program, 4800 Sand Point Way NE,POB 5371 W7830, Seattle, WA 98105 USA. EM karen.murray@seattlechildrens.org OI Chang, Mei Hwei/0000-0002-3648-9261 NR 43 TC 63 Z9 69 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2009 VL 49 IS 2 BP 158 EP 164 PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 477LD UT WOS:000268519700002 PM 19561543 ER PT J AU Crandall, W Hyams, J Kugathasan, S Griffiths, A Zrubek, J Olson, A Liu, G Heuschkel, R Markowitz, J Cohen, S Winter, H Veereman-Wauters, G Ferry, G Baldassano, RN AF Crandall, Wallace Hyams, Jeffrey Kugathasan, Subra Griffiths, Anne Zrubek, Julie Olson, Allan Liu, Grace Heuschkel, Robert Markowitz, James Cohen, Stanley Winter, Harland Veereman-Wauters, Gigi Ferry, George Baldassano, Robert N. TI Infliximab Therapy in Children With Concurrent Perianal Crohn Disease: Observations From REACH SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE Concurrent perianal disease signs and symptoms; Infliximab; Pediatric Crohn disease ID INFLAMMATORY-BOWEL-DISEASE; MAINTENANCE INFLIXIMAB; 6-MERCAPTOPURINE; AZATHIOPRINE; FISTULAS; ADOLESCENTS AB Objective: Post hoc analyses evaluated the effect of infliximab upon Concurrent perianal Crohn disease (CD) in a subpopulation of 31 patients from REACH, a randomized trial of 112 children with moderately to severely active luminal CD. Materials and Methods: The Pediatric Crohn Disease Activity Index perirectal subscore Was used to assess perianal symptom activity and therapeutic response. Patients with no symptoms or asymptomatic tap received a score of 0: those with "1-2 indolent fistula, scant drainage. no tenderness" received a score of 5: and those with "active fistula, drainage, tenderness or abscess" received a score of 10. Initial perirectal subscores of 10 or 5 decreasing to 0 were considered complete response. subscores of 10 decreasing to 5 were considered partial response. All patients were followed for efficacy and safety through week 54. Results: Twenty-two patients with baseline perianal disease were randomized at week 10 following a 3-dose infliximab induction regimen. At week 2, 40.9% (9/22) of patients with signs and symptoms of perianal disease at baseline attained response (4 partial and 5 complete), At week 54, 72.7% (16/22) of patients with signs and symptoms of perianal disease attained response (I partial and 15 complete). Nine patients developed perianal signs and symptoms during treatment; 7 had complete response and 2 had no response at week 54. The incidence of adverse events for patients with perianal symptoms at baseline and for those in the overall REACH Population was similar (95.7% vs 94.6%). Conclusions: Infliximab rapidly reduced Concurrent perianal disease signs and symptoms in this REACH cohort. JPGN 49-183-190, 2009. C1 [Crandall, Wallace] Ohio State Univ, Nationwide Childrens Hosp, Sch Med, Columbus, OH 43205 USA. [Hyams, Jeffrey] Connecticut Childrens Ctr, Hartford, CT USA. [Kugathasan, Subra] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Griffiths, Anne] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Zrubek, Julie] Centocor Inc, Malvern, PA 19355 USA. [Zrubek, Julie] RW Johnson Pharmaceut Res & Dev, La Jolla, CA USA. [Heuschkel, Robert] Addenbrookes Hosp, Cambridge, England. [Markowitz, James] N Shore Long Isl Jewish Hlth Syst, New Hyde Pk, NY USA. [Cohen, Stanley] Childrens Ctr Digest Hlth Care, Atlanta, GA USA. [Winter, Harland] MassGen Hosp Children, Boston, MA USA. [Veereman-Wauters, Gigi] Queen Paola Childrens Hosp, Antwerp, Belgium. [Baldassano, Robert N.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Liu, Grace] RW Johnson Pharmaceut Res & Dev, Titusville, NJ USA. [Ferry, George] Texas Childrens Hosp, Houston, TX 77030 USA. RP Crandall, W (reprint author), Ohio State Univ, Nationwide Childrens Hosp, Sch Med, 700 Childrens Dr, Columbus, OH 43205 USA. EM Wallace.Crandall@NationwideChildrens.org NR 28 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2009 VL 49 IS 2 BP 183 EP 190 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 477LD UT WOS:000268519700006 PM 19561542 ER PT J AU Winter, HS Oleske, JM Hughes, MD McKinney, RE Elgie, C Powell, C Purdue, L Puga, AM Jimenez, E Scott, GB Cruz, MLS Moye, J AF Winter, Harland S. Oleske, James M. Hughes, Michael D. McKinney, Ross E., Jr. Elgie, Carol Powell, Christine Purdue, Lynette Puga, Ana M. Jimenez, Eleanor Scott, Gwendolyn B. Santos Cruz, Maria Leticia Moye, Jack, Jr. CA Pediat AIDS Clinical Trials Grp P TI Randomized Controlled Trial of Feeding a Concentrated Formula to Infants Born to Women Infected by Human Immunodeficiency Virus SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE AIDS; HIV; Nutrition ID WORKING GROUP-REPORT; SUB-SAHARAN AFRICA; PEDIATRIC GASTROENTEROLOGY; ADULT HYPERTENSION; GLUCOSE-TOLERANCE; WORLD CONGRESS; HIV-INFECTION; BIRTH-WEIGHT; GROWTH; NUTRITION AB Objective: We tested the hypothesis that concentrated formula (CF) begun within the first 2 weeks of life increases growth in infants born to human immunodeficiency virus (HIV)-infected mothers. Materials and Methods: HIV-exposed infants from the United States, the Bahamas, and Brazil were randomized in a double-blind, controlled trial to receive either a CF[87 kcal/100 mL 126 kcal/oz]) or a standard formula [SF; 67 kcal/100 mL 120 kcal/oz]) for 8 weeks. This article presents results for infants who were not determined to be HIV infected based oil testing at 4 weeks. Primary outcomes were safety, tolerability, and growth in weight and length. Results: Two thousand ninety-seven infants were enrolled, of whom 1998 were uninfected and had study formula dispensed. At weeks 4 and 8, uninfected infants receiving CF showed higher energy intake than those who were receiving SF (P < 0.001). By week S. uninfected infants assigned to CF weighed more than infants receiving SF. There were no consistent differences in measures of tolerability, and rates of discontinuation or perceived formula intolerance were similar between treatment groups. Conclusions: A CF is well tolerated and results in increased weight gain compared with SF. Until the HIV status of ail infant is reliably determined, early introduction of a CF in HIV-exposed children may have beneficial effects on growth. The role of early nutritional intervention remains to be determined for individuals living in countries with endemic malnutrition for whom formula feeding is a viable option. JPGN 49:222-232, 2009. C1 [Winter, Harland S.] MassGen Hosp Children, Pediat Gastroenterol & Nutr Unit, Boston, MA 02114 USA. [Oleske, James M.] Univ Med & Dent New Jersey, Div Allergy & Immunol, Newark, NJ 07103 USA. [Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [McKinney, Ross E., Jr.] Duke Univ, Med Ctr, Pediat Clin Trials Unit, Durham, NC USA. [Elgie, Carol] Frontier Sci Technol & Res Fdn, Amherst, NY USA. [Powell, Christine] Harvard Univ, Sch Publ Hlth, Ctr Biostat Res, Boston, MA 02115 USA. [Purdue, Lynette] NIAID, NIH, Div Aids, Pharmaceut Affairs Branch,US Dept HHS, Bethesda, MD 20892 USA. [Puga, Ana M.] Childrens Diagnost & Treatment Ctr Inc, Comprehens Family AIDS Program, Ft Lauderdale, FL USA. [Jimenez, Eleanor] San Juan City Hosp, Dept Pediat, San Juan, PR USA. [Scott, Gwendolyn B.] Univ Miami, Dept Pediat, Miami, FL 33152 USA. [Santos Cruz, Maria Leticia] Hosp Servidores Estado, Serv Doencas Infecciosas & Parasitarias, Rio De Janeiro, Brazil. [Moye, Jack, Jr.] NICHHD, NIH,Ctr Res Mothers & Children, Pediat Adolescent & Maternal AIDS Branch, US Dept HHS, Bethesda, MD 20892 USA. RP Winter, HS (reprint author), MassGen Hosp Children, Pediat Gastroenterol & Nutr Unit, 175 Cambridge St,CPZS 5-560, Boston, MA 02114 USA. EM hwinter@partners.org RI Oleske, James/C-1951-2016; OI Oleske, James/0000-0003-2305-5605; moye, john/0000-0001-9976-8586 FU Protocol 247 team; Pediatric AIDS Clinical Trials Group (PACTG) of the National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health; Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development (NICHD) [N01-HD-3-3162, N01-HD-3-3345]; Statistical and Data Management Center of the PACTG [AI-41110]; Ross Products Division of Abbott Laboratories FX The authors would like to express their gratitude to all of the children and their families who participated in this Study. and acknowledge the contributions and support of the entire Protocol 247 team.; This work was Supported by the Pediatric AIDS Clinical Trials Group (PACTG) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, the Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development (NICHD), National Institutes of Health, the Statistical and Data Management Center of the PACTG (NIAID cooperative agreement AI-41110), Ross Products Division of Abbott Laboratories, and NICHD contract numbers N01-HD-3-3162 and N01-HD-3-3345. NR 37 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2009 VL 49 IS 2 BP 222 EP 232 PG 11 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 477LD UT WOS:000268519700012 PM 19543114 ER PT J AU Haffajee, AD Teles, RP Patel, MR Song, X Veiga, N Socransky, SS AF Haffajee, A. D. Teles, R. P. Patel, M. R. Song, X. Veiga, N. Socransky, S. S. TI Factors affecting human supragingival biofilm composition. I. Plaque mass SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE microbiology; bacteria; supragingival plaque; ecology; plaque mass ID DNA-DNA HYBRIDIZATION; EXPERIMENTAL GINGIVITIS AB Background and Objective: Little is known about the factors that affect the microbial composition of supragingival biofilms. This study was designed to examine the relationship between total DNA probe counts of supragingival biofilm samples, clinical parameters and supragingival biofilm composition. Material and Methods: Supragingival plaque samples were taken from 187 systemically healthy adult subjects (n = 4745 samples). All samples were individually analyzed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. The relationship between total DNA probe counts and microbial composition was examined by subsetting the data into 10 groups based on 10 percentile increments of the total DNA probe counts. Differences among groups in terms of species counts and proportions were sought, as well as relationships of total plaque DNA probe count and clinical parameters. Results: There was a wide distribution in mean total DNA probe counts among the 187 subjects. With increasing total plaque levels there was a change in the proportions of individual species and microbial complexes. 'Small plaques' were characterized by high proportions of species in the yellow, orange, purple and 'other' complexes; plaques of moderate mass were characterized by high proportions of Actinomyces and purple complex species, while 'large plaques' exhibited increased proportions of green and orange complex species. Measures of gingival inflammation, pocket depth and recession were significantly positively associated with total DNA probe counts. Increased plaque numbers were related to increased pocket depth irrespective of presence or absence of gingival inflammation. Conclusion: The proportions of individual species and microbial complexes in supragingival biofilms are influenced by the total numbers of organisms in the biofilm. C1 [Haffajee, A. D.; Teles, R. P.; Patel, M. R.; Song, X.; Veiga, N.; Socransky, S. S.] Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA USA. EM ahaffajee@forsyth.org FU National Institute of Dental and Craniofacial Research [DE-12108, DE-14368] FX This work was supported in part by research grants DE-12108 and DE-14368 from the National Institute of Dental and Craniofacial Research. NR 11 TC 21 Z9 21 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD AUG PY 2009 VL 44 IS 4 BP 511 EP 519 DI 10.1111/j.1600-0765.2008.01154.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 463IZ UT WOS:000267426900012 PM 18973540 ER PT J AU Haffajee, AD Teles, RP Patel, MR Song, X Yaskell, T Socransky, SS AF Haffajee, A. D. Teles, R. P. Patel, M. R. Song, X. Yaskell, T. Socransky, S. S. TI Factors affecting human supragingival biofilm composition. II. Tooth position SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE bacteria; supragingival plaque; tooth type; plaque mass ID DNA-DNA HYBRIDIZATION AB Background and Objective: Little is known regarding the factors that affect the microbial composition of supragingival biofilms. This study was designed to test the hypothesis that tooth location affects the microbial composition of supragingival plaque beyond the effect due to plaque mass as reflected by total DNA probe count. Material and Methods: Supragingival plaque samples were taken from the mesiobuccal aspect of each tooth in 187 subjects (n = 4745 samples). All samples were individually analyzed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. Significance of differences in mean species counts and proportions were determined among tooth surfaces and six tooth type categories: molars, bicuspids, incisors/canines in the mandible and maxilla separately using the Kruskal-Wallis test. Stepwise multiple linear regression was employed to examine the relationship between species proportions and total DNA probe count, tooth location, periodontal and smoking status, age and sex. Results: All species differed significantly among tooth types and among the six tooth categories. Higher plaque levels were seen on molars and lower incisors. Some differences observed between tooth types could be partly explained by the level of plaque. Teeth with high plaque mass exhibited high levels of Capnocytophaga gingivalis, Actinomyces naeslundii genospecies 2, Campylobacter rectus and Campylobacter showae. However, certain species, such as Veillonella parvula and Streptococcus sanguinis, differed significantly at different tooth locations despite similarities in plaque mass. Twenty of the test species exhibited a significant association with tooth location after adjusting for total DNA probe count and subject level factors. Conclusion: While plaque mass was associated with differences in proportions of many species in supragingival biofilms, tooth location also was strongly associated with species proportions in both univariate and multivariate analyses. C1 [Haffajee, A. D.; Teles, R. P.; Patel, M. R.; Song, X.; Yaskell, T.; Socransky, S. S.] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM ahaffajee@forsyth.org FU National Institute of Dental and Craniofacial Research. [DE-12108, DE-14368] FX This work was supported in part by research grants DE-12108 and DE-14368 from the National Institute of Dental and Craniofacial Research. NR 5 TC 10 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD AUG PY 2009 VL 44 IS 4 BP 520 EP 528 DI 10.1111/j.1600-0765.2008.01155.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 463IZ UT WOS:000267426900013 PM 18973539 ER PT J AU Lambert, FE Weber, HP Susarla, SA Belser, UC Gallucci, GO AF Lambert, France E. Weber, Hans-Peter Susarla, Srinivas A. Belser, Urs C. Gallucci, German O. TI Descriptive Analysis of Implant and Prosthodontic Survival Rates With Fixed Implant-Supported Rehabilitations in the Edentulous Maxilla SO JOURNAL OF PERIODONTOLOGY LA English DT Review DE Dental implants; edentulous jaws; implant-supported dental prostheses; literature review ID OSSEOINTEGRATED DENTAL IMPLANTS; LONGITUDINAL CLINICAL EFFECTIVENESS; SUBMERGED ITI IMPLANTS; FOLLOW-UP; TITANIUM IMPLANTS; PROSPECTIVE MULTICENTER; ENDOSSEOUS IMPLANTS; MINIATURE PIGS; ORAL IMPLANTS; BONE-GRAFTS AB Background: This descriptive study reviewed the 1- to 15-year survival rates of fixed implant rehabilitations in the edentulous maxilla. Methods: An electronic search was conducted, and cohort studies with 1- to 15-year follow-ups were identified by two independent reviewers. The implant and prosthodontic survival rates were reviewed at 1-, 3-, 5-, 10-, and 15-year endpoints. Descriptive analysis includes surface characteristics, bone-augmentation procedure, prosthetic design, and implant number and distribution along the edentulous maxilla. Results: Thirty-three studies, including 1,320 patients and 8,376 implants, were selected for analysis. The overall calculated implant survival rates ranged from 94% (1 year) to 87.7% (15 years). The implant survival rates for rough-surface implants ranged from 97% (1 year) to 98% (15 years); machined implants showed survival rates of 92% to 87.7%; respectively. Implants placed in native bone had greater survival rates than those placed in augmented bone. The prosthodontic survival rate ranged from 98.2% at 1 year to 92.1% at the 10-year endpoint, and it was only influenced by the implant number and distribution. Conclusions: Implants with rough surfaces showed a statistically higher survival rate than machined implants at all intervals. Implants placed in augmented bone had a statistically lower survival rate, except for rough-surface implants, for which no statistical difference between augmented and non-augmented bone survival rates was found. Machined implants showed a stable survival rate only when placed in native bone. When machined implants were placed in augmented bone, the survival rate decreased significantly at each study endpoint. The prosthetic design, veneering material, and the number of prostheses per arch had no influence on the prosthodontic survival rate. Implant number and distribution along the edentulous maxilla seemed to influence the prosthodontic survival rate. J Periodontol 2009;80:1220-1230. C1 [Lambert, France E.; Weber, Hans-Peter; Gallucci, German O.] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, Boston, MA 02115 USA. [Susarla, Srinivas A.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Belser, Urs C.] Univ Geneva, Sch Dent Med, Dept Fixed Prosthodont & Occlus, Geneva, Switzerland. RP Gallucci, GO (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. EM german_gallucci@hsdm.harvard.edu RI Gallucci, German/H-4505-2011; OI Susarla, Srinivas/0000-0003-0155-8260 FU Department of Restorative Dentistry, Harvard School of Dental Medicine FX The authors express their gratitude to Dr. Sung-Kiang Chuang, Department of Oral Surgery, Massachusetts General Hospital, and Dr. Fan Lin, Harvard School of Public Health, Boston, Massachusetts, for their invaluable assistance in the development of the statistical analysis; Dr. Anna Jotkowitz, Department of Restorative Dentistry, Harvard School of Dental Medicine, for her help in revising this article; and Milica Tomasevic, extrarenal consultant, Boston, Massachusetts, for her input in editing this manuscript. This study was supported by the Department of Restorative Dentistry, Harvard School of Dental Medicine. The authors report no conflicts of interest related to this study. NR 77 TC 68 Z9 68 U1 0 U2 5 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD AUG PY 2009 VL 80 IS 8 BP 1220 EP 1230 DI 10.1902/jop.2009.090109 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 484DV UT WOS:000269024700005 PM 19656021 ER PT J AU McCloskey, MS New, AS Siever, LJ Goodman, M Koenigsberg, HW Flory, JD Coccaro, EF AF McCloskey, Michael S. New, Antonia S. Siever, Larry J. Goodman, Marianne Koenigsberg, Harold W. Flory, Janine D. Coccaro, Emil F. TI Evaluation of behavioral impulsivity and aggression tasks as endophenotypes for borderline personality disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Borderline personality disorder; Endophenotype; Aggression; Impulsivity ID INTERMITTENT EXPLOSIVE DISORDER; AXIS-II DISORDERS; DSM-IV CRITERIA; RESPONSE-INHIBITION; PREFRONTAL CORTEX; BIPOLAR DISORDER; SELF-MUTILATION; TRAITS; SCHIZOPHRENIA; PREVALENCE AB Borderline personality disorder (BIRD) is marked by aggression and impulsive, often self-destructive behavior. Despite the severe risks associated with BPD, relatively little is known about the disorder's etiology. Identification of genetic correlates (endophenotypes) of BPD would improve the prospects of targeted interventions for more homogeneous subsets of borderline patients characterized by specific genetic vulnerabilities. The current study evaluated behavioral measures of aggression and impulsivity as potential endophenotypes for BPD. Subjects with BPD (N = 127), a non cluster B personality disorder (OPD N = 122), or healthy volunteers (HV N = 112) completed self report and behavioral measures of aggression, motor impulsivity and cognitive impulsivity. Results showed that BPD subjects demonstrated more aggression and motor impulsivity than HV (but not OPD) subjects on behavioral tasks. In contrast, BPD subjects self-reported more impulsivity and aggression than either comparison group. Subsequent analyses showed that among BPD subjects behavioral aggression was associated with self-reported aggression, while behavioral and self-report impulsivity measures were more modestly associated. Overall I, the results provide partial support for the use of behavioral measures of aggression and motor impulsivity as endophenotypes for BPD, with stronger support for behavioral aggression measures as an endophenotype for aggression within BPD samples. (c) 2009 Elsevier Ltd. All rights reserved. C1 [McCloskey, Michael S.; Coccaro, Emil F.] Univ Chicago, Pritzker Sch Med, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [New, Antonia S.; Siever, Larry J.; Goodman, Marianne; Koenigsberg, Harold W.] Mt Sinai Sch Med, Psychiat Serv, Bronx, NY 10468 USA. [New, Antonia S.; Siever, Larry J.; Goodman, Marianne; Koenigsberg, Harold W.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Flory, Janine D.] CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. RP McCloskey, MS (reprint author), Univ Chicago, Pritzker Sch Med, Dept Psychiat & Behav Neurosci, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM mmcclosk@yoda.bsd.uchicago.edu FU national institute of health (NIH) [RO1 MH63875]; Veterans Administration (VA); Borderline Personality Disorder Research Foundation (Siever, Coccaro); VA (MERIT award, New) FX The authors would like to thank Bing Chen and Shauna Weinstein for their invaluable assistance with data management and analysis. Funding for this study was provided by the Borderline Personality Disorder Research Foundation (Siever, Coccaro), VA (MERIT award, New) and the NIH (RO1 MH63875, Siever). NR 97 TC 47 Z9 48 U1 4 U2 11 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 AUG PY 2009 VL 43 IS 12 BP 1036 EP 1048 DI 10.1016/j.jpsychires.2009.01.002 PG 13 WC Psychiatry SC Psychiatry GA 487JS UT WOS:000269269900006 PM 19232640 ER PT J AU Mroczek, DK Spiro, A Turiano, NA AF Mroczek, Daniel K. Spiro, Avron, III Turiano, Nicholas A. TI Do health behaviors explain the effect of neuroticism on mortality? Longitudinal findings from the VA Normative Aging Study SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article DE Neuroticism; Personality and health; Personality and mortality; Health behaviors; Smoking ID SEROTONIN TRANSPORTER GENE; NEGATIVE AFFECT; OLDER MEN; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; IMMUNE-SYSTEM; PERSONALITY; RISK; TRAITS; MECHANISMS AB Studies have shown that higher levels of neuroticism are associated with greater risk of mortality. Yet what accounts for this association? One major theoretical position holds that persons higher in neuroticism engage in poorer health behaviors, such as smoking and excessive drinking, thus leading to earlier death. We tested this hypothesis using 30-year mortality in 1788 men from the VA Normative Aging Study. Using proportional hazards (Cox) models we found that one health behavior, smoking, attenuated the effect of neuroticism on mortality by 40%. However, 60% remained unexplained, suggesting that the effects of other pathways (e.g., biological) also influence the relationship between neuroticism and mortality. (C) 2009 Elsevier Inc. All rights reserved. C1 [Mroczek, Daniel K.; Turiano, Nicholas A.] Purdue Univ, Dept Child Dev & Family Studies, W Lafayette, IN 47907 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Normat Aging Study, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Mroczek, DK (reprint author), Purdue Univ, Dept Child Dev & Family Studies, 1200 W State St, W Lafayette, IN 47907 USA. EM dmroczek@purdue.edu FU NIA NIH HHS [R01 AG018436, R01 AG018436-08, P01 AG020166] NR 71 TC 37 Z9 37 U1 5 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD AUG PY 2009 VL 43 IS 4 BP 653 EP 659 DI 10.1016/j.jrp.2009.03.016 PG 7 WC Psychology, Social SC Psychology GA 468EW UT WOS:000267798800014 PM 20161240 ER PT J AU Pratt, SR Kuller, L Talbott, EO McHugh-Pemu, K Buhari, AM Xu, XH AF Pratt, Sheila R. Kuller, Lewis Talbott, Evelyn O. McHugh-Pemu, Kathleen Buhari, Alhaji M. Xu, Xiaohui TI Prevalence of Hearing Loss in Black and White Elders: Results of the Cardiovascular Health Study SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE hearing loss; aging; gender; race ID OLDER-ADULTS; OTOACOUSTIC EMISSIONS; STRIA VASCULARIS; SEX-DIFFERENCES; POSTMENOPAUSAL WOMEN; CIGARETTE-SMOKING; ACOUSTIC TRAUMA; RISK-FACTORS; GUINEA-PIGS; AID USE AB Purpose: The goal of this study was to determine the impact of age, gender, and race on the prevalence and severity of hearing loss in elder adults, aged 72-96 years, after accounting for income, education, smoking, and clinical and subclinical cardiovascular disease. Methods: Air-conduction thresholds for standard and extended high-frequency pure-tones were obtained from a cohort of 548 (out of 717) elderly adults (ages 72-96 years) who were recruited during the Year 11 clinical visit (1999-2000) of the Cardiovascular Health Study (CHS) at the Pittsburgh, Pennsylvania site. Participant smoking, income, education, and cardiovascular disease histories were obtained from the CHS database and were included as factors. Results: Hearing loss was more common and more severe for the participants in their 80s than for those in their 70s-the men more than the women and the White participants more than the Black participants. The inclusion of education, income, smoking, and cardiovascular disease (clinical and subclinical) histories as factors did not substantively impact the overall results. Conclusion: Although the data reported in this article were cross-sectional and a cohort phenomenon might have been operational, they suggested that hearing loss is more substantive in the 8th than the 7th decade of life and that race and gender influence this decline in audition. Given the high prevalence in the aging population and the differences across groups, there is a clear need to understand the nature and causes of hearing loss across various groups in order to improve prevention and develop appropriate interventions. C1 [Pratt, Sheila R.] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. [Pratt, Sheila R.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Pratt, SR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. EM spratt@pitt.edu RI Pratt, Sheila/H-7139-2013; OI Talbott, Evelyn/0000-0002-5198-7939 FU NHLBI NIH HHS [N01 HC015103, N01 HC035129, N01-HC-85081, N01-HC-85083, N01-HC-85085, N01HC85082, N01 HC085086, N01-HC-85079, N01-HC-85080, N01-HC-85082, N01-HC-85084, N01-HC-85086, N01HC085082, N01HC85079, N01HC85086] NR 86 TC 15 Z9 18 U1 2 U2 6 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD AUG PY 2009 VL 52 IS 4 BP 973 EP 989 DI 10.1044/1092-4388(2009/08-0026) PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 476JB UT WOS:000268434900012 PM 19380605 ER PT J AU Bauman, WA Zhang, RL Morrison, N Spungen, AM AF Bauman, William A. Zhang, Run-Lin Morrison, Nancy Spungen, Ann M. TI Acute Suppression of Bone Turnover With Calcium Infusion in Persons With Spinal Cord Injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Immobilization; Tetraplegia; Paraplegia; Vitamin D; Calcium; Parathyroid hormone; N-telopeptide; Bone resorption; Osteoporosis ID VITAMIN-D SUPPLEMENTATION; LOWER-EXTREMITY FRACTURES; PARATHYROID-HORMONE; ANTICONVULSANT THERAPY; POSTMENOPAUSAL WOMEN; ELDERLY-WOMEN; D METABOLISM; AGE; DENSITY; MEN AB Background: Some people with chronic spinal cord injury (SCI) have low vitamin D levels and secondary hyperparathyroidism. Objective: To determine whether, and to what extent, an acute calcium infusion decreased levels of N-telopeptide (NTx), a marker of osteoclastic activity, in individuals with chronic SCI. Study Design: Case series. Subjects: Eight men with chronic SCI. A relatively low serum 25 hydroxyvitamin D concentration (25[ OH] D <= 20 ng/mL) and/or a high parathyroid hormone (PTH) (> 55 pg/mL) was a prerequisite for study inclusion. Methods: Calcium gluconate bolus 0.025 mmol elemental calcium/kg over 20 minutes followed by a constant infusion of 0.025 mmol/kg per hour for 6 hours was infused; blood samples were collected every 2 hours for measurement of serum total calcium, creatinine, NTx, and PTH. Results: All results are expressed as means (+/- SDs). Baseline serum 25-hydroxyvitamin D level was 14.5 +/- 3.5 ng/mL (range: 10.2-19.6 ng/mL); PTH, 70 +/- 25 pg/mL (range: 37-100 pg/mL); and NTx, 21 +/- 7 nM bone collagen equivalents (BCE) (range: 14-34 nM). At 2, 4, and 6 hours after the calcium infusion, serum calcium rose from 9.3 +/- 0.2 to 10.8 +/- 0.9, 10.5 +/- 0.8, and 10.6 +/- 0.6 mg/d; PTH was suppressed from 70 +/- 25 pg/mL to 18 +/- 12, 16 +/- 9, and 15 +/- 9 pg/mL, respectively; NTx fell from 21 +/- 8 nM BCE to 17 +/- 5, 12 +/- 4, and 12 +/- 3 nM BCE, respectively. Conclusions: Serum NTx is a marker for bone collagen catabolism, and its reduction suggests that bone turnover was decreased. A relative deficiency of vitamin D associated with chronically elevated levels of PTH would be expected to increase bone turnover and to worsen the bone loss associated with immobilization. C1 [Bauman, William A.] James J Peters Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Med & Res Serv, Bronx, NY 10468 USA. [Bauman, William A.; Zhang, Run-Lin; Spungen, Ann M.] James J Peters Med Ctr, Vet Affairs Rehabil Res & Dev Ctr Excellence, Bronx, NY 10468 USA. [Bauman, William A.; Zhang, Run-Lin; Spungen, Ann M.] Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Zhang, Run-Lin; Spungen, Ann M.] Mt Sinai Med Ctr, Dept Rehabil Med, New York, NY 10029 USA. RP Bauman, WA (reprint author), James J Peters Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Med & Res Serv, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov FU Department of Veterans Affairs; Center of Excellence for the Medical Consequences of Spinal Cord Injury [B4162C]; United Spinal Association; James J. Peters Veterans Affairs Medical Center, Bronx, NY FX This work was supported by the Department of Veterans Affairs Rehabilitation Research and Development (RR&D) Service, the Center of Excellence for the Medical Consequences of Spinal Cord Injury (B4162C), United Spinal Association, and the James J. Peters Veterans Affairs Medical Center, Bronx, NY. NR 36 TC 8 Z9 9 U1 0 U2 0 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 AUG PY 2009 VL 32 IS 4 BP 398 EP 403 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA V16HX UT WOS:000207861800005 PM 19777860 ER PT J AU Poon, BB Eddington, DK Noel, V Colburn, HS AF Poon, Becky B. Eddington, Donald K. Noel, Victor Colburn, H. Steven TI Sensitivity to interaural time difference with bilateral cochlear implants: Development over time and effect of interaural electrode spacing SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MINIMUM AUDIBLE ANGLE; SPEECH-PERCEPTION; BINAURAL INTERACTION; SOUND LOCALIZATION; NOISE; DISCRIMINATION; FREQUENCY; CHILDREN; RECOGNITION; THRESHOLDS AB Sensitivity to interaural time difference (ITD) in constant-amplitude pulse trains was measured in four sequentially implanted bilateral cochlear implant (CI) subjects. The sensitivity measurements were made as a function of time beginning directly after the second ear was implanted, continued for periods of months before subjects began wearing bilateral sound processors, and extended for months while the subjects used bilateral sound processors in day-to-day listening. Measurements were also made as a function of the relative position of the left/right electrodes. The two subjects with the shortest duration of binaural deprivation before implantation demonstrated ITD sensitivity soon after second-ear implantation (before receiving the second sound processor), while the other two did not demonstrate sensitivity until after months of daily experience using bilateral processors. The interaural mismatch in electrode position required to decrease ITD sensitivity by a factor of 2 (half-width) for CI subjects was five times greater than the half-width for interaural carrier-frequency disparity in normal-hearing subjects listening to sinusoidally amplitude-modulated high-frequency tones. This large half-width is likely to contribute to poor binaural performance in Cl users, especially in environments with multiple broadband sound sources. (C) 2009 Acoustical Society of America. [DOI: 10.1121/1.3158821] C1 [Poon, Becky B.; Eddington, Donald K.; Noel, Victor] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Poon, Becky B.; Eddington, Donald K.] MIT, Speech & Hearing Biosci & Technol Program, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Eddington, Donald K.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Colburn, H. Steven] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Poon, BB (reprint author), Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. FU NIH [R01 DC005775, R01 DC007528, T32 DC00038] FX We are especially indebted to the research subjects for their generous contribution of time and effort. We thank Bertrand Delgutte and two anonymous reviewers for valuable comments on the manuscript and recognize the support of Advanced Bionics Corp. for their donation of the second-ear implant systems. NIH Grant Nos. R01 DC005775 and R01 DC007528 provided major support. B.B.P. was partially supported by NIH Grant No. T32 DC00038. NR 54 TC 41 Z9 42 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD AUG PY 2009 VL 126 IS 2 BP 806 EP 815 DI 10.1121/1.3158821 PG 10 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 483XO UT WOS:000269006800031 PM 19640045 ER PT J AU Herzog, DB Eddy, KT AF Herzog, David B. Eddy, Kamryn T. TI Eating Disorders: What Are the Risks? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 [Herzog, David B.; Eddy, Kamryn T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herzog, David B.; Eddy, Kamryn T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Herzog, DB (reprint author), Massachusetts Gen Hosp, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM dherzog@partners.org FU NIMH NIH HHS [R01 MH038333-09] NR 9 TC 3 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2009 VL 48 IS 8 BP 782 EP 783 DI 10.1097/CHI.0b013e3181aa03d7 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 477UW UT WOS:000268545400003 PM 19628994 ER PT J AU Danforth, N AF Danforth, Nicole TI Untitled SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Danforth, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 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 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2009 VL 48 IS 8 BP 864 EP 864 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 477UW UT WOS:000268545400015 ER PT J AU Ginsburg, R AF Ginsburg, Richard TI Warrior Girls: Protecting Our Daughters Against the Injury Epidemic in Women's Sports. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Ginsburg, Richard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Ginsburg, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM rginsburg@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2009 VL 48 IS 8 BP 867 EP 868 DI 10.1097/01.CHI.0000346431.16377.42 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 477UW UT WOS:000268545400017 ER PT J AU Elston, DM Stratman, E Johnson-Jahangir, H Watson, A Swiggum, S Hanke, CW AF Elston, Dirk M. Stratman, Erik Johnson-Jahangir, Hillary Watson, Alice Swiggum, Susan Hanke, C. William TI Patient safety Part II. Opportunities for improvement in patient safety SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE medical errors; morbidity; mortality; office-based; patient safety; quality; surgery ID SUN PROTECTION BEHAVIORS; PERFORMANCE-MEASUREMENT; PROCEDURAL SIMULATION; MEDICAL-EDUCATION; ADVERSE EVENTS; CURRICULUM; HEALTH; ERROR; CARE; COMPETENCES AB The quality movement in medicine has prompted a shift from a "name, shame, blame" approach to medical errors to one in which each error is regarded as an opportunity to prevent future patient harm. This new culture of patient safety requires, the involvement of all members of the health care team and learned skill sets related to quality improvement. A root cause analysis identifies the Sources of medical errors, allowing system changes that reduce the risk. In large organizations, sentinel events and signals prompt chart reviews and reduce the reliance on Voluntary reporting. Failure mode analysis prompts the development of safety nets in the case of a system failure. The second part of this two-part series on patient safety examines how the culture of patient safety is taught, how medical errors and threats to patient safety can be identified, and how engineering tools can be Used to improve patient care. It also examines efforts to measure clinical effectiveness and Outcomes in the practice of medicine. (J Am Acad Dermatol 2009;61:193-205.) C1 [Elston, Dirk M.] Geisinger Med Ctr, Dept Dermatol, Danville, PA 17822 USA. [Elston, Dirk M.] Geisinger Med Ctr, Dept Pathol, Danville, PA 17822 USA. [Stratman, Erik] Marshfield Clin Fdn Med Res & Educ, Dept Dermatol, Marshfield, WI USA. [Johnson-Jahangir, Hillary] Columbia Univ, Med Ctr, New York, NY USA. [Watson, Alice] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Swiggum, Susan] Univ Ottawa, Canadian Med Protect Assoc, Ottawa, ON K1N 6N5, Canada. [Swiggum, Susan] Univ Ottawa, Dept Med, Div Dermatol, Ottawa, ON K1N 6N5, Canada. RP Elston, DM (reprint author), Geisinger Med Ctr, Dept Dermatol, 100 N Acad Ave, Danville, PA 17822 USA. EM dmelston@geisinger.edu NR 52 TC 6 Z9 6 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2009 VL 61 IS 2 BP 193 EP 205 DI 10.1016/j.jaad.2009.04.055 PG 13 WC Dermatology SC Dermatology GA 480ZH UT WOS:000268775500002 PM 19615536 ER PT J AU Weinstock, MA Lee, KC Chren, MM Marcolivio, K AF Weinstock, Martin A. Lee, Kachiu C. Chren, Mary-Margaret Marcolivio, Kimberly CA VATTC Trial Grp TI Quality of life in the actinic neoplasia syndrome: The VA Topical Tretinoin Chemoprevention (VATTC) Trial SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; SUN SENSITIVITY; INDEX; PREDICTORS; CARCINOMA; MORTALITY; DISEASES; THERAPY; SCALE AB Background: Keratinocyte carcinomas (KCs) are the most common malignancies of the skin. As lesions have a low mortality rate, understanding quality-of-life (QoL) factors is necessary in their management. Objective. To assess QoL and associated patient characteristics in those with a history of keratinocyte carcinomas. Methods. We conducted a cross-sectional Study of veterans with a history of KCs enrolled in a randomized controlled trial for chemoprevention of keratinocyte carcinomas. Study dermatologists Counted actinic keratoses (AKs) and assessed for skin photodamage. QoL was assessed using Skindex-29 and KC-specific questions. Demographics were self-reported. Results: Participants (n = 931) enrolled at 5 clinical sites had worse QoL on all subscales (emotions, functioning, and symptoms) compared to a reference group of patients without skin disease. Univariate analysis demonstrated worse QoL associated with higher AK count, past 5-fluorouracil (5-FU) use, and greater Sun sensitivity. Multivariate analysis demonstrated that higher AK count and past 5-FU use were independently related to diminished QoL. Higher comorbidities showed modest associations on the symptoms and functioning subscales. Number of previous KCs was not independently associated with any QoL differences. Limitations: Study Population may not be generalizable to the general population. Counting of AKs is of limited reliability. Previous 5-FU use is self reported. Conclusions: A history Of ever use Of 5-FU and present AKs was strongly associated with worse QoL. We find it more useful to consider these patients as having the chronic condition "actinic neoplasia syndrome," whose burden may be best measured by factors other than their history of KCs. (J Am Acad Dermatol 2009;61:207-15.) C1 [Weinstock, Martin A.; Lee, Kachiu C.; Marcolivio, Kimberly] Vet Adm Med Ctr, Dermatoepidemiol Unit, Providence, RI 02908 USA. [Weinstock, Martin A.] Rhode Isl Hosp, Dept Dermatol, Providence, RI USA. [Weinstock, Martin A.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Lee, Kachiu C.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dermatol Serv, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. RP Weinstock, MA (reprint author), Vet Adm Med Ctr, Dermatoepidemiol Unit, 830 Chalkstone Ave,Med Serv 111D, Providence, RI 02908 USA. EM maw@brown.edu FU VA Cooperative Studies Program [402]; Office of Research and Development, Department of Veterans Affairs; American Cancer Society; OrthoNeutrogena division of Ortho-McNeil Pharmaceutical, Inc.; National Institutes of Health [R01CA106592, R01CA106807, R25CA087972, R01AR49342]; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [K24-AR052667] FX This trial was supported by the VA Cooperative Studies Program (CSP#402), Office of Research and Development, Department of Veterans Affairs. Additional support was received from the American Cancer Society. The study medication was donated by the OrthoNeutrogena division of Ortho-McNeil Pharmaceutical, Inc. Dr Weinstock is also supported by grants R01CA106592, R01CA106807, R25CA087972, and R01AR49342 from the National Institutes of Health. Dr Chren's work is supported by a Midcareer Investigator Award (K24-AR052667) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. NR 22 TC 28 Z9 28 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2009 VL 61 IS 2 BP 207 EP 215 DI 10.1016/j.jaad.2009.02.022 PG 9 WC Dermatology SC Dermatology GA 480ZH UT WOS:000268775500003 PM 19398145 ER PT J AU Nazarian, RM Van Cott, EM Zembowicz, A Duncan, LM AF Nazarian, Rosalynn M. Van Cott, Elizabeth M. Zembowicz, Artur Duncan, Lyn M. TI Warfarin-induced skin necrosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review DE anticoagulant; coumarin; warfarin; hypercoagulable; protein C; therapeutic complication; thrombosis; thrombotic vasculopathy; warfarin-induced skin necrosis ID HEPARIN-INDUCED THROMBOCYTOPENIA; VENOUS LIMB GANGRENE; PROTEIN-S DEFICIENCY; PATIENT; PATHOGENESIS AB Warfarin-induced skin necrosis is a rare complication of anticoagulant therapy with a high associated morbidity and mortality requiring immediate drug cessation. Cutaneous findings include petechiae that progress to ecchymoses and hemorrhagic bullae. Characteristic dermatopathological findings are diffuse dermal microthrombi with endothelial cell damage and red cell extravasation with progression to full-thickness coagulative necrosis. The lesions of warfarin-induced skin necrosis may be difficult to differentiate from mimickers, but skin biopsy in conjunction with careful consideration of the clinical history, including time of onset, cutaneous distribution of the lesions, and laboratory findings, are essential for prompt diagnosis and patient treatment. Herein, we review the clinical and histologic features helpful for differentiating warfarin-induced skin necrosis and report a case illustrative of the diagnostic difficulty that may at times be encountered in clinical practice. (J Am Acad Dermatol 2009;61:325-32.) C1 [Nazarian, Rosalynn M.; Van Cott, Elizabeth M.; Duncan, Lyn M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nazarian, Rosalynn M.; Van Cott, Elizabeth M.; Duncan, Lyn M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Nazarian, Rosalynn M.; Van Cott, Elizabeth M.; Duncan, Lyn M.] Harvard Univ, Sch Med, Dermatopathol Unit, Boston, MA 02115 USA. [Zembowicz, Artur] Lahey Clin Fdn, Dept Pathol, Burlington, MA USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WRN 827, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 36 TC 38 Z9 44 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2009 VL 61 IS 2 BP 325 EP 332 DI 10.1016/j.jaad.2008.12.039 PG 8 WC Dermatology SC Dermatology GA 480ZH UT WOS:000268775500018 PM 19615543 ER PT J AU Smith, BD Arthur, DW Buchholz, TA Haffty, BG Hahn, CA Hardenbergh, PH Julian, TB Marks, LB Todor, DA Vicini, FA Whelan, TJ White, J Wo, JY Harris, JR AF Smith, Benjamin D. Arthur, Douglas W. Buchholz, Thomas A. Haffty, Bruce G. Hahn, Carol A. Hardenbergh, Patricia H. Julian, Thomas B. Marks, Lawrence B. Todor, Dorin A. Vicini, Frank A. Whelan, Timothy J. White, Julia Wo, Jennifer Y. Harris, Jay R. TI Accelerated Partial Breast Irradiation Consensus Statement from the American Society for Radiation Oncology (ASTRO) SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID BRACHYTHERAPY REGISTRY TRIAL; MAMMOSITE BALLOON BRACHYTHERAPY; INITIAL CLINICAL-EXPERIENCE; SURGICAL ADJUVANT BREAST; DOSE-RATE BRACHYTHERAPY; WHOLE-BREAST; INTERSTITIAL BRACHYTHERAPY; RANDOMIZED-TRIAL; TUMOR-BED; CONSERVING SURGERY C1 [Smith, Benjamin D.] Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. [Arthur, Douglas W.; Todor, Dorin A.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. [Smith, Benjamin D.; Buchholz, Thomas A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Haffty, Bruce G.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Hahn, Carol A.] Duke Univ, Sch Med, Durham, NC USA. [Marks, Lawrence B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Vicini, Frank A.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Whelan, Timothy J.] Juravinski Canc Ctr, Hamilton, ON, Canada. [White, Julia] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Harris, Jay R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Harris, Jay R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hardenbergh, Patricia H.] Shaw Reg Canc Ctr, Vail, CO USA. [Julian, Thomas B.] Allegheny Gen Hosp, Dept Human Oncol, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. [Wo, Jennifer Y.] Harvard Radiat Oncol Residency Program, Boston, MA USA. RP Smith, BD (reprint author), 2200 Bergquist Dr,Ste 1, Lackland AFB, TX 78236 USA. RI White, Julia/J-6336-2014; Whelan, Timothy/D-3185-2017; OI Smith, Benjamin/0000-0001-7866-1093 NR 41 TC 58 Z9 58 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2009 VL 209 IS 2 BP 269 EP 277 DI 10.1016/j.jamcollsurg.2009.02.066 PG 9 WC Surgery SC Surgery GA 480PC UT WOS:000268747300015 PM 19632605 ER PT J AU Vitolins, MZ Anderson, AM Delahanty, L Raynor, H Miller, GD Mobley, C Reeves, R Yamamoto, M Champagne, C Wing, RR Mayer-Davis, E AF Vitolins, Mara Z. Anderson, Andrea M. Delahanty, Linda Raynor, Hollie Miller, Gary D. Mobley, Connie Reeves, Rebecca Yamamoto, Monica Champagne, Catherine Wing, Rena R. Mayer-Davis, Elizabeth CA Look Ahead Res Grp TI Action for Health in Diabetes (Look AHEAD) Trial: Baseline Evaluation of Selected Nutrients and Food Group Intake SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NUTRITION PRINCIPLES; NONDIABETIC PATIENTS; VEGETABLE INTAKE; FRUIT; DIET; RECOMMENDATIONS; COMPLICATIONS; PREVENTION; DISEASE; ADULTS AB Background Little has been reported regarding food and nutrient intake in individuals diagnosed with type 2 diabetes, and most reports have been based on findings in select groups or individuals who self-reported having diabetes. Objective To describe the baseline food and nutrient intake of the Look AHEAD (Action for Health in Diabetes) trial participants, compare participant intake to national guidelines, and describe demographic and health characteristics associated with food group consumption. Methods The Look AHEAD trial is evaluating the effects of a lifestyle intervention (calorie control and increased physical activity for weight loss) compared with diabetes support and education on long-term cardiovascular and other health outcomes. Participants are 45 to 75 years old, overweight or obese (body mass index [BMI] >= 25), and have type 2 diabetes. In this cross-sectional analysis, baseline food consumption was assessed by food frequency questionnaire from 2,757 participants between September 2000 and December 2003. Statistical analysis Descriptive statistics were used to summarize intake by demographic characteristics. Kruskal-Wallis tests assessed univariate effects of characteristics on consumption. Multiple linear regression models assessed factors predictive of intake. Least square estimates were based on final models, and logistic regression determined factors predictive of recommended intake. Results Ninety-three percent of the participants exceeded the recommended percentage of calories from fat, 85% exceeded the saturated fat recommendation, and 92% consumed too much sodium. Also, fewer than half met the minimum recommended servings of fruit, vegetables, dairy, and grains. Conclusions These participants with pre-existing diabetes did not meet recommended food and nutrition guidelines. These overweight adults diagnosed with diabetes are exceeding recommended intake of fat, saturated fats, and sodium, which may contribute to increasing their risk of cardiovascular disease and other chronic diseases. J Ant Diet Assoc. 2009,109:1367-1375. C1 [Vitolins, Mara Z.] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27104 USA. [Anderson, Andrea M.] Wake Forest Univ, Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27104 USA. [Delahanty, Linda] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raynor, Hollie] Univ Tennessee, Dept Nutr, Knoxville, TN 37996 USA. [Miller, Gary D.] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27104 USA. [Mobley, Connie] Univ Nevada, Las Vegas Sch Dent Med, Dept Profess Studies, Las Vegas, NV 89154 USA. [Reeves, Rebecca] Baylor Coll Med, Houston, TX 77030 USA. [Yamamoto, Monica] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Champagne, Catherine] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Wing, Rena R.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Mayer-Davis, Elizabeth] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. RP Vitolins, MZ (reprint author), Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27104 USA. EM mvitolin@wfubmc.edu FU National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01-RR-02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center [M01-RR-01066]; University of Colorado Health Sciences Center General Clinical Research Center and Clinical Nutrition Research Unit [M01 RR00051, P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR00211-40]; University of Pittsburgh General Clinical Research Center [M01 RR000056 44]; NIH [DK 046204]; University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs FX Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01-RR-02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01-RR-01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01 RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR00211-40); the University of Pittsburgh General Clinical Research Center (M01 RR000056 44) and NIH grant (DK 046204); and the University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs. NR 28 TC 35 Z9 35 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 2009 VL 109 IS 8 BP 1367 EP 1375 DI 10.1016/j.jada.2009.05.016 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 480AD UT WOS:000268702800009 PM 19631042 ER PT J AU Framson, C Kristal, AR Schenk, JM Littman, AJ Zeliadt, S Benitez, D AF Framson, Celia Kristal, Alan R. Schenk, Jeannette M. Littman, Alyson J. Zeliadt, Steve Benitez, Denise TI Development and Validation of the Mindful Eating Questionnaire SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID SELF-REPORT; MEDITATION; SCALE AB "Mindful eating" describes a nonjudgmental awareness of physical and emotional sensations associated with eating. This article reports the development of a mindful eating questionnaire (MEQ) to support rigorous scientific inquiry into this concept. An item pool was developed based on hypothesized domains of mindful eating. A cross-sectional survey examined associations of MEQ scores with demographic and health-related characteristics. The MEQ was distributed to seven convenience samples between January and May 2007, with an overall response rate of 62% (n = 303). Participants were mostly women (81%) and white (90%), and had a mean age of 42 +/- 14.4 years (range 18 to 80 years). Exploratory factor analysis was used to identify factors, which were defined as the mean of items scored one to four, where four indicated higher mindfulness; the mean of all factors was the summary MEQ score. Multiple regression analysis was used to measure associations of demographic characteristics, obesity, yoga practice, and physical activity with MEQ scores. Domains of the final 28-item questionnaire were: disinhibition, awareness, external cues, emotional response, and distraction. The mean MEQ score was 2.92 +/- 0.37, with a reliability (Chronbach's alpha) of .64. The covariate-adjusted MEQ score was inversely associated with body mass index (3.02 for body mass index <25 vs 2.54 for body mass index >30, P<0.001). Yoga practice, but neither walking nor moderate/intense physical activity, was associated with higher MEQ score. In this study sample, the MEQ had good measurement characteristics. Its negative association with body mass index and positive association with yoga provide evidence of construct validity. Further evaluation in more diverse populations is warranted. J Am Diet Assoc. 2009;109:1439-1444. C1 [Framson, Celia] Seattle Childrens Hosp, Seattle, WA USA. [Framson, Celia; Kristal, Alan R.] Univ Washington, Interdisciplinary Program Nutr Sci, Seattle, WA 98195 USA. [Kristal, Alan R.; Schenk, Jeannette M.; Littman, Alyson J.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Schenk, Jeannette M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Littman, Alyson J.] Epidemiol Res & Informat Ctr, Dept Vet Affairs, Seattle, WA USA. [Zeliadt, Steve] VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Benitez, Denise] Seattle Yoga Arts, Seattle, WA USA. RP Kristal, AR (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4 B402,POB 19024, Seattle, WA 98109 USA. EM akristal@fhcre.org OI Kristal, Alan/0000-0002-7329-1617 FU institutional new development programs at the Fred Hutchinson Cancer Research Center FX Funding for this study was provided by institutional new development programs at the Fred Hutchinson Cancer Research Center, through the Nutrition Assessment Shared Resource and Cancer Prevention Program. NR 18 TC 54 Z9 55 U1 4 U2 27 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 2009 VL 109 IS 8 BP 1439 EP 1444 DI 10.1016/j.jada.2009.05.006 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 480AD UT WOS:000268702800020 PM 19631053 ER PT J AU Huang, AJ Subak, LL Thom, DH Van den Eeden, SK Ragins, AI Kuppermann, M Shen, H Brown, JS AF Huang, Alison J. Subak, Leslee L. Thom, David H. Van den Eeden, Stephen K. Ragins, Arona I. Kuppermann, Miriam Shen, Hui Brown, Jeanette S. TI Sexual Function and Aging in Racially and Ethnically Diverse Women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Association-for-Cancer-Education CY OCT 12-14, 2006 CL San Diego, CA SP Amer Assoc Canc Educ DE female sexual function; aging; race; ethnicity; sexual activity ID SELF-RATED HEALTH; URINARY-INCONTINENCE; POSTMENOPAUSAL WOMEN; OLDER WOMEN; DYSFUNCTION; HORMONES; IMPACT; CARE AB OBJECTIVES To examine factors influencing sexual activity and functioning in racially and ethnically diverse middle-aged and older women. DESIGN Cross-sectional cohort study. SETTING Integrated healthcare delivery system. PARTICIPANTS One thousand nine hundred seventy-seven women aged 45 to 80. MEASUREMENTS Self-administered questionnaires assessed sexual desire, activity, satisfaction, and problems. RESULTS Of the 1,977 participants (876 white, 388 African American, 347 Latina, and 351 Asian women), 43% reported at least moderate sexual desire, and 60% had been sexually active in the previous 3 months. Half of sexually active participants (n=969) described their overall sexual satisfaction as moderate to high. Among sexually inactive women, the most common reason for inactivity was lack of interest in sex (39%), followed by lack of a partner (36%), physical problem of partner (23%), and lack of interest by partner (11%); only 9% were inactive because of personal physical problems. In multivariable analysis, African-American women were more likely than white women to report at least moderate desire (odds ratio (OR)=1.65, 95% confidence interval (CI)=1.25-2.17) but less likely to report weekly sexual activity (OR=0.68, 95% CI=0.48-0.96); sexually active Latina women were more likely than white women to report at least moderate sexual satisfaction (OR=1.75, 95% CI=1.20-2.55). CONCLUSION A substantial proportion of community-dwelling women remain interested and engaged in sexual activity into older age. Lack of a partner capable of or interested in sex may contribute more to sexual inactivity than personal health problems in this population. Racial and ethnic differences in self-reported sexual desire, activity, and satisfaction may influence discussions about sexual difficulties in middle-aged and older women. C1 [Huang, Alison J.; Shen, Hui] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Huang, Alison J.; Kuppermann, Miriam] Univ Calif San Francisco, Med Effectiveness Res Ctr Diverse Populat, San Francisco, CA 94143 USA. [Subak, Leslee L.; Kuppermann, Miriam; Brown, Jeanette S.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Subak, Leslee L.; Kuppermann, Miriam; Brown, Jeanette S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Subak, Leslee L.; Brown, Jeanette S.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Thom, David H.] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Van den Eeden, Stephen K.; Ragins, Arona I.] Kaiser Permanente, Div Res, Oakland, CA USA. [Shen, Hui] San Francisco VA Med Ctr, San Francisco, CA USA. RP Huang, AJ (reprint author), 1635 Div St,Ste 600, San Francisco, CA 94115 USA. EM ahuang@ucsfmed.org FU NCRR NIH HHS [KL2 RR024130]; NIDDK NIH HHS [DK53335, P50 DK064538, P50 DK064538-067114, R01 DK053335, K24 DK080775] NR 25 TC 28 Z9 32 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2009 VL 57 IS 8 BP 1362 EP 1368 DI 10.1111/j.1532-5415.2009.02353.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 477QH UT WOS:000268533100004 PM 19558473 ER PT J AU Bean-Mayberry, B Yano, EM Mor, MK Bayliss, NK Xu, XY Fine, MJ AF Bean-Mayberry, Bevanne Yano, Elizabeth M. Mor, Maria K. Bayliss, Nichole K. Xu, Xiangyan Fine, Michael J. TI Does Sex Influence Immunization Status for Influenza and Pneumonia in Older Veterans? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE immunizations; preventive health services; women; veterans; elderly ID WOMENS HEALTH-CARE; ELDERLY-PEOPLE; VACCINATION; QUALITY; SYSTEM; INNOVATION; DELIVERY; CLINICS AB OBJECTIVES To compare the prevalence of influenza and pneumococcal immunization rates according to sex in a national sample of older veterans in the Department of Veterans Affairs (VA) healthcare system. DESIGN Retrospective, cross-sectional. SETTING VA healthcare system. PARTICIPANTS Current VA healthcare system users aged 65 and older eligible for immunization in fiscal years 2001 to 2003 (N=48,424 patient records). MEASUREMENTS Generalized estimating equations were performed to analyze combined chart review and administrative data to determine effect of sex on receipt of influenza and pneumococcal immunizations. RESULTS Unadjusted immunization rates were higher for men than women for influenza (73% vs 69%) and pneumococcal (87% vs 83%) vaccine. Adjusting for demographics, clinical comorbidities, use, and region, women had significantly lower odds of influenza (odds ratio (OR)=0.85, 95% confidence interval (CI=0.79-0.92) and pneumococcal (OR=0.77, 95% CI=0.71-0.84) immunization. CONCLUSION Older female veterans have lower rates of immunization than older male veterans in VA settings. Although VA remains above community levels for immunization, older female veterans will benefit from targeted efforts to increase immunization prevalence. C1 [Bean-Mayberry, Bevanne] VA Greater Angeles HSR&D Ctr Excellence, Sepulveda Ambulatory Care Ctr & Nursing Home, Ctr Study Hlth Care Provider Behav, Sepulveda, CA 91343 USA. [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, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Mor, Maria K.; Bayliss, Nichole K.; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Bayliss, Nichole K.] Univ Pittsburgh, Dept Sociol, Pittsburgh, PA USA. [Xu, Xiangyan] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA USA. [Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Bean-Mayberry, B (reprint author), VA Greater Angeles HSR&D Ctr Excellence, Sepulveda Ambulatory Care Ctr & Nursing Home, Ctr Study Hlth Care Provider Behav, 16111 Plummer St, Sepulveda, CA 91343 USA. EM bevanne.bean-mayberry@va.gov FU VA Career Development Award; VA Health Services Research and Development Services (HSR&D) Research Career Development Award [RCD-02-039]; National Institutes of Allergy and Infectious Disease [K24-AIO1769]; VA HSR&D Research Career Scientist Award [RCS 05-195]; VA Investigator Initiated Research [IIR 04-036] FX Conflict of Interest: All of the authors are employed by the VA. This work is supported by a VA Career Development Award to the principal investigator (Bean-Mayberry). None of the authors have a personal or potential conflict of interest in the design, analyses, interpretation of results, or the development of this research. Dr. Bean-Mayberry is funded by a VA Health Services Research and Development Services (HSR&D) Research Career Development Award (RCD-02-039), Dr. Fine was supported in part by a Mid-Career Development Award (K24-AIO1769) from the National Institutes of Allergy and Infectious Disease, and Dr. Yano was supported in part by a VA HSR&D Research Career Scientist Award (RCS 05-195) and in part by a VA Investigator Initiated Research Grant (IIR 04-036). NR 30 TC 14 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2009 VL 57 IS 8 BP 1427 EP 1432 DI 10.1111/j.1532-5415.2009.02316.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 477QH UT WOS:000268533100012 PM 19515114 ER PT J AU Federman, AD Sano, M Wolf, MS Siu, AL Halm, EA AF Federman, Alex D. Sano, Mary Wolf, Michael S. Siu, Albert L. Halm, Ethan A. TI Health Literacy and Cognitive Performance in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE health literacy; cognition; older adults ID MENTAL-STATE-EXAMINATION; VERBAL FLUENCY; IMPAIRMENT; PREVALENCE; MORTALITY; EDUCATION; EXAMPLE; DISEASE; AGE AB OBJECTIVES To study the relationship between health literacy and memory and verbal fluency in older adults. DESIGN Cross-sectional cohort. SETTING Twenty senior centers and apartment buildings in New York, New York. PARTICIPANTS Independently living, English- and Spanish-speaking adults aged 60 and older (N=414). MEASUREMENTS Health literacy was measured using the Short Test of Functional Health Literacy in Adults (S-TOFHLA). The associations between S-TOFHLA scores and immediate and delayed recall (Wechsler Memory Scale II), verbal fluency (Animal Naming), and global cognitive function (Mini-Mental State Examination, MMSE) were modeled using multivariable logistic and linear regression. RESULTS Health literacy was inadequate in 24.3% of participants. Impairment of immediate recall occurred in 20.4%; delayed recall, 15.0%; verbal fluency, 9.9%; and MMSE, 17.4%. Abnormal cognitive function was strongly associated with inadequate health literacy: immediate recall (adjusted odds ratio (AOR)=3.44, 95% confidence interval (CI)=1.71-6.94, P <.001), delayed recall (AOR=3.48, 95% CI=1.58-7.67, P=.002), and verbal fluency (AOR=3.47, 95% CI=1.44-8.38, P=.006). These associations persisted in subgroups that excluded individuals with normal age-adjusted MMSE scores. CONCLUSION Memory and verbal fluency are strongly associated with health literacy, independently of education and health status, even in those with subtle cognitive dysfunction. Reducing the cognitive burden of health information might mitigate the detrimental effects of limited health literacy in older adults. Research that examines the effect of materials modified to older adults' cognitive limitations on health literacy and health outcomes is needed. C1 [Federman, Alex D.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Siu, Albert L.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. [Sano, Mary; Siu, Albert L.] Bronx Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Wolf, Michael S.] Northwestern Univ, Hlth Literacy & Learning Program, Div Gen Internal Med, Chicago, IL 60611 USA. [Halm, Ethan A.] Univ Texas Dallas, Div Gen Internal Med, Dallas, TX 75230 USA. RP Federman, AD (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, 1 Gustave L Levy Pl,Box 1087, New York, NY 10029 USA. EM alex.federman@mssm.edu FU National Institute on Aging [1K23AG028955-01]; Robert Wood Johnson Generalist Physician Faculty Scholars Program; Veterans Affairs Health Services Research and Development Service; Mount Sinai School of Medicine Alzheimer's Disease Research Center [NIH AG0051318] FX This study was supported by a Paul B. Beeson Career Development Award in Aging from the National Institute on Aging (Dr. Federman, 1K23AG028955-01). Dr. Federman received additional support from the Robert Wood Johnson Generalist Physician Faculty Scholars Program during the period of data collection. Dr. Siu is supported by a Mid-career Investigator Award in Patient-oriented Research from the National Institute on Aging. Additional support was provided by the Veterans Affairs Health Services Research and Development Service to the Bronx Veterans Affairs Medical Center Program of Research on Serious Physical and Mental Illness and the Mount Sinai School of Medicine Alzheimer's Disease Research Center (NIH AG0051318). NR 30 TC 51 Z9 53 U1 2 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2009 VL 57 IS 8 BP 1475 EP 1480 DI 10.1111/j.1532-5415.2009.02347.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 477QH UT WOS:000268533100020 PM 19515101 ER PT J AU Zhang, Y Ficarro, SB Li, SJ Marto, JA AF Zhang, Yi Ficarro, Scott B. Li, Shaojuan Marto, Jarrod A. TI Optimized Orbitrap HCD for Quantitative Analysis of Phosphopeptides SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID TRAP MASS-SPECTROMETRY; FRAGMENTATION; DISSOCIATION; PROTEINS; PROTEOME; LEUKEMIA; GENOME; CELLS AB Despite the tremendous commercial success of radio frequency quadrupole ion traps for bottom-up proteomics studies, there is growing evidence that peptides decorated with labile post-translational modifications are less amenable to low-energy, resonate excitation MS/MS analysis. Moreover, multiplexed stable isotope reagents designed for MS/MS-based quantification of peptides rely on accurate and robust detection of low-mass fragments for all precursors. Collectively these observations Suggest that beam-type or tandem in-space MS/MS measurements, such as that available oil traditional triple quadrupole mass spectrometers, may provide beneficial figures of merit for quantitative proteomics analyses. The recent introduction of a multipole collision cell adjacent to all Orbitrap mass analyzer provides for higher energy collisionally activated dissociation (HCD) with efficient capture of fragment ions over a wide mass range. Here we describe optimization of various instrument and post-acquisition parameters that collectively provide for quantification of iTRAQ-labeled phosphorylated peptides isolated from complex cell lysates. Peptides spanning a concentration dynamic range of 100:1 are readily quantified. Our results indicate that appropriate parameterization of collision energy as a function of precursor m/z and z provides for optimal performance in terms of peptide identification and relative quantification by iTRAQ. Using this approach, we readily identify activated signaling pathways downstream of oncogenic Mutants of Flt-3 kinase in a model system of human myeloid leukemia. (J Am Soc Mass Spectrom 2009, 20, 1425-1434) (C) 2009 American Society for Mass Spectrometry C1 [Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst,Blais Prote Ctr, Boston, MA 02115 USA. RP Marto, JA (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu FU Dana-Farber Cancer FX The authors thank Dr. Michael Senko at ThermoFisher Scientific for providing ITCL code and guidance in customization of HCD collision energy parameters. The authors also thank Eric Sinith for helpful discussion and preparation of the figures, and Manor Askenazi for assistance with data analysis. The authors acknowledge support for this work by the Dana-Farber Cancer NR 30 TC 74 Z9 76 U1 9 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD AUG PY 2009 VL 20 IS 8 BP 1425 EP 1434 DI 10.1016/j.jasms.2009.03.019 PG 10 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 480MV UT WOS:000268739900006 PM 19403316 ER PT J AU Melamed, ML Thadhani, R AF Melamed, Michal L. Thadhani, Ravi TI Low Calcidiol Levels and Coronary Artery Calcification: True, True, and Related? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID VITAMIN-D LEVELS; VASCULAR-DISEASE; 25-HYDROXYVITAMIN-D LEVELS; HEMODIALYSIS-PATIENTS; RISK; CALCIUM; ATHEROSCLEROSIS; ASSOCIATION; POPULATION; MORTALITY C1 [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. [Melamed, Michal L.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Melamed, Michal L.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Dept Med, Bullfinch 127, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu FU NHLBI NIH HHS [HL093954]; NIDDK NIH HHS [K23 DK078774] NR 24 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2009 VL 20 IS 8 BP 1663 EP 1665 DI 10.1681/ASN.2009060610 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 482QG UT WOS:000268903200007 PM 19608699 ER PT J AU DeLisser, HM Keirns, CC Clinton, EA Margolis, ML AF DeLisser, Horace M. Keirns, Carla C. Clinton, Esther A. Margolis, Mitchell L. TI "The Air Got to It:" Exploring a Belief About Surgery for Lung Cancer SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE lung; cancer; surgery; cultural competence; health disparities; folk beliefs ID POSITRON-EMISSION-TOMOGRAPHY; MICROMETASTATIC TUMOR-CELLS; STAGE-I; AFRICAN-AMERICANS; THORACOSCOPIC RESECTION; BRONCHOGENIC-CARCINOMA; RACIAL DISPARITY; BONE-MARROW; HEALTH-CARE; METASTASIS AB Background: The belief that exposure of lung cancer to air during surgery causes tumor spread is prevalent but poorly understood. Purpose: The purpose of the study was to summarize the published literature on the potential historical origins of this belief, study the recurrence rates of surgically treated stage I non-small cell lung cancer, research the mechanisms by which surgery might promote tumor growth and metastasis, and examine the social and cultural implications of this belief. Data Sources: Various databases, reference lists, and expert contacts were the sources of data. Findings: Although the origin of this belief is ooscure, Its emergence may have been due to early debates within the medical community about the risks of lung biopsies, the significant surgical morbidity initially associated with thoracic surgery, and the difficulty early on of staging lung cancer patients before surgery. Approximately one-third of patients undergoing curative surgery for stage I lung cancer experience a recurrence of the tumor. Most recurrences are detected in the first 24 months after resection and likely reflect the presence of undetected, occult metastases at the time of surgery. Mechanisms by which surgery could promote tumor growth and worsen prognosis include direct seeding of tumor at local sites, tumor manipulation, stimulation of subclinical tumor by postsurgical inflammation, and accelerated metastatic tumor growth due to loss of inhibitory factors derived from the primary tumor. These beliefs are more likely to be prevalent, and resistant to change, in minority and disadvantaged groups. Conclusions: These findings provide the basis for an approach to patients who fear the spread of their cancer by surgery. C1 [DeLisser, Horace M.] Univ Penn, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. [Keirns, Carla C.] Univ Michigan, Div Gen Med, Ann Arbor, MI 48109 USA. [Clinton, Esther A.] Bowling Green State Univ, Dept Popular Culture, Bowling Green, OH 43403 USA. [Margolis, Mitchell L.] Philadelphia Vet Affairs Med Ctr, Pulm Sect, Philadelphia, PA USA. RP DeLisser, HM (reprint author), Univ Penn, Pulm Allergy & Crit Care Div, SVM Hill Pavil,Rm 410B,380 S Univ Ave, Philadelphia, PA 19104 USA. EM delisser@mail.med.upenn.edu FU National Institutes of Health [K07HLO7921]; Veterans Administration Center for Health Equity and Promotion [72-011] FX This paper was supported by funding from the National Institutes of Health (K07HLO7921, to HMD) and the Veterans Administration Center for Health Equity and Promotion (LIP 72-011, to MLM). NR 83 TC 12 Z9 12 U1 0 U2 1 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 AUG PY 2009 VL 101 IS 8 BP 765 EP 771 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 482PJ UT WOS:000268900900004 PM 19715038 ER PT J AU Gaissert, HA Keum, DY Wright, CD Ancukiewicz, M Monroe, E Donahue, DM Wain, JC Lanuti, M Allan, JS Choi, NC Mathisen, DJ AF Gaissert, Henning A. Keum, Dong Yoon Wright, Cameron D. Ancukiewicz, Marek Monroe, Eric Donahue, Dean M. Wain, John C. Lanuti, Michael Allan, James S. Choi, Noah C. Mathisen, Douglas J. TI POINT: Operative risk of pneumonectomy-Influence of preoperative induction therapy SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID CELL LUNG-CANCER; CONCURRENT CHEMOTHERAPY; PULMONARY RESECTION; SLEEVE LOBECTOMY; SURVIVAL; INCREASE; SURGERY; COMPLICATIONS; RADIATION AB Background: Prior data indicate increased perioperative morbidity and mortality in patients receiving induction chemoradiotherapy before pneumonectomy for lung cancer. Objective: We reviewed a consecutive series of pneumonectomies to determine the impact of induction therapy on operative mortality. Results: Over a 15-year period, 183 patients underwent pneumonectomy for lung cancer. Forty-six received combined preoperative radiochemotherapy (25.2%), and 137 patients underwent resection only. Indications for induction therapy were stage IIB disease in 1, IIIA in 35, IIIB in 8, and IV in 2 patients. Patients receiving induction therapy were younger (mean age 58.4 vs 61.9 years; P=.033), had less heart disease (6.5 vs 26.3%; P=.0035), higher preoperative forced expiratory volume in 1 second (2.48 vs 2.13 L; P=.0018), a lower rate of endobronchial tumor (34.8 vs 67.2%; P=.0002), and underwent intrapericardial procedures more often (71.7 vs 43.1%; P=.0011). Hospital mortality was 4.3% (2/46) after preoperative therapy and 6.6% (9/137) after resection only (P=.73); the difference in cardiopulmonary morbidity was not significant (51.1% vs 40.4%; P=.22). Induction did not predict hospital mortality after adjustment for a propensity score derived from nonoperative and operative variables correlated with neoadjuvant therapy. Conclusions: A regimen of induction radiation and chemotherapy does not increase the operative mortality of pneumonectomy in carefully selected patients. C1 [Gaissert, Henning A.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org NR 20 TC 19 Z9 20 U1 0 U2 1 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 AUG PY 2009 VL 138 IS 2 BP 289 EP 294 DI 10.1016/j.jtcvs.2008.11.069 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 472UM UT WOS:000268157800006 PM 19619768 ER PT J AU Tilleman, TR Richards, WG Zellos, L Johnson, BE Jaklitsch, MT Mueller, J Yeap, BY Mujoomdar, AA Ducko, CT Bueno, R Sugarbaker, DJ AF Tilleman, Tamara R. Richards, William G. Zellos, Lambros Johnson, Bruce E. Jaklitsch, Michael T. Mueller, Jordan Yeap, Beow Yong Mujoomdar, Aneil A. Ducko, Christopher T. Bueno, Raphael Sugarbaker, David J. TI Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: A phase II prospective study SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 10-14, 2008 CL San Diego, CA SP Amer Assoc Thorac Surg ID MODULATED RADIATION-THERAPY; MULTIMODALITY THERAPY; PHOTODYNAMIC THERAPY; TRIMODALITY THERAPY; SURGERY; PLEURECTOMY/DECORTICATION; CHEMOTHERAPY; MANAGEMENT; RADIOTHERAPY; RESECTION AB Objective: We sought to prospectively determine the feasibility and safety of hyperthermic intraoperative intracavitary cisplatin perfusion immediately after extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. Methods: Patients with malignant pleural mesothelioma who were surgical candidates underwent extrapleural pneumonectomy followed by hyperthermic intraoperative intracavitary cisplatin perfusion, consisting of a 1-hour lavage of the chest and abdomen with cisplatin (42 degrees C) at 225 mg/m(2). Pharmacologic cytoprotection consisted of intravenous sodium thiosulfate with or without amifostine. Morbidity and mortality were recorded prospectively. Results: Ninety-six (79%) of 121 enrolled patients underwent extrapleural pneumonectomy, of whom 92 (76%) received hyperthermic intraoperative intracavitary cisplatin perfusion after extrapleural pneumonectomy. Fifty-three (58%) patients had epithelial tumors, and 39 (42%) had nonepithelial histology. Hospital mortality was 4.3%. Morbidity (grade 3 or 4, 49%) included atrial fibrillation in 22 (23.9%) patients, venous thrombosis in 12 (13%) patients, and laryngeal nerve dysfunction in 10 (11%) patients. Nine patients had renal toxicity, which was attributable to cisplatin in 8 of them. Among the 27 patients who also received amifostine (910 mg/m(2)), 1 patient had grade 3 renal toxicity attributable to cisplatin. Recurrence of malignant pleural mesothelioma was documented in 47 (51%) patients, with ipsilateral recurrence in 17.4% of patients. The median survival of the 121 enrolled patients was 12.8 months. Conclusions: Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy can be performed with acceptable morbidity and mortality. The use of amifostine in addition to sodium thiosulfate might reduce cisplatin-associated renal toxicity. Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy might enhance local control in the chest. C1 [Sugarbaker, David J.] Brigham & Womens Hosp, Div Thorac Surg, Dept Thorac Surg, Boston, MA 02115 USA. [Johnson, Bruce E.] Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. [Yeap, Beow Yong] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sugarbaker, DJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, Dept Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM dsugarbaker@partners.org NR 30 TC 64 Z9 66 U1 1 U2 3 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 AUG PY 2009 VL 138 IS 2 BP 405 EP 411 DI 10.1016/j.jtcvs.2009.02.046 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 472UM UT WOS:000268157800021 PM 19619785 ER PT J AU Pipavath, SNJ Schmidt, RA Takasugi, JE Godwin, JD AF Pipavath, Sudhakar N. J. Schmidt, Rodney A. Takasugi, Julie E. Godwin, J. David TI Chronic Obstructive Pulmonary Disease: Radiology-Pathology Correlation SO JOURNAL OF THORACIC IMAGING LA English DT Article DE emphysema; high-resolution computed tomography; bronchitis; secondary pulmonary lobule ID RESOLUTION COMPUTED-TOMOGRAPHY; EMPHYSEMA; CT; LUNG; STANDARDS; RITALIN AB Chronic obstructive pulmonary disease is defined as a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. This review will discuss the relevant anatomy of the secondary pulmonary lobule, the subtypes of emphysema, and their imaging appearances and corresponding pathologic findings. C1 [Pipavath, Sudhakar N. J.; Godwin, J. David] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Schmidt, Rodney A.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. [Takasugi, Julie E.] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. RP Godwin, JD (reprint author), Univ Washington, Med Ctr, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA. EM godwin@u.washington.edu NR 25 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD AUG PY 2009 VL 24 IS 3 BP 171 EP 180 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 489AK UT WOS:000269391600004 PM 19704320 ER PT J AU Lynch, TJ Fenton, D Hirsh, V Bodkin, D Middleman, EL Chiappori, A Halmos, B Favis, R Liu, H Trepicchio, WL Eton, O Shepherd, FA AF Lynch, Thomas J. Fenton, David Hirsh, Vera Bodkin, David Middleman, Edward L. Chiappori, Alberto Halmos, Balazs Favis, Reyna Liu, Hua Trepicchio, William L. Eton, Omar Shepherd, Frances A. TI A Randomized Phase 2 Study of Erlotinib Alone and in Combination with Bortezomib in Previously Treated Advanced Non-small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol DE Advanced non-small cell lung cancer; Bortezomib; Erlotinib; Phase 2 ID PROTEASOME INHIBITOR BORTEZOMIB; ADVANCED SOLID TUMORS; FACTOR RECEPTOR INHIBITORS; GROUP-STUDY BR.21; III TRIAL; BRONCHIOLOALVEOLAR CARCINOMA; 1ST-LINE TREATMENT; SUPPORTIVE CARE; I TRIAL; CHEMOTHERAPY AB Introduction: This phase 2 study was conducted to determine the efficacy and safety of erlotinib alone and with bortezomib in patients with non-small cell lung cancer (NSCLC). Methods: Patients with histologically or cytologically confirmed relapsed or refractory stage IIIb/IV NSCLC were randontized (1:1; stratified by baseline histology, smoking history, sex) to receive erlotinib 150 mg/d alone (arm A, n = 25) or in combination with bortezomib 1.6 mg/m(2), days I and 8 (arm B; n = 25) in 21-day cycles. Responses were assessed using Response Evaluation Criteria in Solid Tumors. Tumor samples were evaluated for mutations predicting response. Six additional patients received the combination in a prior dose deescalation stage and were included in safety analyses. Results: Response rates were 16% in arm A and 9% in arm 13; disease control rates were 52 and 45%, respectively. The study was halted at the planned interim analysis due to insufficient clinical activity in arm B. Median progression-free survival and overall Survival were 2.7 and 7.3 months in arm A, and 1.3 and 8.5 months in arm B. Six-month survival rates were 56.0% in both arms; 12-month rates were 40 and 30% in arms A and B, respectively. Response rate to erlotinib +/- bortezomib was significantly higher in patients with epidermal growth factor receptor mutations (50 versus 9% for wild type). The most common treatment-related grade >= 3 adverse event was skin rash (three patients in each treatment group). Conclusion: Insufficient activity was seen with erlotinib plus bortezomib in patients with relapsed/refractory advanced NSCLC to warrant a phase 3 study of the combination. C1 [Lynch, Thomas J.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. [Fenton, David] Cross Canc Inst, Dept Oncol, Edmonton, AB T6G 1Z2, Canada. [Hirsh, Vera; Shepherd, Frances A.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Bodkin, David] Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. [Middleman, Edward L.] Dallas Oncol Consultants, Dallas, TX USA. [Chiappori, Alberto] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Halmos, Balazs] Univ Hosp Cleveland, Div Hematol Oncol, Cleveland, OH 44106 USA. [Favis, Reyna] Johnson & Johnson Pharmaceut Res & Dev, Dept Pharmacogenom, Raritan, NJ USA. [Liu, Hua; Trepicchio, William L.; Eton, Omar] Millennium Pharmaceut Inc, Cambridge, MA USA. Princess Margaret Hosp, Dept Hematol & Oncol, Toronto, ON M4X 1K9, Canada. RP Lynch, TJ (reprint author), Yale Canc Ctr, 333 Cedar St, New Haven, CT 06520 USA. EM thomas.lynch@yale.edu NR 55 TC 37 Z9 38 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2009 VL 4 IS 8 BP 1002 EP 1009 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 477TF UT WOS:000268541000013 PM 19633475 ER PT J AU Cobb, JP Cairns, CB Bulger, E Wong, HR Parsons, PE Angus, DC Gentile, NT Hoyt, DB Schwinn, DA Wiener-Kronish, JP Upperman, JS AF Cobb, J. Perren Cairns, Charles B. Bulger, Eileen Wong, Hector R. Parsons, Polly E. Angus, Derek C. Gentile, Nina T. Hoyt, David B. Schwinn, Debra A. Wiener-Kronish, Jeanine P. Upperman, Jeffrey S. TI The United States Critical Illness and Injury Trials Group: An Introduction SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT National Summit on Pediatric Disaster and Emergency Services CY SEP 11-12, 2008 CL Los Angeles, CA SP Eastern Assoc Surg Trauma, Trauma Assoc Canada, Western Trauma Assoc DE Clinical; Research; Genomics; Sepsis AB The US Critical Illness and Injury Trials Group is funded to engage the relevant scientific communities and federal agencies to jointly advocate for clinical research. An inclusive, nationwide network of experts has been created to establish national priorities and pursue a strategic plan in conjunction with professional societies and existing research networks. Investigator-initiated clinical proposals will be presented and discussed at the inaugural National Institutes of Health meeting to promote collaboration and establish working groups to develop projects and core resources. Future US Critical Illness and Injury Trials Group meetings will convene triannually, providing a venue to gauge progress on strategic deliverables, foster development of the clinical projects, discuss education and training in clinical trial design, and address the ethical, legal, and social implications of research in the critically ill or injured patients. C1 [Cobb, J. Perren] Washington Univ, Ctr Crit Illness & Hlth Engn, St Louis, MO USA. [Cairns, Charles B.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC USA. [Bulger, Eileen] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Schwinn, Debra A.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Wong, Hector R.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Parsons, Polly E.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Angus, Derek C.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Angus, Derek C.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Angus, Derek C.] Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA USA. [Gentile, Nina T.] Temple Univ, Dept Emergency Med, Philadelphia, PA 19122 USA. [Hoyt, David B.] Univ Calif Irvine, Dept Surg, Irvine, CA 92717 USA. [Wiener-Kronish, Jeanine P.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Upperman, Jeffrey S.] Univ So Calif, Keck Sch Med, Dept Surg, Los Angeles, CA 90033 USA. RP Cobb, JP (reprint author), Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM cobb@wustl.edu RI Angus, Derek/E-9671-2012; OI Wong, Hector/0000-0001-7989-1173 FU NIGMS NIH HHS [U13GM083407] NR 4 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 2009 VL 67 IS 2 BP S159 EP S160 DI 10.1097/TA.0b013e3181ad3473 PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 482OM UT WOS:000268898600022 PM 19667851 ER PT J AU Monson, CM Gradus, JL La Bash, HAJ Griffin, MG Resick, PA AF Monson, Candice M. Gradus, Jaimie L. La Bash, Heidi A. J. Griffin, Michael G. Resick, Patricia A. TI The Role of Couples' Interacting World Assumptions and Relationship Adjustment in Women's Postdisaster PTSD Symptoms SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL-ABUSE SURVIVORS; MENTAL-HEALTH; COGNITIVE DISTORTIONS; DYADIC ADJUSTMENT; DISASTER; PREVALENCE; EXPOSURE; IMPACT; SCALE AB This study examined 58 heterosexual couples' interacting assumptions about the world and relationship adjustment in predicting wives' posttraumatic stress disorder (PTSD) symptoms after severe flooding. Both partners completed the World Assumptions Scale (Janoff-Bulman, 1989), and wives reported on their intimate relationship adjustment and PTSD symptomatology. Neither husbands' nor wives' assumptions alone predicted wives' PTSD symptoms. However the interaction of husbands' and wives' benevolent world assumptions significantly predicted wives' PTSD symptoms. When husbands held less benevolent world assumptions, there was a negative association between wives' assumptions and PTSD symptoms. Additionally, wives' relationship adjustment predicted their PTSD symptomatology when taking in to account individual and interacting self-worth assumptions. Implications for understanding the role of intimate relationships in postdisaster mental health and interpersonally oriented prevention efforts are discussed. C1 [Monson, Candice M.; Gradus, Jaimie L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Griffin, Michael G.] Univ Missouri, St Louis, MO 63121 USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Resick, Patricia A.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Monson, Candice M.; Gradus, Jaimie L.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Dept Psychiat, Boston, MA 02130 USA. RP Monson, CM (reprint author), VA Boston Healthcare Syst 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. EM Candice.Monson@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU NIMH NIH HHS [R01 MH055542, R03 MH052513, 1-R01-MH55542, R03 MH052513-01] NR 38 TC 12 Z9 12 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2009 VL 22 IS 4 BP 276 EP 281 DI 10.1002/jts.20432 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 489AH UT WOS:000269391300003 PM 19626677 ER PT J AU Kelly, KA Rizvi, SL Monson, CM Resick, PA AF Kelly, Kacie A. Rizvi, Shireen L. Monson, Candice M. Resick, Patricia A. TI The Impact of Sudden Gains in Cognitive Behavioral Therapy for Posttraumatic Stress Disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID FEMALE RAPE VICTIMS; PROCESSING THERAPY; PROLONGED EXPOSURE; CRITICAL SESSIONS; DEPRESSION; PSYCHOTHERAPY; PTSD; CLINICIAN; TRAUMA; SCALE AB This study investigated sudden gains, i.e., rapid and stable improvements, in posttraumatic stress disorder (PTSD) symptoms that may occur in cognitive-behavioral therapy. Twenty-nine of 72 participants (39.29%) experienced a sudden gain during treatment. Mixed model ANOVAs analyzed sudden gains impact on clinician-rated PTSD symptom severity, patient-rated PTSD symptom severity, and patient-rated depressive symptom severity. Sudden gains in PTSD symptomology were associated with greater reductions in PTSD symptom severity for the avoidance/numbing and hyperarousal symptom clusters at posttreatment. By 6-month follow-up, the sudden gains group had maintained those reductions in symptoms, but the nonsudden gains group had achieved equal reductions in symptom severity. Participants experiencing sudden gains on PTSD measures had lower depression severity at posttreatment and follow-up. C1 [Rizvi, Shireen L.] New Sch Social Res, Dept Psychol, New York, NY 10011 USA. [Monson, Candice M.; Resick, Patricia A.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Kelly, Kacie A.; Monson, Candice M.; Resick, Patricia A.] VA Boston Healthcare Syst, NCPTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, NCPTSD, WHSD 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. EM Patricia.Resick@va.gov FU NIMH NIH HHS [R01 MH051509, R01 MH051509-09] NR 28 TC 15 Z9 15 U1 3 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2009 VL 22 IS 4 BP 287 EP 293 DI 10.1002/jts.20427 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 489AH UT WOS:000269391300005 PM 19637322 ER PT J AU Jakupcak, M Cook, J Imel, Z Fontana, A Rosenheck, R McFall, M AF Jakupcak, Matthew Cook, Jessica Imel, Zac Fontana, Alan Rosenheck, Robert McFall, Miles TI Posttraumatic Stress Disorder as a Risk Factor for Suicidal Ideation in Iraq and Afghanistan War Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID VIETNAM VETERANS; US VETERANS; SCALE; MODEL AB Posttraumatic stress disorder (PTSD) was examined as a risk factor for suicidal ideation in Iraq and Afghanistan War veterans (N = 407) referred to Veterans Affairs mental health care. The authors also examined if risk for suicidal ideation was increased by the presence of comorbid mental disorders in veterans with PTSD. Veterans who screened positive for PTSD were more than 4 times as likely to endorse suicidal ideation relative to non-PTSD veterans. Among veterans who screened positive for PTSD (n = 202), the risk for suicidal ideation was 5.7 times greater in veterans who screened positive for two or more comorbid disorders relative to veterans with PTSD only. Findings are relevant to identifying risk for suicide behaviors in Iraq and Afghanistan War veterans. C1 [Jakupcak, Matthew; Cook, Jessica; Imel, Zac; McFall, Miles] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. [Jakupcak, Matthew; Cook, Jessica; McFall, Miles] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Imel, Zac] Univ Wisconsin, Dept Counseling Psychol, Madison, WI USA. [Fontana, Alan; Rosenheck, Robert] VA Natl Ctr PTSD, NEPEC, West Haven, CT USA. [Fontana, Alan; Rosenheck, Robert] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Jakupcak, M (reprint author), Puget Sound Hlth Care Syst, Deployment Hlth Clin, 1660 S Columbian Way, Seattle, WA 98108 USA. EM matthew.jakupcak@va.gov OI imel, zachary/0000-0001-9645-7184 NR 13 TC 127 Z9 127 U1 0 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2009 VL 22 IS 4 BP 303 EP 306 DI 10.1002/jts.20423 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 489AH UT WOS:000269391300007 PM 19626682 ER PT J AU Resick, PA Iverson, KM Artz, CE AF Resick, Patricia A. Iverson, Katherine M. Artz, Caroline E. TI Participant Reactions to a Pretreatment Research Assessment During a Treatment Outcome Study for PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID THERAPY; VICTIMS AB Participants' reactions to pretreatment assessments have not been studied as part of a randomized clinical trial (RCT) for posttraumatic stress disorder (PTSD). The current study examined participants' reactions in women with PTSD who completed pretreatment assessments during an RCT We assessed participant reactions (N = 100) to a pretreatment assessment that included self-report questionnaires, interviews, and psychophysiological assessment. Results indicated that participation in pretreatment assessment was well tolerated as measured by participants' reports of distress, interest level perceptions of the appropriateness of assessment length, and willingness to participate in a similar assessment in the future. Participating in lengthy pretreatment assessments did not adversely impact treatment participation or outcome. C1 [Resick, Patricia A.] VA Boston Healthcare Syst, WHSD 116B 3, Natl Ctr PTSD, Boston, MA 02130 USA. [Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, WHSD 116B 3, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM Patricia.Resick@va.gov FU NIMH NIH HHS [R01 MH051509, R01 MH051509-09, T32 MH019836, R01-MH51509, T32MH019836] NR 10 TC 10 Z9 10 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2009 VL 22 IS 4 BP 316 EP 319 DI 10.1002/jts.20428 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 489AH UT WOS:000269391300010 PM 19588513 ER PT J AU McDougal, WS AF McDougal, W. Scott TI Renal Function Assessment in the Era of Chronic Kidney Disease: Renewed Emphasis on Renal Function Centered Patient Care COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. RP McDougal, WS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 2009 VL 182 IS 2 BP 443 EP 444 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 468UW UT WOS:000267850300009 ER PT J AU Banez, LL Sun, L Trock, BJ Han, M Partin, AW Aronson, WJ Terris, MK Presti, JC Kane, CJ Amling, CL Moul, JW Freedland, SJ AF Banez, Lionel L. Sun, Leon Trock, Bruce J. Han, Misop Partin, Alan W. Aronson, William J. Terris, Martha K. Presti, Joseph C., Jr. Kane, Christopher J. Amling, Christopher L. Moul, Judd W. Freedland, Stephen J. TI Body Mass Index and Prostate Specific Antigen as Predictors of Adverse Pathology and Biochemical Recurrence After Prostatectomy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; obesity; prostate-specific antigen; hemodilution ID RADICAL PROSTATECTOMY; CANCER; OBESITY; MEN; PSA; RISK; ASSOCIATION; MORTALITY; PROGRESSION; POPULATION AB Purpose: Preoperative prostate specific antigen is widely used to predict unfavorable pathological features and biochemical relapse after radical prostatectomy. Recent reports that hemodilution may be responsible for lower prostate specific antigen in obese men led to concerns that prostate specific antigen may be less effective for prognosticating in men with increased body mass index. We determined whether the clinical usefulness of prostate specific antigen is negatively impacted by obesity by examining its operating characteristics and predictive accuracy as a function of body mass index. Materials and Methods: We performed a multicenter retrospective analysis of the records of 11,705 men who underwent radical prostatectomy from 1988 to 2007 from Veterans Affairs hospitals of the Shared Equal Access Regional Cancer Hospital Database, the Duke Prostate Center and Johns Hopkins Hospital. ROC curve analysis, the concordance index and the test for interaction were used to compare the ability of prostate specific antigen to predict unfavorable tumor characteristics and biochemical recurrence across body mass index categories. Results: There were no significant differences in the area under ROC curves across increasing body mass index categories for prostate specific antigen to predict pathological Gleason sum (7 or greater, 7 [4 + 3] or greater, or 8 or greater), positive surgical margins, extracapsular extension or seminal vesicle invasion in all 3 cohorts. There was no significant difference in prostate specific antigen accuracy to predict biochemical failure across increasing body mass index categories. Conclusions: In 3 cohorts of men treated with radical prostatectomy the ability of preoperative prostate specific antigen to predict adverse pathological features and posttreatment biochemical recurrence is not significantly affected by obesity. However, adjusting for obesity related hemodilution may still be required to properly interpret prostate specific antigen results in men with increased body mass index. C1 [Banez, Lionel L.; Sun, Leon; Moul, Judd W.; Freedland, Stephen J.] Duke Univ, Med Ctr, Div Urol Surg, Dept Surg, Durham, NC 27710 USA. [Banez, Lionel L.; Sun, Leon; Moul, Judd W.; Freedland, Stephen J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Durham, NC 27710 USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Banez, Lionel L.; Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Trock, Bruce J.; Han, Misop; Partin, Alan W.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Dept Urol, Baltimore, MD 21205 USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Urol Sect, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Kane, Christopher J.] Vet Affairs Med Ctr, Urol Sect, San Diego, CA 92161 USA. [Kane, Christopher J.] Univ Calif San Diego, Dept Urol, San Diego, CA 92103 USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Amling, Christopher L.] Univ Alabama, Urol Sect, Vet Affairs Med Ctr, Birmingham, AL USA. [Amling, Christopher L.] Univ Alabama, Dept Urol, Birmingham, AL USA. RP Banez, LL (reprint author), Duke Univ, Med Ctr, Div Urol Surg, Dept Surg, Box 2626,MSRB I,Suite 455,571 Res Dr, Durham, NC 27710 USA. EM lionel.banez@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50 CA92131-01A1, R01CA100938, P50 CA58236] NR 27 TC 14 Z9 14 U1 1 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 AUG PY 2009 VL 182 IS 2 BP 491 EP 496 DI 10.1016/j.juro.2009.04.007 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 468UW UT WOS:000267850300029 PM 19524974 ER PT J AU Bergman, J Gore, JL Pension, DF Kwan, L Litwin, MS AF Bergman, Jonathan Gore, John L. Pension, David F. Kwan, Lorna Litwin, Mark S. TI Erectile Aid Use by Men Treated for Localized Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE penis; prostatic neoplasms; erectile dysfunction; penile erection; sildenafil ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; DYSFUNCTION; SURVIVORS; BRACHYTHERAPY; RADIATION; EVOLUTION; AMERICAN; OUTCOMES; THERAPY AB Purpose: We evaluated associations between demographic and clinical characteristics, quality of life outcome measures and erectile aids in men treated for localized prostate cancer. Materials and Methods: Patients had clinically localized prostate cancer, were not using erectile aids at baseline and chose treatment with radical prostatectomy (275), external beam radiotherapy (70) or brachytherapy (80). Patient characteristics and health related quality of life outcomes were prospectively assessed at baseline and at regular intervals up to 48 months after treatment. Outcomes were assessed with SF-36 (TM), the American Urological Association symptom index and UCLA-PCI. We categorized use of a phosphodiesterase type 5 inhibitor, urethral alprostadil suppositories, penile injection therapy or a vacuum erection device after treatment as erectile aid use. We created a multivariate model examining baseline demographic, clinical and health related quality of life covariates associated with erectile aid use. Results: Of the 425 patients 237 (56%) used an erectile aid at some point during the posttreatment period. In our multivariate model patients treated with external beam radiation were less likely to use an aid (OR 0.34, 95% CI 0.16-0.69) and men with significant sexual bother (OR 2.68, 95% CI 1.37-5.23), or with 1 or more comorbidities (OR 1.80, 95% CI 1.08-2.93) were more likely to use an aid. Patient demographic characteristics were not associated with erectile aids. Conclusions: After treatment for localized prostate cancer more than half of men use erectile aids, especially when they are significantly bothered by dysfunction. This is most pronounced after radical prostatectomy and in men with significant comorbidity. C1 [Bergman, Jonathan; Gore, John L.; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Kwan, Lorna; Litwin, Mark S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Gore, John L.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Gore, John L.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Pension, David F.] Univ So Calif, Keck Sch Med, Norris Canc Ctr, Los Angeles, CA 90033 USA. RP Bergman, J (reprint author), Univ Calif Los Angeles, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM jbergman@mednet.ucla.edu OI Gore, John/0000-0002-2847-5062 NR 20 TC 19 Z9 19 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 AUG PY 2009 VL 182 IS 2 BP 649 EP 654 DI 10.1016/j.juro.2009.04.001 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 468UW UT WOS:000267850300093 PM 19535108 ER PT J AU Hirata, H Hinoda, Y Nakajima, K Kikuno, N Suehiro, Y Tabatabai, ZL Ishii, N Dahiya, R AF Hirata, Hiroshi Hinoda, Yuji Nakajima, Koichi Kikuno, Nobuyuki Suehiro, Yutaka Tabatabai, Z. Laura Ishii, Nobuhisa Dahiya, Rajvir TI The bcl2-938CC Genotype Has Poor Prognosis and Lower Survival in Renal Cancer SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma, renal cell; polymorphism, single nucleotide; apoptosis; genotype ID CHRONIC-LYMPHOCYTIC-LEUKEMIA; BCL-2 EXPRESSION; CELL CARCINOMA; P53; PHARMACOGENOMICS; POLYMORPHISM; RECURRENCE; APOPTOSIS; PROMOTER; THERAPY AB Purpose: A single nucleotide polymorphism (-938C/A, rs2279115) was found in the bcl2 gene, whose -938A allele is significantly associated with increased Bcl2 expression compared with that of the C allele. Bcl2 up-regulation was reported to be associated with longer survival in patients with renal cancer. However, to our knowledge there is currently no information on the role of the bcl2-938C/A single nucleotide polymorphism in renal cell carcinoma cases. Therefore, we investigated the polymorphism at the bcl2 -938C/A site and its effects on clinical characteristics in patients with renal cell carcinoma. Materials and Methods: We genotyped the bcl2-938C/A single nucleotide polymorphism in 216 patients with renal cancer, and in 209 healthy age and gender matched controls. We also investigated the relationship between the bcl2 -938C/A polymorphism, Bcl2 expression, proliferation and apoptosis status in renal cell carcinoma tissues using immunohistochemistry and TUNEL assay. The association of the bcl2 -938C/A single nucleotide polymorphism with survival in patients with renal cell carcinoma was also analyzed by Kaplan-Meier curves. Results: Survival in Bcl2 positive cases was significantly longer than in negative cases. On univariate and multivariate analyses the bc12 -938CC genotype was independently associated with poor prognosis. Kaplan-Meier analysis showed that survival in patients with CC genotypes was significantly worse than in those with CA+AA genotypes. CC genotype carriers had significantly lower Bcl2 expression and higher proliferative activity in renal cancer tissues than CA+AA genotype carriers. Conclusions: To our knowledge this is the first report to show that the bc12 -938C/C genotype has worse prognosis and lower survival in patients with renal cell carcinoma. In addition, the bc12 -938C/A single nucleotide polymorphism was shown to be an independent adverse prognostic factor for renal cell carcinoma. C1 [Hirata, Hiroshi; Kikuno, Nobuyuki; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Tabatabai, Z. Laura] San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hinoda, Yuji; Suehiro, Yutaka] Yamaguchi Univ, Grad Sch Med, Dept Oncol, Yamaguchi, Japan. [Hinoda, Yuji; Suehiro, Yutaka] Yamaguchi Univ, Grad Sch Med, Lab Med, Yamaguchi, Japan. [Nakajima, Koichi; Kikuno, Nobuyuki] Toho Univ, Dept Urol, Fac Med, Tokyo, Japan. RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Urol Res Ctr, 112F,4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urology.ucsf.edu FU NCI NIH HHS [R01CA101844, R01CA111470]; NIDDK NIH HHS [T32-DK07790] NR 25 TC 21 Z9 24 U1 0 U2 2 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 AUG PY 2009 VL 182 IS 2 BP 721 EP 727 DI 10.1016/j.juro.2009.03.081 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 468UW UT WOS:000267850300125 PM 19539330 ER PT J AU Liu, CH Gervais, DA Hahn, PF Arellano, RS Uppot, RN Mueller, PR AF Liu, Chang-Hsien Gervais, Debra A. Hahn, Peter F. Arellano, Ronald S. Uppot, Raul N. Mueller, Peter R. TI Percutaneous Hepatic Abscess Drainage: Do Multiple Abscesses or Multiloculated Abscesses Preclude Drainage or Affect Outcome? SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PYOGENIC LIVER-ABSCESSES; NEEDLE ASPIRATION; CLINICAL-COURSE; SINGLE; ETIOLOGY; EXPERIENCE; MANAGEMENT; DIAGNOSIS AB PURPOSE: To compare the effectiveness of percutaneous abscess drainage in patients with pyogenic liver abscesses of the following types: single, single multiloculated, multiple, and multiple multiloculated. MATERIALS AND METHODS: One hundred nine patients with 149 liver abscesses who underwent percutaneous drainage during an 11-year period were divided into a single abscess group and a multiple abscess group. Of the 109 patients, 54 had multiloculated abscesses and were divided into single and multiple multiloculated abscess groups. Technical success was defined as the ability to place the catheter within the abscess cavity and clinical success was defined as improvement in the patient's symptoms. Clinical findings, management strategy, complication rate, and success rate were analyzed. RESULTS: Technical success rates were 96% (82 of 85) for a single abscess and 96% (23 of 24) for multiple abscesses (P = 1.0). Clinical success was achieved in 74 of 85 patients (87%) with a single abscess and 22 of 24 patients (92%) with multiple abscesses (P = .729). Technical success rates were 94% (32 of 34) for a single multiloculated abscess and 95% (19 of 20) for multiple multiloculated abscesses (P = 1.0). Clinical success was achieved in 30 of 34 patients (88%) with a single multiloculated abscess and 18 of 20 patients (90%) with multiple multiloculated abscesses (P = 1). No significant difference in hospital stay was seen between single and multiple abscess groups (P = .373) or between single multiloculated and multiple multiloculated abscess groups (P = .180). There were no major complications or mortality related to the procedure. CONCLUSIONS: Percutaneous drainage is a safe and effective procedure in the treatment of pyogenic liver abscess, regardless of abscess complexity and/or multiplicity. C1 [Liu, Chang-Hsien; Gervais, Debra A.; Hahn, Peter F.; Arellano, Ronald S.; Uppot, Raul N.; Mueller, Peter R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Liu, Chang-Hsien] Tri Serv Gen Hosp, Dept Radiol, Taipei, Taiwan. Natl Def Med Ctr, Taipei, Taiwan. RP Gervais, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM dgervais@partners.org NR 18 TC 20 Z9 25 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD AUG PY 2009 VL 20 IS 8 BP 1059 EP 1065 DI 10.1016/j.jvir.2009.04.062 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 488GL UT WOS:000269337200008 PM 19560374 ER PT J AU LaMuraglia, GM Conrad, MF Chung, T Hutter, M Watkins, MT Cambria, RP AF LaMuraglia, Glenn M. Conrad, Mark F. Chung, Tom Hutter, Matthew Watkins, Michael T. Cambria, Richard P. TI Significant perioperative morbidity accompanies contemporary infrainguinal bypass surgery: An NSQIP report SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the Society-for-Vascular-Surgery CY JUN 05-08, 2008 CL San Diego, CA SP Soc Vasc Surg ID PERIPHERAL ARTERIAL-DISEASE; QUALITY IMPROVEMENT PROGRAM; RANDOMIZED CONTROLLED-TRIAL; SUPERFICIAL FEMORAL-ARTERY; LOWER-EXTREMITY; LIMB SALVAGE; VEIN BYPASS; PERCUTANEOUS INTERVENTIONS; INTERMITTENT CLAUDICATION; VASCULAR-SURGERY AB Objectives. A variety of clinical and anatomic factors influence the choice between infrainguinal bypass surgery (BPG) and percutaneous endovascular procedures (PTA) to treat lower extremity vascular disease. The decision, in part, is dependant on periprocedural morbidity. The goal of this study was to document the contemporary morbidity and mortality of infrainguinal BPG, utilizing the previously validated National Surgical Quality Improvement Program (NSQIP) database. Methods: Data from the private sector NSQIP, a prospectively validated systematic-sample database, using Current Procedural Terminology (CPT) codes for all infrainguinal BPG performed between January 1, 2005, and December 31, 2006, were analyzed. Study endpoints included 30-day death and NSQIP-defined major complications, including graft failure, differentiated between systemic vs operative-site related complications. Potentially associated clinical variables were assessed by univariate methods to create the multivariate models of factors associated with study endpoints. Results: There were 2404 infrainguinal BPG (infrapopliteal distal anastomosis 42%, prosthetic 29%) performed in the study interval with patient variables: age 67 +/- 12, male 66%, diabetes 44%, limb salvage indications 48%. The 30-day composite mortality/major morbidity was 19.5%. The overall mortality was 2.7% and correlated with (Pvalue, odds ratio [OR]): patient age (<.001, 1.056), low body weight (.007, 0.988), significant preoperative dyspnea (.03, 1.97), dialysis (.003, 5.26), history transient ischemic attack (.03, 2.43), and bleeding disorder (.02, 2.01). Major complications occurred in 18.7% patients, including 7.4% graft thromboses, and 9.4% wound infections. Major systemic complications occurred in 5.9% and correlated with: age (.001, 1.03), history myocardial infarction (.02, 2.37), dialysis (<.001, 2.52), impaired sensorium (.005, 2.93), and general (vs regional) anesthesia (.04, 1.9). Major operative site-related complications occurred in 15.1% and correlated with: history chronic obstructive pulmonary disease (.04, 1.40), limb salvage indication (<.001, 1.71), impaired sensorium (.01, 2.26), non-independent preoperative functional status (.03, 1.37), and operative time (<.001, 1.002). The combination of dialysis and age >80 was identified as the most powerful high-risk composite for death (13.3-fold) and major complications (2.2-fold). Conclusion: Infrainguinal BPG is accompanied by significant major morbidity and mortality in contemporary practice. These results reinforce the precept that stringent indications for BPG should be maintained, when considering the method of lower extremity revascularization. (J Vase Surg 2009;50:299-304.) C1 [LaMuraglia, Glenn M.; Conrad, Mark F.; Chung, Tom; Watkins, Michael T.; Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Gen Surg Serv, Boston, MA 02114 USA. [LaMuraglia, Glenn M.; Conrad, Mark F.; Chung, Tom; Watkins, Michael T.; Cambria, Richard P.] Harvard Univ, Div Vasc & Endovasc Surg, Sch Med, Boston, MA 02114 USA. [Hutter, Matthew] Harvard Univ, Codman Ctr Clin Effectiveness Surg, Sch Med, Boston, MA 02114 USA. [Hutter, Matthew] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Gen Surg Serv, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. OI Chung, Thomas/0000-0001-6148-1184 NR 48 TC 45 Z9 45 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 2009 VL 50 IS 2 BP 299 EP 304 DI 10.1016/j.jvs.2009.01.043 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 478TA UT WOS:000268610000010 PM 19631864 ER PT J AU Kiernan, TJ Yan, BP Jaff, MR AF Kiernan, Thomas J. Yan, Bryan P. Jaff, Michael R. TI Antiplatelet therapy for the primary and secondary prevention of cerebrovascular events in patients with extracranial carotid artery disease SO JOURNAL OF VASCULAR SURGERY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; TRANSIENT ISCHEMIC ATTACK; LOW-DOSE ASPIRIN; HIGH-RISK PATIENTS; PERCUTANEOUS CORONARY INTERVENTION; GLYCOPROTEIN IIB/IIIA INHIBITION; NONVALVULAR ATRIAL-FIBRILLATION; EXTENDED-RELEASE DIPYRIDAMOLE; QUALITY-CONTROL ASSESSMENT; HEALTH-CARE PROFESSIONALS AB Cerebrovascular disease is a leading cause of morbidity and mortality in developed countries around the world. In the United States, there are an estimated 700,000 cases of stroke annually (of which over 85% are ischemic), costingan estimated $56.8 billion in associated treatment. Large vessel internal carotid artery stenosis is an important cause of ischemic stroke. Population -based studies have shown that the prevalence of carotid stenosis is -0.5% in the sixth decade of life and increases to -10% in the ninth decade. The majority of patients are asymptomatic. Asymptomatic carotid stenosis with:575% lumen loss carries a stroke risk of 1.3% annually, whereas the combined risk of myocardial ischernia and vascular death is as high as 10%. With diameter stenosis >75%, the combined stroke and transient ischernic attack risk increases to -11%annually, with 75% of events ipsilateral to the affected artery. Other studies have also shown that the risk of stroke increases proportionately to tile severity of stenosis. The risk is higher for those patients who are symptomatic. In this review, we will discuss antiplatelet agents to prevent cerebrovascular events in the context of extracraniall carotid artery disease. It is beyond the scope of this article to discuss antiplatelet treatment for other etiologies of stroke. (J Vase Surg 2009;50:431-9.) C1 [Kiernan, Thomas J.; Yan, Bryan P.; Jaff, Michael R.] Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiol, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM mjaff@partners.org RI Yan, Bryan/P-5928-2015 NR 88 TC 5 Z9 5 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 2009 VL 50 IS 2 BP 431 EP 439 DI 10.1016/j.jvs.2009.04.052 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 478TA UT WOS:000268610000033 PM 19631883 ER PT J AU Belshan, M Schweitzer, CJ Donnellan, MR Lu, R Engelman, A AF Belshan, Michael Schweitzer, Cameron J. Donnellan, Meghan R. Lu, Richard Engelman, Alan TI In vivo biotinylation and capture of HIV-1 matrix and integrase proteins SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Human immunodeficiency virus; Insertion mutagenesis; Biotinylation ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 PREINTEGRATION COMPLEXES; REVERSE-TRANSCRIPTASE; NUCLEAR-LOCALIZATION; CELLS; ASSAY; PURIFICATION; MUTAGENESIS; INFECTION; SUBSTRATE AB This report describes the adaptation of the biotin ligase BirA-biotin acceptor sequence (BAS) labeling system to biotinylate specific human immunodeficiency virus 1 (HIV-1) proteins in vivo. Two HIV-1 clones were constructed, with the BAS introduced into the matrix region of gag or the integrase region of pot. Specific biotinylation of target proteins in virions was observed when molecular clones were co-expressed with BirA. Both BAS-containing viruses propagated in SupT1 T-cells although replication of the integrase clone was delayed. Further studies demonstrated that the integrase insertion yielded an approximate 40% reduction in single-round infectivity as assessed on MAGI-5 indicator cells, as well as in the in vitro integration activity of preintegration complexes extracted from acutely infected C8166-45 T-cells. Biotinylation of the integrase BAS tag furthermore rendered this virus non-infectious. The matrix viral clone by contrast displayed wild-type behavior under all conditions tested. These results therefore establish a system whereby biotinylated matrix protein in the context of replication-competent virus could be used to label and capture viral protein complexes in vivo. (C) 2009 Elsevier B.V. All rights reserved. C1 [Belshan, Michael; Schweitzer, Cameron J.; Donnellan, Meghan R.] Creighton Univ, Sch Med, Dept Med Microbiol & Immunol, Omaha, NE 68178 USA. [Belshan, Michael] Nebraska Ctr Virol, Lincoln, NE USA. [Lu, Richard; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Lu, Richard; Engelman, Alan] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Belshan, M (reprint author), Creighton Univ, Sch Med, Dept Med Microbiol & Immunol, 723 N 18th St, Omaha, NE 68178 USA. EM michaelbelshan@creighton.edu FU Nebraska Center for Virology [NIH P20 RR01635]; Creighton Health Futures Foundation; NIH [AI39394] FX The authors wish to thank John Strouboulis for the pEV-BirA expression plasmid, Lee Ratner for the anti-MA antibody, and Duane Grandgenett for the anti-IN antibody. M.B. is supported by the Nebraska Center for Virology (NIH P20 RR01635) and the Creighton Health Futures Foundation; A.E. is supported by NIH grant AI39394. NR 25 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD AUG PY 2009 VL 159 IS 2 BP 178 EP 184 DI 10.1016/j.jviromet.2009.03.017 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 463TC UT WOS:000267454000007 PM 19490971 ER PT J AU Streeck, H Jolin, JS Qi, Y Yassine-Diab, B Johnson, RC Kwon, DS Addo, MM Brumme, C Routy, JP Little, S Jessen, HK Kelleher, AD Hecht, FM Sekaly, RP Rosenberg, ES Walker, BD Carrington, M Altfeld, M AF Streeck, Hendrik Jolin, Jonathan S. Qi, Ying Yassine-Diab, Bader Johnson, Randall C. Kwon, Douglas S. Addo, Marylyn M. Brumme, Chanson Routy, Jean-Pierre Little, Susan Jessen, Heiko K. Kelleher, Anthony D. Hecht, Frederick M. Sekaly, Rafick-Pierre Rosenberg, Eric S. Walker, Bruce D. Carrington, Mary Altfeld, Marcus TI Human Immunodeficiency Virus Type 1-Specific CD8(+) T-Cell Responses during Primary Infection Are Major Determinants of the Viral Set Point and Loss of CD4(+) T Cells SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY HIV-1 INFECTION; GASTROINTESTINAL-TRACT; LYMPHOCYTES; DEPLETION; VIREMIA; EPITOPE; LOAD; AIDS; GAG; SEROCONVERSION AB Primary HIV-1 infection (PHI) is marked by a flu-like syndrome and high levels of viremia that decrease to a viral set point with the first emergence of virus-specific CD8(+) T-cell responses. Here, we investigated in a large cohort of 527 subjects the immunodominance pattern of the first virus-specific cytotoxic T-lymphocyte (CTL) responses developed during PHI in comparison to CTL responses in chronic infection and demonstrated a distinct relationship between the early virus-specific CTL responses and the viral set point, as well as the slope of CD4(+) T-cell decline. CTL responses during PHI followed clear hierarchical immunodominance patterns that were lost during the transition to chronic infection. Importantly, the immunodominance patterns of human immunodeficiency virus type 1 (HIV-1)-specific CTL responses detected in primary, but not in chronic, HIV-1 infection were significantly associated with the subsequent set point of viral replication. Moreover, the preservation of the initial CD8(+) T-cell immunodominance patterns from the acute into the chronic phase of infection was significantly associated with slower CD4(+) T-cell decline. Taken together, these data show that the specificity of the initial CTL response to HIV is critical for the subsequent control of viremia and have important implications for the rational selection of antigens for future HIV-1 vaccines. C1 [Streeck, Hendrik; Jolin, Jonathan S.; Kwon, Douglas S.; Addo, Marylyn M.; Brumme, Chanson; Rosenberg, Eric S.; Walker, Bruce D.; Altfeld, Marcus] MIT, Ragon Inst MGH, Boston, MA 02129 USA. [Streeck, Hendrik; Jolin, Jonathan S.; Kwon, Douglas S.; Addo, Marylyn M.; Brumme, Chanson; Rosenberg, Eric S.; Walker, Bruce D.; Altfeld, Marcus] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Streeck, Hendrik; Jolin, Jonathan S.; Kwon, Douglas S.; Addo, Marylyn M.; Brumme, Chanson; Rosenberg, Eric S.; Walker, Bruce D.; Altfeld, Marcus] Harvard Univ, Sch Med, Boston, MA USA. [Yassine-Diab, Bader; Sekaly, Rafick-Pierre] CHUM, Immunol Lab, Ctr Rech, Montreal, PQ, Canada. [Qi, Ying; Johnson, Randall C.; Carrington, Mary] NCI, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA. [Routy, Jean-Pierre] McGill Univ, Royal Victoria Hosp, Div Hematol & Immunodeficiency Serv, Montreal, PQ H3A 1A1, Canada. [Little, Susan] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Jessen, Heiko K.] HIV Clin Praxis Jessen, Berlin, Germany. [Kelleher, Anthony D.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Darlinghurst, NSW, Australia. [Hecht, Frederick M.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Cahse, MD USA. RP Altfeld, M (reprint author), MIT, Ragon Inst MGH, 149 13th St, Boston, MA 02129 USA. EM maltfeld@partners.org RI Johnson, Randall/B-1517-2014; OI Johnson, Randall/0000-0001-7754-0847; Brumme, Chanson/0000-0003-2722-5288 FU CCR NIH HHS [HHSN261200800001C]; Howard Hughes Medical Institute; Intramural NIH HHS; NCI NIH HHS [HHSN261200800001E, N01-CO-12400, N01CO12400]; NIAID NIH HHS [P01 AI074415, AI43638, R01 AI050429, R01 AI50429, U01 AI043638, U01 AI052403]; PHS HHS [HHSN261200800001E] NR 32 TC 113 Z9 116 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG 1 PY 2009 VL 83 IS 15 BP 7641 EP 7648 DI 10.1128/JVI.00182-09 PG 8 WC Virology SC Virology GA 467OE UT WOS:000267747400029 PM 19458000 ER PT J AU Gray, L Roche, M Churchill, MJ Sterjovski, J Ellett, A Poumbourios, P Sherieff, S Wang, B Saksena, N Purcell, DFJ Wesselingh, S Cunningham, AL Brew, BJ Gabuzda, D Gorry, PR AF Gray, Lachlan Roche, Michael Churchill, Melissa J. Sterjovski, Jasminka Ellett, Anne Poumbourios, Pantelis Sherieff, Shameem Wang, Bin Saksena, Nitin Purcell, Damian F. J. Wesselingh, Steven Cunningham, Anthony L. Brew, Bruce J. Gabuzda, Dana Gorry, Paul R. TI Tissue-Specific Sequence Alterations in the Human Immunodeficiency Virus Type 1 Envelope Favoring CCR5 Usage Contribute to Persistence of Dual-Tropic Virus in the Brain (vol 83, pg 5430, 2009) SO JOURNAL OF VIROLOGY LA English DT Correction C1 [Gray, Lachlan; Roche, Michael; Churchill, Melissa J.; Sterjovski, Jasminka; Ellett, Anne; Poumbourios, Pantelis; Gorry, Paul R.] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. [Gray, Lachlan; Purcell, Damian F. J.; Wesselingh, Steven; Gorry, Paul R.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. [Roche, Michael; Churchill, Melissa J.; Sterjovski, Jasminka; Wesselingh, Steven; Gorry, Paul R.] Monash Univ, Dept Med, Melbourne, Vic, Australia. [Sherieff, Shameem; Wang, Bin; Saksena, Nitin; Cunningham, Anthony L.] Westmead Millennium Inst, Westmead, NSW, Australia. [Brew, Bruce J.] St Vincents Hosp, Dept Neurol, Darlinghurst, NSW 2010, Australia. [Brew, Bruce J.] St Vincents Hosp, St Vincents Ctr Appl Med Res, Darlinghurst, NSW 2010, Australia. [Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gorry, PR (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. RI Brew, Bruce/J-6513-2012 NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG 1 PY 2009 VL 83 IS 15 BP 7794 EP 7794 DI 10.1128/JVI.01082-09 PG 1 WC Virology SC Virology GA 467OE UT WOS:000267747400045 ER PT J AU Snyder, EL Bailey, D Shipitsin, M Polyak, K Loda, M AF Snyder, Eric L. Bailey, Dyane Shipitsin, Michail Polyak, Kornelia Loda, Massimo TI Identification of CD44v6(+)/CD24-breast carcinoma cells in primary human tumors by quantum dot-conjugated antibodies SO LABORATORY INVESTIGATION LA English DT Article DE breast cancer; cancer stem cells; CD44; neoadjuvant; quantum dots ID BREAST-CANCER CELLS; IN-SITU HYBRIDIZATION; STEM-CELLS; SPECTRAL DECONVOLUTION; PROGNOSTIC MARKER; EXPRESSION; CD44; CD24; CHEMOTHERAPY; RADIATION AB Breast carcinoma cells with the CD44(+)/CD24(low) phenotype have been reported to exhibit 'cancer stem cell' ( CSC) characteristics on the basis of their enhanced tumorigenicity and self-renewal potential in immunodeficient mice. We used immunohistochemistry to study the expression of these proteins in whole tissue sections of human breast carcinoma. We found that the fraction of CD44v6(+) cells is higher in estrogen receptor-positive carcinomas after neoadjuvant chemotherapy. We also performed double immunohistochemistry for CD44v6 and for the proliferation marker Ki67. We found that the relative number of quiescent carcinoma cells is higher in the CD44v6(+) population than in the CD44v6(-) population in specific carcinoma subtypes. We then used quantum dots and spectral imaging to increase the number of antigens that could be visualized in a single tissue section. We found that anti-CD44v6 and CD24 antibodies that were directly conjugated to quantum dots retained their ability to recognize antigen in formalin-fixed, paraffin-embedded tissue sections. We then performed triple staining for CD44v6, CD24 and Ki67 to assess the proliferation of each subpopulation of breast carcinoma cells. Our results identify differences between CD44v6- positive and CD44v6- negative breast carcinoma cells in vivo and provide a proof of principle that quantum dot-conjugated antibodies can be used to study specific sub-populations of cancer cells defined by multiple markers in a single tissue section. Laboratory Investigation (2009) 89, 857-866; doi:10.1038/labinvest.2009.54; published online 1 June 2009 C1 [Snyder, Eric L.; Bailey, Dyane; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Bailey, Dyane; Shipitsin, Michail; Polyak, Kornelia; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Snyder, Eric L.; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dana Bldg,15th Floor,D1536, Boston, MA 02115 USA. EM Massimo_loda@dfci.harvard.edu FU Center for Molecular Oncologic Pathology; Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer FX We thank Joshua Rose and Stephen Finn for their assistance with quantum dots, Eyoung Shin for help with immunohistochemistry and Rebecca Gelman for her assistance with statistics. The work was funded by the Center for Molecular Oncologic Pathology and the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer. NR 24 TC 35 Z9 37 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD AUG PY 2009 VL 89 IS 8 BP 857 EP 866 DI 10.1038/labinvest.2009.54 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 476JI UT WOS:000268435900002 PM 19488035 ER PT J AU Veena, MS Qin, M Andersson, A Sharma, S Batra, RK AF Veena, Mysore S. Qin, Min Andersson, Asa Sharma, Sherven Batra, Raj K. TI CAR mediates efficient tumor engraftment of mesenchymal type lung cancer cells SO LABORATORY INVESTIGATION LA English DT Article DE lung cancer; tumorigenesis; EMT; CAR; adhesion molecules ID ADENOVIRUS RECEPTOR CAR; AIRWAY EPITHELIAL-CELLS; ADHESION MOLECULE JAM; HUMAN BLADDER-CANCER; TIGHT-JUNCTION; GENE-TRANSFER; E-CADHERIN; MATRIX-METALLOPROTEINASE; CARCINOMA-CELLS; COXSACKIEVIRUS AB The coxsackie-adenovirus receptor (CAR) is a developmentally regulated intercellular adhesion molecule that was previously observed to be required for efficient tumor formation. To confirm that observation, we compared the tumorigenicity of clonally derived test and control cell subsets that were genetically modified for CAR. Silencing CAR in lung cancer cells with high constitutive expression reduced engraftment efficiency. Conversely, overexpressing CAR in lung cancer cells with low constitutive expression did not affect tumor formation or growth kinetics. A blocking antibody to the extracellular domain of CAR inhibited tumor engraftment, implicating that domain as being important to this process. However, differences in adhesion properties attributable to this domain (barrier function and aggregation) could not be distinguished in the test groups in vitro, and the mechanisms underlying CAR's contribution to tumor engraftment remain elusive. Because high CAR cells displayed a spindle-shaped morphology at baseline, we considered whether this expression was an accompaniment of other mesenchymal features in these lung cancer cells. Molecular correlates of CAR were compared in model epithelial and mesenchymal type lung cancer cells. CAR expression is associated with an absence of E-cadherin, diminished expression of alpha- and gamma-catenin, and increased Zeb1, Snail, and vimentin expression in lung cancer cells. In contrast, epithelial type (NCI-H292, Calu3) lung cancer cells show comparatively low CAR expression. These data suggest that if the mesenchymal cell phenotype is an accurate measure of an undifferentiated and invasive state, then CAR expression may be more closely aligned with this phenotype of lung cancer cells. Laboratory Investigation (2009) 89, 875-886; doi:10.1038/labinvest.2009.56; published online 8 June 2009 C1 [Veena, Mysore S.; Batra, Raj K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90073 USA. [Qin, Min; Andersson, Asa; Sharma, Sherven; Batra, Raj K.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA USA. [Batra, Raj K.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. RP Batra, RK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 11301 Wilshire Blvd 111Q, Los Angeles, CA 90073 USA. EM rbatra@ucla.edu OI Batra, Raj K./0000-0002-1126-543X FU Veterans Administration Medical Research Funds FX This project was supported from the Veterans Administration Medical Research Funds. We thank Dr Ling Zhang for the outstanding technical support. NR 74 TC 10 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD AUG PY 2009 VL 89 IS 8 BP 875 EP 886 DI 10.1038/labinvest.2009.56 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 476JI UT WOS:000268435900004 PM 19506548 ER PT J AU Kunisaki, KM Janoff, EN AF Kunisaki, Ken M. Janoff, Edward N. TI Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses SO LANCET INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LUNG-TRANSPLANT RECIPIENTS; HUMORAL IMMUNE-RESPONSE; STEM-CELL TRANSPLANTATION; RESPIRATORY VIRAL-INFECTIONS; SERUM ANTIBODY-RESPONSE; BRONCHIOLITIS OBLITERANS SYNDROME; AMBULATORY PERITONEAL-DIALYSIS; ACTIVE ANTIRETROVIRAL THERAPY AB Patients that are immunosuppressed might be at risk of serious influenza-associated complications. As a result, multiple guidelines recommend influenza vaccination for patients infected with HIV, who have received solid-organ transplants, who have received haemopoietic stem-cell transplants, and patients on haemodialysis. However, immunosuppression might also limit vaccine responses. To better inform policy, we reviewed the published work relevant to incidence, outcomes, and prevention of influenza infection in these patients, and in patients being treated chemotherapy and with systemic corticosteroids. Available data suggest that most immunosuppressed populations are indeed at higher risk of influenza-associated complications, have a general trend toward impaired humoral vaccine responses (although these data are mixed), and can be safely vaccinated-although longitudinal data are largely lacking. Randomised clinical trial data were limited to one study of HIV-infected patients with high vaccine efficacy. Better trial data would inform vaccination recommendations on the basis of efficacy and cost in these at-risk populations. C1 [Kunisaki, Ken M.] Minneapolis VA Med Ctr, Pulm Sect, Minneapolis, MN 55417 USA. [Kunisaki, Ken M.] Univ Minnesota, Div Pulm Allergy Crit Care & Sleep Med, Minneapolis, MN USA. [Janoff, Edward N.] Univ Colorado Denver, Mucosal & Vaccine Res Ctr, Div Infect Dis, Sch Med, Aurora, CO USA. [Janoff, Edward N.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kunisaki, KM (reprint author), Minneapolis VA Med Ctr, Pulm Sect, 1 Vet Dr,Pulm 111N, Minneapolis, MN 55417 USA. EM kunis001@umn.edu RI Kunisaki, Ken/A-6950-2009; OI Kunisaki, Ken/0000-0001-8644-2827 FU NCRR NIH HHS [K12 RR023247, K12 RR023247-02]; NHLBI NIH HHS [T32 HL007741, T32 HL007741-10, T32 HL07741]; NIAID NIH HHS [R21 AI077069, R21 AI077069-01] NR 168 TC 253 Z9 261 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD AUG PY 2009 VL 9 IS 8 BP 493 EP 504 PG 12 WC Infectious Diseases SC Infectious Diseases GA 478YT UT WOS:000268625400017 PM 19628174 ER PT J AU Choueiri, TK Bellmunt, J AF Choueiri, Toni K. Bellmunt, Joaquim TI Sunitinib in renal-cell carcinoma: expanded indications SO LANCET ONCOLOGY LA English DT Editorial Material C1 [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. [Bellmunt, Joaquim] Univ Pompeu Fabra, IMIM, Univ Hosp Mar, Barcelona, Spain. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jbellmunt@imas.imim.es NR 5 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 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2009 VL 10 IS 8 BP 740 EP 740 DI 10.1016/S1470-2045(09)70185-8 PG 1 WC Oncology SC Oncology GA 479YH UT WOS:000268697700003 PM 19615941 ER PT J AU Richmon, JD Samji, HA Deschler, DG AF Richmon, Jeremy D. Samji, Hussein A. Deschler, Daniel G. TI National Laryngopharyngectomy and Reconstructive Surgery Survey SO LARYNGOSCOPE LA English DT Article DE Laryngopharyngectomy; reconstruction; surgeon preference; otolaryngologist; plastic surgeon ID CIRCUMFERENTIAL PHARYNGOESOPHAGEAL RECONSTRUCTION; FLAP RECONSTRUCTION; FUNCTIONAL OUTCOMES; CARCINOMA; MORBIDITY AB Objectives/Hypothesis: To understand the various methods available to reconstruct total laryngopharyngectomy defects and to understand which, and to what degree, various factors influence the surgeon in choosing a particular reconstructive method. Methods: Otolaryngologists and plastic surgeons who perform head and neck reconstruction were surveyed regarding preference of laryngopharyngectomy reconstruction. Numerical and rank-order data was analyzed using T statistics and Fisher exact test. Results: Two hundred surveys were mailed and 72 physicians (36% response rate) provided data, with otolaryngologists comprising 54% of the respondents. Otolaryngologists were more likely to consider voice (P = .003) and swallowing (P = .02) outcomes compared to plastic surgeons. In contrast, plastic surgeons more often included cosmesis (P = .05) among those factors influencing their reconstructive choice. However, rank-order analysis demonstrated no statistical difference between plastic surgeons and otolaryngologists with respect to each factor. Conclusions: Our study sought to examine what motivates surgeons from several specialties to choose one reconstructive method over another for laryngopharyngeal defects. Otolaryngologists were more likely to consider voice and swallowing function in contrast to plastic surgeons, who more frequently included cosmesis as a factor. However, when physicians were asked to rank the importance of each of the eight factors from most to least important in influencing their reconstructive option, there was no statistical difference between plastic surgeons and otolaryngologists with respect to each factor. Further research is necessary to provide an evidence base for which reconstructive method offers the optimal functional restoration. C1 [Deschler, Daniel G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Head & Neck Oncol, Boston, MA 02114 USA. RP Deschler, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Head & Neck Oncol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_deschler@meei.harvard.edu NR 10 TC 4 Z9 4 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 2009 VL 119 IS 8 BP 1472 EP 1478 DI 10.1002/lary.20251 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 480MR UT WOS:000268739500004 PM 19444893 ER PT J AU Wanner, M Avram, M Gagnon, D Mihm, MC Zurakowski, D Watanabe, K Tannous, Z Anderson, RR Manstein, D AF Wanner, Molly Avram, Mathew Gagnon, Denise Mihm, Martin C., Jr. Zurakowski, David Watanabe, Kanna Tannous, Zeina Anderson, R. Rox Manstein, Dieter TI Effects of Non-Invasive, 1,210 nm Laser Exposure on Adipose Tissue: Results of a Human Pilot Study SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE fat; laser; adipose tissue ID ND-YAG LASER; SWITCHED RUBY-LASER; SELECTIVE PHOTOTHERMOLYSIS; FOCUSED ULTRASOUND; SKIN; BIOMATERIALS; MULTICENTER; NECROSIS; PULSES; DEVICE AB Background and Objectives: Laser radiation (1,210nm) has been previously shown to be capable of selective photothermolysis of adipose tissue in vitro when applied non-invasively. The objective of this pilot study was to evaluate the in vivo effects of this laser in human subjects. Study Design/Materials and Methods: Twenty-four adult subjects were exposed non-invasively on the abdomen to a 1,210 nm laser at fluences of 70,80, and 90 J/cm(2), with a 10mm spot size, 5seconds pre-cooling, and 3 seconds exposure duration delivered with parallel contact cooling. There was an impairment of the skin-cooling device during the study. Exposure and control sites were biopsied at either 1-3 days or 4-7 weeks. Tissue was processed for nitroblue tetrazolium chloride (NBTC) staining, a marker for thermal damage, and hematoxylin and eosin (H&E) staining. Results: Laser exposures were painful, requiring local anesthesia in most subjects, but otherwise well tolerated. At 1-3 days after exposure, there was a fluence-dependent loss of NBTC staining in the fat and dermis. In 2 of 14 subjects (2 of 42 exposure sites) evaluated at 1-3 days after exposure, epidermal damage was noted within a small portion of the test site, likely due to impaired contact cooling. At 4-7 weeks, lipomembranous changes of the fat were seen in 89% of test sites and 33% of control sites. Conclusions: This in Vivo Study shows histologic evidence of laser-induced damage of fat. With further development, this might become a useful treatment for disorders involving the fat and/or lower dermis. Lasers Surg. Med. 41:401-407, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Wanner, Molly; Avram, Mathew; Gagnon, Denise; Watanabe, Kanna; Tannous, Zeina; Anderson, R. Rox; Manstein, Dieter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. [Mihm, Martin C., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Zurakowski, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Anesthesia & Surg, Boston, MA 02114 USA. RP Wanner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, BAR 621,Fruit St, Boston, MA 02114 USA. EM mwanner@partners.org FU Candela Corporation FX Contract grant sponsor: Candela Corporation. NR 32 TC 28 Z9 31 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD AUG PY 2009 VL 41 IS 6 BP 401 EP 407 DI 10.1002/lsm.20785 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 475QP UT WOS:000268375600001 PM 19588533 ER PT J AU Shah, SM Konnikov, N Duncan, LM Tannous, ZS AF Shah, Sonali M. Konnikov, Nellie Duncan, Lyn M. Tannous, Zeina S. TI The Effect of 595 nm Pulsed Dye Laser on Superficial and Nodular Basal Cell Carcinomas SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE pulsed dye laser; non-melanoma skin cancer; angiogenesis ID SPECIMENS; SKIN AB Background and Objective: Basal cell carcinomas (BCCs) have Supporting vasculature that could serve as a target for 595 nm pulsed dye laser (PDL). The objective of this study was to determine the effect of repeated PDL treatments on BCCs Of Superficial and nodular subtypes and of varying diameters. Study Design/Materials and Methods: Twenty biopsy-proven BCCs received Four 595 nm PDL treatments at 2-week intervals. The tumor and 4 mm of peripheral skin were treated using a set of previously optimized laser parameters: one pass, 15 j/cm(2) energy, 3 ms pulse length, no cooling, and 7 mm spot size with 10% overlap. The treated area was excised and evaluated histologically For residual tumor. Histologic response rates of the PDL treated BCCs were compared with that of non-PDL treated, matched control tumors. Results: Nearly all BCCs <1.5 cm in diameter (n=12) showed complete response to four PDL treatments (91.7%; n = 11/12) versus 16.7% of controls (n = 2/12, P-value = 0.0003). BCCs >= 1.5cm in diameter (n=8) showed a complete response rate of 25% (n=2/8) versus 0% of controls (n=0/8, P-value=0.2). Mean clinical tumor diameter of the complete responders was 1.1 cm (n = 13) versus 2.2cm (n=7) for incomplete responders (P-value = 0.005). Tumor histologic types among the complete responders included superficial, nodular, micronodular, and keratinizing. Incompletely responding BCCs showed a significant reduction in tumor burden after PDL treatment, with residual histologic tumor burden ranging from <1% to 29% of the original clinical tumor diameter, compared to 13-68% residual tumor burden for the corresponding controls (P-value = 0.05). Conclusions: PDL is an effective means of reducing tumor burden in patients with large BCCs and may be an alternative therapy in BCCs <1.5 cm in diameter. Lasers Surg.Med.41:417-422, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Tannous, Zeina S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Shah, Sonali M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02215 USA. [Shah, Sonali M.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA. [Shah, Sonali M.; Konnikov, Nellie; Tannous, Zeina S.] Boston Vet Affairs Hlth Care Syst, Dept Dermatol, Boston, MA 02130 USA. [Duncan, Lyn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Dermatopathol Unit, Boston, MA 02114 USA. RP Tannous, ZS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 50 Staniford St,Suite 250, Boston, MA 02114 USA. EM ztanoous@partners.org FU Doris Duke/PASTEUR Clinical Research Fellowship at Harvard Medical School FX Contract grant sponsor Doris Duke/PASTEUR Clinical Research Fellowship at Harvard Medical School. NR 17 TC 22 Z9 23 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD AUG PY 2009 VL 41 IS 6 BP 417 EP 422 DI 10.1002/lsm.20787 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 475QP UT WOS:000268375600003 PM 19588534 ER PT J AU Izikson, L Nelson, JS Anderson, RR AF Izikson, Leonid Nelson, J. Stuart Anderson, R. Rox TI Treatment of Hypertrophic and Resistant Port Wine Stains With a 755 nm Laser: A Case Series of 20 Patients SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE port wine stain; resistant; PDL; alexandrite; Nd:YAG; laser; treatment; endpoint; 595 nm; 755 nm; 1,064 nm ID PULSED-DYE-LASER; BIRTHMARKS; ALEXANDRITE AB Background and Objective: Port wine stains (PWS) are heterogeneous vascular malformations that can be treated with vascular-selective pulsed dye lasers (PDL). Hypertrophic PWS, especially in adults, are consistently less responsive to PDL. Furthermore, many PWS that respond well initially to PDL treatment may reach a response plateau, becoming unresponsive to further PDL treatments, a phenomenon termed "treatment resistance." Based on the theory of selective photothermolysis, vessels in such lesions may also be specifically targeted with a 755 nm laser that has selectivity for deoxyhemoglobin as well as oxyhemoglobin and increased depth of skin penetration. Study Design/Patients and Methods: Retrospective case review of 20 patients with either hypertrophic or PDL-resistant PWS treated with a 755 nm laser alone or in combination with other lasers, including PDL. Results: Hypertrophic PWS showed significant tightening after treatment with a 755 nm laser in combination with PDL. Most PDL-resistant PWS showed moderate improvement after treatment with either a 755 nm laser alone or in combination with another laser, including PDL. Some lesions showed only mild improvement or did not respond. Serious side effects were infrequent. Most commonly encountered complications included pain, edema, bullae, crusting, and rare scarring. Conclusions: Alexandrite 755 nm laser can be useful for the treatment of hypertrophic and treatment-resistant PWS in adult and pediatric patients. Complications are infrequent and predictable. Careful attention to using a fluence at or near the threshold for clinical response with this deeply penetrating laser is essential to prevent serious sequelae. Lasers Surg. Med. 41:427-432, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Izikson, Leonid; Anderson, R. Rox] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Izikson, Leonid; Anderson, R. Rox] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Nelson, J. Stuart] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92617 USA. RP Izikson, L (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BHX 630,Bartlett Hall, Boston, MA 02114 USA. EM lizikson@partners.org FU National Institutes of Health [AR47551, EB002495] FX This project was supported in part by research grants awarded from the National Institutes of Health (AR47551 and EB002495 to JSN). NR 17 TC 45 Z9 51 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD AUG PY 2009 VL 41 IS 6 BP 427 EP 432 DI 10.1002/lsm.20793 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 475QP UT WOS:000268375600005 PM 19588532 ER PT J AU Tefferi, A Stone, RM AF Tefferi, A. Stone, R. M. TI Iron chelation therapy in myelodysplastic syndrome - Cui bono? SO LEUKEMIA LA English DT Editorial Material ID REFRACTORY-ANEMIA; SURVIVAL C1 [Tefferi, A.] Mayo Clin, Rochester, MN 55905 USA. [Stone, R. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tefferi, A (reprint author), Mayo Clin, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu NR 7 TC 20 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2009 VL 23 IS 8 BP 1373 EP 1373 DI 10.1038/leu.2009.39 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 482CR UT WOS:000268862000001 PM 19672273 ER PT J AU Chen, Y Hu, Y Michaels, S Segal, D Brown, D Li, S AF Chen, Y. Hu, Y. Michaels, S. Segal, D. Brown, D. Li, S. TI Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice SO LEUKEMIA LA English DT Article DE omacetaxine; leukemic stem cells; CML; B-ALL; BCR-ABL ID CHRONIC MYELOGENOUS LEUKEMIA; PHILADELPHIA-CHROMOSOME; TYROSINE KINASE; IMATINIB; BCR/ABL; HOMOHARRINGTONINE; PROGENITORS; INDUCTION; EFFICIENT; DISEASE AB Omacetaxine mepesuccinate (formerly homoharringtonine) is a molecule with a mechanism of action that is different from tyrosine kinase inhibitors, and its activity in chronic myeloid leukemia (CML) seems to be independent of the BCR-ABL mutation status. Using BCR-ABL-expressing myelogenous and lymphoid cell lines and mouse models of CML and B-cell acute lymphoblastic leukemia (B-ALL) induced by wild-type BCR-ABL or T315I mutant-BCR-ABL, we evaluated the inhibitory effects of omacetaxine on CML and B-ALL. We showed that more than 90% of the leukemic stem cells were killed after treatment with omacetaxine in vitro. In contrast, less than 9 or 25% of the leukemic stem cells were killed after treating with imatinib or dasatinib, respectively. After 4 days of treatment of CML mice with omacetaxine, Gr-1(+)myeloid leukemia cells decreased in the peripheral blood of the treated CML mice. In the omacetaxine-treated B-ALL mice, only 0.8% of the B220(+)leukemia cells were found in peripheral blood, compared with 34% of the B220(+)leukemia cells in the placebo group. Treatment with omacetaxine decreased the number of leukemia stem cells and prolonged the survival of mice with BCR-ABL-induced CML or B-ALL. Leukemia (2009) 23, 1446-1454; doi:10.1038/leu.2009.52; published online 26 March 2009 C1 [Chen, Y.; Li, S.] Univ Massachusetts, Sch Med, Dept Med, Div Hematol Oncol, Worcester, MA 01605 USA. [Hu, Y.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Michaels, S.; Segal, D.; Brown, D.] ChemGenex Pharmaceut Inc, Dept Canc Discovery, Menlo Pk, CA USA. RP Li, S (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Hematol Oncol, Lazare Res Bldg 315,364 Plantat St, Worcester, MA 01605 USA. EM Shaoguang.Li@umassmed.edu RI chen, yaoyu/A-4236-2011 FU Leukemia & Lymphoma Society; National Institutes of Health [R01-CA114199, R01-CA122142] FX This work is supported by grants from the Leukemia & Lymphoma Society and the National Institutes of Health (R01-CA114199, R01-CA122142) to SL. SL is a Scholar of the Leukemia and Lymphoma Society. NR 22 TC 56 Z9 56 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2009 VL 23 IS 8 BP 1446 EP 1454 DI 10.1038/leu.2009.52 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 482CR UT WOS:000268862000012 PM 19322212 ER PT J AU Wojiski, S Guibal, FC Kindler, T Lee, BH Jesneck, JL Fabian, A Tenen, DG Gilliland, DG AF Wojiski, S. Guibal, F. C. Kindler, T. Lee, B. H. Jesneck, J. L. Fabian, A. Tenen, D. G. Gilliland, D. G. TI PML-RAR alpha initiates leukemia by conferring properties of self-renewal to committed promyelocytic progenitors SO LEUKEMIA LA English DT Article DE self-renewal; progenitor; promyelocyte; APL ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; MURINE MODEL; NEUTROPHIL ELASTASE; BCR-ABL; MICE; TRANSFORMATION; EXPRESSION; HIERARCHY; DISORDER AB Acute promyelocytic leukemia (APL) is characterized by hyperproliferation of promyelocytes, progenitors that are committed to terminal differentiation into granulocytes, making it an ideal disease in which to study the transforming potential of less primitive cell types. We utilized a murine model of APL in which the PML-RAR alpha oncogene is expressed from the endogenous cathepsin G promoter to test the hypothesis that leukemia stem cell (LSC) activity resides within the differentiated promyelocyte compartment. We prospectively purified promyelocytes from transgenic mice at various stages of disease and observed that PML-RAR alpha-expressing promyelocytes from young preleukemic mice had acquired properties of self-renewal both in vitro and in vivo. Progression to acute leukemia was associated with an expansion of the promyelocyte compartment at the expense of other stem, progenitor and terminally differentiated populations. Leukemic promyelocytes exhibited properties of self-renewal, and were capable of engendering leukemia in secondary recipient mice. These data indicate that PML-RAR alpha alone can confer properties of self-renewal to committed hematopoietic progenitors before the onset of disease. These findings are consistent with the hypothesis that cancer stem cells may arise from committed progenitors that lack stem cell properties, provided that the initiating mutation in cancer progression activates programs that confer properties of self-renewal. Leukemia (2009) 23, 1462-1471; doi:10.1038/leu.2009.63; published online 26 March 2009 C1 [Wojiski, S.; Kindler, T.; Lee, B. H.; Fabian, A.; Gilliland, D. G.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. [Wojiski, S.; Kindler, T.; Lee, B. H.; Fabian, A.; Gilliland, D. G.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Guibal, F. C.; Tenen, D. G.] Harvard Inst Med, Dept Hematol Oncol, Boston, MA USA. [Jesneck, J. L.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Jesneck, J. L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Tenen, D. G.; Gilliland, D. G.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, 1 Blackfan Circle, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu RI Kindler, Thomas/K-5995-2013; OI Tenen, Daniel/0000-0002-6423-3888 FU National Institute of Health [DK50654, CA66996]; Leukemia and Lymphoma society FX We thank Maricel Gozo and Dena Leeman for technical support, as well as Stefan Fro r hling, Claudia Scholl and all the members of the Gilliland laboratory for helpful discussions and comments regarding this study. DGG is a Doris Duke Foundation Distinguished Clinical Scientist and a Howard Hughes Medical Institute investigator. Supported in part by National Institute of Health grants DK50654 and CA66996 and by the Leukemia and Lymphoma society to DGG. NR 31 TC 54 Z9 57 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2009 VL 23 IS 8 BP 1462 EP 1471 DI 10.1038/leu.2009.63 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 482CR UT WOS:000268862000014 PM 19322209 ER PT J AU Mrabat, H Beagle, J Hang, Z Garg, HG Hales, CA Quinn, DA AF Mrabat, Hicham Beagle, John Hang, Zhao Garg, Hari G. Hales, Charles A. Quinn, Deborah A. TI Inhibition of HA Synthase 3 mRNA Expression, with a Phosphodiesterase 3 Inhibitor, Blocks Lung Injury in a Septic Ventilated Rat Model SO LUNG LA English DT Article DE HAS3; HA; Phosphodiesterase inhibitor III; Sepsis; Ventilation ID MAMMALIAN HYALURONAN SYNTHASES; RESPIRATORY-DISTRESS-SYNDROME; KAPPA-B; NEUTROPHIL FUNCTION; PULMONARY-EDEMA; III INHIBITORS; FRAGMENTS; CELLS; MACROPHAGES; MILRINONE AB Low-molecular-weight hyaluronan produced by hyaluronan synthase 3 (HAS3) has been shown to play a role in acute lung injury secondary to high-tidal-volume ventilation. Phosphodiesterase 3 inhibitors have been shown to decrease HAS3 expression. We hypothesized that low-molecular-weight hyaluronan (LMW HA) produced by HAS3 mediates LPS-induced lung injury in the mechanically ventilated rat and that milrinone (MIL), by blocking HAS3 mRNA expression, would prevent the injury. Rats were randomized to four groups: controls with mechanical ventilation at 7 cc/kg MV, MV+LPS, MV+MIL, and MV+LPS+MIL. Rats were intubated and ventilated without PEEP for 4 h. Lipopolysaccharide (LPS) (1 mg/kg) was infused into the arterial line 1 h prior to MV. MIL 10 mu g/kg/min ( or an equivalent volume of saline) was infused through the venous line at the beginning of MV. Bronchoalveolar lavage fluid (BAL) was collected after 4 h of ventilation and lungs were saved for histopathology. LPS significantly increased neutrophil infiltration and protein concentration in the BAL and augmented lung injury score on histology. MIL significantly lowered alveolar protein and neutrophil infiltration as well as lung injury in response to LPS. Furthermore, MIL decreased the mRNA expression for HAS3 and MIP2 in lung tissue and decreased the protein content in BAL. MIL, a commonly used inotropic agent, inhibited LPS-induced lung inflammation and lung injury in mechanically ventilated rats. The anti-inflammatory properties of MIL may be mediated by inhibition of HAS3 and/or MIP2 and could be beneficial in the treatment of sepsis. C1 [Mrabat, Hicham] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mrabat, H (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St,Bullfinch 148, Boston, MA 02114 USA. EM hmrabat@partners.org FU National Institutes of Health [HL039150]; Shriners [8620, 8895] FX This work was supported by the National Institutes of Health grant HL039150 (CAH) and Shriners grants 8620 and 8895. Training grant T32HL007874. NR 37 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 EI 1432-1750 J9 LUNG JI Lung PD AUG PY 2009 VL 187 IS 4 BP 233 EP 239 DI 10.1007/s00408-009-9157-3 PG 7 WC Respiratory System SC Respiratory System GA 481ZT UT WOS:000268853500004 PM 19572173 ER PT J AU Vonken, EJ Korosoglou, G Yu, J Schar, M Weissleder, R Stuber, M AF Vonken, Evert-jan Korosoglou, Grigorios Yu, Jing Schaer, Michael Weissleder, Ralph Stuber, Matthias TI On the Dual Contrast Enhancement Mechanism in Frequency-Selective Inversion-Recovery Magnetic Resonance Angiography (IRON-MRA) SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance angiography; off-resonance imaging; blood-pool contrast agent; susceptibility contrast; background suppression ID INPUT FUNCTION; AGENT; SUSCEPTIBILITY AB The susceptibility of blood changes after administration of a paramagnetic contrast agent that shortens T(1). Concomitantly, the resonance frequency of the blood vessels shifts in a geometry-dependent way. This frequency change may be exploited for incremental contrast generation by applying a frequency-selective saturation prepulse prior to the imaging sequence. The dual origin of vascular enhancement depending first on off-resonance and second on T(1) lowering was investigated in vitro, together with the geometry dependence of the signal at 3T. First results obtained in an in vivo rabbit model are presented. Magn Reson Med 62:314-324, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Vonken, Evert-jan; Korosoglou, Grigorios; Yu, Jing; Schaer, Michael; Stuber, Matthias] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Korosoglou, Grigorios] Univ Heidelberg, Dept Cardiol, D-6900 Heidelberg, Germany. [Schaer, Michael] Philips Healthcare, Cleveland, OH USA. [Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Vonken, EJ (reprint author), UMC Utrecht, Dept Radiol, E01-132,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM evertjan@isi.uu.nl RI Stuber, Matthias/B-2949-2010; Schar, Michael/C-8087-2015; OI Stuber, Matthias/0000-0001-9843-2028; Schar, Michael/0000-0002-7044-9941 FU National Institutes of Health (NIH) [R01 HL084186]; Donald W. Reynolds Foundation FX Grant sponsor: National Institutes of Health (NIH); Grant number: R01 HL084186; Grant sponsor: Donald W. Reynolds Foundation. NR 17 TC 2 Z9 2 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2009 VL 62 IS 2 BP 314 EP 324 DI 10.1002/mrm.22027 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 476IH UT WOS:000268432400006 PM 19526511 ER PT J AU Diamond, SG Perdue, KL Boas, DA AF Diamond, Solomon Gilbert Perdue, Katherine L. Boas, David A. TI A cerebrovascular response model for functional neuroimaging including dynamic cerebral autoregulation SO MATHEMATICAL BIOSCIENCES LA English DT Article DE Physiological modeling; Dynamic cerebral autoregulation; NIRS; FMRI; Balloon model; Windkessel ID DIFFUSE OPTICAL TOMOGRAPHY; BLOOD-FLOW; BRAIN ACTIVATION; GAS-EXCHANGE; PRESSURE; OXYGENATION; SIMULATION; REACTIVITY; DISEASE; VOLUME AB Functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) can be used to isolate an evoked response to a stimulus from significant background physiological fluctuations. Data analysis approaches typically use averaging or linear regression to remove this physiological baseline with varying degrees of success. Biophysical model-based analysis of the functional hemodynamic response has also been advanced previously with the Balloon and Windkessel models. In the present work, a biophysical model of systemic and cerebral circulation and gas exchange is applied to resting state NIRS neuroimaging data from 10 human subjects. The model further includes dynamic cerebral autoregulation, which modulates the cerebral arteriole compliance to control cerebral blood flow. This biophysical model allows for prediction, from noninvasive blood pressure measurements, of the background hemodynamic fluctuations in the systemic and cerebral circulations. Significantly higher correlations with the NIRS data were found using the biophysical model predictions compared to blood pressure regression and compared to transfer function analysis (multifactor ANOVA, p < 0.0001). This finding supports the further development and use of biophysical models for removing baseline activity in functional neuroimaging analysis. Future extensions of this work could model changes in cerebrovascular physiology that occur during development, aging, and disease. (c) 2009 Elsevier Inc. All rights reserved. C1 [Diamond, Solomon Gilbert; Perdue, Katherine L.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Boas, David A.] Massachusetts Gen Hosp, Athinoulu A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Diamond, SG (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. EM Solomon.G.Diamond@Dartmouth.edu RI Perdue, Katherine/D-4306-2013; OI Perdue, Katherine/0000-0003-2846-3149; Diamond, Solomon/0000-0002-7589-2942 FU NIH [T32-CA09502, P41-RR14075, R01-EB002482, R01-EB006385]; NSF FX The authors wish to thank M.A. Franceschini for the data, T.J. Huppert for consultation, and S.R. Arridge for an early conceptualization of this project. Funding was provided by NIH T32-CA09502, P41-RR14075, R01-EB002482, R01-EB006385, and the MIND Institute. UP received support from an NSF Graduate Research Fellowship. NR 60 TC 12 Z9 12 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD AUG PY 2009 VL 220 IS 2 BP 102 EP 117 DI 10.1016/j.mbs.2009.05.002 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 484LQ UT WOS:000269046800004 PM 19442671 ER PT J AU Chien, K AF Chien, Kenneth TI Master heart progenitor cells SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract CT 16th Annual Conference of the International-Society-of-Development-Biologists CY SEP 06-10, 2009 CL Edinburgh, SCOTLAND SP Int Soc Dev Biol C1 [Chien, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD AUG PY 2009 VL 126 BP S40 EP S40 DI 10.1016/j.mod.2009.06.1024 PG 1 WC Developmental Biology SC Developmental Biology GA 497DM UT WOS:000270034900100 ER PT J AU Mateus, R Kokel, D Peterson, R AF Mateus, Rita Kokel, David Peterson, Randall TI Understanding neurons through light: A novel behavioral assay SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract CT 16th Annual Conference of the International-Society-of-Development-Biologists CY SEP 06-10, 2009 CL Edinburgh, SCOTLAND SP Int Soc Dev Biol C1 [Mateus, Rita; Kokel, David; Peterson, Randall] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD AUG PY 2009 VL 126 BP S192 EP S192 DI 10.1016/j.mod.2009.06.465 PG 1 WC Developmental Biology SC Developmental Biology GA 497DM UT WOS:000270034900552 ER PT J AU Tseng, KAS Masi, A Levin, M AF Tseng, Kelly Ai-Sun Masi, Alessio Levin, Michael TI Sodium transport is necessary and sufficient for appendage regeneration SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract CT 16th Annual Conference of the International-Society-of-Development-Biologists CY SEP 06-10, 2009 CL Edinburgh, SCOTLAND SP Int Soc Dev Biol C1 [Tseng, Kelly Ai-Sun; Levin, Michael] Tufts Univ, Medford, MA 02155 USA. [Tseng, Kelly Ai-Sun; Masi, Alessio; Levin, Michael] Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD AUG PY 2009 VL 126 BP S46 EP S46 DI 10.1016/j.mod.2009.06.1009 PG 1 WC Developmental Biology SC Developmental Biology GA 497DM UT WOS:000270034900116 ER PT J AU Putt, M Long, JA Montagnet, C Silber, JH Chang, VW Liao, KJ Schwartz, JS Pollack, CE Wong, YN Armstrong, K AF Putt, Mary Long, Judith A. Montagnet, Chantal Silber, Jeffrey H. Chang, Virginia W. Liao, Kaijun Schwartz, J. Sanford Pollack, Craig Evan Wong, Yu-Ning Armstrong, Katrina TI Racial Differences in the Impact of Comorbidities on Survival Among Elderly Men With Prostate Cancer SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE administrative data; comorbidity; disparities; Medicare; prostate cancer; social epidemiology; survival analysis ID CORONARY-ARTERY-DISEASE; ALL-CAUSE MORTALITY; RACIAL/ETHNIC DIFFERENCES; SOCIOECONOMIC-STATUS; RADICAL PROSTATECTOMY; BREAST-CANCER; BLACK; AGE; DISABILITY; HEALTH AB This study investigates differences in the effects of comorbidities on survival in Medicare beneficiaries with prostate cancer. Medicare data were used to assemble a cohort of 65- to 76-year-old Black (n = 6,402) and White (n = 47,458) men with incident localized prostate cancer in 1999 who survived >= 1 year postdiagnosis. Comorbidities were more prevalent among Blacks than among Whites. For both races, greater comorbidity was associated with decreasing survival rates; however, the effect among Blacks was smaller than in Whites. After adjusting for age, socioeconomic status, and community characteristics, the association between increasing comorbidities and survival remained weaker for Blacks than for Whites, and racial disparity in survival decreased with increasing number of comorbidities. Differential effects of comorbidities on survival were also evident when examining different classes of comorbid conditions. Adjusting for treatment had little impact on these results, despite variation in the racial difference in receipt of prostatectomy with differing comorbidity levels. C1 [Schwartz, J. Sanford; Armstrong, Katrina] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Long, Judith A.; Chang, Virginia W.; Pollack, Craig Evan] Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Silber, Jeffrey H.] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA USA. [Silber, Jeffrey H.; Schwartz, J. Sanford] Univ Penn, Wharton Sch Business, Philadelphia, PA 19104 USA. [Pollack, Craig Evan] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. [Armstrong, Katrina] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Putt, Mary] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Armstrong, K (reprint author), Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, 1204 Blockley Hall, Philadelphia, PA 19104 USA. EM karmstro@mail.med.upenn.edu FU Center for Population Health and Health Disparities at the University of Pennsylvania under Public Health Services [P50-CA105641] FX This research was sponsored by the Center for Population Health and Health Disparities at the University of Pennsylvania under Public Health Services Grant P50-CA105641. The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; and the Research Data Assistance Center (ResDAC), University of Minnesota. Please address correspondence to Katrina Armstrong, 1204 Blockley Hall, University of Pennsylvania, Philadelphia, PA 19104; e-mail: karmstro@ mail. med. upenn. edu. NR 42 TC 12 Z9 12 U1 8 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD AUG PY 2009 VL 66 IS 4 BP 409 EP 435 DI 10.1177/1077558709333996 PG 27 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 468FG UT WOS:000267801600002 PM 19357389 ER PT J AU Garfield, JM Garfield, FB Hevelone, ND Bhattacharyya, N Dedrick, DF Ashley, SW Nadel, ES Katz, JT Kim, C Mitani, AA AF Garfield, Joseph M. Garfield, Frances B. Hevelone, Nathanael D. Bhattacharyya, Neil Dedrick, Daniel F. Ashley, Stanley W. Nadel, Eric S. Katz, Joel T. Kim, Christine Mitani, Aya A. TI Doctors in acute and longitudinal care specialties emphasise different professional attributes: implications for training programmes SO MEDICAL EDUCATION LA English DT Article ID MEDICAL PROFESSIONALISM; PHYSICIAN; RESIDENTS; SOCIETY; ANESTHESIOLOGY; COMPLAINTS; CONTRACT AB Objectives Organised medicine mandates that professionalism be taught during specialty training. This study's primary objective was to determine the relative importance that doctors in different specialties place on different attributes of a medical professional. Methods Attending staff and resident doctors in acute care (anaesthesia, emergency medicine, surgery) and longitudinal care (internal medicine, psychiatry) specialties at a large academic hospital completed an anonymous, web-based survey. The forced-choice format required respondents to narrow down 25 professional attributes to three. The main outcome measure was the number of doctors in the two specialty groups who chose one or more attributes in each of six underlying categories. Results Almost two-thirds of respondents in both groups chose Moral and Ethical attributes. Significantly more longitudinal than acute care doctors chose Relationships with Patients attributes (76% versus 58%) and Communication Skills attributes (28% versus 18%), whereas significantly more acute care doctors chose Clinical Competence attributes (44% versus 29%). Specialty group was more important in choice of professional attributes than gender or position as a resident or attending staff doctor. Conclusions Most respondents chose attributes that the literature and organised medicine define as core elements of medical professionalism. The differences between specialty groups suggest that attributes in the Relationships with Patients and Communication Skills categories be emphasised for trainees in acute care specialties, and attributes in the Clinical Competence category be emphasised for trainees in longitudinal care specialties. C1 [Garfield, Joseph M.; Garfield, Frances B.; Dedrick, Daniel F.; Mitani, Aya A.] Brigham & Womens Hosp, Dept Anaesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Hevelone, Nathanael D.] Dana Farber Canc Ctr, Boston, MA USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. [Ashley, Stanley W.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Katz, Joel T.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kim, Christine] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Garfield, JM (reprint author), Brigham & Womens Hosp, Dept Anaesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. EM garfield@zeus.bwh.harvard.edu OI Hevelone, Nathanael/0000-0003-4740-2085 NR 30 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0308-0110 J9 MED EDUC JI Med. Educ. PD AUG PY 2009 VL 43 IS 8 BP 749 EP 756 DI 10.1111/j.1365-2923.2009.03411.x PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 473AZ UT WOS:000268177000006 PM 19659488 ER PT J AU Tsagaan, B Nappi, J Yoshida, H AF Tsagaan, Baigalmaa Naeppi, Janne Yoshida, Hiroyuki TI Nonlinear regression-based method for pseudoenhancement correction in CT colonography SO MEDICAL PHYSICS LA English DT Article DE biological tissues; computerised tomography; phantoms ID VIRTUAL COLONOSCOPY; COLORECTAL-CANCER; POLYP MEASUREMENT; VALIDATION; GUIDELINES; NEOPLASIA AB In CT colonography (CTC), orally administered positive-contrast tagging agents are often used for differentiating residual bowel contents from native colonic structures. However, tagged materials can sometimes hyperattenuate observed CT numbers of their adjacent untagged materials. Such pseudoenhancement complicates the differentiation of colonic soft-tissue structures from tagged materials, because pseudoenhanced colonic structures may have CT numbers that are similar to those of tagged materials. The authors developed a nonlinear regression-based (NLRB) method for performing a local image-based pseudoenhancement correction of CTC data. To calibrate the correction parameters, the CT data of an anthropomorphic reference phantom were correlated with those of partially tagged phantoms. The CTC data were registered spatially by use of an adaptive multiresolution method, and untagged and tagged partial-volume soft-tissue surfaces were correlated by use of a virtual tagging scheme. The NLRB method was then optimized to minimize the difference in the CT numbers of soft-tissue regions between the untagged and tagged phantom CTC data by use of the Nelder-Mead downhill simplex method. To validate the method, the CT numbers of untagged regions were compared with those of registered pseudoenhanced phantom regions before and after the correction. The CT numbers were significantly different before performing the correction (p < 0.01), whereas, after the correction, the difference between the CT numbers was not significant. The effect of the correction was also tested on the size measurement of polyps that were covered by tagging in phantoms and in clinical cases. In phantom cases, before the correction, the diameters of 12 simulated polyps submerged in tagged fluids that were measured in a soft-tissue CT display were significantly different from those measured in an untagged phantom (p < 0.01), whereas after the correction the difference was not significant. In clinical cases, before the correction, the diameters of 29 colonoscopy-confirmed 3-14 mm polyps affected by tagging that were measured in a soft-tissue CT display were significantly different from those measured in a lung CT display (p < 0.0001) or in colonoscopy (p < 0.05), whereas after the correction the difference was not significant. Finally, the effect of the correction was tested on automated detection of 25 polyps >= 6 mm affected by tagging in 56 clinical CTC cases. The application of the correction increased the detection accuracy from 60% with 5.0 FP detections per patient without correction to 96% with 2.9 FP detections with correction. This improvement in detection accuracy was statistically significant (p < 0.05). The results indicate that the proposed NLRB method can yield an accurate pseudoenhancement correction with potentially significant benefits in clinical CTC examinations. C1 [Tsagaan, Baigalmaa; Naeppi, Janne; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tsagaan, Baigalmaa; Naeppi, Janne; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tsagaan, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM yoshida.hiro@mgh.harvard.edu RI Nappi, Janne/B-9424-2008 OI Nappi, Janne/0000-0002-0108-0992 FU U. S. Public Health Service [CA095279]; American Cancer Society [RSG-05-088-01-CCE] FX This study was supported in part by Grant No. CA095279 from the U. S. Public Health Service and by Research Scholar Grant No. RSG-05-088-01-CCE from the American Cancer Society. The authors thank Dr. Michael Zalis (Massachusetts General Hospital) for providing the CT data of the anthropomorphic phantom and Dr. Richard Choi (Virtual Colonoscopy Center, Walter Reed Army Medical Center, Washington, DC) for providing the clinical CTC cases via the Walter Reed Army Medical Center Virtual Colonoscopy Collection. NR 22 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2009 VL 36 IS 8 BP 3596 EP 3606 DI 10.1118/1.3147201 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 476KY UT WOS:000268440600025 PM 19746794 ER PT J AU Rajendran, R Ronald, JA Ye, T Ren, MQ Chen, JW Weissleder, R Rutt, BK Halliwell, B Watt, F AF Rajendran, Reshmi Ronald, John A. Ye, Tao Ren Minqin Chen, John W. Weissleder, Ralph Rutt, Brian K. Halliwell, Barry Watt, Frank TI Nuclear Microscopy: A Novel Technique for Quantitative Imaging of Gadolinium Distribution within Tissue Sections SO MICROSCOPY AND MICROANALYSIS LA English DT Article; Proceedings Paper CT Annual Meeting on Microscopy and Microanalysis CY AUG, 2008 CL Albuquerque, NM DE gadolinium; magnetic resonance imaging; nuclear microscopy; PIXE; STIM; RBS; atherosclerosis ID PLASMA-CHOLESTEROL LEVELS; FED RABBIT MODELS; CONTRAST AGENTS; ATHEROSCLEROSIS; MYELOPEROXIDASE; MRI; MEDIA AB All clinically-approved and many novel gadolinium (Gd)-based contrast agents used to enhance signal intensity in magnetic resonance imaging (MRI) are optically silent. To verify MRI results, a "gold standard" that can map and quantify Gd down to the parts per million (ppm) levels is required. Nuclear microscopy is a relatively new technique that has this capability and is composed of a combination of three ion beam techniques: scanning transmission ion microscopy, Rutherford backscattering spectrometry, and particle induced X-ray emission used in conjunction with a high energy proton microprobe. In this proof-of-concept study, we show that in diseased aortic vessel walls obtained at 2 and 4 h after intravenous injection of the myeloperoxidase-senstitive MRI agent, bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate gadolinium, there was a time-dependant Gd clearance (2 h = 18.86 ppm, 4 h = 8.65 ppm). As expected, the control animal, injected with the clinically-approved conventional agent diethylenetriamine-pentaacetate gadolinium and sacrificed I week after injection, revealed no significant residual Gd in the tissue. Similar to known in vivo Gd pharmacokinetics, we found that Gd concentration dropped by a factor of 2 in vessel wall tissue in 1.64 h. Further high-resolution studies revealed that Gd was relatively uniformly distributed, consistent with random agent diffusion. We conclude that nuclear microscopy is potentially very useful for validation studies involving Gd-based magnetic resonance contrast agents. C1 [Rajendran, Reshmi; Ye, Tao; Ren Minqin; Watt, Frank] Natl Univ Singapore, Dept Phys, Ctr Ion Beam Applicat, Singapore 117548, Singapore. [Ronald, John A.; Rutt, Brian K.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada. [Chen, John W.; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Halliwell, Barry] Natl Univ Singapore, Dept Biochem, Singapore 117548, Singapore. RP Rajendran, R (reprint author), Natl Univ Singapore, Dept Phys, Ctr Ion Beam Applicat, Kent Ridge, Singapore 117548, Singapore. EM reshmi_rajendran@sbic.a-star.edu.sg RI Halliwell, Barry/C-8318-2009; Ronald, John/B-7123-2008 OI Ronald, John/0000-0003-3665-173X FU NHLBI NIH HHS [K08 HL081170-03, KO8HL081170, R01 HL078641, R01 HL078641-03, R01-HL078641, K08 HL081170] NR 24 TC 4 Z9 4 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1431-9276 J9 MICROSC MICROANAL JI Microsc. microanal. PD AUG PY 2009 VL 15 IS 4 BP 338 EP 344 DI 10.1017/S1431927609090813 PG 7 WC Materials Science, Multidisciplinary; Microscopy SC Materials Science; Microscopy GA 476ET UT WOS:000268422000008 PM 19575834 ER PT J AU Maguen, S Stalnaker, M McCaslin, S Litz, BT AF Maguen, Shira Stalnaker, Mark McCaslin, Shannon Litz, Brett T. TI PTSD Subclusters and Functional Impairment in Kosovo Peacekeepers SO MILITARY MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MALE VIETNAM VETERANS; OF-LIFE OUTCOMES; COMBAT VETERANS; PSYCHOMETRIC PROPERTIES; INTERPERSONAL VIOLENCE; PSYCHIATRIC-DISORDERS; ALCOHOL-USE; AGGRESSION; SYMPTOMS AB Peacekeepers deployed to Kosovo (N = 203) were evaluated prospectively, before the mission (August 2000) and at postdeployment, on a number of mental health and functional impairment variables. We examined the association between PTSD symptom subclusters and three indicators of functional impairment using hierarchical regression analyses, controlling for PTSD symptoms before the mission, and history of prior trauma. In the first model, avoidance and hyperarousal symptoms uniquely predicted a conglomerate of functional impact outcomes (e.g., employment, family relationships, social functioning). In the second model, emotional numbing was the only significant predictor of violent behaviors. In the third model, re-experiencing symptoms were the only significant predictor of alcohol abuse problems. Overall, the four PTSD subclusters are differentially associated with varying functional impairment outcomes, which is important to note for evaluation and treatment purposes for veterans returning from overseas deployments. C1 [Maguen, Shira; Stalnaker, Mark; McCaslin, Shannon] San Francisco VA Med Ctr, PTSD Program, San Francisco, CA USA. [Maguen, Shira; Stalnaker, Mark; McCaslin, Shannon] Univ Calif San Francisco, San Francisco 116P, San Francisco, CA 94143 USA. [Litz, Brett T.] Boston Healthcare Syst, Natl Ctr PTSD, Dept Vet Affairs, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program, San Francisco, CA USA. NR 47 TC 24 Z9 26 U1 2 U2 6 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 AUG PY 2009 VL 174 IS 8 BP 779 EP 785 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 601LG UT WOS:000278060300005 PM 19743730 ER PT J AU Huang, H Yu, M Akie, TE Moran, TB Woo, AJ Tu, N Waldon, Z Lin, YY Steen, H Cantor, AB AF Huang, Hui Yu, Ming Akie, Thomas E. Moran, Tyler B. Woo, Andrew J. Tu, Nathan Waldon, Zachary Lin, Yin Yin Steen, Hanno Cantor, Alan B. TI Differentiation-Dependent Interactions between RUNX-1 and FLI-1 during Megakaryocyte Development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; CORE-BINDING FACTOR; MULTIPLE CHROMOSOMAL TRANSLOCATIONS; ACUTE MYELOID-LEUKEMIA; TRANSCRIPTION FACTOR; DNA-BINDING; CBF-BETA; MYELODYSPLASTIC SYNDROME; ADULT HEMATOPOIESIS; AUTO-INHIBITION AB The transcription factor RUNX-1 plays a key role in megakaryocyte differentiation and is mutated in cases of myelodysplastic syndrome and leukemia. In this study, we purified RUNX-1-containing multiprotein complexes from phorbol ester-induced L8057 murine megakaryoblastic cells and identified the ets transcription factor FLI-1 as a novel in vivo-associated factor. The interaction occurs via direct protein-protein interactions and results in synergistic transcriptional activation of the c-mpl promoter. Interestingly, the interaction fails to occur in uninduced cells. Gel filtration chromatography confirms the differentiation-dependent binding and shows that it correlates with the assembly of a complex also containing the key megakaryocyte transcription factors GATA-1 and Friend of GATA-1 (FOG-1). Phosphorylation analysis of FLI-1 with uninduced versus induced L8057 cells suggests the loss of phosphorylation at serine 10 in the induced state. Substitution of Ser10 with the phosphorylation mimic aspartic acid selectively impairs RUNX-1 binding, abrogates transcriptional synergy with RUNX-1, and dominantly inhibits primary fetal liver megakaryocyte differentiation in vitro. Conversely, substitution with alanine, which blocks phosphorylation, augments differentiation of primary megakaryocytes. We propose that dephosphorylation of FLI-1 is a key event in the transcriptional regulation of megakaryocyte maturation. These findings have implications for other cell types where interactions between runx and ets family proteins occur. C1 [Huang, Hui; Yu, Ming; Akie, Thomas E.; Moran, Tyler B.; Woo, Andrew J.; Tu, Nathan; Cantor, Alan B.] Childrens Hosp Boston, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Huang, Hui; Yu, Ming; Akie, Thomas E.; Moran, Tyler B.; Woo, Andrew J.; Tu, Nathan; Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Waldon, Zachary; Lin, Yin Yin; Steen, Hanno] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Pathol, Boston, MA USA. RP Cantor, AB (reprint author), Childrens Hosp Boston, Dept Pediat Hematol Oncol, 300 Longwood Ave,Karp 7, Boston, MA 02115 USA. EM alan.cantor@childrens.harvard.edu RI Yu, Ming/A-3354-2012 FU NIH [R01HL082952]; American Society of Hematology FX This work was supported by a grant from the NIH (R01HL082952) and a Junior Faculty Scholar Award from the American Society of Hematology (A.B.C.). NR 67 TC 45 Z9 45 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2009 VL 29 IS 15 BP 4103 EP 4115 DI 10.1128/MCB.00090-09 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 469ZB UT WOS:000267939400008 PM 19470763 ER PT J AU Bai, XH Wang, DW Kong, L Zhang, Y Luan, Y Kobayashi, T Kronenberg, HM Yu, XP Liu, CJ AF Bai, Xiao-Hui Wang, Da-Wei Kong, Li Zhang, Yan Luan, Yi Kobayashi, Tatsuya Kronenberg, Henry M. Yu, Xiu-Ping Liu, Chuan-ju TI ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID OLIGOMERIC MATRIX PROTEIN; HORMONE-RELATED PEPTIDE; GRANULIN-EPITHELIN PRECURSOR; MULTIPLE EPIPHYSEAL DYSPLASIA; PARATHYROID-HORMONE; INDIAN-HEDGEHOG; CELL-LINE; IN-VITRO; FRONTOTEMPORAL DEMENTIA; PROTEOLYTIC ACTIVITIES AB ADAMTS-7, a metalloproteinase that belongs to ADAMTS family, is important for the degradation of cartilage extracellular matrix proteins in arthritis. Herein we report that ADAMTS-7 is upregulated during chondrocyte differentiation and demonstrates the temporal and spatial expression pattern during skeletal development. ADAMTS-7 potently inhibits chondrocyte differentiation and endochondral bone formation, and this inhibition depends on its proteolytic activity. The cysteine-rich domain of ADAMTS-7 is required for its interaction with the extracellular matrix, and the C-terminal four-thrombospondin motifs are necessary for its full proteolytic activity and inhibition of chondrocyte differentiation. ADAMTS-7 is an important target of canonical PTHrP signaling, since (i) PTHrP induces ADAMTS-7, (ii) ADAMTS-7 is downregulated in PTHrP null mutant (PTHrP-/-) growth plate chondrocytes, and (iii) blockage of ADAMTS-7 almost abolishes PTHrP-mediated inhibition of chondrocyte hypertrophy and endochondral bone growth. ADAMTS-7 associates with granulin-epithelin precursor (GEP), an autocrine growth factor that has been implicated in tissue regeneration, tumorigenesis, and inflammation. In addition, ADAMTS-7 acts as a new GEP convertase and neutralizes GEP-stimulated endochondral bone formation. Collectively, these findings demonstrate that ADAMTS-7, a direct target of PTHrP signaling, negatively regulates endochondral bone formation by associating with and inactivating GEP chondrogenic growth factor. C1 [Bai, Xiao-Hui; Yu, Xiu-Ping; Liu, Chuan-ju] Shandong Univ, Sch Med, Inst Pathogen Biol, Jinan 250012, Shandong, Peoples R China. [Bai, Xiao-Hui; Wang, Da-Wei; Kong, Li; Zhang, Yan; Luan, Yi; Liu, Chuan-ju] NYU, Sch Med, Dept Orthopaed Surg, New York, NY 10003 USA. [Wang, Da-Wei] Shandong Univ, Shandong Prov Hosp, Dept Vasc Surg, Jinan 250012, Shandong, Peoples R China. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Yu, Xiu-Ping] Chinese Minist Educ, Key Lab Expt Teratol, Jinan, Peoples R China. [Liu, Chuan-ju] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. RP Yu, XP (reprint author), Shandong Univ, Sch Med, Inst Pathogen Biol, Jinan 250012, Shandong, Peoples R China. EM yuxp@sdu.edu.cn; chuanju.liu@med.nyu.edu FU NIH [AR053210, AR050620, AG029388]; Arthritis National Research Foundation FX This work was aided by NIH research grants AR053210, AR050620, and AG029388 and a grant from the Arthritis National Research Foundation. NR 99 TC 51 Z9 53 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2009 VL 29 IS 15 BP 4201 EP 4219 DI 10.1128/MCB.00056-09 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 469ZB UT WOS:000267939400016 PM 19487464 ER PT J AU James, MF Han, S Polizzano, C Plotkin, SR Manning, BD Stemmer-Rachamimov, AO Gusella, JF Ramesh, V AF James, Marianne F. Han, Sangyeul Polizzano, Carolyn Plotkin, Scott R. Manning, Brendan D. Stemmer-Rachamimov, Anat O. Gusella, James F. Ramesh, Vijaya TI NF2/Merlin Is a Novel Negative Regulator of mTOR Complex 1, and Activation of mTORC1 Is Associated with Meningioma and Schwannoma Growth SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; NF2 TUMOR-SUPPRESSOR; MEDIATES CONTACT INHIBITION; ACTIN CYTOSKELETON; TSC1-TSC2 COMPLEX; PROTEIN-KINASE; GENE-PRODUCT; ERM PROTEINS; MERLIN; PHOSPHORYLATION AB Inactivating mutations of the neurofibromatosis 2 (NF2) gene, NF2, result predominantly in benign neurological tumors, schwannomas and meningiomas, in humans; however, mutations in murine Nf2 lead to a broad spectrum of cancerous tumors. The tumor-suppressive function of the NF2 protein, merlin, a membrane-cytoskeleton linker, remains unclear. Here, we identify the mammalian target of rapamycin complex 1 (mTORC1) as a novel mediator of merlin's tumor suppressor activity. Merlin-deficient human meningioma cells and merlin knockdown arachnoidal cells, the nonneoplastic cell counterparts of meningiomas, exhibit rapamycin-sensitive constitutive mTORC1 activation and increased growth. NF2 patient tumors and Nf2-deficient mouse embryonic fibroblasts demonstrate elevated mTORC1 signaling. Conversely, the exogenous expression of wild-type merlin isoforms, but not a patient-derived L64P mutant, suppresses mTORC1 signaling. Merlin does not regulate mTORC1 via the established mechanism of phosphoinositide 3-kinase-Akt or mitogen-activated protein kinase/extracellular signal-regulated kinase-mediated TSC2 inactivation and may instead regulate TSC/mTOR signaling in a novel fashion. In conclusion, the deregulation of mTORC1 activation underlies the aberrant growth and proliferation of NF2-associated tumors and may restrain the growth of these lesions through negative feedback mechanisms, suggesting that rapamycin in combination with phosphoinositide 3-kinase inhibitors may be therapeutic for NF2. C1 [James, Marianne F.; Han, Sangyeul; Polizzano, Carolyn; Gusella, James F.; Ramesh, Vijaya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Div Neuropathol, Mol Neurooncol Lab, Boston, MA 02114 USA. [Manning, Brendan D.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM ramesh@helix.mgh.harvard.edu FU National Institute of Health [NS024279, MH079213, NS045776]; S. Sydney De Young Foundation; Neurofibromatosis, Inc., New England FX This work was supported by the National Institute of Health grants NS024279 and MH079213, the S. Sydney De Young Foundation, and Neurofibromatosis, Inc., New England. Packaging and production of viral supernatants for lentiviral infections were supported by the NIH Core Facility grant NS045776. NR 49 TC 95 Z9 99 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2009 VL 29 IS 15 BP 4250 EP 4261 DI 10.1128/MCB.01581-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 469ZB UT WOS:000267939400019 PM 19451225 ER PT J AU Acosta-Jaquez, HA Keller, JA Foster, KG Ekim, B Soliman, GA Feener, EP Ballif, BA Fingar, DC AF Acosta-Jaquez, Hugo A. Keller, Jennifer A. Foster, Kathryn G. Ekim, Bilgen Soliman, Ghada A. Feener, Edward P. Ballif, Bryan A. Fingar, Diane C. TI Site-Specific mTOR Phosphorylation Promotes mTORC1-Mediated Signaling and Cell Growth SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX-1; RICH AKT SUBSTRATE; 40 KDA PRAS40; MAMMALIAN TARGET; KINASE-ACTIVITY; RAPAMYCIN MTOR; PROTEIN-KINASE; GENE-PRODUCTS; FKBP12-RAPAMYCIN-ASSOCIATED PROTEIN; 3T3-L1 ADIPOCYTES AB The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) functions as a rapamycin-sensitive environmental sensor that promotes cellular biosynthetic processes in response to growth factors and nutrients. While diverse physiological stimuli modulate mTORC1 signaling, the direct biochemical mechanisms underlying mTORC1 regulation remain poorly defined. Indeed, while three mTOR phosphorylation sites have been reported, a functional role for site-specific mTOR phosphorylation has not been demonstrated. Here we identify a new site of mTOR phosphorylation (S1261) by tandem mass spectrometry and demonstrate that insulin-phosphatidylinositol 3-kinase signaling promotes mTOR S1261 phosphorylation in both mTORC1 and mTORC2. Here we focus on mTORC1 and show that TSC/Rheb signaling promotes mTOR S1261 phosphorylation in an amino acid-dependent, rapamycin-insensitive, and autophosphorylation- independent manner. Our data reveal a functional role for mTOR S1261 phosphorylation in mTORC1 action, as S1261 phosphorylation promotes mTORC1-mediated substrate phosphorylation (e.g., p70 ribosomal protein S6 kinase 1 [S6K1] and eukaryotic initiation factor 4E binding protein 1) and cell growth to increased cell size. Moreover, Rheb-driven mTOR S2481 autophosphorylation and S6K1 phosphorylation require S1261 phosphorylation. These data provide the first evidence that site-specific mTOR phosphorylation regulates mTORC1 function and suggest a model whereby insulin-stimulated mTOR S1261 phosphorylation promotes mTORC1 autokinase activity, substrate phosphorylation, and cell growth. C1 [Acosta-Jaquez, Hugo A.; Keller, Jennifer A.; Foster, Kathryn G.; Ekim, Bilgen; Soliman, Ghada A.; Fingar, Diane C.] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Soliman, Ghada A.; Fingar, Diane C.] Univ Michigan, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Ann Arbor, MI 48109 USA. [Feener, Edward P.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ballif, Bryan A.] Univ Vermont, Dept Biol, Burlington, VT 05405 USA. [Ballif, Bryan A.] Univ Vermont, Vermont Genet Network Prote Facil, Burlington, VT 05405 USA. RP Fingar, DC (reprint author), Univ Michigan, Sch Med, Dept Cell & Dev Biol, 109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM dfingar@umich.edu FU NIH [R01 DK-078135]; American Diabetes Association; American Cancer Society; Michigan Diabetes Research and Training Center; American Heart Association; Vermont Genetics Network; National Center for Research Resources [NIH P20 RR16462] FX This work was supported by NIH R01 DK-078135, the American Diabetes Association, the American Cancer Society, and the Michigan Diabetes Research and Training Center (D.C.F.); the American Heart Association (G.A.S. and J.A.K.); and the Vermont Genetics Network (NIH P20 RR16462 from the Institutional Development Award Networks of Biomedical Research Excellence Program of the National Center for Research Resources) (B.A.B.). This work utilized the Cell and Molecular Biology Core(s) of the the Michigan Diabetes Research and Training Center funded by NIH5P60 DK20572 from NIDDK at the University of Michigan. NR 77 TC 62 Z9 65 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2009 VL 29 IS 15 BP 4308 EP 4324 DI 10.1128/MCB.01665-08 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 469ZB UT WOS:000267939400024 PM 19487463 ER PT J AU Lu, L Ladinsky, MS Kirchhausen, T AF Lu, Lei Ladinsky, Mark S. Kirchhausen, Tom TI Cisternal Organization of the Endoplasmic Reticulum during Mitosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID NUCLEAR-ENVELOPE BREAKDOWN; MEMBRANE-PROTEINS; MAMMALIAN-CELLS; PLASMA-MEMBRANE; LIVING CELLS; DYNAMICS; GOLGI; RESOLUTION; MICROTUBULES; INHERITANCE AB The endoplasmic reticulum ( ER) of animal cells is a single, dynamic, and continuous membrane network of interconnected cisternae and tubules spread out throughout the cytosol in direct contact with the nuclear envelope. During mitosis, the nuclear envelope undergoes a major rearrangement, as it rapidly partitions its membrane-bound contents into the ER. It is therefore of great interest to determine whether any major transformation in the architecture of the ER also occurs during cell division. We present structural evidence, from rapid, live-cell, three-dimensional imaging with confirmation from high-resolution electron microscopy tomography of samples preserved by high-pressure freezing and freeze substitution, unambiguously showing that from prometaphase to telophase of mammalian cells, most of the ER is organized as extended cisternae, with a very small fraction remaining organized as tubules. In contrast, during interphase, the ER displays the familiar reticular network of convolved cisternae linked to tubules. C1 [Lu, Lei; Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Lu, Lei; Kirchhausen, Tom] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Ladinsky, Mark S.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Ladinsky, Mark S.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu RI Lu, Lei/A-2225-2011 OI Lu, Lei/0000-0002-8192-1471 FU National Institutes of Health [R01 GM-075252] FX This work is funded by National Institutes of Health grant R01 GM-075252 (to T. K.). We thank Eric Marino for assistance in maintaining the microscope facility in the Kirchhausen laboratory and Tom Rapoport, Randall King, Jennifer Lippincott-Schwartz, and Howard Worman for generously providing reagents. NR 30 TC 80 Z9 82 U1 0 U2 8 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD AUG 1 PY 2009 VL 20 IS 15 BP 3471 EP 3480 DI 10.1091/mbc.E09-04-0327 PG 10 WC Cell Biology SC Cell Biology GA 477UV UT WOS:000268545300003 PM 19494040 ER PT J AU Modrek, B Ge, L Pandita, A Lin, E Mohan, S Yue, P Guerrero, S Lin, WM Pham, T Modrusan, Z Seshagiri, S Stern, HM Waring, P Garraway, LA Chant, J Stokoe, D Cavet, G AF Modrek, Barmak Ge, Lin Pandita, Ajay Lin, Eva Mohan, Sankar Yue, Peng Guerrero, Steve Lin, William M. Pham, Thinh Modrusan, Zora Seshagiri, Somasekar Stern, Howard M. Waring, Paul Garraway, Levi A. Chant, John Stokoe, David Cavet, Guy TI Oncogenic Activating Mutations Are Associated with Local Copy Gain SO MOLECULAR CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; NUCLEOTIDE POLYMORPHISM ARRAYS; FACTOR RECEPTOR GENE; K-RAS; GEFITINIB SENSITIVITY; NUMBER; GENOME; ADENOCARCINOMA; PROTOONCOGENES; TRANSFORMATION AB Although activating mutations and gains in copy number are key mechanisms for oncogene activation, the relationship between the two is not well understood. In this study, we focused on KRAS copy gains and mutations in non-small cell lung cancer. We found that KRAS copy gains occur more frequently in tumors with KRAS activating mutations and are associated with large increases in KRAS expression. These copy gains tend to be more focal in tumors with activating mutations than in those with wild-type KRAS. Fluorescence in situ hybridization analysis revealed that some tumors have homogeneous low-level gains of the KRAS locus, whereas others have high-level amplification of KRAS, often in only a fraction of tumor cells. Associations between activating mutation and copy gains were also observed for other oncogenes (EGFR in non-small cell lung cancer, BRAF and NRAS in melanoma). Activating mutations were associated with copy gains only at the mutated oncogene locus but not other oncogene loci. However, KRAS activating mutations in colorectal cancer were not associated with copy gains. Future work is warranted to clarify the relationship among the different mechanisms of oncogene activation. (Mol Cancer Res 2009;7(8):1244-52) C1 [Modrek, Barmak; Yue, Peng; Guerrero, Steve; Cavet, Guy] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA. [Pandita, Ajay; Mohan, Sankar] Genentech Inc, Dept Res Oncol, San Francisco, CA 94080 USA. [Ge, Lin; Lin, Eva; Modrusan, Zora; Seshagiri, Somasekar; Chant, John; Stokoe, David] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. [Pham, Thinh; Stern, Howard M.; Waring, Paul] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA. [Lin, William M.; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lin, William M.; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA USA. RP Cavet, G (reprint author), Crescendo Biosci, 400 E Jamie Court, San Francisco, CA 94080 USA. EM glcavet@gmail.com NR 35 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD AUG PY 2009 VL 7 IS 8 BP 1244 EP 1252 DI 10.1158/1541-7786.MCR-08-0532 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 486BK UT WOS:000269170200006 PM 19671679 ER PT J AU Willers, H Taghian, AG Luo, CM Treszezamsky, A Sgroi, DC Powell, SN AF Willers, Henning Taghian, Alphonse G. Luo, Chen-Mei Treszezamsky, Alejandro Sgroi, Dennis C. Powell, Simon N. TI Utility of DNA Repair Protein Foci for the Detection of Putative BRCA1 Pathway Defects in Breast Cancer Biopsies SO MOLECULAR CANCER RESEARCH LA English DT Article ID FANCONI-ANEMIA; HOMOLOGOUS RECOMBINATION; SPORADIC BREAST; DAMAGE RESPONSE; NUCLEAR FOCI; PHENOTYPE; PHOSPHORYLATION; MUTATIONS; PROMOTER; SUBTYPE AB The DNA damage response pathway controlled by the breast cancer and Fanconi anemia (FA) genes can be disrupted by genetic or epigenetic mechanisms in breast cancer. Defects in this pathway may render the affected tumors hypersensitive to DNA-damaging agents. The identification of these defects poses a challenge because of the large number of genes involved in the FA/BRCA pathway. Many pathway components form subnuclear repair protein foci upon exposure to ionizing radiation in vitro, but it was unknown whether foci can be detected in live cancer tissues. Thus, the goal of this pilot study was to identify pathway defects by using a novel ex vivo foci biomarker assay on tumor biopsies. Fresh pretreatment biopsy specimens from patients with locally advanced sporadic breast cancer were irradiated or mock-treated in the laboratory (ex vivo). Foci formation of DNA repair proteins BRCA1, FANCD2, and RAD51 was detected by immunofluorescence microscopy. Three out of seven tumors showed intact radiation-induced foci formation, whereas the other four tumors exhibited a defective foci response. Notably, three of the foci-defective tumors were estrogen receptor/progesterone receptor/HER2-negative (triple-negative), a phenotype that has been associated with BRCA1 deficiency. In conclusion, in this pilot study, we report the successful detection of BRCA1, FANCD2, and RAD51 foci in breast cancer biopsies irradiated ex vivo. Our approach represents a potentially powerful biomarker assay for the detection of pre-existing and functionally important defects within the complex FA/BRCA pathway, which may ultimately allow us to tailor cancer treatment to the DNA repair profile of individual tumors. (Mol Cancer Res 2009;7(8):1304-9) C1 [Powell, Simon N.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA. [Willers, Henning; Taghian, Alphonse G.; Luo, Chen-Mei; Treszezamsky, Alejandro; Powell, Simon N.] Harvard Univ, Massachusetts Gen Hosp, Lab Cellular & Mol Radiat Oncol, Dept Radiat Oncol,Canc Ctr,Med Sch, Charlestown, MA USA. [Sgroi, Dennis C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Dept Pathol, Charlestown, MA USA. RP Powell, SN (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA. EM powells@mskcc.org FU Avon-NCI Progress for Patients Award [CA089393] FX Grant support: Avon-NCI Progress for Patients Award on the Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence in Breast Cancer CA089393 (A.G. Taghian). NR 29 TC 69 Z9 69 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD AUG PY 2009 VL 7 IS 8 BP 1304 EP 1309 DI 10.1158/1541-7786.MCR-09-0149 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 486BK UT WOS:000269170200011 PM 19671671 ER PT J AU Duan, ZF Choy, E Harmon, D Yang, C Ryu, K Schwab, J Mankin, H Hornicek, FJ AF Duan, Zhenfeng Choy, Edwin Harmon, David Yang, Cao Ryu, Keinosuke Schwab, Joseph Mankin, Henry Hornicek, Francis J. TI Insulin-like growth factor-I receptor tyrosine kinase inhibitor cyclolignan picropodophyllin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID UVEAL MELANOMA; EWINGS-SARCOMA; BREAST-CANCER; TUMOR-GROWTH; MOUSE MODEL; EXPRESSION; PATHWAY; IGF-1R; PPP; ACTIVATION AB Insulin-like growth factor-I receptor (IGF-IR) is an important mediator of tumor cell survival and shows prognostic significance in sarcoma. To explore potential therapeutic strategies for interrupting signaling through this pathway, we assessed the ability of cyclolignan picropodophyllin (PPP), a member of the cyclolignan family, to selectively inhibit the receptor tyrosine kinase activity of IGF-IR in several sarcoma cell line model systems. Of the diverse sarcoma subtypes studied, osteosarcoma cell lines were found to be particularly sensitive to IGF-IR inhibition, including several multidrug resistant osteosarcoma cell lines with documented resistance to various conventional anticancer drugs. PPP shows relatively little toxicity in human osteoblast cell lines when compared with osteosarcoma cell lines. These studies show that PPP significantly inhibits IGF-IR expression and activation in both chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cell lines. This inhibition of the IGF-IR pathway correlates with suppression of proliferation of osteosarcoma cell lines and with apoptosis induction as measured by monitoring of poly(ADP-ribose) polymerase and its cleavage product and by quantitative measurement of apoptosis-associated CK18Asp396. Importantly, PPP increases the cytotoxic effects of doxorubicin in doxorubicin-resistant osteosarcoma cell lines U-2OS(MR) and KHOS(MR). Furthermore, small interfering RNA down-regulation of IGF-IR expression in drug-resistant cell lines also caused resensitization to doxorubicin. Our data suggest that inhibition of IGF-IR with PPP offers a novel and selective therapeutic strategy for ostosarcoma, and at the same time, PPP is effective at reversing the drug-resistant phenotype in osteosarcoma cell lines. [Mol Cancer Ther 2009;8(8):2122-30] C1 [Duan, Zhenfeng; Yang, Cao; Ryu, Keinosuke; Schwab, Joseph; Mankin, Henry; Hornicek, Francis J.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Choy, Edwin; Harmon, David] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Choy, Edwin; Harmon, David] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Jackson Bldg,Room 1115,55 Fruit St, Boston, MA 02114 USA. EM zduan@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU Gattegno and Wechsler funds; Ovarian Cancer Research Foundation (OCRF); National Cancer Institute; NIH [R01-CA119617]; Jennifer Hunter Yates Foundation FX The Gattegno and Wechsler funds; the Ovarian Cancer Research Foundation (OCRF) and National Cancer Institute, NIH (Nanotechnology Platform Partnership) grant R01-CA119617 (Z. Duan); and the Jennifer Hunter Yates Foundation (E. Choy). NR 41 TC 45 Z9 46 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2009 VL 8 IS 8 BP 2122 EP 2130 DI 10.1158/1535-7163.MCT-09-0115 PG 9 WC Oncology SC Oncology GA 484FM UT WOS:000269029300007 PM 19638450 ER PT J AU Liu, JY Park, SH Morisseau, C Hwang, SH Hammock, BD Weiss, RH AF Liu, Jun-Yan Park, See-Hyoung Morisseau, Christophe Hwang, Sung Hee Hammock, Bruce D. Weiss, Robert H. TI Sorafenib has soluble epoxide hydrolase inhibitory activity, which contributes to its effect profile in vivo SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RENAL-CELL CARCINOMA; REFRACTORY SOLID TUMORS; ARACHIDONIC-ACID; EPOXYEICOSATRIENOIC ACIDS; EPOXYGENASE METABOLITES; BLOOD-PRESSURE; KIDNEY CANCER; PHASE-I; HYPERTENSION; SUNITINIB AB The advent of multikinase inhibitors targeting the vascular endothelial growth factor (VEGF) receptor has revolutionized the treatment of highly angiogenic malignancies such as renal cell carcinoma. Interestingly, several such inhibitors are commercially available, and they each possess diverse specific beneficial and adverse effect profiles. In examining the structure of sorafenib, it was hypothesized that this compound would possess inhibitory effects on the soluble epoxide hydrolase, an enzyme with pleiotropic effects on inflammation and vascular disease. We now show that sorafenib but not another VEGF receptor targeted inhibitor sunitinib is a potent inhibitor of the human soluble epoxide hydrolase in vitro (K(1) = 17 +/- 4 nmol/L). Furthermore, sorafenib causes the expected in vivo shift in oxylipid profile resulting from soluble epoxide hydrolase inhibition, evidence of a reduction in the acute inflammatory response. Lipopolysaccharide-induced hypotension was reversed with sorafenib but not sunitinib treatment, suggesting that soluble epoxide hydrolase inhibition accounts for at least part of the anti-inflammatory effect of sorafenib. The pharmacokinetic studies presented here in light of the known potency of sorafenib as a soluble epoxide hydrolase inhibitor indicate that the soluble epoxide hydrolase will be largely inhibited at therapeutic doses of sorafenib. Thus, it is likely that soluble epoxide hydrolase inhibition contributes to the beneficial effects from the inhibition of the VEGF receptor and other kinases during treatment with sorafenib. [Mol Cancer Ther 2009;8(8):2193-203] C1 [Weiss, Robert H.] Univ Calif Davis, Div Nephrol, Dept Internal Med, Genome & Biomed Sci Facil, Davis, CA 95616 USA. [Liu, Jun-Yan; Morisseau, Christophe; Hwang, Sung Hee; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Morisseau, Christophe; Hammock, Bruce D.; Weiss, Robert H.] Univ Calif Davis, Canc Res Ctr, Davis, CA 95616 USA. [Park, See-Hyoung; Weiss, Robert H.] Univ Calif Davis, Comparat Pathol Grad Grp, Davis, CA 95616 USA. [Weiss, Robert H.] Med Ctr, US Dept Vet Affairs, Sacramento, CA USA. RP Weiss, RH (reprint author), Univ Calif Davis, Div Nephrol, Dept Internal Med, Genome & Biomed Sci Facil, Room 6312,1 Shields Ave, Davis, CA 95616 USA. EM rhweiss@ucdavis.edu RI LIU, JUNYAN/B-2515-2010 FU National Institute of Environmental Health Sciences (NIEHS) [R37 ES02710]; NIEHS SBRP [P42 ES04699]; NIH [HL85727]; Early Detection Research Network, National Cancer Institute, U.S. NIH [5UO1CA86402]; Morris Animal Foundation [D06CA-065] FX National Institute of Environmental Health Sciences (NIEHS) grant R37 ES02710, NIEHS SBRP grant P42 ES04699, and NIH HL85727 (J-Y. Liu, C. Morisseau, and B.D. Hammock), and grant 5UO1CA86402 (Early Detection Research Network, National Cancer Institute, U.S. NIH) and grant D06CA-065 from the Morris Animal Foundation (S-H. Park and R.H. Weiss). NR 53 TC 39 Z9 39 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2009 VL 8 IS 8 BP 2193 EP 2203 DI 10.1158/1535-7163.MCT-09-0119 PG 11 WC Oncology SC Oncology GA 484FM UT WOS:000269029300014 PM 19671760 ER PT J AU Ma, YL Peng, JY Liu, WJ Zhang, P Huang, L Gao, BB Shen, TY Zhou, YK Chen, HQ Chu, ZX Zhang, M Qin, HL AF Ma, Yanlei Peng, Jiayuan Liu, Weijie Zhang, Peng Huang, Long Gao, Benbo Shen, Tongyi Zhou, Yukun Chen, Hongqi Chu, Zhaoxin Zhang, Ming Qin, Huanlong TI Proteomics Identification of Desmin as a Potential Oncofetal Diagnostic and Prognostic Biomarker in Colorectal Cancer SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; SERUM TUMOR-MARKER; GEL-ELECTROPHORESIS; HEPATOCELLULAR-CARCINOMA; ALPHA-FETOPROTEIN; SKELETAL-MUSCLE; CELLS; ANTIGENS; DIFFERENTIATION; PROGRESSION AB Colorectal cancer (CRC) is the third most common cancer worldwide and has poor prognosis. To identify the oncofetal proteins involved in CRC carcinogenesis, differentially expressed proteins among fetal colorectal tissues, CRC, and the paired tumor-adjacent normal colorectal tissues were investigated by a two-dimensional gel electrophoresis and MALDI-TOF/TOF-based proteomics approach. 42 protein spots were differentially expressed among these tissues, and 22 proteins were identified by MS analysis. Desmin and zinc finger protein 829 were found to be elevated in CRC tissue and fetal colorectal tissue compared with normal colorectal tissue. The elevated expression of desmin in CRC tissue and different developmental stages of fetus colon was confirmed by RT-PCR and Western blot analysis. Immunohistochemical analysis showed that the elevated expression of desmin was correlated with the severity and differentiation of CRC and decreased survival rate of CRC patients. Finally by developing a highly sensitive immunoassay, desmin could be detected in human serum and was significantly elevated in CRC patients compared with healthy volunteers. We propose that desmin be considered a potential oncofetal serum tumor marker for CRC that may have significance in the detection of patients with CRC. Molecular & Cellular Proteomics 8: 1878-1890, 2009. C1 [Ma, Yanlei; Peng, Jiayuan; Liu, Weijie; Zhang, Peng; Huang, Long; Shen, Tongyi; Zhou, Yukun; Chen, Hongqi; Chu, Zhaoxin; Zhang, Ming; Qin, Huanlong] Shanghai Jiao Tong Univ, Peoples Hosp 6, Dept Surg, Shanghai 200233, Peoples R China. [Gao, Benbo] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Qin, HL (reprint author), Shanghai Jiao Tong Univ, Peoples Hosp 6, Dept Surg, 600 Yishan Rd, Shanghai 200233, Peoples R China. EM hl-qin@hotmail.com RI huanlong, Qin/B-3844-2015 FU Shanghai Science and Technology Development Fund [05DJ14010]; Major Basic Research Program of Shanghai [07DZ19505]; National 973 Basic Research Program of China [2008CB517403] FX This work was supported by Shanghai Science and Technology Development Fund Grant 05DJ14010), Major Basic Research Program of Shanghai Grant 07DZ19505, and National 973 Basic Research Program of China Grant 2008CB517403. NR 53 TC 63 Z9 69 U1 3 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2009 VL 8 IS 8 BP 1878 EP 1890 DI 10.1074/mcp.M800541-MCP200 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 483IX UT WOS:000268958700010 PM 19460759 ER PT J AU Marto, JA AF Marto, J. A. TI Quantitative Proteomics Analysis of C/EBP alpha Transcription Factor Complexes in Leukemia SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Marto, J. A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dept Canc Biol, Boston, MA USA. [Marto, J. A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2009 BP S55 EP S55 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 483CH UT WOS:000268939000090 ER PT J AU Kondo, T El Khattabi, I Nishimura, W Laybutt, DR Geraldes, P Shah, S King, G Bonner-Weir, S Weir, G Sharma, A AF Kondo, Takuma El Khattabi, Ilham Nishimura, Wataru Laybutt, D. Ross Geraldes, Pedro Shah, Samit King, George Bonner-Weir, Susan Weir, Gordon Sharma, Arun TI p38 MAPK Is a Major Regulator of MafA Protein Stability under Oxidative Stress SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID INSULIN GENE-TRANSCRIPTION; BETA-CELL DIFFERENTIATION; EMBRYONIC STEM-CELLS; CHRONIC HYPERGLYCEMIA; C-MAF; LENS DEVELOPMENT; EXPRESSION; GLUCOSE; PHOSPHORYLATION; MICE AB Mammalian MafA/RIPE3b1 is an important glucose-responsive transcription factor that regulates function, maturation, and survival of beta-cells. Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function. Because MafA is a highly phosphorylated protein, we examined whether regulating activity of protein kinases can increase MafA expression by enhancing its stability. We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3. Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose. We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation. Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK. Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA. These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations. Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function. (Molecular Endocrinology 23: 1281-1290, 2009) C1 [Kondo, Takuma; El Khattabi, Ilham; Nishimura, Wataru; Shah, Samit; Bonner-Weir, Susan; Weir, Gordon; Sharma, Arun] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Geraldes, Pedro; King, George] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA 02215 USA. [Kondo, Takuma; El Khattabi, Ilham; Nishimura, Wataru; Geraldes, Pedro; King, George; Bonner-Weir, Susan; Weir, Gordon; Sharma, Arun] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Laybutt, D. Ross] St Vincents Hosp, Garvan Inst Med Res, Diabet & Obes Res Program, Sydney, NSW 2010, Australia. RP Sharma, A (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM arun.sharma@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656; Nishimura, Wataru/0000-0002-8068-1277 FU National Institutes of Health (NIH) [DK060127, T32 DK07260, DK-36836]; American Diabetes Association (ADA) [7-08-RA-146]; National Health and Medical Research Council of Australia [427616]; Adler Foundation; Juvenile Diabetes Research Foundation [3-2005-74] FX This study was supported by National Institutes of Health (NIH) Research Grant DK060127 and American Diabetes Association (ADA) Grant 7-08-RA-146 (to A. S.); National Health and Medical Research Council of Australia Grant 427616 (to D. R. L.). T. K., I. E. K., and W.N. were supported in part by postdoctoral fellowships from The Adler Foundation, NIH Institutional Training Grant (NIH T32 DK07260), and Juvenile Diabetes Research Foundation (3-2005-74), respectively. We acknowledge the Diabetes Endocrinology Research Center (NIH DK-36836)-supported Media and Advanced Microscopy (Histology and Confocal facilities) Cores at the Joslin. NR 48 TC 16 Z9 17 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 2009 VL 23 IS 8 BP 1281 EP 1290 DI 10.1210/me.2008-0482 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 475GI UT WOS:000268346200015 PM 19407223 ER PT J AU Kraus, JP Hasek, J Kozich, V Collard, R Venezia, S Janosikova, B Wang, J Stabler, SP Allen, RH Jakobs, C Finn, CT Chien, YH Hwu, WL Hegele, RA Mudd, SH AF Kraus, Jan P. Hasek, Jindrich Kozich, Viktor Collard, Renata Venezia, Sarah Janosikova, Bohumila Wang, Jian Stabler, Sally P. Allen, Robert H. Jakobs, Cornelis Finn, Christine T. Chien, Yin-Hsiu Hwu, Wuh-Liang Hegele, Robert A. Mudd, S. Harvey TI Cystathionine gamma-lyase: Clinical, metabolic, genetic, and structural studies SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Cystathionine gamma-lyase; Cystathioninuria; Hypercystathioninemia; Mutations; Deletion ID CHROMATOGRAPHY MASS-SPECTROMETRY; TOTAL HOMOCYSTEINE; FOLATE-DEFICIENCY; HYDROGEN-SULFIDE; TRANSSULFURATION; CYSTEINE; SERUM; POLYMORPHISM; ELEVATION; COBALAMIN AB We report studies of six individuals with marked elevations of cystathionine in plasma and/or urine. Studies of CTH, the gene that encodes cystathionine gamma-lyase, revealed the presence among these individuals of either homozygous or compound heterozygous forms of a novel large deletion, p.Gly57_Gln196-del, two novel missense mutations, c.589C>T (p.Arg197Cys) and c.932C>T (p.Thr311Ile), and one previously reported alteration, c.200C>T (p.Thr67Ile). Another novel missense mutation, c.185G>T (p.Arg62His), was found in heterozygous form in three mildly hypercystathioninemic members of a Taiwanese family. In one severely hypercystathioninemic individual no CTH mutation was found. Brief clinical histories of the cystathioninemic/cystathioninuric patients are presented. Most of the novel mutations were expressed and the CTH activities of the mutant proteins determined. The crystal structure of the human enzyme, hCTH, and the evidence available as to the effects of the mutations in question, as well as those of the previously reported p.Gln240Glu, on protein structure, enzymatic activity, and responsiveness to vitamin B-6 administration are discussed. Among healthy Czech controls, 9.3% were homozygous for CTH c.1208G>T (p.Ser403Ile), previously found homozygously in 7.5% of Canadians for whom plasma total homocysteine (tHcy) had been measured. Compared to wild-type homozygotes, among the 55 Czech c.1208G>T (p.Ser403Ile) homozygotes a greater level of plasma cystathionine was found only after methionine loading. Three of the four individuals homozygous or compound heterozygous for inactivating CTH mutations had mild plasma tHcy elevations, perhaps indicating a cause-and-effect relationship. The experience with the present patients provides no evidence that severe loss of CTH activity is accompanied by adverse clinical effects. Published by Elsevier Inc. C1 [Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. [Kraus, Jan P.; Collard, Renata; Venezia, Sarah] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Hasek, Jindrich] Acad Sci Czech Republic, Inst Macromol Chem, Dept Struct Anal, Prague, Czech Republic. [Kozich, Viktor; Janosikova, Bohumila] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Dis, Prague, Czech Republic. [Wang, Jian; Hegele, Robert A.] Robarts Res Inst, London, ON N6A 5C1, Canada. [Stabler, Sally P.; Allen, Robert H.] Univ Colorado, Hlth Sci Ctr, Div Hematol, Aurora, CO USA. [Jakobs, Cornelis] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Amsterdam, Netherlands. [Finn, Christine T.] Massachusetts Gen Hosp, Dept Psychiat, Harvard Partners Ctr Genet & Genom, Boston, MA 02114 USA. [Chien, Yin-Hsiu; Hwu, Wuh-Liang] Natl Taiwan Univ Hosp, Dept Med Genet, Taipei, Taiwan. [Chien, Yin-Hsiu; Hwu, Wuh-Liang] Natl Taiwan Univ Hosp, Dept Pediat, Taipei 10016, Taiwan. RP Mudd, SH (reprint author), NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. EM muddh@mail.nih.gov RI Hasek, Jindrich/G-3267-2014; Hegele, Robert/G-3301-2011; Janosikova, Bohumila/D-2940-2017; Kozich, Viktor/A-7672-2008 OI Hasek, Jindrich/0000-0001-7973-1815; Janosikova, Bohumila/0000-0002-0081-4018; HWU, WUH-LIANG/0000-0001-6690-4879; Kozich, Viktor/0000-0001-5820-5277 FU American Heart Association [AHA 2-5-80663]; NIH [HL065217-06A2, AG09834]; Jerome Lejeune foundation [305/07/1073]; Wellcome Trust [070255/Z/03/Z]; Ministry of Education of the Czech Republic [MSM0021620806] FX The authors thank Dr. William M. Sugden, Wisconsin Alumni Research Foundation for establishing the immortalized line of lymphocytes from patient #3051. The plasmid pET22b+hCTH was a generous gift from Dr. Markus Wahl. We are grateful to Dr. Harvey Levy for help in gathering patient information. This work was supported by grants from the American Heart Association (AHA 2-5-80663), from the NIH (HL065217-06A2 and AG09834) and Jerome Lejeune foundation to J.PX, by grants from the Grant Agency of the Czech Republic 305/07/1073, GAAV CR lAA500500701, and MSMT T400500402 to J.H., and from the Wellcome Trust (Reg. No. 070255/Z/03/Z) and the Ministry of Education of the Czech Republic (MSM0021620806) to VX A generous gift from Ms. Margie McGlynn is also acknowledged. NR 31 TC 17 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD AUG PY 2009 VL 97 IS 4 BP 250 EP 259 DI 10.1016/j.ymgme.2009.04.001 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 472TW UT WOS:000268156100004 PM 19428278 ER PT J AU Halling-Brown, M Shaban, R Frampton, D Sansom, CE Davies, M Flower, D Duffield, M Titball, RW Brusic, V Moss, DS AF Halling-Brown, Mark Shaban, Raheel Frampton, Dan Sansom, Clare E. Davies, Matthew Flower, Darren Duffield, Melanie Titball, Richard W. Brusic, Vladimir Moss, David S. TI Proteins accessible to immune surveillance show significant T-cell epitope depletion: Implications for vaccine design SO MOLECULAR IMMUNOLOGY LA English DT Article DE MHC binding; T-cell response; Subcellular location; Immune escape; In silico vaccine design ID MHC CLASS-I; BINDING PREDICTION SERVERS; TAP TRANSPORT EFFICIENCY; PEPTIDE BINDING; PROTEASOMAL CLEAVAGE; SUBUNIT VACCINES; RESPONSES; ANTIGENS; MOLECULES; AFFINITY AB T cell activation is the final step in a complex pathway through which pathogen-derived peptide fragments can elicit an immune response. For it to occur, peptides must form stable complexes with Major Histocompatibility Complex (MHC) molecules and be presented on the cell surface. Computational predictors of MHC binding are often used within in silico vaccine design pathways. We have previously shown that, paradoxically, most bacterial proteins known experimentally to elicit an immune response in disease models are depleted in peptides predicted to bind to human MHC alleles. The results presented here, derived using software proven through benchmarking to be the most accurate currently available, show that vaccine antigens contain fewer predicted MHC-binding peptides than control bacterial proteins from almost all subcellular locations with the exception of cell wall and some cytoplasmic proteins. This effect is too large to be explained from the undoubted lack of precision of the software or from the amino acid composition of the antigens. Instead, we propose that pathogens have evolved under the influence of the host immune system so that surface proteins are depleted in potential MHC-binding peptides, and suggest that identification of a protein likely to contain a single immuno-dominant epitope is likely to be a productive strategy for vaccine design. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Halling-Brown, Mark; Shaban, Raheel; Sansom, Clare E.; Moss, David S.] Univ London Birkbeck Coll, Sch Crystallog, London WC1E 7HX, England. [Frampton, Dan] UCL, Div Infect & Immun, Ctr Virol, London WC1E 6BT, England. [Davies, Matthew; Flower, Darren] Univ Oxford, Jenner Inst, Compton RG20 7NN, Berks, England. [Duffield, Melanie] Dstl Porton Down, Salisbury SP4 0JQ, Wilts, England. [Titball, Richard W.] Univ Exeter, Sch Biosci, Exeter EX4 4QD, Devon, England. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Sansom, CE (reprint author), Univ London Birkbeck Coll, Sch Crystallog, Malet St, London WC1E 7HX, England. EM c.sansom@mail.cryst.bbk.ac.uk RI Flower, Darren/F-1263-2010 OI Flower, Darren/0000-0002-8542-7067 FU European Commission [FP6-2004-IST-028069]; Senior Jenner Fellowship; Wellcome Trust [WT079287MA] FX M.H.-B. was funded through the European Commission ImmunoGrid project (http://www.immunogrid.org), STREP project i/d FP6-2004-IST-028069. D.R.F. received salary support from a Senior Jenner Fellowship, the Wellcome Trust Grant WT079287MA, and is a Jenner Institute Investigator. The authors declare no competing financial interests. NR 32 TC 4 Z9 4 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 2009 VL 46 IS 13 BP 2699 EP 2705 DI 10.1016/j.molimm.2009.05.027 PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 484SY UT WOS:000269069000030 PM 19560824 ER PT J AU Zuniga, J Romero, V Azocar, J Terreros, D Vargas-Rojas, MI Torres-Garcia, D Jimenez-Alvarez, L Vargas-Alarcon, G Granados-Montiel, J Husain, Z Chung, RT Alper, CA Yunis, EJ AF Zuniga, Joaquin Romero, Viviana Azocar, Jose Terreros, Daniel Ines Vargas-Rojas, Maria Torres-Garcia, Diana Jimenez-Alvarez, Luis Vargas-Alarcon, Gilberto Granados-Montiel, Julio Husain, Zaheed Chung, Raymond T. Alper, Chester A. Yunis, Edmond J. TI Protective KIR-HLA interactions for HCV infection in intravenous drug users SO MOLECULAR IMMUNOLOGY LA English DT Article DE KIR; HLA; NK cells; HCV ID C VIRUS-INFECTION; INHIBITORY RECEPTOR GENES; NATURAL-KILLER-CELLS; CHRONIC HEPATITIS-C; CLASS-II; POPULATION STRATIFICATION; NK-CELLS; T-CELLS; ASSOCIATION; CLEARANCE AB Intravenous drug use has become the principal route of hepatitis C virus (HCV) transmission due to the sharing of infected needles. In this study, we analyzed the distribution of HLA-KIR genotypes among 160 Puerto Rican intravenous drug users (IDUs) with HCV infection and 92 HCV-negative Puerto Rican IDUs. We found a significant association between the presence of different combinations of KIR inhibitory receptor genes (KIR2DL2 and/or KIR2DL3, pC=0.01, OR=0.07; KIR2DL2 and/or KIR2DL3 + KIR2DS4, pC=0.01, OR=0.39) and HLA-C1 homozygous genotypes (HLA-C1 + KIR2DS4, pC=0.02, OR=0.43; HLA-C1 + KIR2DL2 + KIR2DS4, pC=0.02, OR=0.40) together with the activating receptor KIR2DS4 (HLA-C1 + KIR2DS4 + KIR2DL3 and/or KIR2DL2, pC=0.004, OR=0.38) with protection from HCV infection. Our findings in HCV-infected and non-infected IDUs suggest an important role for KIRs (KIR2DL2 and KIR2DL3) with group HLA-C1 molecules, in the presence of activating KIR2DS4, in protection from HCV infection. These results support the hypothesis that activator signaling, mediated by KIR2DS4, plays a determinant role in the regulation of NK cell antiviral-activity. Published by Elsevier Ltd. C1 [Husain, Zaheed; Alper, Chester A.] Immune Dis Inst, Boston, MA 02115 USA. [Husain, Zaheed; Alper, Chester A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Zuniga, Joaquin; Ines Vargas-Rojas, Maria; Torres-Garcia, Diana; Jimenez-Alvarez, Luis] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Immunobiol & Genet, Mexico City 14080, DF, Mexico. [Zuniga, Joaquin; Romero, Viviana; Granados-Montiel, Julio; Yunis, Edmond J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Azocar, Jose] Northgate Med Ctr, Springfield, MA 01103 USA. [Terreros, Daniel] Texas Tech Hlth Sci Ctr, El Paso, TX 79905 USA. [Vargas-Alarcon, Gilberto] Inst Nacl Cardiol Ignacio Chavez, Dept Mol Biol, Mexico City 14050, DF, Mexico. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Yunis, Edmond J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alper, CA (reprint author), Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM alper@idi.harvard.edu; Edmond_yunis@dfci.harvard.edu FU NIH [AI49213, HL29583, HL59838, AI69939]; Northgate Medical Center, Springfield, MA FX This work was supported by NIH grants AI49213 (EJY, VR), HL29583 (EJY, VR, CAA) and HL59838 (EJY, VR), and AI69939 (RTC). JA was supported by Northgate Medical Center, Springfield, MA. NR 36 TC 22 Z9 23 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 2009 VL 46 IS 13 BP 2723 EP 2727 DI 10.1016/j.molimm.2009.05.014 PG 5 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 484SY UT WOS:000269069000033 PM 19552960 ER PT J AU Sheffler, DJ Williams, R Bridges, TM Xiang, ZX Kane, AS Byun, NE Jadhav, S Mock, MM Zheng, F Lewis, LM Jones, CK Niswender, CM Weaver, CD Lindsley, CW Conn, PJ AF Sheffler, Douglas J. Williams, Richard Bridges, Thomas M. Xiang, Zixiu Kane, Alexander S. Byun, Nellie E. Jadhav, Satyawan Mock, Mathew M. Zheng, Fang Lewis, L. Michelle Jones, Carrie K. Niswender, Colleen M. Weaver, Charles D. Lindsley, Craig W. Conn, P. Jeffrey TI A Novel Selective Muscarinic Acetylcholine Receptor Subtype 1 Antagonist Reduces Seizures without Impairing Hippocampus-Dependent Learning SO MOLECULAR PHARMACOLOGY LA English DT Article ID N-DESMETHYLCLOZAPINE; PYRAMIDAL CELLS; MUTANT MICE; ACTIVATION; ANTIBODIES; DISORDERS; CLOZAPINE; PROTEINS; AGONISTS; DISEASE AB Previous studies suggest that selective antagonists of specific subtypes of muscarinic acetylcholine receptors (mAChRs) may provide a novel approach for the treatment of certain central nervous system (CNS) disorders, including epileptic disorders, Parkinson's disease, and dystonia. Unfortunately, previously reported antagonists are not highly selective for specific mAChR subtypes, making it difficult to definitively establish the functional roles and therapeutic potential for individual subtypes of this receptor subfamily. The M 1 mAChR is of particular interest as a potential target for treatment of CNS disorders. We now report the discovery of a novel selective antagonist of M(1) mAChRs, termed VU0255035 [N-(3-oxo-3-(4-(pyridine-4-yl)piperazin-1-yl)propyl)benzo[c][1,2,5]thiadiazole-4-sulfonamide]. Equilibrium radioligand binding and functional studies demonstrate a greater than 75-fold selectivity of VU0255035 for M(1) mAChRs relative to M(2)-M(5). Molecular pharmacology and mutagenesis studies indicate that VU0255035 is a competitive orthosteric antagonist of M(1) mAChRs, a surprising finding given the high level of M(1) mAChR selectivity relative to other orthosteric antagonists. Whole-cell patch-clamp recordings demonstrate that VU0255035 inhibits potentiation of N-methyl-D-aspartate receptor currents by the muscarinic agonist carbachol in hippocampal pyramidal cells. VU0255035 has excellent brain penetration in vivo and is efficacious in reducing pilocarpine-induced seizures in mice. We were surprised to find that doses of VU0255035 that reduce pilo-carpine-induced seizures do not induce deficits in contextual freezing, a measure of hippocampus-dependent learning that is disrupted by nonselective mAChR antagonists. Taken together, these data suggest that selective antagonists of M(1) mAChRs do not induce the severe cognitive deficits seen with nonselective mAChR antagonists and could provide a novel approach for the treatment certain of CNS disorders. C1 [Sheffler, Douglas J.; Williams, Richard; Bridges, Thomas M.; Xiang, Zixiu; Kane, Alexander S.; Jadhav, Satyawan; Jones, Carrie K.; Niswender, Colleen M.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Lindsley, Craig W.] Vanderbilt Univ, Med Ctr, Dept Chem, Nashville, TN 37232 USA. [Byun, Nellie E.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA. [Williams, Richard; Jadhav, Satyawan; Jones, Carrie K.; Niswender, Colleen M.; Weaver, Charles D.; Lindsley, Craig W.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. [Lewis, L. Michelle; Weaver, Charles D.; Lindsley, Craig W.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Chem Biol, Nashville, TN 37232 USA. [Jones, Carrie K.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN USA. [Mock, Mathew M.; Zheng, Fang] Univ Arkansas, Med Ctr, Dept Pharmacol & Toxicol, Little Rock, AR 72204 USA. RP Conn, PJ (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Light Hall MRB 4,Room 1215D,2215 B Garland Ave, Nashville, TN 37232 USA. EM jeff.conn@vanderbilt.edu RI Conn, Peter/D-7848-2012; Zheng, Fang/J-1400-2016; OI Zheng, Fang/0000-0002-6626-1938; Xiang, Zixiu/0000-0002-1678-209X FU NIBIB NIH HHS [T32 EB001628]; NIMH NIH HHS [1 X01-MH077606-01, 1 U54-MH084659, 3 U54-MH074427, 3 U54-MH074427-02S1] NR 40 TC 45 Z9 46 U1 1 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 2009 VL 76 IS 2 BP 356 EP 368 DI 10.1124/mol.109.056531 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 472SV UT WOS:000268153400012 PM 19407080 ER PT J AU Smith, EN Bloss, CS Badner, JA Barrett, T Belmonte, PL Berrettini, W Byerley, W Coryell, W Craig, D Edenberg, HJ Eskin, E Foroud, T Gershon, E Greenwood, TA Hipolito, M Koller, DL Lawson, WB Liu, C Lohoff, F McInnis, MG McMahon, FJ Mirel, DB Murray, SS Nievergelt, C Nurnberger, J Nwulia, EA Paschall, J Potash, JB Rice, J Schulze, TG Scheftner, W Panganiban, C Zaitlen, N Zandi, PP Zollner, S Schork, NJ Kelsoe, JR AF Smith, E. N. Bloss, C. S. Badner, J. A. Barrett, T. Belmonte, P. L. Berrettini, W. Byerley, W. Coryell, W. Craig, D. Edenberg, H. J. Eskin, E. Foroud, T. Gershon, E. Greenwood, T. A. Hipolito, M. Koller, D. L. Lawson, W. B. Liu, C. Lohoff, F. McInnis, M. G. McMahon, F. J. Mirel, D. B. Murray, S. S. Nievergelt, C. Nurnberger, J. Nwulia, E. A. Paschall, J. Potash, J. B. Rice, J. Schulze, T. G. Scheftner, W. Panganiban, C. Zaitlen, N. Zandi, P. P. Zoellner, S. Schork, N. J. Kelsoe, J. R. TI Genome-wide association study of bipolar disorder in European American and African American individuals SO MOLECULAR PSYCHIATRY LA English DT Article DE ANK3; Bipolar Genome Study; genetic background; allelic heterogeneity; GAIN ID FAMILY-BASED ASSOCIATION; NEUROTROPHIC FACTOR GENE; BRAIN; TRANSMISSION; LINKAGE; SUSCEPTIBILITY; SCHIZOPHRENIA; METAANALYSIS; DISEASE; MODELS AB To identify bipolar disorder (BD) genetic susceptibility factors, we conducted two genome-wide association (GWA) studies: one involving a sample of individuals of European ancestry (EA; n=1001 cases; n=1033 controls), and one involving a sample of individuals of African ancestry (AA; n=345 cases; n=670 controls). For the EA sample, single-nucleotide polymorphisms (SNPs) with the strongest statistical evidence for association included rs5907577 in an intergenic region at Xq27.1 (P=1.6 x 10(-6)) and rs10193871 in NAP5 at 2q21.2 (P=9.8 x 10(-6)). For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P=1.5 x 10(-6)) and rs2769605 in NTRK2 at 9q21.33 (P=4.5 x 10(-5)). We also investigated whether we could provide support for three regions previously associated with BD, and we showed that the ANK3 region replicates in our sample, along with some support for C15Orf53; other evidence implicates BD candidate genes such as SLITRK2. We also tested the hypothesis that BD susceptibility variants exhibit genetic background-dependent effects. SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P=1.4 x 10(-6)), rs4657247 in RGS5 at 1q23.3 (P=4.1 x 10(-6)), and rs7078071 in BTBD16 at 10q26.13 (P=4.5 x 10(-6)). This study is the first to conduct GWA of BD in individuals of AA and suggests that genetic variations that contribute to BD may vary as a function of ancestry. Molecular Psychiatry (2009) 14, 755-763; doi:10.1038/mp.2009.43; published online 2 June 2009 C1 [Smith, E. N.; Murray, S. S.; Schork, N. J.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Smith, E. N.; Bloss, C. S.; Murray, S. S.; Schork, N. J.] Scripps Translat Sci Inst, La Jolla, CA USA. [Bloss, C. S.; Murray, S. S.; Schork, N. J.] Scripps Hlth, La Jolla, CA USA. [Badner, J. A.; Gershon, E.; Liu, C.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Barrett, T.] Portland VA Med Ctr, Dept Psychiat, Portland, OR USA. [Belmonte, P. L.; Potash, J. B.; Zandi, P. P.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. [Berrettini, W.; Lohoff, F.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Byerley, W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Coryell, W.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Craig, D.; Panganiban, C.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA. [Edenberg, H. J.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. [Edenberg, H. J.; Foroud, T.] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Eskin, E.; Zaitlen, N.] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA. [Greenwood, T. A.; Nievergelt, C.; Kelsoe, J. R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Hipolito, M.; Lawson, W. B.; Nwulia, E. A.] Howard Univ, Dept Psychiat, Washington, DC 20059 USA. [Koller, D. L.; Nurnberger, J.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [McInnis, M. G.; Zoellner, S.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [McMahon, F. J.; Schulze, T. G.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mirel, D. B.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Mirel, D. B.] MIT, Cambridge, MA 02139 USA. [Paschall, J.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Rice, J.] Washington Univ, Div Biostat, St Louis, MO USA. [Scheftner, W.] Rush Univ, Dept Psychiat, Chicago, IL 60612 USA. [Kelsoe, J. R.] VA San Diego Healthcare Syst, Dept Psychiat, La Jolla, CA USA. RP Schork, NJ (reprint author), Scripps Res Inst, Dept Mol & Expt Med, 10550 N Torrey Pines Ave,MEM 275, La Jolla, CA 92037 USA. EM nschork@scripps.edu RI Smith, Erin/E-5933-2011; Liu, Chunyu/G-7561-2012; McInnis, Melvin/F-6963-2012; Eskin, Eleazar/J-9187-2012; Greenwood, Tiffany/F-6356-2012; Schulze, Thomas/H-2157-2013; Lohoff, Falk/M-7951-2016; OI Liu, Chunyu/0000-0002-5986-4415; McInnis, Melvin/0000-0002-0375-6247; Eskin, Eleazar/0000-0003-1149-4758; Greenwood, Tiffany/0000-0002-6080-6503; Lawson, William/0000-0002-9324-7090; Nurnberger, John/0000-0002-7674-1767; Nievergelt, Caroline/0000-0001-5766-8923; McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690 FU NIMH [R01 MH59553, U01 MH46282, R01 MH59545, U01 MH46280, R01 MH059534, U01 MH46274, R01 MH59533, R01 MH60068, R01 MH059548, R01 MH59535, R01 MH59567, R01 MH059556]; NHGRI [MH078151, MH081804, MH059567]; Genetic Association Information Network ( GAIN; NIH [R01 MH59553, K08 MH080372, 1U54RR025204-01]; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD; NIMH Intramural Research Program, Bethesda, MD [1Z01MH00281001] FX We thank the participants in the study, as without them this work would not have been possible. For best estimate diagnostic work, we thank Vegas Coleman, Robert Schweitzer, N Leela Rau and Kelly Rhoadarmer. For data management, we thank Mariano Erpe and for study coordination Carre Fisher RN. This work was supported by grants from the NIMH and NHGRI to JRK (MH078151, MH081804, MH059567 supplement), and by the Genetic Association Information Network ( GAIN). This work was additionally supported by the NIMH Intramural Research Program (FJM and TGS). WHB was supported by a grant from the Tzedakah Foundation, a grant from NIH (R01 MH59553) and a grant from Philip and Marcia Cohen. Falk Lohoff was supported by the Daland Fellowship Award from the American Philosophical Society and by NIH grant K08 MH080372. David Craig and Corrie Panganiban acknowledge the Stardust foundation. Follow-up genotyping was performed in the laboratory of HE at Indiana University School of Medicine. This research was also supported, in part, by the Intramural Research Program of the NIH, National Library of Medicine. Dr Smith, Dr Bloss, Dr Murray and Dr Schork are supported in part by National Institutes of Health grant NIH 1U54RR025204-01. Data and biomaterials were collected in four projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1991 to 1998, the principal investigators and coinvestigators were: Indiana University, Indianapolis, IN, U01 MH46282, John Nurnberger, Marvin Miller and Elizabeth Bowman; Washington University, St Louis, MO, U01 MH46280, Theodore Reich, Allison Goate and John Rice; Johns Hopkins University, Baltimore, MD U01 MH46274, J Raymond DePaulo, Jr, Sylvia Simpson and Colin Stine; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD, Elliot Gershon, Diane Kazuba and Elizabeth Maxwell. Data and biomaterials were collected as part of 10 projects that participated in the National Institute of Mental Health ( NIMH) Bipolar Disorder Genetics Initiative. From 1999 to 2007, the principal investigators and coinvestigators were: Indiana University, Indianapolis, IN, R01 MH59545, John Nurnberger, Marvin J Miller, Elizabeth S Bowman, N Leela Rau, P Ryan Moe, Nalini Samavedy, Rif El-Mallakh ( at University of Louisville), Husseini Manji ( at Wayne State University), Debra A Glitz ( at Wayne State University), Eric T Meyer, Carrie Smiley, Tatiana Foroud, Leah Flury, Danielle M Dick, Howard Edenberg; Washington University, St Louis, MO, R01 MH059534, John Rice, Theodore Reich, Allison Goate, Laura Bierut; Johns Hopkins University, Baltimore, MD, R01 MH59533, Melvin McInnis, J Raymond DePaulo, Jr, Dean F MacKinnon, Francis M Mondimore, James B Potash, Peter P Zandi, Dimitrios Avramopoulos and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553, Wade Berrettini; University of California at Irvine, CA, R01 MH60068, William Byerley and Mark Vawter; University of Iowa, IA, R01 MH059548, William Coryell and Raymond Crowe; University of Chicago, IL, R01 MH59535, Elliot Gershon, Judith Badner, Francis McMahon, Chunyu Liu, Alan Sanders, Maria Caserta, Steven Dinwiddie, Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567, John Kelsoe, Rebecca McKinney; Rush University, IL, R01 MH059556, William Scheftner, Howard M Kravitz, Diana Marta, Annette VaughnBrown and Laurie Bederow; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH00281001, Francis J McMahon, Layla Kassem, Sevilla DeteraWadleigh, Lisa Austin, Dennis L Murphy. NR 32 TC 198 Z9 201 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD AUG PY 2009 VL 14 IS 8 BP 755 EP 763 DI 10.1038/mp.2009.43 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 473VR UT WOS:000268239200005 PM 19488044 ER PT J AU Ng, MYM Levinson, DF Faraone, SV Suarez, BK DeLisi, LE Arinami, T Riley, B Paunio, T Pulver, AE Irmansyah Holmans, PA Escamilla, M Wildenauer, DB Williams, NM Laurent, C Mowry, BJ Brzustowicz, LM Maziade, M Sklar, P Garver, DL Abecasis, GR Lerer, B Fallin, MD Gurling, HMD Gejman, PV Lindholm, E Moises, HW Byerley, W Wijsman, EM Forabosco, P Tsuang, MT Hwu, HG Okazaki, Y Kendler, KS Wormley, B Fanous, A Walsh, D O'Neill, FA Peltonen, L Nestadt, G Lasseter, VK Liang, KY Papadimitriou, GM Dikeos, DG Schwab, SG Owen, MJ O'Donovan, MC Norton, N Hare, E Raventos, H Nicolini, H Albus, M Maier, W Nimgaonkar, VL Terenius, L Mallet, J Jay, M Godard, S Nertney, D Alexander, M Crowe, RR Silverman, JM Bassett, AS Roy, MA Merette, C Pato, CN Pato, MT Roos, JL Kohn, Y Amann-Zalcenstein, D Kalsi, G McQuillin, A Curtis, D Brynjolfson, J Sigmundsson, T Petursson, H Sanders, AR Duan, J Jazin, E Myles-Worsley, M Karayiorgou, M Lewis, CM AF Ng, M. Y. M. Levinson, D. F. Faraone, S. V. Suarez, B. K. DeLisi, L. E. Arinami, T. Riley, B. Paunio, T. Pulver, A. E. Irmansyah Holmans, P. A. Escamilla, M. Wildenauer, D. B. Williams, N. M. Laurent, C. Mowry, B. J. Brzustowicz, L. M. Maziade, M. Sklar, P. Garver, D. L. Abecasis, G. R. Lerer, B. Fallin, M. D. Gurling, H. M. D. Gejman, P. V. Lindholm, E. Moises, H. W. Byerley, W. Wijsman, E. M. Forabosco, P. Tsuang, M. T. Hwu, H-G Okazaki, Y. Kendler, K. S. Wormley, B. Fanous, A. Walsh, D. O'Neill, F. A. Peltonen, L. Nestadt, G. Lasseter, V. K. Liang, K. Y. Papadimitriou, G. M. Dikeos, D. G. Schwab, S. G. Owen, M. J. O'Donovan, M. C. Norton, N. Hare, E. Raventos, H. Nicolini, H. Albus, M. Maier, W. Nimgaonkar, V. L. Terenius, L. Mallet, J. Jay, M. Godard, S. Nertney, D. Alexander, M. Crowe, R. R. Silverman, J. M. Bassett, A. S. Roy, M-A Merette, C. Pato, C. N. Pato, M. T. Roos, J. Louw Kohn, Y. Amann-Zalcenstein, D. Kalsi, G. McQuillin, A. Curtis, D. Brynjolfson, J. Sigmundsson, T. Petursson, H. Sanders, A. R. Duan, J. Jazin, E. Myles-Worsley, M. Karayiorgou, M. Lewis, C. M. TI Meta-analysis of 32 genome-wide linkage studies of schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE genome; human; humans; schizophrenia/genetics; genetic predisposition to disease; linkage (genetics); meta-analysis ID SUSCEPTIBILITY LOCI; BIPOLAR DISORDER; SUGGESTIVE EVIDENCE; SCAN METAANALYSIS; COMPLEX DISEASES; GENETIC-LINKAGE; CROHN-DISEASE; COSTA-RICA; FOLLOW-UP; FAMILIES AB A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. Molecular Psychiatry (2009) 14, 774-785; doi:10.1038/mp.2008.135; published online 30 December 2008 C1 [Ng, M. Y. M.; Forabosco, P.; Lewis, C. M.] Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England. [Levinson, D. F.; Alexander, M.] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA. [Faraone, S. V.; Myles-Worsley, M.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. [Suarez, B. K.] Washington Univ, St Louis, MO USA. [DeLisi, L. E.] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10016 USA. [DeLisi, L. E.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Arinami, T.] Univ Tsukuba, Dept Med Genet, Tsukuba, Ibaraki, Japan. [Riley, B.; Kendler, K. S.; Wormley, B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA USA. [Peltonen, L.] Natl Publ Hlth Inst, Dept Mol Med, Helsinki, Finland. [Paunio, T.] Univ Helsinki, Dept Psychiat, Cent Hosp, SF-00180 Helsinki, Finland. [Pulver, A. E.; Nestadt, G.; Lasseter, V. K.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Irmansyah] Univ Indonesia, Dept Psychiat, Jakarta, Indonesia. [Holmans, P. A.; Williams, N. M.; Owen, M. J.; O'Donovan, M. C.; Norton, N.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales. [Escamilla, M.; Hare, E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wildenauer, D. B.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Ctr Clin Res Neuropsychiat, Perth, WA 6009, Australia. [Laurent, C.; Jay, M.] Univ Paris 06, Dept Child Psychiat, Paris, France. [Mallet, J.] Hop La Pitie Salpetriere, CNRS, Lab Genet Mol Neurotransmiss & Proc Neurodegenera, Paris, France. [Mowry, B. J.; Nertney, D.] Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia. [Mowry, B. J.; Nertney, D.] Univ Queensland, Brisbane, Qld, Australia. [Brzustowicz, L. M.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA. [Maziade, M.; Roy, M-A; Merette, C.] Univ Laval, Dept Psychiat, Quebec City, PQ, Canada. [Maziade, M.; Roy, M-A; Merette, C.] Univ Laval Robert Giffard, Ctr Rech, Quebec City, PQ, Canada. [Sklar, P.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sklar, P.] Harvard Univ, Sch Med, Boston, MA USA. [Garver, D. L.] VA Med Ctr, Asheville, NC USA. [Abecasis, G. R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Lerer, B.; Kohn, Y.] Hadassah Hebrew Univ, Med Ctr, Dept Psychiat, Jerusalem, Israel. [Fallin, M. D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gurling, H. M. D.; Kalsi, G.; McQuillin, A.] UCL, Dept Mental Hlth Sci, London, England. [Gejman, P. V.; Sanders, A. R.; Duan, J.] NorthShore Univ HealthSyst, Res Inst, Ctr Psychiat Genet, Evanston, IL USA. [Gejman, P. V.; Sanders, A. R.; Duan, J.] Northwestern Univ, Evanston, IL USA. [Lindholm, E.; Jazin, E.] Uppsala Univ, Dept Genet & Dev, Uppsala, Sweden. [Moises, H. W.] Univ Kiel, Kiel, Germany. [Byerley, W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wijsman, E. M.] Univ Washington, Dept Med, Seattle, WA USA. [Wijsman, E. M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Tsuang, M. T.] Univ Calif San Diego, Ctr Behav Genom, San Diego, CA 92103 USA. [Tsuang, M. T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Tsuang, M. T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Hwu, H-G] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Hwu, H-G] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Okazaki, Y.] Tokyo Metropolitan Matsuzawa Hosp, Tokyo, Japan. [Fanous, A.] Washington VA Med Ctr, Washington, DC USA. [Fanous, A.] Virginia Commonwealth Univ, Georgetown Univ Med Ctr, Dept Psychiat, Richmond, VA USA. [Walsh, D.] Hlth Res Board, Dublin, Ireland. [O'Neill, F. A.] Queens Univ Belfast, Dept Psychiat, Belfast, Antrim, North Ireland. [Peltonen, L.] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Peltonen, L.] MIT, Broad Inst, Boston, MA USA. [Peltonen, L.] Wellcome Trust Sanger Inst, Cambridge, England. [Liang, K. Y.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Papadimitriou, G. M.; Dikeos, D. G.] Univ Athens, Sch Med, Dept Psychiat 1, GR-11527 Athens, Greece. [Papadimitriou, G. M.; Dikeos, D. G.] Univ Mental Hlth Res Inst, Athens, Greece. [Schwab, S. G.] Univ Western Australia, Western Australian Inst Med Res, Perth, WA 6009, Australia. [Schwab, S. G.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. [Schwab, S. G.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Raventos, H.] Univ Costa Rica, Sch Biol, San Jose, Costa Rica. [Raventos, H.] Univ Costa Rica, CIBCM, San Jose, Costa Rica. [Nicolini, H.] Carracci Med Grp, Mexico City, DF, Mexico. [Nicolini, H.] Univ Autonoma Ciudad Mexico, Mexico City, DF, Mexico. [Albus, M.] State Mental Hosp, Haar, Germany. [Maier, W.] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. [Nimgaonkar, V. L.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Nimgaonkar, V. L.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Terenius, L.] Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden. [Godard, S.] Hop La Pitie Salpetriere, INSERM, Inst Myol, Paris, France. [Crowe, R. R.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Silverman, J. M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Bassett, A. S.] Univ Toronto, Clin Genet Res Program, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Bassett, A. S.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Pato, C. N.; Pato, M. T.] Univ So Calif, Ctr Genom Psychiat, Los Angeles, CA USA. [Roos, J. Louw] Univ Pretoria, Weskoppies Hosp, Dept Psychiat, ZA-0002 Pretoria, South Africa. [Amann-Zalcenstein, D.] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. [Curtis, D.] St Bartholomews & Royal London Sch Med & Dent, Dept Psychol Med, London, England. [Brynjolfson, J.; Sigmundsson, T.; Petursson, H.] Gen Hosp, Dept Psychiat, Reykjavik, Iceland. [Karayiorgou, M.] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. [Karayiorgou, M.] Columbia Univ, Dept Genet & Dev, Med Ctr, New York, NY USA. [Lewis, C. M.] Kings Coll London, Inst Psychiat, MRC SGDP, London WC2R 2LS, England. RP Lewis, CM (reprint author), Kings Coll London, Guys Hosp, Dept Med & Mol Genet, 8th Floor Tower Wing, London SE1 9RT, England. EM Cathryn.lewis@kcl.ac.uk RI O'Neill, Francis/C-5582-2008; Lewis, Cathryn/A-5225-2010; Abecasis, Goncalo/B-7840-2010; turton, miranda/F-4682-2011; McQuillin, Andrew/C-1623-2008; Liang, Kung-Yee/F-8299-2011; Ng, Mandy/D-8661-2012; Gurling, Hugh/A-5029-2010; Holmans, Peter/F-4518-2015; OI Abecasis, Goncalo/0000-0003-1509-1825; Roos, Johannes/0000-0002-0572-1072; O'Neill, Francis Anthony/0000-0002-7531-7657; Faraone, Stephen/0000-0002-9217-3982; Lewis, Cathryn/0000-0002-8249-8476; McQuillin, Andrew/0000-0003-1567-2240; Moises, Hans/0000-0003-1522-3226; Nicolini, Humberto/0000-0003-2494-0067; O'Donovan, Michael/0000-0001-7073-2379; Raventos, Henriette/0000-0001-9423-8308; Holmans, Peter/0000-0003-0870-9412; HWU, HAI-GWO/0000-0002-2582-2807 FU Medical Research Council (UK) [G0400960, G9309834]; National Institute of Mental Health [7R01MH062276]; DFL [ Aust/ US]; France/La Re'union; ENH [5R01MH068922]; Johns Hopkins [5R01MH068921]; VCU/Ireland [5R01MH068881, MH-41953, MH63356, MH80299, MH58586, MH 56242, MH61399]; NIMH [MH062440, R01-MH44245, MH60881, MH60875]; Canadian Institutes of Health Research [MOP-53216, MOP-12155]; Wellcome Trust [055379] FX The work reported here was supported by: Medical Research Council (UK) Grants G0400960 (CML) and G9309834 ( MO); National Institute of Mental Health Grants 7R01MH062276 ( to DFL [ Aust/ US], CL [France/La Re'union], MO [ Cardiff] and DW [ Bonn]), 5R01MH068922 ( to PG [ENH]), 5R01MH068921 ( to AEP [ Johns Hopkins]), 5R01MH068881 ( to BR [VCU/Ireland]), MH-41953 (to KSK [VCU/Ireland]); MH63356 and MH80299 ( to WB [ Palau]); MH58586 ( to JMS [ Aust/ US]); MH 56242 ( to VLM [ US/ Sweden]), MH61399 ( EMW, MK [Kosrae,South Africa]), NIMH Grant MH062440, Canadian Institutes of Health Research Grants MOP-53216 and MOP-12155, a National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award and Canada Research Chair in Schizophrenia Genetics (LMB, ASB [ Canada]); Australian National Health and Medical Research Council Grants 910234, 941087, and 971095 ( to BJM [ Aust/ US]), MRC project Grant G880473N, The European Science Foundation, SANE, the Iceland Department of Health, the General Hospital Reykjavik, the Joseph Levy Charitable Foundation, the Wellcome Trust Grant 055379, The Priory Hospital, the Neuroscience Research Charitable Trust, the University of Iceland and the Icelandic Science Council (HMDG [UCL]); Warner-Lambert, Parke-Davis Pharmaceuticals Company and NIMH Grant R01-MH44245 (LEL [US/International]); the Deutsche Forschungsgemeinschaft (HWM [ Kiel]; MA WM, SGS, DBW [ Indonesia]); the German Israeli Foundation for Scientific Research (BL; DBW); Mammalian Genotyping Service HV48141 ( DBW [ Indonesia]; CREST of JST ( Japan Science and Technology Agency) TA [ Japan]; Pfizer, Inc. and the SANE Foundation ( LEL [ Costa Rica]); the Israel Science Foundation, US. Israel Binational Science Foundation, the National Alliance for Research on Schizophrenia and Depression, and the Harry Stern Family Foundation ( BL and YK [ Israel]); the VA Merit Review Program ( AF); recruitment of the NIMH Genetics Initiative sample was supported by NIMH Grants 5 UO1MH46318, UO1MH46289 and UO1MH46276; the Taiwan Schizophrenia Linkage Study was supported by NIMH Grant 1R01 MH59624-01 and Grant NHRI-90-8825PP, NHRI - EX91,92-9113PP from the National Health Research Institute, Taiwan, and support from the Genomic Medicine Research Program of Psychiatric Disorders, National Taiwan University Hospital; the VA Linkage Study was supported by funds from the Department of Veterans Affairs Cooperative Studies Program; the US/Mexico/Central America study was supported by a collaborative NIMH grant ('Genetics of Schizophrenia in Latino Populations') (MH60881 and MH60875) to ME [ University of Texas Health Science Center at San Antonio], R Mendoza [ University of California at Los Angeles-Harbor], HR [University of Costa Rica, San Jose, Costa Rica], A Ontiveros [Instituto de Informacion de Investigacion en Salud Mental, Monterrey, Mexico], HN [ Medical and Family Research Group, Carracci SC, Mexico City, Mexico], and R Munoz [ Family Health Centers of San Diego, CA]. NR 72 TC 130 Z9 135 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD AUG PY 2009 VL 14 IS 8 BP 774 EP 785 DI 10.1038/mp.2008.135 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 473VR UT WOS:000268239200007 PM 19349958 ER PT J AU Benjamin, EJ Rice, KM Arking, DE Pfeufer, A van Noord, C Smith, AV Schnabel, RB Bis, JC Boerwinkle, E Sinner, MF Dehghan, A Lubitz, SA D'Agostino, RB Lumley, T Ehret, GB Heeringa, J Aspelund, T Newton-Cheh, C Larson, MG Marciante, KD Soliman, EZ Rivadeneira, F Wang, TJ Eiriksdottir, G Levy, D Psaty, BM Li, M Chamberlain, AM Hofman, A Vasan, RS Harris, TB Rotter, JI Kao, WHL Agarwal, SK Stricker, BHC Wang, K Launer, LJ Smith, NL Chakravarti, A Uitterlinden, AG Wolf, PA Sotoodehnia, N Kottgen, A van Duijn, CM Meitinger, T Mueller, M Perz, S Steinbeck, G Wichmann, HE Lunetta, KL Heckbert, SR Gudnason, V Alonso, A Kaab, S Ellinor, PT Witteman, JCM AF Benjamin, Emelia J. Rice, Kenneth M. Arking, Dan E. Pfeufer, Arne van Noord, Charlotte Smith, Albert V. Schnabel, Renate B. Bis, Joshua C. Boerwinkle, Eric Sinner, Moritz F. Dehghan, Abbas Lubitz, Steven A. D'Agostino, Ralph B., Sr. Lumley, Thomas Ehret, Georg B. Heeringa, Jan Aspelund, Thor Newton-Cheh, Christopher Larson, Martin G. Marciante, Kristin D. Soliman, Elsayed Z. Rivadeneira, Fernando Wang, Thomas J. Eiriksdottir, Gudny Levy, Daniel Psaty, Bruce M. Li, Man Chamberlain, Alanna M. Hofman, Albert Vasan, Ramachandran S. Harris, Tamara B. Rotter, Jerome I. Kao, W. H. Linda Agarwal, Sunil K. Stricker, Bruno H. Ch Wang, Ke Launer, Lenore J. Smith, Nicholas L. Chakravarti, Aravinda Uitterlinden, Andre G. Wolf, Philip A. Sotoodehnia, Nona Koettgen, Anna van Duijn, Cornelia M. Meitinger, Thomas Mueller, Martina Perz, Siegfried Steinbeck, Gerhard Wichmann, H-Erich Lunetta, Kathryn L. Heckbert, Susan R. Gudnason, Vilmundur Alonso, Alvaro Kaeaeb, Stefan Ellinor, Patrick T. Witteman, Jacqueline C. M. TI Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry SO NATURE GENETICS LA English DT Article ID TRANSCRIPTION FACTOR ATBF1; LIFETIME RISK; DIFFERENTIATION; PREVALENCE AB We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 x 10(-7)). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined RR = 1.25; combined P = 1.8 x 10(-15)). C1 [Benjamin, Emelia J.; Schnabel, Renate B.; D'Agostino, Ralph B., Sr.; Newton-Cheh, Christopher; Larson, Martin G.; Wang, Thomas J.; Levy, Daniel; Vasan, Ramachandran S.; Wolf, Philip A.; Lunetta, Kathryn L.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Rice, Kenneth M.; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Arking, Dan E.; Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Pfeufer, Arne; Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Dept Human Genet, D-8000 Munich, Germany. [Pfeufer, Arne] German Natl Res Ctr Environm Hlth, Helmholtz Ctr Munich, Dept Human Genet, Munich, Germany. [van Noord, Charlotte; Dehghan, Abbas; Heeringa, Jan; Rivadeneira, Fernando; Hofman, Albert; Stricker, Bruno H. Ch; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [van Noord, Charlotte] Dutch Med Evaluat Board, The Hague, Netherlands. [van Noord, Charlotte; Witteman, Jacqueline C. M.] Netherlands Consortium Healthy Aging, Leiden, Netherlands. [Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Gutenberg Heart Study, Med Clin Cardiol 2, Mainz, Germany. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Houston, TX USA. [Sinner, Moritz F.; Mueller, Martina; Steinbeck, Gerhard; Kaeaeb, Stefan] Univ Munich, Klinikum Grosshadern, Dept Med 1, D-8000 Munich, Germany. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Lubitz, Steven A.; Newton-Cheh, Christopher; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [D'Agostino, Ralph B., Sr.; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Marciante, Kristin D.; Psaty, Bruce M.; Sotoodehnia, Nona] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Marciante, Kristin D.] Univ Washington, Dept Gen Internal Med, Seattle, WA 98195 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA. [Rivadeneira, Fernando; Stricker, Bruno H. Ch; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Psaty, Bruce M.; Smith, Nicholas L.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.; Heckbert, Susan R.] Ctr Hlth Studies, Grp Hlth, Washington, DC USA. [Li, Man; Kao, W. H. Linda; Koettgen, Anna] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Chamberlain, Alanna M.; Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Agarwal, Sunil K.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Stricker, Bruno H. Ch] Inspectorate Hlth Care, The Hague, Netherlands. [Wang, Ke; Lunetta, Kathryn L.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA USA. [Uitterlinden, Andre G.] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands. [Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Mueller, Martina; Wichmann, H-Erich] Deutsch Forschungszentrum Gesundheit & Umwelt, Inst Epidemiol, Helmholtz Zentrum Munchen, Munich, Germany. [Perz, Siegfried] Deutsch Forschungszentrum Gesundheit & Umwelt Gmb, Inst Med Informat, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM emelia@bu.edu; j.witteman@erasmusmc.nl RI Smith, Albert/K-5150-2015; Alonso, Alvaro/A-4917-2010; Rivadeneira, Fernando/O-5385-2015; Soliman, Elsayed/D-8124-2011; Aspelund, Thor/F-4826-2011; EHRET, Georg/A-9532-2009; Kottgen, Anna/D-2920-2012; Kaab, Stefan/H-3915-2012; Rice, Kenneth/A-4150-2013; Pfeufer, Arne/B-6634-2013; Aspelund, Thor/C-5983-2008; Schnabel, Renate/F-6527-2014; Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015 OI Smith, Albert/0000-0003-1942-5845; Lunetta, Kathryn/0000-0002-9268-810X; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Dehghan, Abbas/0000-0001-6403-016X; Alonso, Alvaro/0000-0002-2225-8323; Rivadeneira, Fernando/0000-0001-9435-9441; Soliman, Elsayed/0000-0001-5632-8150; EHRET, Georg/0000-0002-5730-0675; Rice, Kenneth/0000-0001-5779-4495; Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084; FU NCRR NIH HHS [M01 RR000425-30S1, UL1 RR025005, M01 RR000069]; NHGRI NIH HHS [U01 HG004402, U01 HG004402-01]; NHLBI NIH HHS [N01 HC015103, N01 HC025195, N01 HC035129, N01 HC045133, N01 HC055015, N01 HC055016, N01 HC055018, N01 HC055019, N01 HC055020, N01 HC055021, N01 HC055022, N01 HC055222, N01 HC075150, N01 HC085079, N01 HC085080, N01 HC085081, N01 HC085082, N01 HC085083, N01 HC085084, N01 HC085085, N01 HC085086, N01HC25195, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC55222, N01HC75150, N01HC85079, N01HC85086, N02 HL64278, R01 HL059367, R01 HL059367-02, R01 HL076784, R01 HL076784-01, R01 HL080124, R01 HL080124-01, R01 HL086694, R01 HL086694-01A1, R01 HL086694-02, R01 HL087641, R01 HL087641-01, R01 HL087652, R01 HL087652-01, R01 HL088456, R01 HL088456-01, R01 HL092577, R01 HL092577-01A1, R01 HL093328, R01 HL093328-01, R01 HL104156, T32 HL007575, T32 HL007575-23, U01 HL080295, U01 HL080295-01]; NIA NIH HHS [N01 AG012100, N01AG12100, R01 AG028321, R01 AG028321-01]; NIDDK NIH HHS [P30 DK063491, P30 DK063491-019004, P30 DK063491-029004, P30 DK063491-039004, P30 DK063491-049004, P30 DK063491-05, P30 DK063491-06, R01 DK033651]; NINDS NIH HHS [R01 NS017950, R01 NS017950-23] NR 14 TC 196 Z9 198 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2009 VL 41 IS 8 BP 879 EP 881 DI 10.1038/ng.416 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 476IM UT WOS:000268432900008 PM 19597492 ER PT J AU Pomerantz, MM Ahmadiyeh, N Jia, L Herman, P Verzi, MP Doddapaneni, H Beckwith, CA Chan, JA Hills, A Davis, M Yao, KL Kehoe, SM Lenz, HJ Haiman, CA Yan, CL Henderson, BE Frenkel, B Barretina, J Bass, A Tabernero, J Baselga, J Regan, MM Manak, JR Shivdasani, R Coetzee, GA Freedman, ML AF Pomerantz, Mark M. Ahmadiyeh, Nasim Jia, Li Herman, Paula Verzi, Michael P. Doddapaneni, Harshavardhan Beckwith, Christine A. Chan, Jennifer A. Hills, Adam Davis, Matt Yao, Keluo Kehoe, Sarah M. Lenz, Heinz-Josef Haiman, Christopher A. Yan, Chunli Henderson, Brian E. Frenkel, Baruch Barretina, Jordi Bass, Adam Tabernero, Josep Baselga, Jose Regan, Meredith M. Manak, J. Robert Shivdasani, Ramesh Coetzee, Gerhard A. Freedman, Matthew L. TI The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer SO NATURE GENETICS LA English DT Article ID WIDE ASSOCIATION SCAN; CHROMOSOME 8Q24; BETA-CATENIN; GENOME; ACTIVATION; ENHANCERS; PROSTATE; APC AB An inherited variant on chromosome 8q24, rs6983267, is significantly associated with cancer pathogenesis. We present evidence that the region harboring this variant is a transcriptional enhancer, that the alleles of rs6983267 differentially bind transcription factor 7-like 2 (TCF7L2) and that the risk region physically interacts with the MYC protooncogene. These data provide strong support for a biological mechanism underlying this non-protein-coding risk variant. C1 [Pomerantz, Mark M.; Ahmadiyeh, Nasim; Herman, Paula; Verzi, Michael P.; Beckwith, Christine A.; Hills, Adam; Davis, Matt; Yao, Keluo; Kehoe, Sarah M.; Barretina, Jordi; Bass, Adam; Shivdasani, Ramesh; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ahmadiyeh, Nasim] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Jia, Li; Yan, Chunli; Coetzee, Gerhard A.] USC, Keck Sch Med, Dept Urol, Los Angeles, CA USA. [Doddapaneni, Harshavardhan; Manak, J. Robert] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA. [Chan, Jennifer A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 1N4, Canada. [Lenz, Heinz-Josef; Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Frenkel, Baruch] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA. [Tabernero, Josep; Baselga, Jose] Vall Hebron Univ Hosp, Vall Hebron Inst Oncol, Catalonia, Spain. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Freedman, Matthew L.] Broad Inst Harvard, Cambridge, MA USA. [Freedman, Matthew L.] MIT, Cambridge, MA 02139 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM freedman@broad.mit.edu RI Davis, Matt/F-9045-2012 FU National Institutes of Health [R01 CA129435, R01 CA109147]; Mayer Foundation; H. L. Snyder Medical Foundation; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE [5P50CA90381]; Prostate Cancer Foundation; Whittier Foundation; American Cancer Society Institutional Research [IRG -58-007-48]; American Society of Clinical Oncology FX M. L. F. is a Howard Hughes Medical Institute Physician-Scientist Early Career Awardee and is a recipient of a 2006 Doris Duke Clinical Scientist Development Award. This work was supported by grants from the US National Institutes of Health (R01 CA129435 to M. L. F. and R01 CA109147 to G. A. C.), the Mayer Foundation (to M. L. F.), the H. L. Snyder Medical Foundation (to M. L. F.), the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute Grant No. 5P50CA90381), the Prostate Cancer Foundation (to G. A. C. and to M. M. P.), the Whittier Foundation (to G. A. C.), the American Cancer Society Institutional Research Grant (IRG -58-007-48 to L. J.) and the American Society of Clinical Oncology (to M. M. P.). We also acknowledge M. A. Brown for his support and guidance. NR 15 TC 359 Z9 369 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2009 VL 41 IS 8 BP 882 EP 884 DI 10.1038/ng.403 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 476IM UT WOS:000268432900010 PM 19561607 ER PT J AU Greenway, SC Pereira, AC Lin, JC DePalma, SR Israel, SJ Mesquita, SM Ergul, E Conta, JH Korn, JM McCarroll, SA Gorham, JM Gabriel, S Altshuler, DM Quintanilla-Dieck, MD Artunduaga, MA Eavey, RD Plenge, RM Shadick, NA Weinblatt, ME De Jager, PL Hafler, DA Breitbart, RE Seidman, JG Seidman, CE AF Greenway, Steven C. Pereira, Alexandre C. Lin, Jennifer C. DePalma, Steven R. Israel, Samuel J. Mesquita, Sonia M. Ergul, Emel Conta, Jessie H. Korn, Joshua M. McCarroll, Steven A. Gorham, Joshua M. Gabriel, Stacey Altshuler, David M. Quintanilla-Dieck, Maria de Lourdes Artunduaga, Maria Alexandra Eavey, Roland D. Plenge, Robert M. Shadick, Nancy A. Weinblatt, Michael E. De Jager, Philip L. Hafler, David A. Breitbart, Roger E. Seidman, Jonathan G. Seidman, Christine E. TI De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot SO NATURE GENETICS LA English DT Article ID CONGENITAL HEART-DISEASE; DEPENDENT PROBE AMPLIFICATION; MUTATIONS CAUSE NOONAN; HYPERTROPHIC CARDIOMYOPATHY; CHROMOSOME 1Q21.1; ALAGILLE-SYNDROME; HUMAN GENOME; SCHIZOPHRENIA; DELETIONS; DUPLICATIONS AB Tetralogy of Fallot (TOF), the most common severe congenital heart malformation, occurs sporadically, without other anomaly, and from unknown cause in 70% of cases. Through a genome-wide survey of 114 subjects with TOF and their unaffected parents, we identified 11 de novo copy number variants (CNVs) that were absent or extremely rare (<0.1%) in 2,265 controls. We then examined a second, independent TOF cohort (n = 398) for additional CNVs at these loci. We identified CNVs at chromosome 1q21.1 in 1% (5/512, P = 0.0002, OR = 22.3) of nonsyndromic sporadic TOF cases. We also identified recurrent CNVs at 3p25.1, 7p21.3 and 22q11.2. CNVs in a single subject with TOF occurred at six loci, two that encode known (NOTCH1, JAG1) disease-associated genes. Our findings predict that at least 10% (4.5-15.5%, 95% confidence interval) of sporadic nonsyndromic TOF cases result from de novo CNVs and suggest that mutations within these loci might be etiologic in other cases of TOF. C1 [Greenway, Steven C.; Lin, Jennifer C.; DePalma, Steven R.; Israel, Samuel J.; Korn, Joshua M.; McCarroll, Steven A.; Gorham, Joshua M.; Altshuler, David M.; Quintanilla-Dieck, Maria de Lourdes; Artunduaga, Maria Alexandra; Seidman, Jonathan G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Pereira, Alexandre C.; Mesquita, Sonia M.] Univ Sao Paulo, Sch Med, Inst Heart, Lab Genet & Mol Cardiol, Sao Paulo, Brazil. [Ergul, Emel; Conta, Jessie H.; Breitbart, Roger E.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Korn, Joshua M.; McCarroll, Steven A.; Gabriel, Stacey; Altshuler, David M.; Plenge, Robert M.; De Jager, Philip L.; Hafler, David A.] Broad Inst Harvard, Cambridge, MA USA. [Korn, Joshua M.; McCarroll, Steven A.; Gabriel, Stacey; Altshuler, David M.; Plenge, Robert M.; De Jager, Philip L.; Hafler, David A.] MIT, Cambridge, MA 02139 USA. [Quintanilla-Dieck, Maria de Lourdes; Artunduaga, Maria Alexandra; Eavey, Roland D.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Plenge, Robert M.; Shadick, Nancy A.; Weinblatt, Michael E.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [De Jager, Philip L.; Hafler, David A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Seidman, Christine E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Seidman, CE (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM cseidman@genetics.med.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU Howard Hughes Medical Institute; US National Institutes of Health; Broad Institute; Pediatric Scientist Development Program; Sarnoff Cardiovascular Research Foundation FX We gratefully acknowledge the participation of families. We also thank C. Sougnez and M. Parkin for technical assistance and R. Geggel for supplying TOF images. This work was supported by grants from the Howard Hughes Medical Institute (C. E. S.), US National Institutes of Health (to C. E. S., J. G. S. and R. E. B. and to the Broad Institute (National Center for Research Resources)), Pediatric Scientist Development Program (S. C. G.) and Sarnoff Cardiovascular Research Foundation (J. C. L.). Multiple sclerosis controls were genotyped in collaboration with Affymetrix, Inc. NR 38 TC 210 Z9 221 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2009 VL 41 IS 8 BP 931 EP U98 DI 10.1038/ng.415 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 476IM UT WOS:000268432900020 PM 19597493 ER PT J AU Sharma, S Rao, A AF Sharma, Sonia Rao, Anjana TI RNAi screening: tips and techniques SO NATURE IMMUNOLOGY LA English DT Editorial Material ID NF-KAPPA-B; IDENTIFIES GENES; CANCER-CELLS; CA2+ INFLUX; INTERFERENCE; GENOME; SIRNA; REPLICATION; PATHWAYS; HIV-1 AB By identifying gene products whose knockdown is associated with phenotypic changes, large-scale RNA-mediated interference screens have demonstrated previously unknown components of biological pathways. This commentary provides general guidelines for using such screens to answer questions of immunological interest. C1 [Sharma, Sonia; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. [Sharma, Sonia; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Sharma, S (reprint author), Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu FU NIAID NIH HHS [R01 AI040127, R01 AI040127-19, R01 AI040127-20, R01 AI084167, R01 AI084167-05] NR 41 TC 23 Z9 23 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD AUG PY 2009 VL 10 IS 8 BP 799 EP 804 DI 10.1038/ni0809-799 PG 6 WC Immunology SC Immunology GA 472OM UT WOS:000268141400003 PM 19621037 ER PT J AU Matthews, AGW Oettinger, MA AF Matthews, Adam G. W. Oettinger, Marjorie A. TI RAG: a recombinase diversified SO NATURE IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN GENE; V(D)J RECOMBINATION; B-CELL; HISTONE ACETYLATION; IN-VITRO; IMMUNOGLOBULIN LOCI; GENOMIC INSTABILITY; PLANT HOMEODOMAIN; NUCLEOSOMAL DNA; C-TERMINUS AB During B cell and T cell development, the lymphoid-specific proteins RAG-1 and RAG-2 act together to initiate the assembly of antigen receptor genes through a series of site-specific somatic DNA rearrangements that are collectively called variable-diversity-joining (V(D) J) recombination. In the past 20 years, a great deal has been learned about the enzymatic activities of the RAG-1-RAG-2 complex. Recent studies have identified several new and exciting regulatory functions of the RAG-1-RAG-2 complex. Here we discuss some of these functions and suggest that the RAG-1-RAG-2 complex nucleates a specialized subnuclear compartment that we call the 'V(D) J recombination factory'. C1 [Matthews, Adam G. W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Matthews, Adam G. W.; Oettinger, Marjorie A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Matthews, AGW (reprint author), MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. EM adamgm@mit.edu; oettinger@molbio.mgh.harvard.edu FU US National Institutes of Health; Damon Runyon Cancer Research Foundation [DRG-1981-08] FX We apologize to those whose work we were unable to cite because of space limitations. Supported by the US National Institutes of Health ( M. A. O.) and the Damon Runyon Cancer Research Foundation ( DRG-1981-08 to A. G. W. M.). NR 53 TC 34 Z9 34 U1 4 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD AUG PY 2009 VL 10 IS 8 BP 817 EP 821 DI 10.1038/ni.1776 PG 5 WC Immunology SC Immunology GA 472OM UT WOS:000268141400009 PM 19621044 ER PT J AU Lo, EH AF Lo, Eng H. TI T time in the brain SO NATURE MEDICINE LA English DT Editorial Material ID EXPERIMENTAL STROKE; ISCHEMIC-STROKE; INJURY; NEUROPROTECTION; ENLIMOMAB; THERAPY; TRIAL AB Inflammation in neural tissue has long been suspected to have a role in stroke. A new study in mouse models of focal cerebral ischemia suggest that a stereotyped sequence of T cell infiltration and activation may underlie the progression of brain injury that can last up to days after stroke onset (pages 946-950). C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. EM lo@helix.mgh.harvard.edu NR 13 TC 24 Z9 24 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2009 VL 15 IS 8 BP 844 EP 846 DI 10.1038/nm0809-844 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 480XK UT WOS:000268770400021 PM 19661986 ER PT J AU Feuerer, M Herrero, L Cipolletta, D Naaz, A Wong, J Nayer, A Lee, J Goldfine, AB Benoist, C Shoelson, S Mathis, D AF Feuerer, Markus Herrero, Laura Cipolletta, Daniela Naaz, Afia Wong, Jamie Nayer, Ali Lee, Jongsoon Goldfine, Allison B. Benoist, Christophe Shoelson, Steven Mathis, Diane TI Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters SO NATURE MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; NECROSIS-FACTOR-ALPHA; ADIPOSE-TISSUE; INSULIN-RESISTANCE; IN-VIVO; DENDRITIC CELLS; IKK-BETA; MICE; MACROPHAGES; ACTIVATION AB Obesity is accompanied by chronic, low-grade inflammation of adipose tissue, which promotes insulin resistance and type-2 diabetes. These findings raise the question of how fat inflammation can escape the powerful armamentarium of cells and molecules normally responsible for guarding against a runaway immune response. CD4(+) Foxp3(+) T regulatory (T(reg)) cells with a unique phenotype were highly enriched in the abdominal fat of normal mice, but their numbers were strikingly and specifically reduced at this site in insulin-resistant models of obesity. Loss-of-function and gain-of-function experiments revealed that these T(reg) cells influenced the inflammatory state of adipose tissue and, thus, insulin resistance. Cytokines differentially synthesized by fat-resident regulatory and conventional T cells directly affected the synthesis of inflammatory mediators and glucose uptake by cultured adipocytes. These observations suggest that harnessing the anti-inflammatory properties of T(reg) cells to inhibit elements of the metabolic syndrome may have therapeutic potential. (C) 2009 Nature America, Inc. All rights reserved. C1 [Cipolletta, Daniela] European Sch Mol Med, Naples, Italy. [Feuerer, Markus; Herrero, Laura; Cipolletta, Daniela; Naaz, Afia; Wong, Jamie; Nayer, Ali; Lee, Jongsoon; Goldfine, Allison B.; Benoist, Christophe; Shoelson, Steven; Mathis, Diane] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Joslin Diabetes Ctr, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM dm@hms.harvard.edu RI Herrero, Laura/D-4011-2014 OI Herrero, Laura/0000-0003-4244-4673 FU Young Chair funds; US National Institutes of Health [DK51729, DK73547, T32 DK7260]; Adler Chair funds; Joslin's National Institutes of Diabetes and Digestive and Kidney Diseases-funded Diabetes and Endocrinology Research Center core facilities; German Research Foundation [FE 801/1-1]; Charles A. King Trust Postdoctoral Fellowship; Ministry of Science of Spain; European School of Molecular Medicine, respectively FX We thank D. Littman (New York University) for the DTR construct, L. Roser and K. Hattori for assistance with mice, S. Rudensky (Memorial Sloan Kettering Cancer Center) for providing us with Foxp3DTR mice, J. LaVecchio and G. Buruzala for flow cytometry and J. Hill, J. Perez and R. Melamed for help with the microarray analysis. This work was supported by Young Chair funds to D. M. and C. B., by the US National Institutes of Health (DK51729 and DK73547) and Adler Chair funds to S. S. and by Joslin's National Institutes of Diabetes and Digestive and Kidney Diseases-funded Diabetes and Endocrinology Research Center core facilities. Postdoctoral fellowship support for M. F. was from the German Research Foundation (Emmy-Noether Fellowship, FE 801/1-1) and the Charles A. King Trust Postdoctoral Fellowship, and for L. H. from the Ministry of Science of Spain. J. W. and D. C. were supported by predoctoral fellowships from the US National Institutes of Health (T32 DK7260) and the European School of Molecular Medicine, respectively. NR 58 TC 727 Z9 755 U1 0 U2 36 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2009 VL 15 IS 8 BP 930 EP U137 DI 10.1038/nm.2002 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 480XK UT WOS:000268770400038 PM 19633656 ER PT J AU Liu, J Divoux, A Sun, J Zhang, J Clement, K Glickman, JN Sukhova, GK Wolters, PJ Du, J Gorgun, CZ Doria, A Libby, P Blumberg, RS Kahn, BB Hotamisligil, GS Shi, GP AF Liu, Jian Divoux, Adeline Sun, Jiusong Zhang, Jie Clement, Karine Glickman, Jonathan N. Sukhova, Galina K. Wolters, Paul J. Du, Juan Gorgun, Cem Z. Doria, Alessandro Libby, Peter Blumberg, Richard S. Kahn, Barbara B. Hotamisligil, Goekhan S. Shi, Guo-Ping TI Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice SO NATURE MEDICINE LA English DT Article ID BROWN ADIPOSE-TISSUE; TUMOR-GROWTH; CATHEPSIN-S; ANGIOGENESIS; INFLAMMATION; EXPRESSION; RESPONSES; ACCUMULATION; INFILTRATION; DEPRIVATION AB Although mast cell functions have classically been related to allergic responses(1-3), recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm and cancer(4-8). This study presents evidence that mast cells also contribute to diet-induced obesity and diabetes. For example, white adipose tissue (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Furthermore, in the context of mice on a Western diet, genetically induced deficiency of mast cells, or their pharmacological stabilization, reduces body weight gain and levels of inflammatory cytokines, chemokines and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer experiments of cytokine-deficient mast cells show that these cells, by producing interleukin-6 (IL-6) and interferon-c (IFN-gamma), contribute to mouse adipose tissue cysteine protease cathepsin expression, apoptosis and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance. Our results showing reduced obesity and diabetes in mice treated with clinically available mast cell-stabilizing agents suggest the potential of developing new therapies for these common human metabolic disorders. C1 [Liu, Jian; Sun, Jiusong; Zhang, Jie; Glickman, Jonathan N.; Sukhova, Galina K.; Du, Juan; Libby, Peter; Blumberg, Richard S.; Shi, Guo-Ping] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Liu, Jian; Sun, Jiusong; Zhang, Jie; Glickman, Jonathan N.; Sukhova, Galina K.; Du, Juan; Doria, Alessandro; Libby, Peter; Blumberg, Richard S.; Kahn, Barbara B.; Shi, Guo-Ping] Harvard Univ, Sch Med, Boston, MA USA. [Divoux, Adeline; Clement, Karine] Inst Natl Sante & Rech Med, U872, Paris, France. [Clement, Karine] Univ Paris 06, Cordeliers Res Ctr, Paris, France. [Clement, Karine] Hop La Pitie Salpetriere, AP HP, Dept Nutr, Paris, France. [Wolters, Paul J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Gorgun, Cem Z.; Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Doria, Alessandro] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Kahn, Barbara B.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Shi, GP (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM gshi@rics.bwh.harvard.edu RI Wolters, Paul/A-7181-2009 FU American Heart Association [0840118N]; US National Institutes of Health [HL60942, HL67283, HL81090, HL88547, HL34636, DK57521, DK56116, DK52539, DK64360]; Programme Hospitalier de Recherche Clinique; Assistance Publique des Hopitaux de Paris [AOR 02076]; French National Agency of Research [NdegreesANR05-PCOD-030-02]; Commission of the European Communities FX We thank S. Rizkalla and C. Poitou, who contributed to the clinical investigation program. We also thank B. Spiegelman and R. K. Gupta for their help with the 3T3-L1 culture. This study was supported partially by the Established Investigator Award from the American Heart Association (0840118N) (to G.-P. S.) and by US National Institutes of Health grants HL60942, HL67283, HL81090, HL88547 (G.-P. S.), HL34636 (P. L.), DK57521, DK56116 (B. B. K.) and DK52539 and DK64360 (G. S. H.). The clinical work was supported by the Programme Hospitalier de Recherche Clinique, Assistance Publique des Hopitaux de Paris (AOR 02076), a grant from French National Agency of Research (RIOMA program N degrees ANR05-PCOD-030-02), and by the Commission of the European Communities (ADAPT project) (to K. C.). NR 35 TC 335 Z9 355 U1 2 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2009 VL 15 IS 8 BP 940 EP U144 DI 10.1038/nm.1994 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 480XK UT WOS:000268770400039 PM 19633655 ER PT J AU Meier, A Chang, JJ Chan, ES Pollard, RB Sidhu, HK Kulkarni, S Wen, TF Lindsay, RJ Orellana, L Mildvan, D Bazner, S Streeck, H Alter, G Lifson, JD Carrington, M Bosch, RJ Robbins, GK Altfeld, M AF Meier, Angela Chang, J. Judy Chan, Ellen S. Pollard, Richard B. Sidhu, Harlyn K. Kulkarni, Smita Wen, Tom Fang Lindsay, Robert J. Orellana, Liliana Mildvan, Donna Bazner, Suzane Streeck, Hendrik Alter, Galit Lifson, Jeffrey D. Carrington, Mary Bosch, Ronald J. Robbins, Gregory K. Altfeld, Marcus TI Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1 SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; IFN-ALPHA PRODUCTION; IMMUNE ACTIVATION; VIRAL LOAD; PROGNOSTIC VALUE; SIV INFECTION; RNA LEVELS; T-CELLS; I INTERFERON; SERUM-LEVELS AB Manifestations of viral infections can differ between women and men(1), and marked sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral loads early in HIV-1 infection but progress faster to AIDS for a given viral load than men(2-7). Here we show substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce markedly more interferon-alpha (IFN-alpha) in response to HIV-1-encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived from men, resulting in stronger secondary activation of CD8(+) T cells. In line with these in vitro studies, treatment-naive women chronically infected with HIV-1 had considerably higher levels of CD8(+) T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs may account for higher immune activation in women compared to men at a given HIV-1 viral load and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1-associated pathology. C1 [Meier, Angela; Chang, J. Judy; Sidhu, Harlyn K.; Wen, Tom Fang; Lindsay, Robert J.; Bazner, Suzane; Streeck, Hendrik; Alter, Galit; Altfeld, Marcus] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Chan, Ellen S.; Orellana, Liliana; Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Pollard, Richard B.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Kulkarni, Smita; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21701 USA. [Lifson, Jeffrey D.] NCI, Sci Applicat Int Corp Frederick, AIDS & Canc Virus Program, Frederick, MD 21701 USA. [Mildvan, Donna] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Bazner, Suzane; Robbins, Gregory K.; Altfeld, Marcus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Altfeld, M (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. EM maltfeld@partners.org RI Robbins, Gregory/F-7988-2011; Orellana, Liliana/S-3302-2016 OI Orellana, Liliana/0000-0003-3736-4337 FU US National Institutes of Health (NIH)-National Institute of Allergy Infectious Diseases [R21 AI071806, PO1 AI074415, K01AI062435]; Harvard University Center for AIDS Research; Bill & Melinda Gates Foundation; Doris Duke Charitable Foundation; German Research Society (Deutsche Forschungsgemeinschaft); National Health and Medical Research Council of Australia [519578]; National Institute of Allergy and Infectious Diseases [AI38855, AI27659, AI38858, AI25879, AI27666]; Agouron/Pfizer, Bristol Myers Squibb and GlaxoSmithKline; US National Cancer Institute (NCI), NIH [HHSN261200800001E] FX We thank S. Deeks, P. Hunt, B. Walker and J. Spritzler for valuable intellectual input and discussions and the ACTG 384 main study and immunology A5007 substudy teams. These studies were supported by US National Institutes of Health (NIH)-National Institute of Allergy and Infectious Diseases grants to M. A. (R21 AI071806, PO1 AI074415) and G. K. R. (K01AI062435), the Harvard University Center for AIDS Research, the Bill & Melinda Gates Foundation and the Doris Duke Charitable Foundation. A. M. was supported by a fellowship from the German Research Society (Deutsche Forschungsgemeinschaft), and J. J. C. was supported by a Fellowship awarded from the National Health and Medical Research Council of Australia (519578). ACTG 384 was supported in part by National Institute of Allergy and Infectious Diseases grants AI38855, AI27659, AI38858, AI25879 and AI27666 and by Agouron/Pfizer, Bristol Myers Squibb and GlaxoSmithKline. This project has been funded in whole or in part with federal funds from the US National Cancer Institute (NCI), NIH, under Contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Support Program of the NIH, NCI, Center for Cancer Research. M. A. is a Distinguished Clinical Scientist of the Doris Duke Charitable Foundation. We thank the Mark and Lisa Schwartz Foundation and the Phillip T. and Susan M. Ragon Foundation for their support. NR 39 TC 198 Z9 202 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2009 VL 15 IS 8 BP 955 EP U161 DI 10.1038/nm.2004 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 480XK UT WOS:000268770400042 PM 19597505 ER PT J AU Manichaikul, A Ghamsari, L Hom, EFY Lin, CW Murray, RR Chang, RL Balaji, S Hao, T Shen, Y Chavali, AK Thiele, I Yang, XP Fan, CY Mello, E Hill, DE Vidal, M Salehi-Ashtiani, K Papin, JA AF Manichaikul, Ani Ghamsari, Lila Hom, Erik F. Y. Lin, Chenwei Murray, Ryan R. Chang, Roger L. Balaji, S. Hao, Tong Shen, Yun Chavali, Arvind K. Thiele, Ines Yang, Xinping Fan, Changyu Mello, Elizabeth Hill, David E. Vidal, Marc Salehi-Ashtiani, Kourosh Papin, Jason A. TI Metabolic network analysis integrated with transcript verification for sequenced genomes SO NATURE METHODS LA English DT Article ID FLUX BALANCE ANALYSIS; CHLAMYDOMONAS-REINHARDTII; RECONSTRUCTION; SCALE; PREDICTION; ALIGNMENT; PROTEINS; GATEWAY; MODELS AB With sequencing of thousands of organisms completed or in progress, there is a growing need to integrate gene prediction with metabolic network analysis. Using Chlamydomonas reinhardtii as a model, we describe a systems-level methodology bridging metabolic network reconstruction with experimental verification of enzyme encoding open reading frames. Our quantitative and predictive metabolic model and its associated cloned open reading frames provide useful resources for metabolic engineering. C1 [Ghamsari, Lila; Lin, Chenwei; Murray, Ryan R.; Balaji, S.; Hao, Tong; Shen, Yun; Yang, Xinping; Fan, Changyu; Mello, Elizabeth; Hill, David E.; Vidal, Marc; Salehi-Ashtiani, Kourosh] Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Ghamsari, Lila; Lin, Chenwei; Murray, Ryan R.; Balaji, S.; Hao, Tong; Shen, Yun; Yang, Xinping; Fan, Changyu; Mello, Elizabeth; Hill, David E.; Vidal, Marc; Salehi-Ashtiani, Kourosh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ghamsari, Lila; Lin, Chenwei; Murray, Ryan R.; Balaji, S.; Hao, Tong; Shen, Yun; Yang, Xinping; Fan, Changyu; Mello, Elizabeth; Hill, David E.; Vidal, Marc; Salehi-Ashtiani, Kourosh] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Manichaikul, Ani; Chavali, Arvind K.; Papin, Jason A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. [Hom, Erik F. Y.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Chang, Roger L.; Thiele, Ines] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Salehi-Ashtiani, K (reprint author), Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM kourosh_salehi-ashtiani@dfci.harvard.edu; papin@virginia.edu RI Manichaikul, Ani/B-7726-2009; Hill, David/B-6617-2011; Chavali, Arvind/L-7157-2016; Thiele, Ines/A-7629-2014; Hom, Erik/B-3889-2008; OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243; Thiele, Ines/0000-0002-8071-7110; Hom, Erik/0000-0003-0964-0031; Manichaikul, Ani/0000-0002-5998-795X; Papin, Jason/0000-0002-2769-5805 FU US Department of Energy [DE-FG02-07ER64496]; Jane Coffin Childs Memorial Fund for Medical Research; National Science Foundation [DGE0504645] FX This research was supported by the Office of Science (Biological and Environmental Research), US Department of Energy, grant DE-FG02-07ER64496 (to J.A.P. and K.S.-A.), the Jane Coffin Childs Memorial Fund for Medical Research (to E.F.Y.H.) and by National Science Foundation IGERT training grant DGE0504645 (to R.L.C.). NR 27 TC 41 Z9 44 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD AUG PY 2009 VL 6 IS 8 BP 589 EP U53 DI 10.1038/NMETH.1348 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 477CA UT WOS:000268493700018 PM 19597503 ER PT J AU Engelman, JA AF Engelman, Jeffrey A. TI Targeting PI3K signalling in cancer: opportunities, challenges and limitations SO NATURE REVIEWS CANCER LA English DT Review ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; TUMOR-SUPPRESSOR GENE; PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; PHOSPHOINOSITIDE 3-KINASE/AKT PATHWAY; RICTOR-MTOR COMPLEX; ANTITUMOR-ACTIVITY; BREAST-CANCER; ACQUIRED-RESISTANCE AB There are ample genetic and laboratory studies that suggest the PI3K-Akt pathway is vital to the growth and survival of cancer cells. Inhibitors targeting this pathway are entering the clinic at a rapid pace. In this Review, the therapeutic potential of drugs targeting PI3K-Akt signalling for the treatment of cancer is discussed. I focus on the advantages and drawbacks of different treatment strategies for targeting this pathway, the cancers that might respond best to these therapies and the challenges and limitations that confront their clinical development. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. EM jengelman@partners.org RI lv, xiaoqing/A-2591-2012 FU National Institutes of Health FX I am grateful to L. Cantley and the members of his laboratory for discussions and insights regarding PI3K signalling. I thank my laboratory, P. Janne's laboratory and J. Settleman's laboratory for discussions regarding oncogene addiction and resistance to targeted therapies. I apologize to the many authors whose work I could not cite directly because of space limitations. This work was supported by the National Institutes of Health. NR 159 TC 1146 Z9 1178 U1 35 U2 236 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD AUG PY 2009 VL 9 IS 8 BP 550 EP 562 DI 10.1038/nrc2664 PG 13 WC Oncology SC Oncology GA 480MY UT WOS:000268740200013 PM 19629070 ER PT J AU Dotto, GP AF Dotto, G. Paolo TI Crosstalk of Notch with p53 and p63 in cancer growth control SO NATURE REVIEWS CANCER LA English DT Review ID NF-KAPPA-B; MULTIPLE SIGNALING PATHWAYS; CELL-CYCLE ARREST; ACUTE LYMPHOBLASTIC-LEUKEMIA; FACTOR RECEPTOR PROMOTER; TUMOR-SUPPRESSOR GENE; STEM-CELL; P53-DEFICIENT MICE; BREAST-CANCER; TGF-BETA AB Understanding the complexity of cancer depends on an elucidation of the underlying regulatory networks, at the cellular and intercellular levels and in their temporal dimension. This Opinion article focuses on the multilevel crosstalk between the Notch pathway and the p53 and p63 pathways. These two coordinated signalling modules are at the interface of external damaging signals and control of stem cell potential and differentiation. Positive or negative reciprocal regulation of the two pathways can vary with cell type and cancer stage. Therefore, selective or combined targeting of the two pathways could improve the efficacy and reduce the toxicity of cancer therapies. C1 [Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. EM gian-paolo.dotto@unil.ch FU NIAMS NIH HHS [AR054856, AR39190, R01 AR054856] NR 157 TC 85 Z9 87 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD AUG PY 2009 VL 9 IS 8 BP 587 EP 595 DI 10.1038/nrc2675 PG 9 WC Oncology SC Oncology GA 480MY UT WOS:000268740200016 PM 19609265 ER PT J AU Braunwald, E AF Braunwald, Eugene TI BNP measurement predicts AMI risk in the elderly SO NATURE REVIEWS CARDIOLOGY LA English DT Editorial Material ID BRAIN NATRIURETIC PEPTIDE; ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; PROGNOSTIC VALUE; MORTALITY AB With the aging of the population, the frequency of acute myocardial infarction is rising most rapidly among the elderly, a subgroup at high risk of a fatal outcome. Lorgis et al. observe that N-terminal pro-brain natriuretic peptide, combined with a simple clinical risk score, provides an accurate estimate of prognosis. C1 [Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 10 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD AUG PY 2009 VL 6 IS 8 BP 503 EP 504 DI 10.1038/nrcardio.2009.118 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 474XF UT WOS:000268317400005 PM 19633678 ER PT J AU Liu, PX Cheng, HL Roberts, TM Zhao, JJ AF Liu, Pixu Cheng, Hailing Roberts, Thomas M. Zhao, Jean J. TI Targeting the phosphoinositide 3-kinase pathway in cancer SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID TUMOR-SUPPRESSOR GENE; SQUAMOUS-CELL CARCINOMA; PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; INCREASED INSULIN SENSITIVITY; MAMMARY EPITHELIAL-CELLS; ETHER LIPID ANALOGS; CHROMOSOME ARM 10Q; IMPAIRED B-CELL; LUNG-CANCER; PROSTATE-CANCER AB The phosphoinositide 3-kinase (PI3K) pathway is a key signal transduction system that links oncogenes and multiple receptor classes to many essential cellular functions, and is perhaps the most commonly activated signalling pathway in human cancer. This pathway therefore presents both an opportunity and a challenge for cancer therapy. Even as inhibitors that target PI3K isoforms and other major nodes in the pathway, including AKT and mammalian target of rapamycin (mTOR), reach clinical trials, major issues remain. Here, we highlight recent progress that has been made in our understanding of the PI3K pathway and discuss the potential of and challenges for the development of therapeutic agents that target this pathway in cancer. C1 [Liu, Pixu; Cheng, Hailing; Roberts, Thomas M.; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhao, JJ (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu FU National Institutes of Health [CA030002, CA089021, CA050661, CA134502-01]; Department of Defense for Cancer Research [BC051565]; V Foundation; Claudia Barr Program FX We thank N. Gray and Q. Liu for providing compound structures and helpful discussions. We thank the reviewers for their helpful suggestions. We apologize to colleagues whose primary papers were not cited owing to space constraints. This work was supported in part by the National Institutes of Health (CA030002, CA089021 and CA050661 to T. M. R. and CA134502-01 to J. J. Z.), the Department of Defense for Cancer Research (BC051565 to J. J. Z.), the V Foundation (J. J. Z.) and the Claudia Barr Program (J. J. Z.). NR 203 TC 1016 Z9 1055 U1 24 U2 157 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD AUG PY 2009 VL 8 IS 8 BP 627 EP 644 DI 10.1038/nrd2926 PG 18 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 477KI UT WOS:000268517600020 PM 19644473 ER PT J AU Stolerman, ES Florez, JC AF Stolerman, Elliot S. Florez, Jose C. TI Genomics of type 2 diabetes mellitus: implications for the clinician SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID SINGLE NUCLEOTIDE POLYMORPHISMS; NUCLEAR FACTOR-4-ALPHA GENE; POPULATION-BASED SAMPLE; FASTING GLUCOSE-LEVELS; BETA-CELL FUNCTION; WIDE ASSOCIATION; COMMON VARIANTS; INSULIN-RESISTANCE; TCF7L2 GENE; SULFONYLUREA RECEPTOR AB Our understanding of the genetics of type 2 diabetes mellitus (T2DM) has changed, in part owing to implementation of genome-wide association studies as a method for unraveling the genetic architecture of complex traits. These studies enable a global search throughout the nuclear genome for variants that are associated with specific phenotypes. Currently, single nucleotide polymorphisms in about 24 different genetic loci have been associated with T2DM. Most of these genetic loci are associated with the insulin secretion pathway rather than insulin resistance. study design, heritability differences and the intrinsic properties of in vivo insulin resistance measures might partially explain why only a few loci associated with insulin resistance have been detected through genome-wide association approaches. Despite the success of these approaches at detecting loci associated with T2DM, currently known associations explain only a small amount of the genetic variance involved in the disease. Compared with previous studies, larger cohorts might be needed to identify variants of smaller effect sizes and lower allele frequencies. Finally, the current list of genetic loci that are related to T2DM does not seem to offer greater predictive value in determining diabetes risk than do commonly used phenotypic risk factors and family history. C1 [Stolerman, Elliot S.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Simches Res Bldg CPZN 5-250, Boston, MA 02114 USA. EM jcflorez@partners.org FU NIH [T32 GM007748]; Doris Duke Charitable Foundation; Massachusetts General Hospital FX E. S. Stolerman is supported by NIH Training Grant T32 GM007748 in Genetics. J. C. Florez is supported by a Physician scientist Development Award by the Massachusetts General Hospital and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. NR 83 TC 51 Z9 53 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD AUG PY 2009 VL 5 IS 8 BP 429 EP 436 DI 10.1038/nrendo.2009.129 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 475CY UT WOS:000268336400006 PM 19564886 ER PT J AU Medarova, Z Moore, A AF Medarova, Zdravka Moore, Anna TI MRI as a tool to monitor islet transplantation SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; BETA-CELL MASS; DIABETIC NUDE-MICE; IN-VIVO; PANCREATIC-ISLETS; REAL-TIME; MAGNETIC NANOPARTICLES; INSULIN-SECRETION; EDMONTON PROTOCOL; GLUCOSE TOXICITY AB The development of new methods for noninvasive imaging is an area of biotechnology that is of great relevance for the diagnosis and characterization of diabetes mellitus. Noninvasive imaging can be used to study the dynamics of beta-cell mass and function; beta-cell death; vascularity, innervation and autoimmune attack of pancreatic islets; and the efficacy of islet transplantation to remedy beta-cell loss in patients with diabetes mellitus. in this review, we focus on the application of MRI for monitoring islet transplantation and on the potential causes of islet graft failure, which are still poorly understood. Questions that have been addressed by MRI studies encompass graft longevity, and the effects of immune rejection, glucose toxic effects, and the transplanted islets' purity on graft fate. we also highlight novel technologies for simultaneous imaging and delivery of experimental therapies that aim to extend the lifespan and functionality of islet grafts. On the basis of this evidence, MRI represents a valuable platform for a thorough investigation of beta-cell function in the context of islet transplantation. State-of-the-art multimodality approaches, such as PET-MRI, can extend our current capabilities and help answer the critical questions that currently inhibit the prevention and cure of diabetes mellitus. C1 [Medarova, Zdravka; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Mol Imaging Lab, Athinoula A Martinos Ctr Biomed Imaging,MIT,Med S, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Mol Imaging Lab, Athinoula A Martinos Ctr Biomed Imaging,MIT,Med S, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu NR 66 TC 42 Z9 44 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD AUG PY 2009 VL 5 IS 8 BP 444 EP 452 DI 10.1038/nrendo.2009.130 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 475CY UT WOS:000268336400008 PM 19546863 ER PT J AU Zha, S Boboila, C Alt, FW AF Zha, Shan Boboila, Cristian Alt, Frederick W. TI Mre11: roles in DNA repair beyond homologous recombination SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID DOUBLE-STRAND-BREAK; CLASS-SWITCH RECOMBINATION; END-JOINING PATHWAY; V(D)J RECOMBINATION; GENOMIC INSTABILITY; MRE11/RAD50 COMPLEX; CELL-CYCLE; LIGASE-IV; B-CELLS; TRANSLOCATIONS AB The Mre11 protein has well-documented functions in the repair of DNA double-strand breaks via homologous recombination. Now, several new studies reveal that Mre11 also has a role in mammalian DNA double-strand break repair by nonhomologous end joining. C1 [Zha, Shan; Boboila, Cristian; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,CBR Inst Biomed Res, Boston, MA 02115 USA. RP Zha, S (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu NR 44 TC 46 Z9 47 U1 3 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD AUG PY 2009 VL 16 IS 8 BP 798 EP 800 DI 10.1038/nsmb0809-798 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 480MJ UT WOS:000268738700002 PM 19654615 ER PT J AU Zhang, Y Moqtaderi, Z Rattner, BP Euskirchen, G Snyder, M Kadonaga, JT Liu, XS Struhl, K AF Zhang, Yong Moqtaderi, Zarmik Rattner, Barbara P. Euskirchen, Ghia Snyder, Michael Kadonaga, James T. Liu, X. Shirley Struhl, Kevin TI Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; HIGH-RESOLUTION; GENOME-WIDE; SEQUENCE; YEAST; PROMOTER; BINDING; ELONGATION; CHROMATIN; TRANSCRIPTION AB We assess the role of intrinsic histone-DNA interactions by mapping nucleosomes assembled in vitro on genomic DNA. Nucleosomes strongly prefer yeast DNA over Escherichia coli DNA, indicating that the yeast genome evolved to favor nucleosome formation. Many yeast promoter and terminator regions intrinsically disfavor nucleosome formation, and nucleosomes assembled in vitro show strong rotational positioning. Nucleosome arrays generated by the ACF assembly factor have fewer nucleosome-free regions, reduced rotational positioning and less translational positioning than obtained by intrinsic histone-DNA interactions. Notably, nucleosomes assembled in vitro have only a limited preference for specific translational positions and do not show the pattern observed in vivo. Our results argue against a genomic code for nucleosome positioning, and they suggest that the nucleosomal pattern in coding regions arises primarily from statistical positioning from a barrier near the promoter that involves some aspect of transcriptional initiation by RNA polymerase II. C1 [Moqtaderi, Zarmik; Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, Yong; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zhang, Yong; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rattner, Barbara P.; Kadonaga, James T.] Univ Calif San Diego, Mol Biol Sect, La Jolla, CA 92093 USA. [Euskirchen, Ghia; Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. RP Struhl, K (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM kevin@hms.harvard.edu RI Zhang, Yong/B-4838-2011; OI Zhang, Yong/0000-0001-6316-2734; Rattner, Barbara/0000-0002-1339-0920 FU US National Institutes of Health [GM 58272, HG 4069, GM 30186] FX We thank I. Albert, Z. Zhang and F. Pugh for analyses and commentary during the early stages of this work, and Y. Lei and H. Shin for help with the heat maps and power spectrum analysis, respectively. This work was supported by grants to J.T.K. ( GM 58272), X. S. L. ( HG 4069) and K. S. ( GM 30186) from the US National Institutes of Health. NR 34 TC 242 Z9 242 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD AUG PY 2009 VL 16 IS 8 BP 847 EP U70 DI 10.1038/nsmb.1636 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 480MJ UT WOS:000268738700012 PM 19620965 ER PT J AU Koga, T Morita, A Maruyama, K Tanaka, M Ino, Y Shibahara, J Louis, DN Reifenberger, G Itami, J Hara, R Saito, N Todo, T AF Koga, Tomoyuki Morita, Akio Maruyama, Keisuke Tanaka, Minoru Ino, Yasushi Shibahara, Junji Louis, David N. Reifenberger, Guido Itami, Jun Hara, Ryusuke Saito, Nobuhito Todo, Tomoki TI Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation SO NEURO-ONCOLOGY LA English DT Article DE glioma; pleomorphic xanthoastrocytoma; stereotactic irradiation; stereotactic radiosurgery ID MALIGNANT-TRANSFORMATION; CYBERKNIFE RADIOSURGERY; GENETIC ALTERATIONS; SURGICAL RESECTION; EXPERIENCE; GLIOMA AB Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm of the brain. Some PXAs are accompanied by anaplastic features and are difficult to manage because of frequent recurrences that lead to early death. No previous reports have demonstrated consistent efficacy of adjuvant radiotherapy or chemotherapy for this disease. We report a case of PXA with anaplastic features treated with stereotactic irradiation (STI) that resulted in long-term control of repeatedly recurring nodules throughout the neuraxis. A 47-year-old woman presented with an epileptic seizure due to a large tumor in the right frontal lobe. The tumor was resected and diagnosed as PXA with anaplastic features. Sixteen months later, a relapse at the primary site was noted and treated with stereotactic radiosurgery using Gamma Knife. Two years later, the patient developed a tumor nodule in the cervical spinal cord that histologically corresponded to a small-cell glioma with high cellularity and prominent MIB-1 (mindbomb homolog 1) labeling. In the following months, multiple nodular lesions appeared throughout the CNS, and STI was performed six times for eight intracranial lesions using Gamma Knife and twice using a linear accelerator, for three spinal cord lesions in total. All lesions treated with STI were well controlled, and the patient was free from symptomatic progression for 50 months. However, diffuse dissemination along the craniospinal axis eventually progressed, and she died 66 months after initial diagnosis. Autopsy showed that the nodules remained well demarcated from the surrounding nervous system tissue. STI may be an effective therapeutic tool for controlling nodular dissemination of PXA with anaplastic features. Neuro-Oncology 11, 446-451, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00090, January 22, 2009. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-112) C1 [Koga, Tomoyuki; Morita, Akio; Maruyama, Keisuke; Tanaka, Minoru; Ino, Yasushi; Saito, Nobuhito; Todo, Tomoki] Tokyo Univ Hosp, Dept Neurosurg, Bunkyo Ku, Tokyo 1138655, Japan. [Shibahara, Junji] Tokyo Univ Hosp, Dept Pathol, Tokyo 1138655, Japan. [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Reifenberger, Guido] Univ Dusseldorf, Dept Neuropathol, Dusseldorf, Germany. [Itami, Jun; Hara, Ryusuke] Int Med Ctr Japan, Dept Radiat Therapy & Oncol, Tokyo, Japan. RP Todo, T (reprint author), Tokyo Univ Hosp, Dept Neurosurg, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM kouga-tky@umin.ac.jp; toudou-nsu@umin.ac.jp NR 25 TC 19 Z9 22 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2009 VL 11 IS 4 BP 446 EP 451 DI 10.1215/15228517-2008-112 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 483BU UT WOS:000268937600012 PM 19164434 ER PT J AU Scherzer, CR AF Scherzer, Clemens R. TI Chipping away at diagnostics for neurodegenerative diseases SO NEUROBIOLOGY OF DISEASE LA English DT Review DE Gene expression; Transcriptional profiling; Microarray; Biomarker; Blood; Biological fluids; Variation; Stability; Reproducibility; Validation; Parkinson's disease; Alzheimer's disease; Multiple sclerosis; SORL1; LR11; alpha-Synuclein ID PERIPHERAL-BLOOD LYMPHOCYTES; AMYLOID PRECURSOR PROTEIN; GENE-EXPRESSION MEASUREMENTS; NEGATIVE BREAST-CANCER; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; HUNTINGTONS-DISEASE; OSTEOPONTIN LEVELS; MESSENGER-RNA AB Biomarkers are needed to overcome critical roadblocks in the development of disease-modifying therapeutics for neurodegenerative diseases. Evolving genome-wide expression technologies can comprehensively search for molecular biomarkers and allow fascinating insights into the expanding complexity of the human transcriptome. The technology has matured to the point where some applications are deemed reliable enough for use in patient care. In the neurosciences, it has led to the discoveries of osteopontin in multiple sclerosis and SORL1/LR11 in Alzheimer's, and recent studies indicate its potential for identifying neurogenomic biomarkers. Advances in pre-analytical and analytical methods are improving search efficiency and reproducibility and may lead to a pipeline of biomarker candidates suitable for development into future neurologic diagnostics. (C) 2009 Elsevier Inc. All rights reserved. C1 [Scherzer, Clemens R.] Harvard Univ, Sch Med, Ctr Neurol Dis, Cambridge, MA 02139 USA. [Scherzer, Clemens R.] Brigham & Womens Hosp, Cambridge, MA 02139 USA. [Scherzer, Clemens R.] Harvard NeuroDiscovery Ctr, Biomarker Program, Cambridge, MA 02139 USA. [Scherzer, Clemens R.] Massachusetts Gen Hosp, Partners Parkinsons Dis & Movement Disorders Ctr, Boston, MA 02114 USA. [Scherzer, Clemens R.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Scherzer, CR (reprint author), Harvard Univ, Sch Med, Ctr Neurol Dis, 65 Landsdowne St,Suite 307A, Cambridge, MA 02139 USA. EM cscherzer@rics.bwh.harvard.edu FU NIA [K08AG024816]; American Federation for Aging Research, NINDS [NS064155, NS060227, NS058793]; Harvard NeuroDiscovery Center; US Department of Defense; M.E.M.O. Hoffman Foundation; RJG Foundation; Michael J. Fox Foundation FX Dr. Steven Hersch and Dr. Peter Lansbury provided insightful comments and analyses of critical roadblocks in the development of disease-modifying therapeutics for HD and PD. I thank the members of the Scherzer lab for their excellent contributions. I am particularly grateful to Drs. John Growdon, Bernard Ravina, and Alberto Ascherio for their expertise. Dr. Scherzer's work is supported by a Paul B. Beeson K08AG024816 from the NIA and the American Federation for Aging Research, NINDS grants NS064155, NS060227, and NS058793, the Harvard NeuroDiscovery Center, the US Department of Defense, the M.E.M.O. Hoffman Foundation, the RJG Foundation, and the Michael J. Fox Foundation. NR 101 TC 16 Z9 16 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD AUG PY 2009 VL 35 IS 2 BP 148 EP 156 DI 10.1016/j.nbd.2009.02.016 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 471SJ UT WOS:000268078300005 PM 19285134 ER PT J AU Leslie-Mazwi, TM Avery, LL Sims, JR AF Leslie-Mazwi, T. M. Avery, Laura L. Sims, John R. TI Intra-arterial Air Thrombogenesis after Cerebral Air Embolism Complicating Lower Extremity Sclerotherapy SO NEUROCRITICAL CARE LA English DT Article DE Hyperbaric oxygen; Cerebral infarction; Thrombosis; Arterial gas embolism; Sclerotherapy; Complication ID VARICOSE-VEINS; FOAM SCLEROTHERAPY; GAS EMBOLISM; MICROEMBOLISM; MANAGEMENT; POSITION; BLOOD AB Cerebral arterial gas embolism is a potentially life-threatening event. Intraarterial air can occlude blood flow directly or cause thrombosis. Sclerotherapy is an extremely rare cause of cerebral arterial gas embolism. Case-report. A 38-year-old female suffered acute onset of a left middle cerebral artery (LMCA) syndrome with an NIH stroke score of 11 approximately ten minutes after lower extremity sclerotherapy. CT angiogram demonstrated LMCA intraarterial air. Patient fully recovered after hyperbaric oxygen treatment with complete resolution of intraarterial air. However, thrombus replaced intraarterial air despite anticoagulation with heparin. We provide radiological evidence of hyperbaric oxygen therapy resolving intraarterial air but also demonstrate the thrombogenic potential of this procedural complication. C1 [Sims, John R.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Avery, Laura L.] Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02129 USA. [Sims, John R.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Leslie-Mazwi, T. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Avery, Laura L.] Massachusetts Gen Hosp, Dept Emergency Radiol, Boston, MA 02114 USA. RP Sims, JR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Bldg 149,Rm 6403,13th St, Charlestown, MA 02129 USA. EM tleslie-mazwi@partners.org; lavery@partners.org; jsims@partners.org NR 20 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD AUG PY 2009 VL 11 IS 1 BP 97 EP 100 DI 10.1007/s12028-009-9202-3 PG 4 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 468AU UT WOS:000267786400018 PM 19277906 ER PT J AU Fischl, B Stevens, AA Rajendran, N Yeo, BTT Greve, DN Van Leemput, K Polimeni, JR Kakunoori, S Buckner, RL Pacheco, J Salat, DH Melcher, J Frosch, MP Hyman, BT Grant, PE Rosen, BR van der Kouwe, AJW Wiggins, GC Wald, LL Augustinack, JC AF Fischl, Bruce Stevens, Allison A. Rajendran, Niranjini Yeo, B. T. Thomas Greve, Douglas N. Van Leemput, Koen Polimeni, Jonathan R. Kakunoori, Sita Buckner, Randy L. Pacheco, Jennifer Salat, David H. Melcher, Jennifer Frosch, Matthew P. Hyman, Bradley T. Grant, P. Ellen Rosen, Bruce R. van der Kouwe, Andre J. W. Wiggins, Graham C. Wald, Lawrence L. Augustinack, Jean C. TI Predicting the location of entorhinal cortex from MRI SO NEUROIMAGE LA English DT Review DE Morphometry; MRI; Alzheimer's disease ID MILD COGNITIVE IMPAIRMENT; MAGNETIC-RESONANCE IMAGES; EARLY ALZHEIMERS-DISEASE; SURFACE-BASED ANALYSIS; IN-VIVO DETECTION; AREA 35 CORTICES; TEMPORAL-LOBE; HUMAN-BRAIN; INTERSUBJECT VARIABILITY; HIPPOCAMPAL VOLUME AB Entorhinal cortex (EC) is a medial temporal lobe area critical to memory formation and spatial navigation that is among the earliest parts of the brain affected by Alzheimer's disease (AD). Accurate localization of EC would thus greatly facilitate early detection and diagnosis of AD. In this study, we used ultra-high resolution ex vivo MRI to directly visualize the architectonic features that define EC rostrocaudally and mediolaterally, then applied surface-based registration techniques to quantify the variability of EC with respect to cortical geometry, and made predictions of its location on in vivo scans. The results indicate that EC can be localized quite accurately based on cortical folding patterns, within 3 mm in vivo, a significant step forward in our ability to detect the earliest effects of AD when clinical intervention is most likely to be effective. (C) 2009 Elsevier Inc. All rights reserved. C1 [Fischl, Bruce; Stevens, Allison A.; Greve, Douglas N.; Van Leemput, Koen; Polimeni, Jonathan R.; Kakunoori, Sita; Buckner, Randy L.; Salat, David H.; Grant, P. Ellen; Rosen, Bruce R.; van der Kouwe, Andre J. W.; Wald, Lawrence L.; Augustinack, Jean C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr,Dept Radiol, Charlestown, MA 02129 USA. [Fischl, Bruce; Yeo, B. T. Thomas; Van Leemput, Koen] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Frosch, Matthew P.; Hyman, Bradley T.] Harvard Univ, Sch Med, MGH, Dept Neurol, Charlestown, MA 02129 USA. [Melcher, Jennifer] Harvard Univ, Sch Med, MGH, Dept Otol & Laryngol, Charlestown, MA 02129 USA. [Rajendran, Niranjini] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [Pacheco, Jennifer] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Wiggins, Graham C.] NYU Med Ctr, Ctr Biomed Imaging, New York, NY 10016 USA. RP Fischl, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr,Dept Radiol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fischl@nmr.mgh.harvard.edu RI Van Leemput, Koen/A-9197-2009; Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009; OI Van Leemput, Koen/0000-0001-6466-5309; Polimeni, Jonathan/0000-0002-1348-1179; Yeo, B.T. Thomas/0000-0002-0119-3276 FU National Center for Research Resources [P41-RR14075, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550, R01EB006758]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; Mental illness and Neuroscience Discovery (MIND) Institute; National Alliance for Medical Image Computing (NAMIC) [U54 EB005149]; Ellison Medical Foundation FX Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01 EB001550, R01EB006758), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01) as well as the Mental illness and Neuroscience Discovery (MIND) Institute, and is part of the National Alliance for Medical Image Computing (NAMIC), funded through the NIH Roadmap for Medical Research, Grant U54 EB005149. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation. Finally, we acknowledge a research agreement and research support from Siemens Healthcare. One of the authors (LLW) has obtained consulting income from Siemens Healthcare. NR 102 TC 42 Z9 42 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 1 PY 2009 VL 47 IS 1 BP 8 EP 17 DI 10.1016/j.neuroimage.2009.04.033 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 457YW UT WOS:000266975300003 PM 19376238 ER PT J AU Langers, DRM AF Langers, Dave R. M. TI Blind source separation of fMRI data by means of factor analytic transformations SO NEUROIMAGE LA English DT Article DE Functional magnetic resonance imaging; Blind source separation; Factor analysis; Independent component analysis ID INDEPENDENT COMPONENT ANALYSIS; FUNCTIONAL MRI DATA; TIME-SERIES; HUMAN-BRAIN; ROTATION; CONNECTIVITY; ALGORITHMS; CRITERION; ICA AB In this study, the application of factor analytic (FA) rotation methods in the context of neuroimaging data analysis was explored. Three FA algorithms (ProMax, QuartiMax, and VariMax) were employed to carry out blind source separation in a functional magnetic resonance imaging (fMRI) experiment that involved a basic audiovisual stimulus paradigm. The outcomes were compared with those from three common independent component analysis (ICA) methods (FastICA, InfoMax, and jade). When applied in the spatial domain (sFA), all three FA methods performed satisfactorily and comparably to the ICA methods. The QuartiMax and VariMax methods resulted in highly similar outcomes, while the ProMax results more closely resembled those from the FastICA and InfoMax ICA analyses. All methods were able to identify multiple distinct contributing factors of neural origin, including e.g. the central auditory system, the mediotemporal limbic lobe, the basal ganglia, and the motor system. in addition, various contributions from artifacts could be observed, but these constituted different factors that were well separated from those with neural effects. When applied in the temporal domain (tFA), the factor analytic methods performed drastically worse, in the sense that the spatial activation maps revealed activation much more diffusely throughout the brain and the corresponding time courses were less pronouncedly related to the employed stimulus paradigm. Temporal ICA performed better than tFA, with the possible exception of the Jade method, but still did worse than any of the spatial FA or ICA methods. In conclusion, the present findings suggest that sFA forms a viable and useful alternative to ICA in the context of fMRI data analyses, and indicate that sFA methods complement the range of blind source separation methods that are currently in use in fMRI already. (C) 2009 Elsevier Inc. All rights reserved. C1 [Langers, Dave R. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Otorhinolaryngol Head & Neck Surg, Groningen, Netherlands. [Langers, Dave R. M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Langers, DRM (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Otorhinolaryngol Head & Neck Surg, Groningen, Netherlands. EM d.r.m.langers@med.umcg.nl RI Langers, Dave/F-6249-2011 OI Langers, Dave/0000-0002-1053-5645 FU Netherlands organisation for scientific research (NWO) [016.096.011]; Netherlands organization for health research and development (ZonMw) FX The author was partly funded by VENI research grant 016.096.011 from the Netherlands organisation for scientific research (NWO) and the Netherlands organization for health research and development (ZonMw). Furthermore, he would like to express his gratitude for the fruitful cooperation with the Melcher research group at the Eaton-Peabody Laboratory in Boston (USA) and particularly acknowledge the generous contributions of Jennifer Melcher and Gianwen Gu, who indispensably contributed in the design of the neuroimaging experiment, the recruitment of the Subjects, and the acquisition of the data. NR 46 TC 8 Z9 9 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 1 PY 2009 VL 47 IS 1 BP 77 EP 87 DI 10.1016/j.neuroimage.2009.04.017 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 457YW UT WOS:000266975300012 PM 19362596 ER PT J AU Napadow, V Dhond, R Park, K Kim, J Makris, N Kwong, KK Harris, RE Purdon, PL Kettner, N Hui, KKS AF Napadow, Vitaly Dhond, Rupali Park, Kyungmo Kim, Jieun Makris, Nikos Kwong, Kenneth K. Harris, Richard E. Purdon, Patrick L. Kettner, Norman Hui, Kathleen K. S. TI Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture SO NEUROIMAGE LA English DT Article DE Habituation; Cardiac gating; Brainstem; Alternative medicine; Endorphin; Dopamine; Serotonin; Monoamine ID DYNAMIC-MECHANICAL ALLODYNIA; PERIAQUEDUCTAL GRAY; CARDIOVASCULAR-RESPONSES; FOS EXPRESSION; SIGNAL CHANGE; ELECTROACUPUNCTURE; PAIN; STIMULATION; ACTIVATION; ANALGESIA AB Acupuncture modulation of activity in the human brainstem is not well known. This structure is plagued by physiological artifact in neuroimaging experiments. In addition, most Studies have used short (< 15 min) block designs, which miss delayed responses following longer duration stimulation. We used brainstem-focused cardiac-gated fMRI and evaluated time-variant brain response to longer duration (>30 min) stimulation with verum (VA, electro-stimulation at acupoint ST-36) or sham point (SPA, non-acupoint electro-stimulation) acupuncture. Our results provide evidence that acupuncture modulates brainstem nuclei important to endogenous monoaminergic and opioidergic systems. Specifically, VA modulated activity in the substantia nigra (SN), nucleus raphe magnus, locus ceruleus, nucleus cuneiformis, and periaqueductal gray (PAG). Activation in the ventrolateral PAG was greater for VA compared to SPA. Linearly decreasing time-variant activation, suggesting classical habituation, was found in response to both VA and SPA in sensorimotor (Sit, posterior insula, premotor cortex) brain regions. However, VA also produced linearly time-variant activity in limbic regions (amygdala, hippocampus, and SN), which was bimodal and not likely habituation - consisting of activation in early blocks, and deactivation by the end of the run. Thus, acupuncture induces different brain response early, compared to 20-30 min after stimulation. We attribute the fMRI differences between VA and SPA to more varied and stronger psychophysical response induced by VA. Our Study demonstrates that acupuncture modulation of brainstem Structures can be Studied noninvasively in humans. allowing for comparison to animal Studies. Our protocol also demonstrates a fMRI approach to study habituation and other time-variant phenomena over longer time durations. (C) 2009 Elsevier Inc. All rights reserved. C1 [Napadow, Vitaly; Dhond, Rupali; Kwong, Kenneth K.; Purdon, Patrick L.; Hui, Kathleen K. S.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Napadow, Vitaly; Dhond, Rupali; Kettner, Norman] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. [Park, Kyungmo; Kim, Jieun] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. [Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. [Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Purdon, Patrick L.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Napadow, V (reprint author), MGH MIT HMS Ctr Biomed Imaging, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu RI Harris, Richard/F-1307-2011 FU National Center for Complementary and Alternative Medicine, NIH [K01-AT002166, P01-AT002048, K01-AT004481, F05-AT003770, K24-AT004095]; National Institute of Neurological Disorders and Stroke [K25-NS057580]; NCRR [P41-RR14075, M01-RR01066]; Mental Illness and Neuroscience Discovery (MIND) Institute; Institute of Information Technology Advancement, Korea [IITA-2008-(C1090-0801-0002)]; Department of Army grant DAMD [W81XWH-07-2-0050]; Dana Foundation Award in Brain and Immuno-imaging FX We would like to thank the National Center for Complementary and Alternative Medicine, NIH for funding support: K01-AT002166 (to VN), P01-AT002048 (VN, KKSH), K01-AT004481 (RD), F05-AT003770 (KP) and K24-AT004095. We also acknowledge the National Institute of Neurological Disorders and Stroke (K25-NS057580 to PLP), the NCRR (P41-RR14075, GCRC M01-RR01066), and the Mental Illness and Neuroscience Discovery (MIND) Institute. Dr. Park was also supported by the Institute of Information Technology Advancement, Korea IITA-2008-(C1090-0801-0002). Dr. Harris was also supported by Department of Army grant DAMD Award Number W81XWH-07-2-0050, and Dana Foundation Award in Brain and Immuno-imaging. The content is solely the responsibility of the authors and does not necessarily represent the official views of our funding agencies. NR 74 TC 45 Z9 53 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 1 PY 2009 VL 47 IS 1 BP 289 EP 301 DI 10.1016/j.neuroimage.2009.03.060 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 457YW UT WOS:000266975300032 PM 19345268 ER PT J AU Mintzopoulos, D Astrakas, LG Khanicheh, A Konstas, AA Singhal, A Moskowitz, MA Rosen, BR Tzika, AA AF Mintzopoulos, Dionyssios Astrakas, Loukas G. Khanicheh, Azadeh Konstas, Angelos A. Singhal, Aneesh Moskowitz, Michael A. Rosen, Bruce R. Tzika, A. Aria TI Connectivity alterations assessed by combining fMRI and MR-compatible hand robots in chronic stroke SO NEUROIMAGE LA English DT Article DE Functional Magnetic Resonance Imaging (fMRI); Brain; Stroke; Robotic devices; Dynamical causal modeling; Connectivity; Parallel Imaging; GRAPPA ID NONINVASIVE CORTICAL STIMULATION; POSITRON EMISSION TOMOGRAPHY; POSTERIOR PARIETAL CORTEX; PRIMARY MOTOR CORTEX; MAGNETIC-RESONANCE; SUBCORTICAL STROKE; FUNCTIONAL MRI; BRAIN ACTIVATION; TALAIRACH ATLAS; BLOOD-FLOW AB The aim of this study was to investigate functional reorganization of motor systems by probing connectivity between motor related areas in chronic stroke patients using functional magnetic resonance imaging (fMRI) in conjunction with a novel MR-compatible hand-induced, robotic device (MR_CHIROD). We evaluated data sets obtained from healthy volunteers and right-hand-dominant patients with first-ever left-sided stroke >= 6 months prior and mild to moderate hemiparesis affecting the right hand. We acquired T1-weighted echo planar and fluid attenuation inversion recovery MR images and multi-level fMRI data using parallel imaging by means of the GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) algorithm on a 3 T MR system. Participants underwent fMRI while performing a motor task with the MR_CHIROD in the MR scanner. Changes in effective connectivity among a network of primary motor cortex (M1), supplementary motor area (SMA) and cerebellum (Ce) were assessed using dynamic causal modeling. Relative to healthy controls, stroke patients exhibited decreased intrinsic neural coupling between M1 and Ce, which was consistent with a dysfunctional M1 to Ce connection. Stroke patients also showed increased SMA to M1 and SMA to cerebellum coupling, suggesting that changes in SMA and Ce connectivity may occur to compensate for a dysfunctional M1. The results demonstrate for the first time that connectivity alterations between motor areas may help counterbalance a functionally abnormal M1 in chronic stroke patients. Assessing changes in connectivity by means of fMRI and MR_CHIROD might be used in the future to further elucidate the neural network plasticity that underlies functional recovery in chronic stroke patients. (C) 2009 Elsevier Inc. All rights reserved. C1 [Mintzopoulos, Dionyssios; Astrakas, Loukas G.; Tzika, A. Aria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,NMR Surg Lab, Boston, MA 02114 USA. [Mintzopoulos, Dionyssios; Astrakas, Loukas G.; Tzika, A. Aria] Harvard Univ, Shriners Burn Inst, Sch Med, Boston, MA 02114 USA. [Mintzopoulos, Dionyssios; Astrakas, Loukas G.; Singhal, Aneesh; Moskowitz, Michael A.; Rosen, Bruce R.; Tzika, A. Aria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02129 USA. [Khanicheh, Azadeh] Northeastern Univ, Dept Mech Ind Engn, Boston, MA 02115 USA. [Konstas, Angelos A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Singhal, Aneesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Stroke Res,Dept Neurol, Boston, MA 02114 USA. [Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurosci Ctr, Boston, MA 02129 USA. [Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02129 USA. RP Tzika, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu RI Astrakas, Loukas/F-5918-2011 FU NIBIB NIH HHS [R21 EB004665, R21 EB004665-01A2] NR 80 TC 26 Z9 26 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2009 VL 47 BP T90 EP T97 DI 10.1016/j.neuroimage.2009.03.007 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 487FX UT WOS:000269257400014 PM 19286464 ER PT J AU Prakash, N Uhlemann, F Sheth, SA Bookheimer, S Martin, N Toga, AW AF Prakash, Neal Uhlemann, Falk Sheth, Sameer A. Bookheimer, Susan Martin, Neil Toga, Arthur W. TI Current trends in intraoperative optical imaging for functional brain mapping and delineation of lesions of language cortex SO NEUROIMAGE LA English DT Article DE Intraoperative; Optical imaging; Intrinsic signal; BOLD signal; Functional brain mapping; Neurosurgery; Tumor resection; Language mapping; Cerebral cortex ID CEREBRAL-BLOOD-FLOW; RAT SOMATOSENSORY CORTEX; TEMPORAL-LOBE EPILEPSY; RODENT BARREL CORTEX; INTRINSIC SIGNALS; NEURONAL-ACTIVITY; IN-VIVO; ADULT CORTEX; HEMODYNAMIC-RESPONSE; NEURAL ACTIVITY AB Resection of a cerebral arteriovenous malformation (AVM), epileptic focus, or glioma, ideally has a prerequisite of microscopic delineation of the lesion borders in relation to the normal gray and white matter that mediate critical functions. Currently, Wada testing and functional magnetic resonance imaging (fMRI) are used for preoperative mapping of critical function, whereas electrical stimulation mapping (ESM) is used for intraoperative mapping. For lesion delineation, MRI and positron emission tomography (PET) are used preoperatively, whereas microscopy and histological sectioning are used intraoperatively. However, for lesions near eloquent cortex, these imaging techniques may lack sufficient resolution to define the relationship between the lesion and language function, and thus not accurately determine which patients will benefit from neurosurgical resection of the lesion without iatrogenic aphasia. Optical techniques such as intraoperative optical imaging of intrinsic signals (iOIS) show great promise for the precise functional mapping of cortices, as well as delineation of the borders of AVMs, epileptic foci, and gliomas. Here we first review the physiology of neuroimaging, and then progress towards the validation and justification of using intraoperative optical techniques, especially in relation to neurosurgical planning of resection AVMs, epileptic foci, and gliomas near or in eloquent Cortex. We conclude with a short description of potential novel intraoperative optical techniques. Published by Elsevier Inc. C1 [Prakash, Neal] Dept Neurol, Honolulu, HI 96819 USA. [Prakash, Neal; Uhlemann, Falk; Sheth, Sameer A.; Toga, Arthur W.] Univ Calif Los Angeles, Lab Neuro Imaging, Los Angeles, CA 90095 USA. [Prakash, Neal] Univ Hawaii, Dept Med, John A Burns Sch Med, Honolulu, HI 96813 USA. [Uhlemann, Falk] Univ Auckland, Dept Comp Sci, Auckland 1, New Zealand. [Sheth, Sameer A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Bookheimer, Susan] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA 90095 USA. [Bookheimer, Susan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Ctr Cognit Neurosci, Los Angeles, CA 90095 USA. [Martin, Neil] Univ Calif Los Angeles, David Geffen Sch Med, Div Neurosurg, Stroke Ctr,Brain Injury Res Ctr, Los Angeles, CA 90095 USA. RP Prakash, N (reprint author), Dept Neurol, Honolulu, HI 96819 USA. EM neal.prakash@gmail.com RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Martin, Neil/0000-0002-6565-4131 FU NIMH NIH HHS [MH52083, R01 MH052083-09, R01 MH052083-05, R01 MH052083-08, R01 MH052083, R01 MH052083-10, R01 MH052083-11, R01 MH052083-07A1, R01 MH052083-06] NR 127 TC 16 Z9 17 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2009 VL 47 BP T116 EP T126 DI 10.1016/j.neuroimage.2008.07.066 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 487FX UT WOS:000269257400017 PM 18786643 ER PT J AU Sheth, SA Prakash, N Guiou, M Toga, AW AF Sheth, Sameer A. Prakash, Neal Guiou, Michael Toga, Arthur W. TI Validation and visualization of two-dimensional optical spectroscopic imaging of cerebral hemodynamics SO NEUROIMAGE LA English DT Article ID NEURONAL-ACTIVITY; HEMOGLOBIN OXYGENATION; BLOOD-FLOW; CORTEX; VOLUME; STIMULATION; RESPONSES; BRAIN; RAT AB Perfusion-based functional brain imaging techniques such as fMRI and optical intrinsic signal (OIS) imaging are becoming increasingly important in both neuroscience research and intraoperative brain mapping. Recent Studies have applied a spectroscopic approach to OIS imaging data, which we will call "two-dimensional optical spectroscopy" (2DOS), generating images of functional changes in hemoglobin oxygenation and blood volume. This improvement comes at the cost of several assumptions. Whereas the "gold standard" technique of fiber spectroscopy decomposes reflected light over a spectral axis, 2DOS retains both spatial dimensions by acquiring images at several wavelengths, sacrificing spectral resolution for the extra spatial dimension. Furthermore, 2DOS data are acquired interleaved within or between trials, but combined during the spectroscopic analysis as if acquired simultaneously. Thus far, the few studies employing this approach have assumed both that the reduced spectral resolution is tolerable, and that sufficient trial averaging can compensate for the temporally staggered data acquisition. To test these assumptions, we compared 2DOS results to those produced by traditional fiber spectroscopy by observing the hemodynamic response to hindpaw electrical stimulation over primary somatosensory cortex in anesthetized rats. Comparisons revealed low fitting residuals and a high level of correlation between the two, but noteworthy differences in response magnitudes. Inspection of individual timecourses revealed a lower signal-to-noise ratio for 2DOS data. For visualization and interpretation of the 2DOS images, we present a parameterized visualization strategy, in which oxy-, deoxy-, and total hemoglobin are assigned to individual color channels. The resulting composite image conveniently displays the evolution of hemodynamic responses through parenchymal and vascular compartments in space and time. (C) 2008 Elsevier Inc. All rights reserved. C1 [Sheth, Sameer A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Prakash, Neal; Toga, Arthur W.] Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuro Imaging, Los Angeles, CA 90095 USA. [Prakash, Neal] Dept Neurol, Honolulu, HI 96819 USA. [Guiou, Michael] Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. RP Sheth, SA (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA. EM sasheth@partners.org FU NIGMS NIH HHS [GM08042, T32 GM008042]; NIMH NIH HHS [F30 MH067432-02, MH52083, MH67432, F30 MH067432-01, R01 MH052083, F30 MH067432] NR 18 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2009 VL 47 BP T36 EP T43 DI 10.1016/j.neuroimage.2008.09.060 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 487FX UT WOS:000269257400007 PM 19013531 ER PT J AU Foerch, C Montaner, J Furie, KL Ning, MM Lo, EH AF Foerch, C. Montaner, J. Furie, K. L. Ning, M. M. Lo, E. H. TI Invited Article: Searching for oracles? Blood biomarkers in acute stroke SO NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; FIBRILLARY ACIDIC PROTEIN; MIDDLE CEREBRAL-ARTERY; PREDICTS HEMORRHAGIC TRANSFORMATION; INTRACEREBRAL HEMORRHAGE; THROMBOLYTIC THERAPY; GENE-EXPRESSION; CELLULAR-FIBRONECTIN; DIAGNOSTIC-TEST AB Emerging data suggest that a wide array of measurable biomarkers in blood may provide a novel window into the pathophysiology of stroke. In this review, we survey the state of progress in the field. Three specific questions are assessed. Can biomarkers augment the clinical examination and powerful brain imaging tools to enhance the accuracy of the diagnostic process? Can biomarkers be used to help triage patients for thrombolytic therapy? Can biomarkers help predict patients who are most susceptible to malignant infarction? Many encouraging molecular candidates have been found that appear to match the known cascades of neurovascular injury after stroke. However, whether these putative biomarkers may indeed have direct clinical utility remains to be quantitatively validated. Larger clinical trials are warranted to establish the sensitivity and specificity of biomarkers for routine use in clinical stroke. Neurology (R) 2009; 73: 393-399 C1 [Foerch, C.] Univ Frankfurt, Dept Neurol, D-60528 Frankfurt, Germany. [Foerch, C.; Ning, M. M.; Lo, E. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA USA. [Furie, K. L.; Ning, M. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA USA. [Ning, M. M.; Lo, E. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Prote Res Ctr,Dept Neurol, Boston, MA USA. [Montaner, J.] Vall Hebron Hosp, Dept Neurol, Stroke Unit, Neurovasc Res Lab, Barcelona, Spain. RP Foerch, C (reprint author), Univ Frankfurt, Dept Neurol, Schleusenweg 2-16, D-60528 Frankfurt, Germany. EM foerch@em.uni-frankfurt.de RI Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015 FU European, Spanish, and Catalan governments [EUSTROKE F2-2008-202213, EC07/ 90195, EC08/00137, MD07/00209, FIS08/361, RENEVAS RD06/026, SGR614]; NIH [NS051588, NS052498, R37-NS37074, R01-NS56458, P01NS55104, P50-NS51343]; AHA FX Dr. Foerch is designated as an inventor in the European patent application # 03021571.9: " Use of GFAP for identification of intracerebral haemorrhage." Dr. Montaner has received speaker honoraria from Sanofi, Ferrer, Boehringer Ingelheim, and Genzyme; serves as a consultant for Biomerieux; receives research support from Biosite, Proteom Sciences, Ferrer, Uriach, and Boehringer Ingelheim; and has received public grants from the European, Spanish, and Catalan governments (EUSTROKE F2-2008-202213, EC07/ 90195, EC08/00137, MD07/00209, FIS08/361, RENEVAS RD06/026 and SGR614). Dr. Furie serves on advisory boards for GE Healthcare and Novartis. Dr. Ning receives research support from the NIH [NS051588 (PI) and NS052498 (PI)]. Dr. Lo serves as a consultant for Mitsubishi and has received research support from Boehringer Ingelheim, the NIH [R37-NS37074 (PI), R01-NS56458 (PI), P01NS55104 (PI), and P50-NS51343 (Co-PI)], and the AHA. NR 43 TC 54 Z9 57 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 2009 VL 73 IS 5 BP 393 EP 399 DI 10.1212/WNL.0b013e3181b05ef9 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 479DQ UT WOS:000268640300011 PM 19652144 ER PT J AU Anselm, IA Sweadner, KJ Gollamudi, S Ozelius, LJ Darras, BT AF Anselm, I. A. Sweadner, K. J. Gollamudi, S. Ozelius, L. J. Darras, B. T. TI RAPID-ONSET DYSTONIA-PARKINSONISM IN A CHILD WITHA NOVEL ATP1A3 GENE MUTATION SO NEUROLOGY LA English DT Editorial Material ID PUMP C1 [Anselm, I. A.; Darras, B. T.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Sweadner, K. J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Gollamudi, S.; Ozelius, L. J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Gollamudi, S.; Ozelius, L. J.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. RP Darras, BT (reprint author), Childrens Hosp, Dept Neurol, Fegan 11,300 Longwood Ave, Boston, MA 02115 USA. EM basil.darras@childrens.harvard.edu FU NINDS NIH HHS [NS058949] NR 7 TC 32 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 2009 VL 73 IS 5 BP 400 EP 401 DI 10.1212/WNL.0b013e3181b04acd PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 479DQ UT WOS:000268640300012 PM 19652145 ER PT J AU Dunn, IF Kim, DH Rubin, PA Blinder, R Gates, J Golby, AJ AF Dunn, Ian F. Kim, Dong H. Rubin, Peter A. Blinder, Russell Gates, Jonathan Golby, Alexandra J. TI ORBITOCRANIAL WOODEN FOREIGN BODY: A PRE-, INTRA-, AND POSTOPERATIVE CHRONICLE: CASE REPORT SO NEUROSURGERY LA English DT Article DE Orbital trauma; Wooden foreign body AB OBJECTIVE: Intraorbital wooden foreign bodies-usually from a low-velocity puncture-are elusive and demand a low threshold for further imaging. In patients with traumatic injuries, orbital and intracranial air from fractures may be present, and it is particularly easy to overlook a wooden fragment CLINICAL PRESENTATION: A 53-year-old equestrian was kicked in the face by the rear hoof of a horse. The event was captured on video by her husband. Although no obvious entry point in and around the eye was observed, her ocular examination was notable for superior orbital fissure syndrome and increasing intraocular pressure in the left eye. Closer inspection revealed a 5-mm laceration above her superior lid margin; imaging revealed a foreign body at the orbital apex with apparent communication with the cranial vault. INTERVENTION: We proceeded with cranio-orbital exploration because of the risk of continued ocular damage in the setting of increasing intraocular pressure and the potential for infection of both the eye and the intracranial space from a suspected foreign body. A 3.0 cm x 0.5 cm fragment was found lodged in the orbital apex and removed. CONCLUSION: The patient recovered well after surgery and a course of antibiotics and has returned to riding. This case report presents an algorithm for approaching cranio-orbital foreign objects of unclear identity and the favorable outcomes that may be achieved. C1 [Dunn, Ian F.; Kim, Dong H.; Golby, Alexandra J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Blinder, Russell] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Gates, Jonathan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Rubin, Peter A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Oculoplast & Orbital Surg Serv, Boston, MA 02114 USA. RP Dunn, IF (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. NR 0 TC 14 Z9 16 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 2009 VL 65 IS 2 BP 383 EP 384 DI 10.1227/01.NEU.0000347474.69080.A1 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 477MM UT WOS:000268523200041 PM 19625895 ER PT J AU Benita, Y Kikuchi, H Smith, AD Zhang, MQ Chung, DC Xavier, RJ AF Benita, Yair Kikuchi, Hirotoshi Smith, Andrew D. Zhang, Michael Q. Chung, Daniel C. Xavier, Ramnik J. TI An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; ENDOTHELIAL GROWTH-FACTOR; CIS-REGULATORY MODULES; NF-KAPPA-B; TRANSCRIPTIONAL REGULATION; EXPRESSION PROFILES; MICROARRAY EXPERIMENTS; DEPENDENT REGULATION; CANCER-THERAPY; CELL-CYCLE AB The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a central role in the transcriptional response to oxygen flux. To gain insight into the molecular pathways regulated by HIF-1, it is essential to identify the downstream-target genes. We report here a strategy to identify HIF-1-target genes based on an integrative genomic approach combining computational strategies and experimental validation. To identify HIF-1-target genes microarrays data sets were used to rank genes based on their differential response to hypoxia. The proximal promoters of these genes were then analyzed for the presence of conserved HIF-1-binding sites. Genes were scored and ranked based on their response to hypoxia and their HIF-binding site score. Using this strategy we recovered 41% of the previously confirmed HIF-1-target genes that responded to hypoxia in the microarrays and provide a catalogue of predicted HIF-1 targets. We present experimental validation for ANKRD37 as a novel HIF-1-target gene. Together these analyses demonstrate the potential to recover novel HIF-1-target genes and the discovery of mammalian-regulatory elements operative in the context of microarray data sets. C1 [Benita, Yair; Xavier, Ramnik J.] Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Kikuchi, Hirotoshi; Chung, Daniel C.] Harvard Univ, Sch Med, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Andrew D.; Zhang, Michael Q.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Xavier, RJ (reprint author), Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu RI Benita, Yair/E-3094-2012; Smith, Andrew/G-4104-2013 OI Smith, Andrew/0000-0002-3337-1970 FU Harris Fellowship; National Institutes of Health [DK043351, AI062773, DK83756, HG001696, CA92594] FX Harris Fellowship to Y.B.; National Institutes of Health [grant number DK043351, AI062773, DK83756] for work in RJX lab; National Institutes of Health [grant number HG001696] for work in MZQ lab; and National Institutes of Health [grant number CA92594] for work in DCC lab. Funding for open access charge: [grant number HG001696, CA45508] for MZQ lab. NR 95 TC 159 Z9 160 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG PY 2009 VL 37 IS 14 BP 4587 EP 4602 DI 10.1093/nar/gkp425 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 484AO UT WOS:000269015400006 PM 19491311 ER PT J AU Bhat-Nakshatri, P Wang, GH Collins, NR Thomson, MJ Geistlinger, TR Carroll, JS Brown, M Hammond, S Srour, EF Liu, YL Nakshatri, H AF Bhat-Nakshatri, Poornima Wang, Guohua Collins, Nikail R. Thomson, Michael J. Geistlinger, Tim R. Carroll, Jason S. Brown, Myles Hammond, Scott Srour, Edward F. Liu, Yunlong Nakshatri, Harikrishna TI Estradiol-regulated microRNAs control estradiol response in breast cancer cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; GENE-EXPRESSION; MESSENGER-RNA; CLINICAL-IMPLICATIONS; TARGETS; PROLIFERATION; LET-7; REPRESSION; RESISTANCE; REVEALS AB Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta). E2-inducible proteins c-Myc and E2Fs are required for optimal ER alpha activity and secondary estrogen responses, respectively. We show that E2 induces 21 microRNAs and represses seven microRNAs in MCF-7 breast cancer cells; these microRNAs have the potential to control 420 E2-regulated and 757 non-E2-regulated mRNAs at the post-transcriptional level. The serine/threonine kinase, AKT, alters E2-regulated expression of microRNAs. E2 induced the expression of eight Let-7 family members, miR-98 and miR-21 microRNAs; these microRNAs reduced the levels of c-Myc and E2F2 proteins. Dicer, a ribonuclease III enzyme required for microRNA processing, is also an E2-inducible gene. Several E2-regulated microRNA genes are associated with ER alpha-binding sites or located in the intragenic region of estrogen-regulated genes. We propose that the clinical course of ER alpha-positive breast cancers is dependent on the balance between E2-regulated tumor-suppressor microRNAs and oncogenic microRNAs. Additionally, our studies reveal a negative-regulatory loop controlling E2 response through microRNAs as well as differences in E2-induced transcriptome and proteome. C1 [Bhat-Nakshatri, Poornima; Collins, Nikail R.; Nakshatri, Harikrishna] Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Wang, Guohua; Srour, Edward F.; Liu, Yunlong] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Thomson, Michael J.; Hammond, Scott] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. [Geistlinger, Tim R.; Carroll, Jason S.; Brown, Myles] Harvard Univ, Sch Med, Dana Farber Med Sch, Dept Med Oncol, Boston, MA USA. [Nakshatri, Harikrishna] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. RP Nakshatri, H (reprint author), Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46202 USA. EM hnakshat@iupui.edu OI Brown, Myles/0000-0002-8213-1658 FU Department of Defense [BC053295]; National Institutes of Health [R01CA89153]; IU Simon Cancer Center [R01DK074967]; NCI; DFCI Women's Cancers Program; Institutional funds FX Department of Defense BC053295 concept award; National Institutes of Health (R01CA89153); IU Simon Cancer Center breast cancer pilot grant to HN; R01DK074967, DF/HCC Breast Cancer Spore from NCI, and the DFCI Women's Cancers Program to MB. Funding for open access charge: Institutional funds. NR 58 TC 174 Z9 179 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG PY 2009 VL 37 IS 14 BP 4850 EP 4861 DI 10.1093/nar/gkp500 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 484AO UT WOS:000269015400028 PM 19528081 ER PT J AU Douglas, SM Marblestone, AH Teerapittayanon, S Vazquez, A Church, GM Shih, WM AF Douglas, Shawn M. Marblestone, Adam H. Teerapittayanon, Surat Vazquez, Alejandro Church, George M. Shih, William M. TI Rapid prototyping of 3D DNA-origami shapes with caDNAno SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-CROSSOVER MOLECULES; DESIGN; TILES AB DNA nanotechnology exploits the programmable specificity afforded by base-pairing to produce self-assembling macromolecular objects of custom shape. For building megadalton-scale DNA nanostructures, a long 'scaffold' strand can be employed to template the assembly of hundreds of oligonucleotide 'staple' strands into a planar antiparallel array of cross-linked helices. We recently adapted this 'scaffolded DNA origami' method to producing 3D shapes formed as pleated layers of double helices constrained to a honeycomb lattice. However, completing the required design steps can be cumbersome and time-consuming. Here we present caDNAno, an open-source software package with a graphical user interface that aids in the design of DNA sequences for folding 3D honeycomb-pleated shapes A series of rectangular-block motifs were designed, assembled, and analyzed to identify a well-behaved motif that could serve as a building block for future studies. The use of caDNAno significantly reduces the effort required to design 3D DNA-origami structures. The software is available at http://cadnano.org/, along with example designs and video tutorials demonstrating their construction. The source code is released under the MIT license. C1 [Douglas, Shawn M.; Marblestone, Adam H.; Shih, William M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Douglas, Shawn M.; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Douglas, Shawn M.; Teerapittayanon, Surat; Vazquez, Alejandro; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Douglas, Shawn M.; Church, George M.; Shih, William M.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Cambridge, MA 02138 USA. [Marblestone, Adam H.] Yale Univ, Dept Phys, New Haven, CT 06520 USA. RP Shih, WM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM william_shih@dfci.harvard.edu OI Douglas, Shawn/0000-0001-5398-9041; Marblestone, Adam/0000-0001-9833-9931 FU National Institutes of Health [1DP2OD004641-01]; Claudia Adams Barr Program in Innovative Cancer Research FX National Institutes of Health [grant number 1DP2OD004641-01]; the Claudia Adams Barr Program in Innovative Cancer Research. Funding for open access charge: National Institutes of Health Grant 1DP2OD004641-01. NR 19 TC 246 Z9 247 U1 24 U2 114 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG PY 2009 VL 37 IS 15 BP 5001 EP 5006 DI 10.1093/nar/gkp436 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496YN UT WOS:000270016400010 PM 19531737 ER PT J AU Goedecke, JH Levitt, NS Lambert, EV Utzschneider, KM Faulenbach, MV Dave, JA West, S Victor, H Evans, J Olsson, T Walker, BR Seckl, JR Kahn, SE AF Goedecke, Julia H. Levitt, Naomi S. Lambert, Estelle V. Utzschneider, Kristina M. Faulenbach, Mirjam V. Dave, Joel A. West, Sacha Victor, Hendriena Evans, Juliet Olsson, Tommy Walker, Brian R. Seckl, Jonathan R. Kahn, Steven E. TI Differential Effects of Abdominal Adipose Tissue Distribution on Insulin Sensitivity in Black and White South African Women SO OBESITY LA English DT Article ID FAT DISTRIBUTION; BODY-FAT; RESISTANCE; OBESITY; RISK; DETERMINANTS; COMPARTMENTS; AMERICANS; DISEASE; WEIGHT AB Black South African women are more insulin resistant than BMI-matched white women. The objective of the study was to characterize the determinants of insulin sensitivity in black and white South African women matched for BMI. A total of 57 normal-weight (BMI 18-25 kg/m(2)) and obese (BMI > 30 kg/m(2)) black and white premenopausal South African women underwent the following measurements: body composition (dual-energy X-ray absorptiometry), body fat distribution (computerized tomography (CT)), insulin sensitivity (S(1), frequently sampled intravenous glucose tolerance test), dietary intake (food frequency questionnaire), physical activity (Global Physical Activity Questionnaire), and socioeconomic status (SES, demographic questionnaire). Black women were less insulin sensitive (4.4 +/- 0.8 vs. 9.5 +/- 0.8 and 3.0 +/- 0.8 vs. 6.0 +/- 0.8 x 10(-5)/min/(pmol/l), for normal-weight and obese women, respectively, P < 0.001), but had less visceral adipose tissue (VAT) (P = 0.051), more abdominal superficial subcutaneous adipose tissue (SAT) (P = 0.003), lower SES (P < 0.001), and higher dietary fat intake (P = 0.001) than white women matched for BMI. S I correlated with deep and superficial SAT in both black (R = -0.594, P = 0.002 and R = 0.495, P = 0.012) and white women (R = -0.554, P = 0.005 and R = -0.546, P = 0.004), but with VAT in white women only (R = -0.534, P = 0.005). In conclusion, body fat distribution is differentially associated with insulin sensitivity in black and white women. Therefore, the different abdominal fat depots may have varying metabolic consequences in women of different ethnic origins. C1 [Goedecke, Julia H.; Lambert, Estelle V.; West, Sacha; Victor, Hendriena; Evans, Juliet] Univ Cape Town, Dept Human Biol, UCT MRC Res Unit Exercise Sci & Sports Med, ZA-7925 Cape Town, South Africa. [Goedecke, Julia H.] S African MRC, Cape Town, South Africa. [Levitt, Naomi S.; Dave, Joel A.] Univ Cape Town, Dept Med, Endocrine Unit, ZA-7925 Cape Town, South Africa. [Utzschneider, Kristina M.; Faulenbach, Mirjam V.; Kahn, Steven E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Evans, Juliet; Olsson, Tommy] Umea Univ, Dept Med, Dept Publ Hlth & Clin Med, Umea, Sweden. [Walker, Brian R.; Seckl, Jonathan R.] Univ Edinburgh, Ctr Cardiovasc Sci, Endocrinol Unit, Edinburgh, Midlothian, Scotland. RP Goedecke, JH (reprint author), Univ Cape Town, Dept Human Biol, UCT MRC Res Unit Exercise Sci & Sports Med, ZA-7925 Cape Town, South Africa. EM julia.goedecke@uct.ac.za RI Seckl, Jonathan/C-3555-2013; Goedecke, Julia/J-8628-2013; Goedecke, Julia/E-1820-2016; OI Goedecke, Julia/0000-0001-6795-4771; Goedecke, Julia/0000-0001-6795-4771; Olsson, Tommy/0000-0001-7768-1076; Kahn, Steven/0000-0001-7307-9002 FU Medical Research Council of South Africa; National Research Foundation of South Africa; Royal Society SA-UK Science Networks Programme; University of Cape Town; British Heart Foundation; Wellcome Trust; United States Department of Veterans Affairs FX We thank the research volunteers for their participation in this study, Nandipha Sinyanya for her excellent field work, Judy Belonje for her expert technical assistance and Madelaine Carstens for performing the dietary analyses. Jack Bergman, Naomi Fenton of Symington Radiology, and Linda Bewerunge are thanked for performing the CT and dual-energy X-ray absorptiometry scans. This study was funded by the Medical Research Council of South Africa (Career Development Award to J. H. G.), the International Atomic Energy Agency, the National Research Foundation of South Africa, and Royal Society SA-UK Science Networks Programme, the University of Cape Town, the British Heart Foundation, the Wellcome Trust and the United States Department of Veterans Affairs. NR 33 TC 38 Z9 38 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD AUG PY 2009 VL 17 IS 8 BP 1506 EP 1512 DI 10.1038/oby.2009.73 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 475QD UT WOS:000268374200007 PM 19300428 ER PT J AU Irwin, ML Alvarez-Reeves, M Cadmus, L Mierzejewski, E Mayne, ST Yu, H Chung, GG Jones, B Knobf, MT DiPietro, L AF Irwin, Melinda L. Alvarez-Reeves, Marty Cadmus, Lisa Mierzejewski, Eileen Mayne, Susan T. Yu, Herbert Chung, Gina G. Jones, Beth Knobf, M. Tish DiPietro, Loretta TI Exercise Improves Body Fat, Lean Mass, and Bone Mass in Breast Cancer Survivors SO OBESITY LA English DT Article ID RECEIVING ADJUVANT CHEMOTHERAPY; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; WEIGHT-LOSS; LIFE-STYLE; INTERVENTION; HEALTH; TRIAL; DIAGNOSIS AB Given the negative effects of a breast cancer diagnosis and its treatments on body weight and bone mass, we investigated the effects of a 6-month randomized controlled aerobic exercise intervention vs. usual care on body composition in breast cancer survivors. Secondary aims were to examine the effects stratified by important prognostic and physiologic variables. Seventy-five physically inactive postmenopausal breast cancer survivors were recruited through the Yale-New Haven Hospital Tumor Registry and randomly assigned to an exercise (n = 37) or usual care (n = 38) group. The exercise group participated in 150 min/week of supervised gym-and home-based moderate-intensity aerobic exercise. The usual care group was instructed to maintain their current physical activity level. Body composition was assessed at baseline and 6-months through dual-energy X-ray absorptiometry (DXA) by one radiologist blinded to the intervention group of the participants. On an average, exercisers increased moderate-intensity aerobic exercise by 129 min/week over and above baseline levels compared with 45 min/week among usual care participants (P < 0.001). Exercisers experienced decreases in percent body fat (P = 0.0022) and increases in lean mass (P = 0.047) compared with increases in body fat and decreases in lean mass in usual care participants. Bone mineral density (BMD) was also maintained among exercisers compared with a loss among usual care participants (P = 0.043). In summary, moderate-intensity aerobic exercise, such as brisk walking, produces favorable changes in body composition that may improve breast cancer prognosis. C1 [Irwin, Melinda L.; Cadmus, Lisa; Mierzejewski, Eileen; Mayne, Susan T.; Yu, Herbert; Chung, Gina G.; Jones, Beth; DiPietro, Loretta] Yale Univ, Sch Med, New Haven, CT 06504 USA. [Alvarez-Reeves, Marty] Dana Farber Canc Inst, Boston, MA 02115 USA. [Knobf, M. Tish] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [DiPietro, Loretta] John B Pierce Fdn Lab, New Haven, CT 06519 USA. RP Irwin, ML (reprint author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06504 USA. EM melinda.irwin@yale.edu FU American Cancer Society [MRSG-04-006-01-CPPB]; Susan G. Komen Breast Cancer Foundation [BCTR0201916]; National Center of Research Resources, National Institutes of Health [M01-RR00125] FX We thank Rebecca Latka, Christian Stoddard, Linda Saucier, Andrew Wiley, and Mary O'Neil for their assistance. We are indebted to the participants in the Yale Exercise and Survivorship Study for their dedication. This study was supported by grants from American Cancer Society (MRSG-04-006-01-CPPB) and the Susan G. Komen Breast Cancer Foundation (BCTR0201916). This study was also supported in part by a General Clinical Research Center grant from the National Center of Research Resources, National Institutes of Health (Grant # M01-RR00125) awarded to Yale University School of Medicine. NR 39 TC 66 Z9 67 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD AUG PY 2009 VL 17 IS 8 BP 1534 EP 1541 DI 10.1038/oby.2009.18 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 475QD UT WOS:000268374200011 PM 19629060 ER PT J AU MacDonald, NE Riley, LE Steinhoff, MC AF MacDonald, Noni E. Riley, Laura E. Steinhoff, M. C. TI Influenza Immunization in Pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID UNITED-STATES; VACCINATION; WOMEN; CHILDREN; INFANTS; SAFETY AB Among healthy persons, two groups are notable for increased risk of serious illness and hospitalization with influenza infection: healthy women in pregnancy and their healthy infants (aged 0 to 6 months). Inactivated influenza vaccine has been used in pregnant women since the 1960s in both the United States and Canada; however, currently, only 15% of pregnant women receive the vaccine. A randomized, controlled trial has shown influenza immunization of pregnant women reduced influenza-like illness by more than 30% in both the mothers and the infants and reduced laboratory-proven influenza infections in 0- to 6-month-old infants by 63%. Physicians caring for pregnant women should be aware of the risks of influenza and of the availability of an effective and cost-saving intervention. (Obstet Gynecol 2009;114:365-8) C1 [Steinhoff, M. C.] Cincinnati Childrens Hosp, Med Ctr, Childrens Global Hlth Ctr, Cincinnati, OH 45229 USA. Dalhousie Univ, Div Pediat Infect Dis, IWK Hlth Ctr, Halifax, NS, Canada. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Steinhoff, MC (reprint author), Cincinnati Childrens Hosp, Med Ctr, Childrens Global Hlth Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM m.steinhoff@gmail.com NR 16 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 2009 VL 114 IS 2 BP 365 EP 368 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 476DO UT WOS:000268418200022 PM 19622998 ER PT J AU Chung, E Kim, YH Tang, WT Sheppard, CJR So, PTC AF Chung, Euiheon Kim, Yang-Hyo Tang, Wai Teng Sheppard, Colin J. R. So, Peter T. C. TI Wide-field extended-resolution fluorescence microscopy with standing surface-plasmon-resonance waves SO OPTICS LETTERS LA English DT Article ID INTERNAL-REFLECTION MICROSCOPY; POINT-SPREAD-FUNCTION; COUPLED EMISSION; SUPERLENS AB The resolution of conventional surface-plasmon-resonance (SPR) imaging has been limited by the diffraction nature of light. A wide-field extended-resolution optical imaging technique, standing-wave SPR fluorescence (SW-SPRF) microscopy, has been developed. Based on evanescent SPR standing waves, SW-SPRF provides lateral resolution approaching 100 nm and offers the advantages of significant signal enhancement and background-noise reduction. SW-SPRF has the potential for sensitive biomolecular detection, nanoscale imaging, and lithographic applications. (C) 2009 Optical Society of America C1 [Chung, Euiheon; Kim, Yang-Hyo; So, Peter T. C.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Chung, Euiheon] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Tang, Wai Teng] Natl Univ Singapore, Singapore MIT Alliance, Singapore 117576, Singapore. [Sheppard, Colin J. R.] Natl Univ Singapore, Div Bioengn, Singapore 117576, Singapore. [So, Peter T. C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP So, PTC (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ptso@mit.edu RI Sheppard, Colin/B-9593-2008; OI Chung, Euiheon/0000-0002-3326-6927 FU National Science Foundation (NSF) [MCB-9604382]; National Institutes of Health (NIH) [P01HL64858]; Singapore-MIT Alliance FX This research was funded by the National Science Foundation (NSF) (MCB-9604382), the National Institutes of Health (NIH) (P01HL64858), and Singapore-MIT Alliance. The authors thank Sunyoung Lee, Kimin Jun, and Seung Woo Lee of MIT for assisting in AFM and ellipsometry measurements. NR 14 TC 18 Z9 18 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD AUG 1 PY 2009 VL 34 IS 15 BP 2366 EP 2368 PG 3 WC Optics SC Optics GA 489FQ UT WOS:000269405900041 PM 19649099 ER PT J AU Pomarico, L Cerqueira, DF Soares, RMD de Souza, IPR Castro, GFBD Socransky, S Haffajee, A Teles, RP AF Pomarico, Luciana Cerqueira, Daniella Ferraz de Araujo Soares, Rosangela Maria Ribeiro de Souza, Ivete Pomarico Barbosa de Araujo Castro, Gloria Fernanda Socransky, Sigmund Haffajee, Anne Teles, Ricardo Palmier TI Associations among the use of highly active antiretroviral therapy, oral candidiasis, oral Candida species and salivary immunoglobulin A in HIV-infected children SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID PROTEASE INHIBITORS; POSITIVE CHILDREN; PAROTID-SALIVA; ALBICANS; PREVALENCE; HAART; IGA; ANTIBODIES; LESIONS; MANIFESTATIONS AB Objectives. The aim was to examine the impact of antiretroviral therapy on the prevalence of oral candidiasis, recovery of oral Candida spp., and salivary levels of total secretory immunoglobulin A (SIgA) and Candida-specific SIgA in human immunodeficiency virus (HIV)-infected children. Study design. Sixty-six HIV+ and 40 HIV- children were cross-sectionally examined for the presence of oral lesions. Whole stimulated saliva samples were collected for the identification of Candida spp. using culture and measurement of total and specific SIgA using enzyme-linked immunosorbent assay (ELISA). Results. The HIV+ children had a higher prevalence of oral candidiasis (P < .05), higher frequency of detection of Candida spp. (P < .05), and higher levels of total (P < .05) and Candida-specific SIgA (P < .001) than the HIV- children. Among the HIV+ subjects, antiretroviral users had lower viral loads (P < .001) and lower levels of Candida spp. (P < .05) and total SIgA (P < .05) compared with antiretroviral nonusers. Conclusions. The use of antiretroviral therapy was associated with decreases in the prevalence of oral candidiasis. This diminished exposure to Candida spp. was accompanied by decreases in levels of total and Candida-specific SIgA. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: 203-210) C1 [Pomarico, Luciana; Cerqueira, Daniella Ferraz; Ribeiro de Souza, Ivete Pomarico; Barbosa de Araujo Castro, Gloria Fernanda] Univ Fed Rio de Janeiro, Sch Dent, Dept Pediat Dent & Orthodont, Rio De Janeiro, Brazil. [de Araujo Soares, Rosangela Maria] Univ Fed Rio de Janeiro, Inst Microbiol Prof Paulo de Goes, Rio De Janeiro, Brazil. [Socransky, Sigmund; Haffajee, Anne] Forsyth Inst, Dept Periodont, Boston, MA USA. RP Pomarico, L (reprint author), 370-202 Flamengo, BR-22210030 Rio De Janeiro, Brazil. EM lupomarico@superig.com.br FU National Institute of Dental and Craniofacial Research [DE-016700]; CNPq [305731/2003-3] FX Supported by research grant DE-016700 from the National Institute of Dental and Craniofacial Research and by CNPq (305731/2003-3). NR 38 TC 16 Z9 18 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD AUG PY 2009 VL 108 IS 2 BP 203 EP 210 DI 10.1016/j.tripleo.2009.05.008 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 471JE UT WOS:000268052600012 PM 19615660 ER PT J AU Zhu, TF Szostak, JW AF Zhu, Ting F. Szostak, Jack W. TI A Robust Pathway for Protocell Growth and Division Under Plausible Prebiotic Conditions SO ORIGINS OF LIFE AND EVOLUTION OF BIOSPHERES LA English DT Meeting Abstract C1 [Zhu, Ting F.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Zhu, Ting F.; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Zhu, Ting F.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM tzhu@mit.edu NR 0 TC 1 Z9 2 U1 4 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0169-6149 J9 ORIGINS LIFE EVOL B JI Orig. Life Evol. Biosph. PD AUG PY 2009 VL 39 IS 3-4 BP 349 EP 350 PG 2 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 458OL UT WOS:000267033300176 ER PT J AU O, TM Tan, ML Tarango, M Fink, L Mihm, M Ma, YP Waner, M AF O, Teresa M. Tan, Melin Tarango, Mark Fink, Lou Mihm, Martin Ma, Yupo Waner, Milton TI Differential expression of SKI oncogene protein in hemangiomas SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; HUMAN-MELANOMA; CO-REPRESSOR; IN-VIVO; PROTOONCOGENE; PROGRESSION; CANCER; 1P36; MICE AB OBJECTIVE: The pathogenesis for benign tumorigenesis in hemangiomas is unknown. Oncogene proteins may be influential in this process. SKI proteins have been previously described in various malignancies. We investigated the differential expression of the SKI (sarcoma viral oncogene) protein in hemangiomas. STUDY DESIGN: Prospective basic science study. SUBJECTS AND METHODS: Paraffin-embedded hemangioma tissues were obtained from the senior author from 2005 to 2006. We created the first vascular tissue array composed of 12 hemangioma specimens at various stages of growth and anatomic location. Two cores were taken from each sample. Controls were also included. Immunohistochemical studies were performed using SKI, CD31, and Ki67. RESULTS: All 12 hemangioma tissues overexpressed the SKI protein. The staining pattern was perinuclear within the endothelial cells. The intensity of staining was inversely proportional to the growth stage. The endothelial cells that were SKI-positive were involved in active cell division. CONCLUSION: SKI oncogene protein is differentially and specifically expressed in hemangioma tissues. SKI acts as a transcriptional co-repressor and inhibits the TGF-beta pathway, thus leading to uncontrolled cellular proliferation and transformation. All vascular controls were negative for SKI staining. CLINICAL SIGNIFICANCE OF STUDY: The SKI oncogene protein is upregulated by hemangiomas and may play a role in hemangioma tumorigenesis. (c) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 [O, Teresa M.; Waner, Milton] Beth Israel Deaconess Med Ctr, Vasc Birthmarks Inst, New York, NY 10023 USA. [O, Teresa M.] St Lukes Roosevelt Hosp, New York, NY 10025 USA. [Tan, Melin] New York Eye & Ear Infirm, Dept Otolaryngol, New York, NY 10003 USA. [Tarango, Mark; Fink, Lou; Ma, Yupo] Nevada Canc Inst, Dept Pathol, Las Vegas, NV USA. [Mihm, Martin] Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. RP O, TM (reprint author), Beth Israel Deaconess Med Ctr, Vasc Birthmarks Inst, 126 W 60 St, New York, NY 10023 USA. EM tminjungo@yahoo.com FU Vascular Birthmarks Foundation FX Funded by the Vascular Birthmarks Foundation (no role in any part of the research: funding is for any hemangioma or vascular anomalies research). NR 17 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2009 VL 141 IS 2 BP 213 EP 218 DI 10.1016/j.otohns.2009.05.005 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 477ZV UT WOS:000268558400010 PM 19643254 ER PT J AU Lin, HW Wieland, AM Ostrower, ST AF Lin, Harrison W. Wieland, Aaron M. Ostrower, Samuel T. TI Child abuse presenting as oral cavity bruising SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material C1 [Lin, Harrison W.; Wieland, Aaron M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA. [Lin, Harrison W.; Wieland, Aaron M.; Ostrower, Samuel T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Ostrower, Samuel T.] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02115 USA. EM harrison_lin@meei.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2009 VL 141 IS 2 BP 290 EP 291 DI 10.1016/j.otohns.2009.03.018 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 477ZV UT WOS:000268558400025 PM 19643269 ER PT J AU Stankovic, KM Mrugala, MM Martuza, RL Silver, K Betensky, KA Nadol, JB Stemmer-Rachamimov, AO AF Stankovic, Konstantina M. Mrugala, Maciej M. Martuza, Robert L. Silver, Kmichael Betensky, Krebecca A. Nadol, Joseph B., Jr. Stemmer-Rachamimov, Anat O. TI Genetic Determinants of Hearing Loss Associated With Vestibular Schwannomas SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Carcinoembryonic antigen; Hearing loss; Peroxisomal biogenesis factor 5-like; Platelet factor 4; Prostate-specific membrane antigen-like; RAD54B; Vestibular schwannoma ID COMPARATIVE GENOMIC HYBRIDIZATION; CARCINOEMBRYONIC ANTIGEN; CEREBROSPINAL-FLUID; ACOUSTIC NEUROMA; GLUTAMATE; MUTATION; CANCER; NERVE; HISTOPATHOLOGY; IDENTIFICATION AB Hypothesis: The severity of hearing loss (HL) associated with vestibular schwannomas (VSs) is influenced by genes expressed by the VSs. Background: Hearing loss is the most common presenting symptoms in patients with VSs, yet its pathophysiology remains elusive. Previous studies have suggested that VSs cause HL not only by inducing degeneration of the auditory nerve by compression but also by promoting degeneration of the inner ear. This study aimed to determine whether there is a molecular basis for differences in HL associated with VSs. Methods: Surgical specimens of VSs were collected from 13 patients and were divided into a group associated with good (word recognition 970% and pure-tone average <= 30 dB) or poor hearing. Whole-genome expression profiling of VSs was performed with the Affymetrix GeneChip Human X3P Array. The expression of select genes was validated using real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Because of a small sample size, exact nonparametric tests were used to assess the association between good versus poor hearing and specific histological features of the tumors and patient demographics. Results: Using gene set enrichment analysis, the chromosomal region 3q27 was found to be significantly different between the 2 groups of tumors. This region includes peroxisomal biogenesis factor 5-like gene, which was underexpressed in VSs with poor hearing. The expression of 3 other genes from different chromosomes was significantly different between the 2 groups: RAD54B, prostate-specific membrane antigen-like, and carcinoembryonic antigen. Conclusion: This study identified several molecular alterations in VSs stratified by hearing. These alterations may determine the severity of HL associated with VSs and may represent potential therapeutic targets to prevent or reduce HL in theses patients. C1 [Stankovic, Konstantina M.; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Stankovic, Konstantina M.; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Stankovic, Konstantina M.; Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Mrugala, Maciej M.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Martuza, Robert L.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Silver, Kmichael; Betensky, Krebecca A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.org FU Massachusetts Eye and Ear Infirmary; Children's Tumor Foundation FX This work has been supported by the Foundation of the Massachusetts Eye and Ear Infirmary (J.B.N.) and by the Children's Tumor Foundation (A.O.S.-R.). NR 45 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD AUG PY 2009 VL 30 IS 5 BP 661 EP 667 DI 10.1097/MAO.0b013e3181a66ece PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 586QM UT WOS:000276926400016 PM 19546833 ER PT J AU Phuong, L Garg, S Duda, JE Stern, MB Weintraub, D AF Phuong, Lisa Garg, Shalini Duda, John E. Stern, Matthew B. Weintraub, Daniel TI Involuntary emotional expression disorder (IEED) in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Involuntary emotional expression disorder; Pseudobulbar affect; Emotional lability; Depression; Parkinson's disease ID PSEUDOBULBAR AFFECT; MULTIPLE-SCLEROSIS; DEXTROMETHORPHAN/QUINIDINE; LABILITY; TRIAL; SCALE AB Objective: To estimate the frequency and correlates Of involuntary emotional expression disorder (IEED) in Parkinson's disease (PD) using the Center for Neurologic Study-Lability Scale (CNS-LS) and recently-proposed diagnostic criteria for IEED. Background: IEED is characterized by uncontrollable emotional episodes, typically unrelated to or in excess of the underlying mood, and occurring with minimal or no stimulus. IEED has been reported to occur in many neurological disorders and neurodegenerative diseases, but its prevalence and correlates in PD have not been well studied. Additionally, there is no published research using recently-proposed IEED diagnostic criteria in any population. Methods: 193 patients with idiopathic PD were assessed with a neuropsychiatric battery, including the CNS-LS and the 15-item Geriatric Depression Scale (GDS-15). A subset (N = 100) was also administered a diagnostic interview by a blinded rater that applied criteria for both IEED and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) depressive disorders. Results: Applying formal diagnostic criteria, 7.0% of patients were diagnosed with IEED, and an additional 7.0% had subsyndromal IEED symptoms. Applying recommended CNS-LS cutoff scores from other populations, either 42.5% (cutoff >= 13) or 16.6% (cutoff >= 17) screened positive for IEED. Depressive symptoms were associated with higher CNS-LS scores (B[SE] = 0.27[.08], P=.001) but not with a diagnosis of IEED (odds ratio = 1.1, [95% CI=1.0-1.31, P=.16). The CNS-LS had Poor discriminant validity for an IEED diagnosis (AUC=.79, no cutoff value with sensitivity and specificity both >60%). Conclusions: IEED and depression are overlapping but distinct disorders in PD. IEED symptoms may occur in up to 15% of PD patients, but a disorder occurs in only half of those, suggesting that often IEED symptoms are not clinically significant in this population. The CNS-LS does not appear to be a good screening instrument for IEED in PD, in part due to its high correlation with depressive symptoms. Published by Elsevier Ltd. C1 [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Duda, John E.; Stern, Matthew B.; Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Phuong, Lisa; Garg, Shalini; Duda, John E.; Stern, Matthew B.; Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, 3615 Chestnut St,330,3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU National Institute of Mental Health [K23 067894] FX Supported by a grant from the National Institute of Mental Health (K23#067894). NR 15 TC 6 Z9 6 U1 0 U2 1 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 AUG PY 2009 VL 15 IS 7 BP 511 EP 515 DI 10.1016/j.parkreldis.2009.01.001 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 483US UT WOS:000268994500006 PM 19181560 ER PT J AU Waxler, JL Levine, K Pober, BR AF Waxler, Jessica L. Levine, Karen Pober, Barbara R. TI Williams Syndrome: A Multidisciplinary Approach to Care SO PEDIATRIC ANNALS LA English DT Article ID SUPRAVALVULAR AORTIC-STENOSIS; BEUREN-SYNDROME; CHILDREN; ADOLESCENTS; ADULTS; DISABILITIES; ASSOCIATION; DISEASE; MODEL C1 [Pober, Barbara R.] Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. [Levine, Karen] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pober, BR (reprint author), Massachusetts Gen Hosp, Ctr Human Genet, Simches Res Bldg,Room 222,185 Cambridge St, Boston, MA 02114 USA. EM barba-ra.pober@childrens.harvard.edu NR 36 TC 2 Z9 3 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD AUG PY 2009 VL 38 IS 8 BP 456 EP 463 DI 10.3280/0904481-20090723-10 PG 8 WC Pediatrics SC Pediatrics GA 483NC UT WOS:000268972600010 PM 19711883 ER PT J AU Kearney, SL Dahlberg, SE Levy, DE Voss, SD Sallan, SE Silverman, LB AF Kearney, Susan L. Dahlberg, Suzanne E. Levy, Donna E. Voss, Stephan D. Sallan, Stephen E. Silverman, Lewis B. TI Clinical Course and Outcome in Children With Acute Lymphoblastic Leukemia and Asparaginase-Associated Pancreatitis SO PEDIATRIC BLOOD & CANCER LA English DT Article DE asparaginase; leukemia; pancreatitis ID ESCHERICHIA-COLI-ASPARAGINASE; RECEIVING L-ASPARAGINASE; DANA-FARBER; INTENSIVE ASPARAGINASE; THERAPY; CANCER; SYNTHETASE; INDUCTION AB Background. Asparaginase, an agent used in the treatment of acute lymphoblastic leukemia (ALL), is associated with the development of pancreatitis. The clinical course and long-term outcome of patients experiencing this complication has not been extensively detailed. Procedure. We reviewed the clinical course for all children with ALL diagnosed with pancreatitis at the Dana-Farber Cancer Institute/Children's Hospital Boston between 1987 and 2003. The outcome of these patients was compared with that of patients with ALL who did not experience pancreatitis. Results. Twenty-eight of 403 children (7%) were diagnosed with pancreatitis. Patients 10-18 years old at diagnosis had 2.4 times the risk of developing pancreatitis compared with Younger patients. Pancreatitis typically Occurred early in the Course of therapy (median 4 weeks after first close of asparaginase). Ninety-three percent of affected patients were hospitalized and 57% received parenteral nutrition. No patient developed chronic sequelae or died as a result of pancreatitis. Sixteen (57%) patients were re-treated with asparaginase, 10 of whom had another episode of pancreatitis. No significant differences in event-free survival were observed when comparing patients with and without a history of pancreatitis. Conclusion. Asparaginase-associated pancreatitis was more common in older children, and caused significant acute morbidity. It tended to occur after the first few doses of asparaginase, Suggesting a predisposition to this complication rather than a cumulative drug effect. Re-treatment with asparaginase after an episode of pancreatitis was associated with a high risk of recurrent pancreatitis. Pediatr Blood Cancer 2009;53:162-167. (C) 2009 Wiley-Liss, Inc. C1 [Kearney, Susan L.] Univ Minnesota, Div Pediat Hematol Oncol Blood & Marrow Transplan, Minneapolis, MN USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Levy, Donna E.] Rho Inc, Chapel Hill, NC USA. [Voss, Stephan D.; Sallan, Stephen E.; Silverman, Lewis B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Voss, Stephan D.] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Kearney, SL (reprint author), 420 Delaware St SE, Minneapolis, MN 55455 USA. EM kearn054@umn.edu FU National Cancer Institute [5P01CA68484] FX Grant sponsor: National Cancer Institute: Grant number: 5P01CA68484. NR 29 TC 46 Z9 52 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD AUG PY 2009 VL 53 IS 2 BP 162 EP 167 DI 10.1002/pbc.22076 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 461DJ UT WOS:000267244500007 PM 19405141 ER PT J AU Andrews, EB Colvin, L Hernandez-Diaz, S Holmes, L Chambers, T Margulis, A Mitchell, A AF Andrews, Elizabeth B. Colvin, Lyn Hernandez-Diaz, Sonia Holmes, Lewis Chambers, Tina Margulis, Andrea Mitchell, Allen TI Evaluating Study Designs for the Measurement of Drug Exposure in Pregnancy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Andrews, Elizabeth B.] RTI, Res Triangle Pk, NC USA. [Colvin, Lyn] Univ Western Australia, Telethon Inst Child Hlth Res, Ctr Child Hlth Res, Perth, WA, Australia. [Hernandez-Diaz, Sonia; Margulis, Andrea] Harvard Univ, Sch Publ Hlth, Program Pharmacoepidemiol, Boston, MA 02115 USA. [Holmes, Lewis] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chambers, Tina] UCSD, La Jolla, CA USA. [Mitchell, Allen] Boston Univ, SEC, Boston, MA 02215 USA. RI Colvin, Lyn/F-6886-2012 OI Colvin, Lyn/0000-0002-8492-9954 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S28 EP S29 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900065 ER PT J AU Choueiri, TK Brick, AJ McDermott, D Clement, J Kwabi, C Shah, K Antras, L Chen, K Jayawant, SS Duh, MS Luka, A Neary, M Oh, WK AF Choueiri, Toni K. Brick, Ashley J. McDermott, David Clement, Jessica Kwabi, Christabel Shah, Karishma Antras, Lucia Chen, Kristina Jayawant, Sujata S. Duh, Mei Sheng Luka, Andi Neary, Maureen Oh, William K. TI Treatment (Tx) and Dosing Patterns for Angiogenesis Inhibitor (AI) Therapies in Patients (Pts) with Metastatic Renal Cell Carcinoma (mRCC) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Choueiri, Toni K.; Brick, Ashley J.; Oh, William K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McDermott, David; Clement, Jessica; Kwabi, Christabel; Shah, Karishma] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Antras, Lucia; Chen, Kristina; Jayawant, Sujata S.; Duh, Mei Sheng; Luka, Andi] Anal Grp Inc, Boston, MA USA. [Neary, Maureen] GlaxoSmithKline Inc, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S36 EP S36 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900083 ER PT J AU Gagnon, DR Fonda, JR Scranton, R Lawler, EV AF Gagnon, David R. Fonda, Jennifer R. Scranton, Richard Lawler, Elizabeth V. TI The Role of Medical Comorbidities in the Association of Proton Pump Inhibitors [PPIs] and Fractures SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Gagnon, David R.; Fonda, Jennifer R.; Lawler, Elizabeth V.] VA Cooperat Studies Program, MAVERIC, Boston, MA USA. [Gagnon, David R.] Boston Univ SPH, Boston, MA USA. [Scranton, Richard] Veroscience, Tiverton, RI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S18 EP S18 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900041 ER PT J AU Linsky, A Gupta, K Lawler, E Fonda, J Hermos, J AF Linsky, Amy Gupta, Kalpana Lawler, Elizabeth Fonda, Jennifer Hermos, John TI Proton Pump Inhibitors and Risk for Recurrent Clostridium difficile Associated Diarrhea SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Linsky, Amy; Hermos, John] Boston Med Ctr, Boston, MA USA. [Gupta, Kalpana; Lawler, Elizabeth; Fonda, Jennifer; Hermos, John] Massachusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S19 EP S19 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900043 ER PT J AU McDermott, D Choueiri, TK Clement, J Brick, AJ Kwabi, C Shah, K Antras, L Jayawant, SS Wang, ST Luka, A Duh, MS Neary, M Oh, WK AF McDermott, David Choueiri, Toni K. Clement, Jessica Brick, Ashley J. Kwabi, Christabel Shah, Karishma Antras, Lucia Jayawant, Sujata S. Wang, Si-Tien Luka, Andi Duh, Mei Sheng Neary, Maureen Oh, William K. TI Patients (Pts) with Metastatic Renal Cell Carcinoma (mRCC) Receiving Angiogenesis Inhibitor (AI) Therapies: Treatment Efficacy and Safety in Clinical Practice SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [McDermott, David; Clement, Jessica; Kwabi, Christabel; Shah, Karishma] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Choueiri, Toni K.; Brick, Ashley J.; Oh, William K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Antras, Lucia; Jayawant, Sujata S.; Wang, Si-Tien; Luka, Andi; Duh, Mei Sheng] Anal Grp Inc, Boston, MA USA. [Neary, Maureen] GlaxoSmithKline Inc, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S111 EP S112 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900255 ER PT J AU McDonald, JR Pittman, C Zeringue, AL Eisen, SA Cunningham, F Wehmeier, K Caplan, L AF McDonald, Jay R. Pittman, Cory Zeringue, Angelique L. Eisen, Seth A. Cunningham, Fran Wehmeier, Kent Caplan, Liron TI Atrial Fibrillation in US Veteran Fracture Patients Treated with Bisphosphonates SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [McDonald, Jay R.; Pittman, Cory; Zeringue, Angelique L.] St Louis VAMC, St Louis, MO USA. [McDonald, Jay R.; Zeringue, Angelique L.] Washington Univ, Sch Med, St Louis, MO USA. [Pittman, Cory] Mercy Med Ctr, Des Moines, IA USA. [Eisen, Seth A.] Dept Vet Affairs, HSR&D Serv, Washington, DC USA. [Cunningham, Fran] Dept Vet Affairs, Hines, IL USA. [Wehmeier, Kent] Univ Florida, Sch Med, Jacksonville, FL USA. [Caplan, Liron] Denver VAMC, Denver, CO USA. [Caplan, Liron] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RI Zeringue, Angelique/I-1755-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S220 EP S220 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900502 ER PT J AU Setoguchi, S Higgins, J Raisa, L Mootha, V Avorn, J AF Setoguchi, Soko Higgins, John Raisa, Levin Mootha, Vamsi Avorn, Jerry TI Propranolol May Be Associated with Increased Risk of Hospitalized Myopathy: A Hypothesis Generated by Chemical Genomics SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Setoguchi, Soko; Raisa, Levin; Avorn, Jerry] Brigham & Womens Hosp, Boston, MA 02115 USA. [Higgins, John; Mootha, Vamsi] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S8 EP S8 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900018 ER PT J AU Signorovitch, JE Gu, A Sengupta, A Raut, M Mody, SH Grant, R Schein, J Fisher, AC Ng, D Duh, MS AF Signorovitch, James E. Gu, Anna Sengupta, Anirban Raut, Monika Mody, Samir H. Grant, Richard Schein, Jeff Fisher, Alan C. Ng, Daniel Duh, Mei Sheng TI The Risk of Hospitalization or Emergency Care Following Outpatient Treatment of Community-Acquired Pneumonia (CAP) with Levofloxacin Versus Moxifloxacin SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Signorovitch, James E.; Gu, Anna; Sengupta, Anirban; Duh, Mei Sheng] Anal Grp Inc, Boston, MA USA. [Raut, Monika; Mody, Samir H.; Schein, Jeff; Fisher, Alan C.; Ng, Daniel] Ortho McNeil Janssen Sci Affairs LLC, Raritan, NJ USA. [Grant, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S212 EP S212 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900484 ER PT J AU Skarin, AT Vekeman, F Laliberte, F Afonja, O Lafeuille, MH Barghout, V Duh, MS AF Skarin, A. T. Vekeman, F. Laliberte, F. Afonja, O. Lafeuille, M. H. Barghout, V. Duh, M. S. TI Pattern of Utilization of Pegfilgrastim (PEGFIL) in Patients with Chemotherapy-Induced Neutropenia: A Retrospective Analysis of Administrative Claims Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Skarin, A. T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vekeman, F.; Laliberte, F.; Lafeuille, M. H.; Duh, M. S.] Anal Grp Inc, Boston, MA USA. [Afonja, O.; Barghout, V.] Bayer HealthCare Pharmaceut Inc, Wayne, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S2 EP S3 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900006 ER PT J AU Bradbury, PA Kulke, MH Heist, RS Zhou, W Ma, C Xu, W Marshall, AL Zhai, R Hooshmand, SM Asomaning, K Su, L Shepherd, FA Lynch, TJ Wain, JC Christiani, DC Liu, G AF Bradbury, Penelope A. Kulke, Matthew H. Heist, Rebecca S. Zhou, Wei Ma, Clement Xu, Wei Marshall, Ariela L. Zhai, Rihong Hooshmand, Susanne M. Asomaning, Kofi Su, Li Shepherd, Frances A. Lynch, Thomas J. Wain, John C. Christiani, David C. Liu, Geoffrey TI Cisplatin pharmacogenetics, DNA repair polymorphisms, and esophageal cancer outcomes SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE DNA repair; esophageal cancer; genetic polymorphisms ID CELL LUNG-CANCER; NUCLEOTIDE EXCISION-REPAIR; XPD POLYMORPHISMS; GENETIC POLYMORPHISMS; ADENOCARCINOMA RISK; COLORECTAL-CANCER; CONTINUOUS TRAITS; OVARIAN-CANCER; CHEMOTHERAPY; ERCC1 AB Objectives Genetic variations or polymorphisms within genes of the nucleotide excision repair (NER) pathway alter DNA repair capacity. Reduced DNA repair (NER) capacity may result in tumors that are more susceptible to cisplatin chemotherapy, which functions by causing DNA damage. We investigated the potential predictive significance of functional NER single nucleotide polymorphisms in esophageal cancer patients treated with (n=262) or without (n=108) cisplatin. Methods Four NER polymorphisms XPD Asp312Asn; XPD Lys751Gln, ERCC1 8092C/A, and ERCC1 codon 118C/T were each assessed in polymorphism-cisplatin treatment interactions for overall survival (OS), with progression-free survival (PFS) as a secondary endpoint. Results No associations with ERCC1 118 were found. Polymorphism-cisplatin interactions were highly significant in both OS (P=0.002, P=0.0001, and P<0.0001) and PFS (P=0.006, P=0.008, and P=0.0007) for XPD 312, XPD 751, and ERCC1 8092, respectively. In cisplatin-treated patients, variant alleles of XPD 312, XPD 751, and ERCC1 8092 were each associated with significantly improved OS (and PFS): adjusted hazard ratios of homozygous variants versus wild-type ranged from 0.22 [95% confidence interval (Cl): 0.1-0.5] to 0.31 (95% Cl: 0.1-0.7). In contrast, in patients who did not receive cisplatin, variant alleles of XPD 751 and ERCC1 8092 had significantly worse survival, with adjusted hazard ratios of homozygous variants ranging from 2.47 (95% Cl: 1.1-5.5) to 3.73 (95% Cl: 1.6-8.7). Haplotype analyses affirmed these results. Conclusion DNA repair polymorphisms are associated with OS and PFS, and if validated may predict for benefit from cisplatin therapy in patients with esophageal cancer. Pharmacogenetics and Genomics 19:613-625 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Liu, Geoffrey] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Bradbury, Penelope A.; Ma, Clement; Xu, Wei; Shepherd, Frances A.; Liu, Geoffrey] Univ Toronto, Toronto, ON, Canada. [Kulke, Matthew H.; Hooshmand, Susanne M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kulke, Matthew H.; Heist, Rebecca S.; Lynch, Thomas J.; Wain, John C.; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Med, Boston, MA USA. [Heist, Rebecca S.; Zhou, Wei; Marshall, Ariela L.; Zhai, Rihong; Asomaning, Kofi; Su, Li; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Heist, Rebecca S.; Lynch, Thomas J.; Wain, John C.; Christiani, David C.; Liu, Geoffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Liu, G (reprint author), Princess Margaret Hosp, Ontario Canc Inst, 610 Univ Ave,Suite 7-124, Toronto, ON M5G 2M9, Canada. EM Geoffrey.Liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [K23 CA093401, K23 CA093401-01A2, K23 CA093401-02, K23 CA093401-03, K23 CA093401-04, K23 CA093401-05, R01 CA074386, R01 CA074386-11] NR 37 TC 45 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD AUG PY 2009 VL 19 IS 8 BP 613 EP 625 DI 10.1097/FPC.0b013e32832f3010 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 480JN UT WOS:000268730700005 PM 19620936 ER PT J AU Kahle, KT Simard, JM Staley, KJ Nahed, BV Jones, PS Sun, DD AF Kahle, Kristopher T. Simard, J. Marc Staley, Kevin J. Nahed, Brian V. Jones, Pamela S. Sun, Dandan TI Molecular Mechanisms of Ischemic Cerebral Edema: Role of Electroneutral Ion Transport SO PHYSIOLOGY LA English DT Review ID NA-K-CL; CATION-CHLORIDE COTRANSPORTERS; ARTERY OCCLUSION MODEL; CENTRAL-NERVOUS-SYSTEM; CELL-VOLUME; BRAIN EDEMA; NA-K-2CL COTRANSPORTER; DECREASES EDEMA; BUMETANIDE; STROKE AB The brain achieves homeostasis of its intracellular and extracellular fluids by precisely regulating the transport of solute and water across its major cellular barriers: endothelia of the blood-brain barrier (BBB), choroid plexus epithelia, and neuroglial cell membranes. Cerebral edema, the pathological accumulation of fluid in the brain's intracellular and extracellular spaces, is a major cause of morbidity and mortality following stroke and other forms of ischemic brain injury. Until recently, mechanisms of cerebral edema formation have been obscure; consequently, its treatment has been empiric and suboptimal. Here, we provide a paradigm for understanding ischemic cerebral edema, showing that its molecular pathogenesis is a complex yet step-wise process that results largely from impaired astrocytic cell volume regulation and permeability alterations in the cerebral microvasculature, both of which arise from pathological changes in the activities of specific ion channels and transporters. Recent data has implicated the bumetanide-sensitive NKCC1, an electroneutral cotransporter expressed in astrocytes and the BBB, in cerebral edema formation in several different rodent models of stroke. Pharmacological inhibition or genetic deficiency of NKCC1 decreases ischemia-induced cell swelling, BBB breakdown, cerebral edema, and neurotoxicity. Combination pharmacological strategies that include NKCC1 as a target might thus prove beneficial for the treatment of ischemic, and potentially other types of, cerebral edema. C1 [Kahle, Kristopher T.; Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Div Pediat Neurol, Boston, MA 02114 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Jones, Pamela S.] Tulane Univ, Dept Neurosurg, New Orleans, LA 70118 USA. [Sun, Dandan] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurosurg, Madison, WI USA. RP Kahle, KT (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM kkahle@partners.org NR 55 TC 97 Z9 107 U1 2 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 J9 PHYSIOLOGY JI Physiology PD AUG PY 2009 VL 24 IS 4 BP 257 EP 265 DI 10.1152/physiol.00015.2009 PG 9 WC Physiology SC Physiology GA 482VM UT WOS:000268917400007 PM 19675357 ER PT J AU O'Neill, AC Randolph, MA Bujold, KE Kochevar, IE Redmond, RW Winograd, JM AF O'Neill, Anne C. Randolph, Mark A. Bujold, Kenneth E. Kochevar, Irene E. Redmond, Robert W. Winograd, Jonathan M. TI Preparation and Integration of Human Amnion Nerve Conduits Using a Light-Activated Technique SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the British-Association-of-Plastic-Reconstructive-and-Aesthetic-Surgery CY JUL 04-06, 2007 CL Deauville, FRANCE SP British Assoc Plast Reconstruct & Aesthet Surg ID PHOTOCHEMICAL CROSS-LINKING; CORNEAL INCISIONS; IN-VIVO; REGENERATION; REPAIR; COLLAGEN; KERATODESMOS; IMPROVES; SCAFFOLDS; MEMBRANE AB Background: Photochemical tissue bonding is a developing light-activated technique that facilitates watertight sealing between tissue surfaces. Previous work has shown that sealing with photochemical tissue bonding can improve regeneration following primary nerve repair. The authors evaluated sealing of nerve stumps with photochemical tissue bonding within customized human amnion conduits. The authors hypothesized that light-activated integration could enhance regeneration across the nerve gap. Methods: Photochemical crosslinked amnion conduits were placed across 1-cm sciatic nerve gaps in Sprague-Dawley rats and either secured with sutures or sealed using photochemical tissue bonding. Reversed autologous nerve grafts were used in the control group. Functional recovery was measured by walking track analysis; histology and histomorphometry of nerves and gastrocnemius muscles were evaluated. Results: Regeneration within the photochemical tissue bonding-sealed amnion conduit was significantly better than that observed in the amnion conduit secured with sutures and did not differ significantly from that in the autologous nerve graft. Conclusions: Photochemical crosslinked amnion appears suitable as a nerve conduit. Sealing of compatible conduits with photochemical tissue bonding may have the potential to maximize regeneration. ( Plast. Reconstr. Surg. 124: 428, 2009.) C1 [Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, WAC 435,15 Parkman St, Boston, MA 02114 USA. EM marandolph@partners.org NR 35 TC 19 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD AUG PY 2009 VL 124 IS 2 BP 428 EP 437 DI 10.1097/PRS.0b013e3181af010c PG 10 WC Surgery SC Surgery GA 481MC UT WOS:000268814500012 PM 19644257 ER PT J AU Adams, JC Keiser, MJ Basuino, L Chambers, HF Lee, DS Wiest, OG Babbitt, PC AF Adams, James Corey Keiser, Michael J. Basuino, Li Chambers, Henry F. Lee, Deok-Sun Wiest, Olaf G. Babbitt, Patricia C. TI A Mapping of Drug Space from the Viewpoint of Small Molecule Metabolism SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; THYMIDYLATE SYNTHASE; DRUGGABLE GENOME; SYSTEMS BIOLOGY; DISCOVERY; INHIBITORS; TARGETS; METABOLOMICS; STRATEGIES; NETWORK AB Small molecule drugs target many core metabolic enzymes in humans and pathogens, often mimicking endogenous ligands. The effects may be therapeutic or toxic, but are frequently unexpected. A large-scale mapping of the intersection between drugs and metabolism is needed to better guide drug discovery. To map the intersection between drugs and metabolism, we have grouped drugs and metabolites by their associated targets and enzymes using ligand-based set signatures created to quantify their degree of similarity in chemical space. The results reveal the chemical space that has been explored for metabolic targets, where successful drugs have been found, and what novel territory remains. To aid other researchers in their drug discovery efforts, we have created an online resource of interactive maps linking drugs to metabolism. These maps predict the "effect space" comprising likely target enzymes for each of the 246 MDDR drug classes in humans. The online resource also provides species-specific interactive drug-metabolism maps for each of the 385 model organisms and pathogens in the BioCyc database collection. Chemical similarity links between drugs and metabolites predict potential toxicity, suggest routes of metabolism, and reveal drug polypharmacology. The metabolic maps enable interactive navigation of the vast biological data on potential metabolic drug targets and the drug chemistry currently available to prosecute those targets. Thus, this work provides a large-scale approach to ligand-based prediction of drug action in small molecule metabolism. C1 [Adams, James Corey] Univ Calif San Francisco, Grad Program Pharmaceut Sci & Pharmacogenom, San Francisco, CA 94143 USA. [Keiser, Michael J.] Univ Calif San Francisco, Grad Program Bioinformat, San Francisco, CA 94143 USA. [Basuino, Li; Chambers, Henry F.] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA. [Lee, Deok-Sun] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Lee, Deok-Sun] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Lee, Deok-Sun] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Lee, Deok-Sun] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Lee, Deok-Sun] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Lee, Deok-Sun] Inha Univ, Dept Nat Med Sci, Inchon, South Korea. [Wiest, Olaf G.] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Babbitt, Patricia C.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Babbitt, Patricia C.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. [Babbitt, Patricia C.] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94143 USA. RP Adams, JC (reprint author), Univ Calif San Francisco, Grad Program Pharmaceut Sci & Pharmacogenom, San Francisco, CA 94143 USA. EM Babbitt@cgl.ucsf.edu RI Lee, Deok-Sun/D-1335-2011; Keiser, Michael/F-2825-2016 OI Keiser, Michael/0000-0002-1240-2192 FU National Institutes of Health (NIH) [GM60595, U01-AI070499, GA1070499-01, P41 RR-01081]; National Science Foundation; [GM67547] FX This work was supported by National Institutes of Health (NIH) GM60595 to PCB and U01-AI070499 to OGW. MJK was supported by Training Grant GM67547 and a National Science Foundation graduate fellowship. D-SL was supported by NIH GA1070499-01. Tools used for visualization of metabolic networks and SEA links were created by the UCSF Resource for Biocomputing, Visualization, and Informatics (RBVI) supported by NIH P41 RR-01081. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 23 Z9 23 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD AUG PY 2009 VL 5 IS 8 AR e1000474 DI 10.1371/journal.pcbi.1000474 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 506TR UT WOS:000270799700018 PM 19701464 ER PT J AU Colijn, C Brandes, A Zucker, J Lun, DS Weiner, B Farhat, MR Cheng, TY Moody, DB Murray, M Galagan, JE AF Colijn, Caroline Brandes, Aaron Zucker, Jeremy Lun, Desmond S. Weiner, Brian Farhat, Maha R. Cheng, Tan-Yun Moody, D. Branch Murray, Megan Galagan, James E. TI Interpreting Expression Data with Metabolic Flux Models: Predicting Mycobacterium tuberculosis Mycolic Acid Production SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID ESCHERICHIA-COLI; GENE-EXPRESSION; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; DESULFOVIBRIO-VULGARIS; LIPID BIOSYNTHESIS; PROTEIN ABUNDANCE; BALANCE MODELS; GROWTH; DRUG AB Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these reactions. We present a novel method for modeling metabolic states using whole cell measurements of gene expression. Our method, which we call E-Flux (as a combination of flux and expression), extends the technique of Flux Balance Analysis by modeling maximum flux constraints as a function of measured gene expression. In contrast to previous methods for metabolically interpreting gene expression data, E-Flux utilizes a model of the underlying metabolic network to directly predict changes in metabolic flux capacity. We applied E-Flux to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). Key components of mycobacterial cell walls are mycolic acids which are targets for several first-line TB drugs. We used E-Flux to predict the impact of 75 different drugs, drug combinations, and nutrient conditions on mycolic acid biosynthesis capacity in M. tuberculosis, using a public compendium of over 400 expression arrays. We tested our method using a model of mycolic acid biosynthesis as well as on a genome-scale model of M. tuberculosis metabolism. Our method correctly predicts seven of the eight known fatty acid inhibitors in this compendium and makes accurate predictions regarding the specificity of these compounds for fatty acid biosynthesis. Our method also predicts a number of additional potential modulators of TB mycolic acid biosynthesis. E-Flux thus provides a promising new approach for algorithmically predicting metabolic state from gene expression data. C1 [Colijn, Caroline; Brandes, Aaron; Lun, Desmond S.; Weiner, Brian; Galagan, James E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Zucker, Jeremy] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Colijn, Caroline; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Farhat, Maha R.] Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. [Colijn, Caroline] Univ Bristol, Dept Engn Math, Bristol, Avon, England. [Cheng, Tan-Yun; Moody, D. Branch] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Lun, Desmond S.] Univ S Australia, Phen & Bioinformat Res Ctr, Sch Math & Stat, Mawson Lakes, SA, Australia. [Lun, Desmond S.] Univ S Australia, Australian Ctr Plant Funct Genom, Mawson Lakes, SA, Australia. [Galagan, James E.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Galagan, James E.] Boston Univ, Dept Microbiol, Boston, MA 02215 USA. RP Colijn, C (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM C.Colijn@bristol.ac.uk RI Zucker, Jeremy/M-3643-2016; OI Zucker, Jeremy/0000-0002-7276-9009; Galagan, James/0000-0003-0542-3291; Farhat, Maha/0000-0002-3871-5760 FU National Institute of Allergy and Infectious Disease (NIAID) [1U19AI076217, R01 071155]; National Institutes of Health (NIH) [HHSN 26620040000IC]; Department of Health and Human Services [HHSN266200400001C]; NIH/NIAID [014334-001]; Bill & Melinda Gates Foundation; Ellison Medical Foundation; Burroughs Wellcome Fund [ID-SS-0693-04] FX This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Disease (NIAID; http://www3.niaid.nih.gov/), National Institutes of Health (NIH; http://www.nih.gov/) Department of Health and Human Services, under Contract No. HHSN266200400001C. Support has also been provided by NIAID 1U19AI076217; NIAID R01 071155; NIH HHSN 26620040000IC; NIH/NIAID Network for Large-Scale Sequencing of Microbial Genomes (014334-001); the Bill & Melinda Gates Foundation (http://www.gatesfoundation.org/) Dedicated Tuberculosis Gene Expression Database; the Ellison Medical Foundation (http://www.ellisonfoundation.org/) ID-SS-0693-04 and by the Burroughs Wellcome Fund (http://www.bwfund.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 136 Z9 137 U1 0 U2 27 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD AUG PY 2009 VL 5 IS 8 AR e1000489 DI 10.1371/journal.pcbi.1000489 PG 14 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 506TR UT WOS:000270799700011 PM 19714220 ER PT J AU Baughman, JM Nilsson, R Gohil, VM Arlow, DH Gauhar, Z Mootha, VK AF Baughman, Joshua M. Nilsson, Roland Gohil, Vishal M. Arlow, Daniel H. Gauhar, Zareen Mootha, Vamsi K. TI A Computational Screen for Regulators of Oxidative Phosphorylation Implicates SLIRP in Mitochondrial RNA Homeostasis SO PLOS GENETICS LA English DT Article ID NUCLEAR RESPIRATORY FACTORS; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; INTEGRATIVE GENOMICS; ATP SYNTHASE; COMPLEX-I; EXPRESSION PROFILES; HEART-MITOCHONDRIA; POLY(A) POLYMERASE; BINDING-PROTEIN AB The human oxidative phosphorylation (OxPhos) system consists of approximately 90 proteins encoded by nuclear and mitochondrial genomes and serves as the primary cellular pathway for ATP biosynthesis. While the core protein machinery for OxPhos is well characterized, many of its assembly, maturation, and regulatory factors remain unknown. We exploited the tight transcriptional control of the genes encoding the core OxPhos machinery to identify novel regulators. We developed a computational procedure, which we call expression screening, which integrates information from thousands of microarray data sets in a principled manner to identify genes that are consistently co-expressed with a target pathway across biological contexts. We applied expression screening to predict dozens of novel regulators of OxPhos. For two candidate genes, CHCHD2 and SLIRP, we show that silencing with RNAi results in destabilization of OxPhos complexes and a marked loss of OxPhos enzymatic activity. Moreover, we show that SLIRP plays an essential role in maintaining mitochondrial-localized mRNA transcripts that encode OxPhos protein subunits. Our findings provide a catalogue of potential novel OxPhos regulators that advance our understanding of the coordination between nuclear and mitochondrial genomes for the regulation of cellular energy metabolism. C1 [Baughman, Joshua M.; Nilsson, Roland; Gohil, Vishal M.; Arlow, Daniel H.; Gauhar, Zareen; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Baughman, Joshua M.; Nilsson, Roland; Gohil, Vishal M.; Arlow, Daniel H.; Gauhar, Zareen; Mootha, Vamsi K.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Baughman, Joshua M.; Nilsson, Roland; Gohil, Vishal M.; Arlow, Daniel H.; Gauhar, Zareen; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Baughman, JM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu FU National Science Foundation; Wallenberg Foundation; United Mitochondrial Disease Foundation; Burroughs Wellcome Fund Career Award in the Biomedical Sciences; Howard Hughes Medical Institute; Charles E. Culpeper Scholarship in Medical Science FX This research was supported by a National Science Foundation graduate student fellowship (JMB) and by postdoctoral fellowships from the Wallenberg Foundation (RN) and the United Mitochondrial Disease Foundation (VMG). VKM is supported by a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, an Early Career Award from the Howard Hughes Medical Institute, and a Charles E. Culpeper Scholarship in Medical Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 53 Z9 53 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2009 VL 5 IS 8 AR e1000590 DI 10.1371/journal.pgen.1000590 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 516HS UT WOS:000271533500005 PM 19680543 ER PT J AU Coleman, JJ Rounsley, SD Rodriguez-Carres, M Kuo, A Wasmann, CC Grimwood, J Schmutz, J Taga, M White, GJ Zhou, SG Schwartz, DC Freitag, M Ma, LJ Danchin, EGJ Henrissat, B Coutinho, PM Nelson, DR Straney, D Napoli, CA Barker, BM Gribskov, M Rep, M Kroken, S Molnar, I Rensing, C Kennell, JC Zamora, J Farman, ML Selker, EU Salamov, A Shapiro, H Pangilinan, J Lindquist, E Lamers, C Grigoriev, IV Geiser, DM Covert, SF Temporini, E VanEtten, HD AF Coleman, Jeffrey J. Rounsley, Steve D. Rodriguez-Carres, Marianela Kuo, Alan Wasmann, Catherine C. Grimwood, Jane Schmutz, Jeremy Taga, Masatoki White, Gerard J. Zhou, Shiguo Schwartz, David C. Freitag, Michael Ma, Li-jun Danchin, Etienne G. J. Henrissat, Bernard Coutinho, Pedro M. Nelson, David R. Straney, Dave Napoli, Carolyn A. Barker, Bridget M. Gribskov, Michael Rep, Martijn Kroken, Scott Molnar, Istvan Rensing, Christopher Kennell, John C. Zamora, Jorge Farman, Mark L. Selker, Eric U. Salamov, Asaf Shapiro, Harris Pangilinan, Jasmyn Lindquist, Erika Lamers, Casey Grigoriev, Igor V. Geiser, David M. Covert, Sarah F. Temporini, Esteban VanEtten, Hans D. TI The Genome of Nectria haematococca: Contribution of Supernumerary Chromosomes to Gene Expansion SO PLOS GENETICS LA English DT Article ID SOLANI SPECIES COMPLEX; PATHOGENICITY PEP GENES; FUSARIUM-SOLANI; NEUROSPORA-CRASSA; FILAMENTOUS FUNGI; IN-VITRO; DISPENSABLE CHROMOSOME; PISATIN DEMETHYLATION; HETERODERA-GLYCINES; HORIZONTAL TRANSFER AB The ascomycetous fungus Nectria haematococca, (asexual name Fusarium solani), is a member of a group of >50 species known as the "Fusarium solani species complex". Members of this complex have diverse biological properties including the ability to cause disease on >100 genera of plants and opportunistic infections in humans. The current research analyzed the most extensively studied member of this complex, N. haematococca mating population VI (MPVI). Several genes controlling the ability of individual isolates of this species to colonize specific habitats are located on supernumerary chromosomes. Optical mapping revealed that the sequenced isolate has 17 chromosomes ranging from 530 kb to 6.52 Mb and that the physical size of the genome, 54.43 Mb, and the number of predicted genes, 15,707, are among the largest reported for ascomycetes. Two classes of genes have contributed to gene expansion: specific genes that are not found in other fungi including its closest sequenced relative, Fusarium graminearum; and genes that commonly occur as single copies in other fungi but are present as multiple copies in N. haematococca MPVI. Some of these additional genes appear to have resulted from gene duplication events, while others may have been acquired through horizontal gene transfer. The supernumerary nature of three chromosomes, 14, 15, and 17, was confirmed by their absence in pulsed field gel electrophoresis experiments of some isolates and by demonstrating that these isolates lacked chromosome-specific sequences found on the ends of these chromosomes. These supernumerary chromosomes contain more repeat sequences, are enriched in unique and duplicated genes, and have a lower G+C content in comparison to the other chromosomes. Although the origin(s) of the extra genes and the supernumerary chromosomes is not known, the gene expansion and its large genome size are consistent with this species' diverse range of habitats. Furthermore, the presence of unique genes on supernumerary chromosomes might account for individual isolates having different environmental niches. C1 [Coleman, Jeffrey J.; Rounsley, Steve D.; Rodriguez-Carres, Marianela; Wasmann, Catherine C.; White, Gerard J.; Napoli, Carolyn A.; Barker, Bridget M.; Kroken, Scott; Zamora, Jorge; Temporini, Esteban; VanEtten, Hans D.] Univ Arizona, Dept Plant Sci, Tucson, AZ 85721 USA. [Coleman, Jeffrey J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rounsley, Steve D.] Univ Arizona, Inst BIO5, Tucson, AZ USA. [Rodriguez-Carres, Marianela] Duke Univ, Dept Biol, Durham, NC USA. [Kuo, Alan; Salamov, Asaf; Shapiro, Harris; Pangilinan, Jasmyn; Lindquist, Erika; Grigoriev, Igor V.] Energy Joint Genome Inst, US Dept, Walnut Creek, CA USA. [Grimwood, Jane; Schmutz, Jeremy] Stanford Human Genome Ctr, Joint Genome Inst, Palo Alto, CA USA. [Grimwood, Jane; Schmutz, Jeremy] Hudson Alpha Inst Biotechnol, Hudson Alpha Genome Sequencing Ctr, Huntsville, AL USA. [Taga, Masatoki] Okayama Univ, Dept Biol, Okayama, Japan. [Zhou, Shiguo; Schwartz, David C.; Lamers, Casey] Univ Wisconsin, Lab Mol & Computat Genom, Madison, WI USA. [Freitag, Michael] Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA. [Freitag, Michael] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. [Ma, Li-jun] Broad Inst, Cambridge, MA USA. [Danchin, Etienne G. J.; Henrissat, Bernard; Coutinho, Pedro M.] Univ Aix Marseille 1, CNRS, Architecture & Fonct Macromol Biol, Marseille, France. [Danchin, Etienne G. J.; Henrissat, Bernard; Coutinho, Pedro M.] Univ Aix Marseille 2, CNRS, Architecture & Fonct Macromol Biol, F-13284 Marseille 07, France. [Danchin, Etienne G. J.] Ctr Rech, Inst Natl Rech Agron, Sophia Antipolis, France. [Nelson, David R.] Univ Tennessee, Dept Mol Sci, Memphis, TN USA. [Straney, Dave] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. [Gribskov, Michael] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Rep, Martijn] Univ Amsterdam, Amsterdam, Netherlands. [Molnar, Istvan] Univ Arizona, SW Ctr Nat Prod Res & Commercializat, Off Arid Lands Studies, Tucson, AZ USA. [Rensing, Christopher] Univ Arizona, Dept Soil Water & Environm Sci, Tucson, AZ USA. [Kennell, John C.] St Louis Univ, Dept Biol, St Louis, MO 63103 USA. [Farman, Mark L.] Univ Kentucky, Dept Plant Pathol, Lexington, KY 40546 USA. [Selker, Eric U.] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. [Geiser, David M.] Penn State Univ, Fusarium Res Ctr, Dept Plant Pathol, University Pk, PA 16802 USA. [Covert, Sarah F.] Univ Georgia, Warnell Sch Forestry & Nat Resources, Athens, GA 30602 USA. [Temporini, Esteban] Vilmorin Inc, Tucson, AZ USA. RP Coleman, JJ (reprint author), Univ Arizona, Dept Plant Sci, Tucson, AZ 85721 USA. EM vanetten@ag.arizona.edu RI Henrissat, Bernard/J-2475-2012; Danchin, Etienne/A-6648-2008; Zhou, Shiguo/B-3832-2011; Rensing, Christopher/D-3947-2011; Geiser, David/J-9950-2013; Molnar, Istvan/A-5863-2008; Taga, Masatoki/B-2089-2011; Coleman, Jeffrey/E-2981-2015; OI Nelson, David/0000-0003-0583-5421; Barker, Bridget/0000-0002-3439-4517; Coleman, Jeffrey/0000-0001-8579-1996; Danchin, Etienne/0000-0003-4146-5608; Zhou, Shiguo/0000-0001-7421-2506; Rensing, Christopher/0000-0002-5012-7953; Molnar, Istvan/0000-0002-3627-0454; Gribskov, Michael/0000-0002-1718-0242; Ma, Li-Jun/0000-0002-2733-3708 FU US Department of Energy's Office of Science; Biological and Environmental Research Program; University of California, Lawrence Berkeley National Laboratory [DE-AC02-05CH11231]; Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; Los Alamos National Laboratory [DE-AC02-06NA25396] FX This work was performed under the auspices of the US Department of Energy's Office of Science, Biological and Environmental Research Program, and by the University of California, Lawrence Berkeley National Laboratory under Contract DE-AC02-05CH11231, Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, and Los Alamos National Laboratory under Contract DE-AC02-06NA25396. Personnel at these laboratories were involved in all aspects of this research. The sequence of Nectria haematococca is available at http://www.jgi.doe.gov/nectria. Partial support for personnel was also obtained from NRA/USDA grant 2008-00645. NR 102 TC 158 Z9 221 U1 7 U2 49 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 AUG PY 2009 VL 5 IS 8 AR e1000618 DI 10.1371/journal.pgen.1000618 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 516HS UT WOS:000271533500032 PM 19714214 ER PT J AU Jia, L Landan, G Pomerantz, M Jaschek, R Herman, P Reich, D Yan, CL Khalid, O Kantoff, P Oh, W Manak, JR Berman, BP Henderson, BE Frenkel, B Haiman, CA Freedman, M Tanay, A Coetzee, GA AF Jia, Li Landan, Gilad Pomerantz, Mark Jaschek, Rami Herman, Paula Reich, David Yan, Chunli Khalid, Omar Kantoff, Phil Oh, William Manak, J. Robert Berman, Benjamin P. Henderson, Brian E. Frenkel, Baruch Haiman, Christopher A. Freedman, Matthew Tanay, Amos Coetzee, Gerhard A. TI Functional Enhancers at the Gene-Poor 8q24 Cancer-Linked Locus SO PLOS GENETICS LA English DT Article ID PROSTATE-CANCER; ANDROGEN RECEPTOR; HUMAN GENOME; MULTIETHNIC COHORT; TRANSCRIPTION; SIGNATURES; DISTINCT; CELLS; RISK; LINE AB Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their biological activities have been unknown. Here we profiled a 5-megabase chromatin segment encompassing all the risk regions for RNA expression, histone modifications, and locations occupied by RNA polymerase II and androgen receptor (AR). This led to the identification of several transcriptional enhancers, which were verified using reporter assays. Two enhancers in one risk region were occupied by AR and responded to androgen treatment; one contained a single nucleotide polymorphism (rs11986220) that resides within a FoxA1 binding site, with the prostate cancer risk allele facilitating both stronger FoxA1 binding and stronger androgen responsiveness. The study reported here exemplifies an approach that may be applied to any risk-associated allele in nonprotein coding regions as it emerges from genome-wide association studies to better understand the genetic predisposition of complex diseases. C1 [Jia, Li; Yan, Chunli; Khalid, Omar; Henderson, Brian E.; Haiman, Christopher A.; Coetzee, Gerhard A.] Univ So Calif, Dept Prevent Med, USC Norris Canc Ctr, Los Angeles, CA 90089 USA. [Jia, Li; Khalid, Omar; Coetzee, Gerhard A.] Univ So Calif, Dept Urol, Los Angeles, CA 90089 USA. [Landan, Gilad; Jaschek, Rami; Tanay, Amos] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel. [Pomerantz, Mark; Herman, Paula; Kantoff, Phil; Oh, William; Freedman, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Manak, J. Robert] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA. [Berman, Benjamin P.] Univ So Calif, Keck Sch Med, USC Epigenome Ctr, Los Angeles, CA 90033 USA. [Frenkel, Baruch] Univ So Calif, Inst Med Genet, Dept Orthoped Surg, Los Angeles, CA 90089 USA. [Frenkel, Baruch] Univ So Calif, Inst Med Genet, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. [Freedman, Matthew] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Jia, L (reprint author), Univ So Calif, Dept Prevent Med, USC Norris Canc Ctr, Los Angeles, CA 90089 USA. EM amos.tanay@weizmann.ac.il; coetzee@usc.edu RI Oh, William/B-9163-2012; Berman, Benjamin/D-5942-2014 OI Oh, William/0000-0001-5113-8147; FU NIH [R01 CA109147, R01 CA129435]; Prostate Cancer Foundation; Whittier Foundation; American Cancer Society Institutional Research [IRG-58-007-48]; Mayer Foundation; Snyder Medical Foundation; the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE [5P50CA90381]; Israeli Science Foundation; Alon Fellowship; J. Harold and Edna L. LaBriola Chair in Genetic Orthopaedic Research FX Grant support from the NIH (R01 CA109147 to GAC and R01 CA129435 to MLF), the Prostate Cancer Foundation (to GAC), the Whittier Foundation (to GAC), the American Cancer Society Institutional Research Grant (IRG-58-007-48 to LJ), the Mayer Foundation (to MLF), the H. L. Snyder Medical Foundation (to MLF), the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute Grant No. 5P50CA90381), the Israeli Science Foundation (to AT), an Alon Fellowship (to AT), and the J. Harold and Edna L. LaBriola Chair in Genetic Orthopaedic Research (held by BF). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 138 Z9 138 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2009 VL 5 IS 8 AR e1000597 DI 10.1371/journal.pgen.1000597 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 516HS UT WOS:000271533500012 PM 19680443 ER PT J AU Prigerson, HG Horowitz, MJ Jacobs, SC Parkes, CM Aslan, M Goodkin, K Raphael, B Marwit, SJ Wortman, C Neimeyer, RA Bonanno, GA Block, SD Kissane, D Boelen, P Maercker, A Litz, BT Johnson, JG First, MB Maciejewski, PK AF Prigerson, Holly G. Horowitz, Mardi J. Jacobs, Selby C. Parkes, Colin M. Aslan, Mihaela Goodkin, Karl Raphael, Beverley Marwit, Samuel J. Wortman, Camille Neimeyer, Robert A. Bonanno, George A. Block, Susan D. Kissane, David Boelen, Paul Maercker, Andreas Litz, Brett T. Johnson, Jeffrey G. First, Michael B. Maciejewski, Paul K. TI Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-V and ICD-11 SO PLOS MEDICINE LA English DT Article ID BEREAVEMENT-RELATED DEPRESSION; COMPLICATED GRIEF; TRAUMATIC GRIEF; PSYCHIATRIC-DISORDERS; DIAGNOSTIC-CRITERIA; PHYSICAL HEALTH; MENTAL-HEALTH; LATER LIFE; SYMPTOMS; ANXIETY AB Background: Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction. Methods and Findings: A total of 291 bereaved respondents were interviewed three times, grouped as 0-6, 6-12, and 12-24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e. g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment. Conclusions: The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11. C1 [Prigerson, Holly G.; Block, Susan D.; Maciejewski, Paul K.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Prigerson, Holly G.; Block, Susan D.; Maciejewski, Paul K.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Prigerson, Holly G.; Block, Susan D.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Horowitz, Mardi J.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Jacobs, Selby C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Parkes, Colin M.] St Christophers Hosp, Sydenham, England. [Parkes, Colin M.] St Josephs Hosp, Hackney, England. [Aslan, Mihaela] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Goodkin, Karl] Cedars Sinai Med Ctr, Dept Psychiat & Behav Neurosci, Los Angeles, CA 90048 USA. [Goodkin, Karl] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Raphael, Beverley] Univ Western Sydney, Sch Med, Dept Populat Mental Hlth & Disasters, Penrith, NSW 1797, Australia. [Marwit, Samuel J.] Univ Missouri, Dept Psychol, St Louis, MO 63121 USA. [Wortman, Camille] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Neimeyer, Robert A.] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Bonanno, George A.] Columbia Univ, Teachers Coll, Dept Counseling & Clin Psychol, New York, NY 10027 USA. [Kissane, David] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Boelen, Paul] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. [Maercker, Andreas] Univ Zurich, Dept Clin Psychol, Zurich, Switzerland. [Litz, Brett T.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Litz, Brett T.] Natl Ctr PTSD, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Johnson, Jeffrey G.; First, Michael B.] Columbia Univ, Dept Psychiat, New York, NY USA. RP Prigerson, HG (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. EM Holly_Prigerson@dfci.harvard.edu FU National Institute of Mental Health [MH56529, MH63892]; National Cancer Institute [CA106370]; NIH [NS044316] FX HGP was supported by National Institute of Mental Health grants MH56529 and MH63892, and National Cancer Institute grant CA106370. PKM was supported by NIH grant NS044316. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 73 TC 325 Z9 339 U1 13 U2 54 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD AUG PY 2009 VL 6 IS 8 AR e1000121 DI 10.1371/journal.pmed.1000121 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 486VX UT WOS:000269229800016 PM 19652695 ER PT J AU Punjabi, NM Caffo, BS Goodwin, JL Gottlieb, DJ Newman, AB O'Connor, GT Rapoport, DM Redline, S Resnick, HE Robbins, JA Shahar, E Unruh, ML Samet, JM AF Punjabi, Naresh M. Caffo, Brian S. Goodwin, James L. Gottlieb, Daniel J. Newman, Anne B. O'Connor, George T. Rapoport, David M. Redline, Susan Resnick, Helaine E. Robbins, John A. Shahar, Eyal Unruh, Mark L. Samet, Jonathan M. TI Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study SO PLOS MEDICINE LA English DT Article ID POSITIVE AIRWAY PRESSURE; CORONARY-ARTERY-DISEASE; ALL-CAUSE MORTALITY; BLOOD-PRESSURE; HEART HEALTH; APNOEA/HYPOPNOEA SYNDROME; RESPIRATORY DISTURBANCE; CARDIOVASCULAR-DISEASE; APNEA-HYPOPNEA; RISK-FACTOR AB Background: Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older. Methods and Findings: We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea-hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0-14.9 events/h), moderate (AHI: 15.0-29.9 events/h), and severe (AHI: >= 30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80-1.08), 1.17 (95% CI: 0.97-1.42), and 1.46 (95% CI: 1.14-1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40-70 y (hazard ratio: 2.09; 95% CI: 1.31-3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease-related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality. Conclusions: Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40-70 y with severe sleep-disordered breathing. C1 [Punjabi, Naresh M.; Caffo, Brian S.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Goodwin, James L.; Shahar, Eyal] Univ Arizona, Tucson, AZ USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Newman, Anne B.; Unruh, Mark L.] Univ Pittsburgh, Pittsburgh, PA USA. [O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rapoport, David M.] NYU, Sch Med, New York, NY USA. [Redline, Susan] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Resnick, Helaine E.] Amer Assoc Homes & Serv Aging, Washington, DC USA. [Robbins, John A.] Univ Calif Davis, Davis, CA 95616 USA. [Samet, Jonathan M.] Univ So Calif, Los Angeles, CA USA. RP Punjabi, NM (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. EM npunjabi@jhmi.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; O'Connor, George/0000-0002-6476-3926; Rapoport, David/0000-0002-4855-2600 FU National Heart, Lung, and Blood Institute [U01-HL53940] FX Supported by the National Heart, Lung, and Blood Institute through the following cooperative agreements: U01-HL53940 (University of Washington), U01-HL53941 (Boston University), U01-HL63463 (Case Western Reserve University), U01-HL53937 (Johns Hopkins University), U01-HL53938 (University of Arizona), U01-HL53916 (University of California, Davis), U01-HL53934 (University of Minnesota), U01-HL63429 (Missouri Breaks Research), and U01-HL53931 (New York University). The funding institutions had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 456 Z9 471 U1 2 U2 26 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD AUG PY 2009 VL 6 IS 8 AR e1000132 DI 10.1371/journal.pmed.1000132 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 486VX UT WOS:000269229800012 PM 19688045 ER PT J AU Barth, JT Camiolo-Reddy, C Zafonte, R AF Barth, Jeffrey T. Camiolo-Reddy, Cara Zafonte, Ross TI Sports Concussion in an Adolescent SO PM&R LA English DT Editorial Material C1 [Barth, Jeffrey T.] Univ Virginia, Sch Med, Brain Injury & Sports Concuss Inst, Charlottesville, VA 22908 USA. [Camiolo-Reddy, Cara] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Zafonte, Ross] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Zafonte, Ross] Harvard Univ, Boston, MA 02115 USA. RP Barth, JT (reprint author), Univ Virginia, Sch Med, Brain Injury & Sports Concuss Inst, Charlottesville, VA 22908 USA. EM rzafonte@partners.org NR 22 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD AUG PY 2009 VL 1 IS 8 BP 769 EP 773 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LL UT WOS:000208411800012 PM 19695530 ER PT J AU Howard, G Cushman, M Prineas, RJ Howard, VJ Moy, CS Sullivan, LM D'Agostino, RB McClure, LA Pulley, L Safford, MM AF Howard, George Cushman, Mary Prineas, Ronald J. Howard, Virginia J. Moy, Claudia S. Sullivan, Lisa M. D'Agostino, Ralph B., Sr. McClure, Leslie A. Pulley, LeaVonne Safford, Monika M. TI Advancing the hypothesis that geographic variations in risk factors contribute relatively little to observed geographic variations in heart disease and stroke mortality SO PREVENTIVE MEDICINE LA English DT Article DE Stroke; Coronary heart disease; Geography; Risk factors; Mortality ID SOUTHEASTERN UNITED-STATES; HYPERTENSION; PREDICTION; PROFILE; BELT AB Purpose. Geographic variation in risk factors may underlie geographic disparities in coronary heart disease (CHD) and stroke mortality. Methods. Framingham CHD Risk Score (FCRS) and Stroke Risk Score (FSRS) were calculated for 25,770 stroke-free and 22,247 CHD-free participants from the REasons for Geographic And Racial Differences in Stroke cohort. Vital statistics provided age-adjusted CHD and stroke mortality rates. In an ecologic analysis, the age-adjusted, race-sex weighted, average state-level risk factor levels were compared to state-level mortality rates. Results. There was no relationship between CHD and stroke mortality rates (r=0.04; p=0.78), but there was between CHD and stroke risk scores at the individual (r=0.68: p<0.0001) and state (r=0.64, p<0.0001) level. There was a stronger (p<0.0001) association between state-level FCRS and state-level CHD mortality (r=0.28, p=0.18), than between FSRS and stroke mortality (r=0.12, p=0.56). Conclusions. weak associations between CHD and stroke mortality and strong associations between CHD and stroke risk scores suggest that geographic variation in risk factors may not underlie geographic variations in stroke and CHID mortality. The relationship between risk factor scores and mortality was stronger for CHID than stroke. (C) 2009 Elsevier Inc. All rights reserved. C1 [Howard, George; McClure, Leslie A.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Cushman, Mary] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Prineas, Ronald J.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Howard, Virginia J.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Moy, Claudia S.; D'Agostino, Ralph B., Sr.] NINDS, NIH, Bethesda, MD 20892 USA. [Sullivan, Lisa M.] Dept Biostat & Framingham Study, Boston, MA USA. [Pulley, LeaVonne] Univ Arkansas Hlth Sci Univ, Dept Hlth Behav, Little Rock, AR USA. [Safford, Monika M.] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Safford, Monika M.] Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. RP Howard, G (reprint author), Univ Alabama, Sch Publ Hlth, Dept Biostat, 1665 Univ Blvd, Birmingham, AL 35294 USA. EM ghoward@uab.edu RI McClure, Leslie/P-2929-2015; OI Sullivan, Lisa/0000-0003-0726-7149 FU National Institute of Neurological Disorders and Stroke [NS 041588] FX The research reported in this article was supported by cooperative agreement NS 041588 from the National Institute of Neurological Disorders and Stroke. NR 17 TC 22 Z9 23 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD AUG-SEP PY 2009 VL 49 IS 2-3 BP 129 EP 132 DI 10.1016/j.ypmed.2009.03.004 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 503TF UT WOS:000270562200011 PM 19285103 ER PT J AU Magruder, KM Yeager, DE AF Magruder, Kathryn M. Yeager, Derik E. TI The Prevalence of PTSD across War Eras and the Effect of Deployment on PTSD: a Systematic Review and Meta-analysis SO PSYCHIATRIC ANNALS LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; PERSIAN-GULF-WAR; SELF-REPORTED SYMPTOMS; HEALTH-STATUS; VIETNAM VETERANS; PHYSICAL HEALTH; PRISONERS; ILLNESS; EPIDEMIOLOGY; RESERVISTS C1 [Magruder, Kathryn M.; Yeager, Derik E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Magruder, Kathryn M.; Yeager, Derik E.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. RP Magruder, KM (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. EM magrudkm@musc.edu NR 31 TC 25 Z9 25 U1 5 U2 12 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2009 VL 39 IS 8 BP 778 EP 788 DI 10.3928/00485713-20090728-04 PG 11 WC Psychiatry SC Psychiatry GA 483EP UT WOS:000268945500003 ER PT J AU Nash, WP Silva, C Litz, B AF Nash, William P. Silva, Caroline Litz, Brett TI The Historic Origins of Military and Veteran Mental Health Stigma and the Stress Injury Model as a Means to Reduce It SO PSYCHIATRIC ANNALS LA English DT Article ID METAANALYSIS; DISORDER; CORTEX; CARE C1 [Nash, William P.] Def Ctr Excellence Psychol Hlth, Arlington, VA USA. [Silva, Caroline] Boston Vet Healthcare Syst, Boston, MA USA. [Litz, Brett] Natl Ctr PTSD, Boston, MA USA. [Nash, William P.] Def Cter Traumat Brain Injury, Arlington, VA USA. RP Nash, WP (reprint author), 9259 Old Keene Mill Rd,Suite 100, Burke, VA 22015 USA. EM william.nash@cox.net OI Silva, Caroline/0000-0002-7477-1495 NR 33 TC 22 Z9 22 U1 0 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2009 VL 39 IS 8 BP 789 EP 794 DI 10.3928/00485713-20090728-05 PG 6 WC Psychiatry SC Psychiatry GA 483EP UT WOS:000268945500004 ER PT J AU Vine, AE McQuillin, A Bass, NJ Pereira, A Kandaswamy, R Robinson, M Lawrence, J Anjorin, A Sklar, P Gurling, HMD Curtis, D AF Vine, Anna E. McQuillin, Andrew Bass, Nicholas J. Pereira, Ana Kandaswamy, Radhika Robinson, Michele Lawrence, Jacob Anjorin, Adebayo Sklar, Pamela Gurling, Hugh M. D. Curtis, David TI No evidence for excess runs of homozygosity in bipolar disorder SO PSYCHIATRIC GENETICS LA English DT Article DE bipolar; homozygosity; deletion ID EXTENDED HOMOZYGOSITY; HUMAN-POPULATIONS; SCHIZOPHRENIA; ASSOCIATION AB Background Recent studies have reported large common regions of homozygosity (ROHs) that are the result of autozygosity, that is, the cooccurrence within individuals of long haplotypes that have a high frequency in the population. A recent study reports that such are found more commonly in individuals with schizophrenia compared with controls, and identified nine 'risk ROHs' that were individually more common in cases. Of these, four contained or neighboured genes associated with schizophrenia (NOS1AP/UHMK1, ATF2, NSF and PIK3C3). Methods We have applied the same methodology to a UK sample of 506 cases with bipolar disorder and 510 controls. Results There was no overall excess of common ROHs among bipolar individuals. With one exception, the haplotypes accounting for the ROHs appeared to be distributed according to the Hardy-Weinberg equilibrium. One ROH was individually more common among cases (uncorrected P=0.0003). This ROH spanned the chromosome 2p23.3 gene ITSN2 (the gene for 2 isoform 2). However, inspection of the homozygous haplotypes and haplotype-based tests for association failed to provide a clearer understanding of why this ROH was occurring more commonly. Conclusion Overall, we conclude that, in contrast with schizophrenia, common ROHs are rarely associated with susceptibility to bipolar disorder. This supports the idea that predominantly different genes are increasing susceptibility to schizophrenia and bipolar affective disorders. Psychiatr Genet 19:165-170 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Vine, Anna E.; Gurling, Hugh M. D.; Curtis, David] UCL, Windeyer Inst Med Sci, Dept Mental Hlth Sci, Barts & London Sch Med & Dent,Ctr Psychiat, London, England. [McQuillin, Andrew; Bass, Nicholas J.; Pereira, Ana; Kandaswamy, Radhika; Robinson, Michele; Lawrence, Jacob; Anjorin, Adebayo; Gurling, Hugh M. D.; Curtis, David] UCL, Windeyer Inst Med Sci, Dept Mental Hlth Sci, Mol Psychiat Lab, London, England. [Sklar, Pamela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Sklar, Pamela] Harvard Univ, Ctr Human Genet Res, Sch Med, Boston, MA USA. [Sklar, Pamela] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Sklar, Pamela] Harvard Univ, Sch Med, Dept Psychiat Med, Boston, MA USA. [Sklar, Pamela] Harvard & MIT, Broad Inst, Cambridge, MA USA. RP Curtis, D (reprint author), Royal London Hosp, Barts & London Sch Med & Dent, London E1 1BB, England. EM david.curtis@qmul.ac.uk RI Gurling, Hugh/A-5029-2010; McQuillin, Andrew/C-1623-2008 OI McQuillin, Andrew/0000-0003-1567-2240 FU Broad Institute [076392] FX Genotyping for the GWA study was carried out at the Broad Institute. A.E.V is supported by the Wellcome Trust Project Grant 076392. NR 11 TC 20 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD AUG PY 2009 VL 19 IS 4 BP 165 EP 170 DI 10.1097/YPG.0b013e32832a4faa PG 6 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 470GP UT WOS:000267963500001 PM 19451863 ER PT J AU Milner, KK Healy, D Barry, KL Blow, FC Irmiter, C De Chavez, P AF Milner, Karen K. Healy, Daniel Barry, Kristen L. Blow, Frederic C. Irmiter, Cheryl De Chavez, Peter TI Implementation of Computerized Medication Prescribing Algorithms in a Community Mental Health System SO PSYCHIATRIC SERVICES LA English DT Editorial Material ID PHASE-3 TMAP-3; PROJECT; RATIONALE; DISORDER; DESIGN AB This column describes a Michigan initiative to implement medication prescribing algorithms for schizophrenia, bipolar disorder, and major depression. The algorithms were incorporated into the electronic medical records system of a four-county community mental health system. Guideline adherence of 30 providers who treated nearly 3,000 patients was measured at mid- and endpoints of the first year. They were adherent for about a third of their patients in the first six months (32%) and more than half in the second (52%). Scores on scales measuring providers' perceptions of algorithm ease of use and usefulness were in the midrange at both time points. (Psychiatric Services 60: 1010-1012, 2009) C1 [Milner, Karen K.; Healy, Daniel; Barry, Kristen L.; Blow, Frederic C.; Irmiter, Cheryl; De Chavez, Peter] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Milner, Karen K.; Healy, Daniel] Washtenaw Community Hlth Org, Ypsilanti, MI USA. [Barry, Kristen L.; Blow, Frederic C.] US Dept Vet Affairs, Serious Mental Illness Treatment Res & Evaluat Ct, Ann Arbor, MI USA. [Irmiter, Cheryl] Amer Med Assoc, Chicago, IL 60610 USA. RP Milner, KK (reprint author), Univ Michigan, Dept Psychiat, Rachel Upjohn Bldg,4250 Plymouth Rd,SPC 5740, Ann Arbor, MI 48109 USA. EM kmilner@med.umich.edu NR 10 TC 3 Z9 3 U1 1 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 AUG 1 PY 2009 VL 60 IS 8 BP 1010 EP 1012 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 477RU UT WOS:000268537000002 PM 19648185 ER PT J AU Muriel, AC Hwang, VS Kornblith, A Greer, J Greenberg, DB Temel, J Schapira, L Pirl, W AF Muriel, Anna C. Hwang, Vivian S. Kornblith, Alice Greer, Joseph Greenberg, Donna B. Temel, Jennifer Schapira, Lidia Pirl, William TI Management of Psychosocial Distress by Oncologists SO PSYCHIATRIC SERVICES LA English DT Article ID HEALTH-CARE AB Objective: Little is known about the nature of psychosocial care delivered by oncologists. The goal of this study was to survey oncologists about their management of psychosocial distress, referencing the National Comprehensive Cancer Network guidelines. Methods: A random sample of 1,000 oncologists were sent an e-mail requesting their participation in an online survey; nonrespondents were sent the survey through postal mail. Regression analyses were conducted to identify independent predictors of care. Results: Forty-six percent (448 of 965) of oncologists responded. Practice locations included: community (63%), cancer center (25%), and hospital (7%). Respondents estimated that over one-third of their patients (mean+/-SD=38%+/-22%) experience psychosocial distress warranting intervention, although only 225 of 447 (50%) indicated having mental health services affiliated with their practice. Nearly half (212 of 447, 47%) reported only initiating a referral for psychosocial services, and 214 of 447 (48%) reported both making a referral and starting psychiatric medications, mainly selective serotonin reuptake inhibitors and benzodiazepines. Conclusions: Most oncologists delivered some level of psychosocial care, although only half had affiliated mental health services. (Psychiatric Services 60: 1132-1134, 2009) C1 [Muriel, Anna C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Kornblith, Alice] Dana Farber Canc Inst, Dept Psychooncol Res, Boston, MA 02115 USA. [Hwang, Vivian S.; Greer, Joseph; Greenberg, Donna B.; Pirl, William] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Temel, Jennifer; Schapira, Lidia] Massachusetts Gen Hosp, Hematol & Oncol Unit, Boston, MA 02114 USA. RP Muriel, AC (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 44 Binney St, Boston, MA 02115 USA. EM amuriel@partners.org FU National Cancer Institute [R03 CA113104, K23 CA115908] FX This research was supported by grants R03 CA113104 and K23 CA115908 from the National Cancer Institute. NR 10 TC 24 Z9 24 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD AUG 1 PY 2009 VL 60 IS 8 BP 1132 EP 1134 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 477RU UT WOS:000268537000021 PM 19648204 ER PT J AU Doyle, AE Wozniak, J Wilens, TE Henin, A Seidman, LJ Petty, C Fried, R Gross, LM Faraone, SV Biederman, J AF Doyle, A. E. Wozniak, J. Wilens, T. E. Henin, A. Seidman, L. J. Petty, C. Fried, R. Gross, L. M. Faraone, S. V. Biederman, J. TI Neurocognitive impairment in unaffected siblings of youth with bipolar disorder SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Endophenotype; executive functions; pediatric bipolar disorder ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; 1ST-DEGREE RELATIVES; EXECUTIVE FUNCTIONS; NEUROPSYCHOLOGICAL PERFORMANCE; ENDOPHENOTYPE CONCEPT; I DISORDER; ADHD; CHILDREN; ONSET; ADOLESCENTS AB Background. There is growing evidence for the familiality of pediatric bipolar disorder (BPD) and its association with impairments on measures of processing speed, verbal learning and 'executive' functions. The current study investigated whether these neurocognitive impairments index the familial risk underlying the diagnosis. Method. Subjects were 170 youth with BPD (mean age 12.3 years), their 118 non-mood-disordered siblings and 79 non-mood-disordered controls. Groups were compared on a battery of neuropsychological tests from the Wechsler Intelligence Scales, the Stroop Color Word Test, the Wisconsin Card Sorting Test (WCST), the Rey-Osterrieth Complex Figure (ROCF), an auditory working memory Continuous Performance Test (CPT) and the California Verbal Learning Test-Children's Version (CVLT-C). Measures were factor analyzed for data reduction purposes. All analyses controlled for age, sex and attention-deficit/hyperactivity disorder (ADHD). Results. Principal components analyses with a promax rotation yielded three factors reflecting: (1) processing speed/verbal learning, (2) working memory/interference control and (3) abstract problem solving. The CPT working memory measure with interference filtering demands (WM INT) was only administered to subjects aged >= 12 years and was therefore analyzed separately. BPD youth showed impairments versus controls and unaffected relatives on all three factors and on the WM INT. Unaffected relatives exhibited impairments versus controls on the abstract problem-solving factor and the WM INT. They also showed a statistical trend (p=0.07) towards worse performance on the working memory/interference control factor. Conclusions. Neurocognitive impairments in executive functions may reflect the familial neurobiological risk mechanisms underlying pediatric BPD and may have utility as endophenotypes in molecular genetic studies of the condition. C1 [Doyle, A. E.] Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Doyle, AE (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, YAW 6-6A,55 Fruit St, Boston, MA 02114 USA. EM doylea@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH [K08-MH66072, K08-MH01503]; NIH [R01 DA12945, K24 DA016264]; Neal/Kimmerly Fund for the Study of Cognition in Psychiatric Illness at the Massachusetts General Hospital FX This work was supported in part by a Harvard Medical School 50th Anniversary Scholars Fellowship in Honor of Joseph B. Martin M.D. Ph.D. and NIMH K08-MH66072 to Dr Doyle, K08-MH01503 to Dr Wozniak, and NIH R01 DA12945 and K24 DA016264 to Dr Wilens. Support also came in part from the Neal/Kimmerly Fund for the Study of Cognition in Psychiatric Illness at the Massachusetts General Hospital. NR 64 TC 27 Z9 27 U1 1 U2 10 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 AUG PY 2009 VL 39 IS 8 BP 1253 EP 1263 DI 10.1017/S0033291708004832 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 472XC UT WOS:000268165300004 PM 19079809 ER PT J AU Antshel, KM Faraone, SV Maglione, K Doyle, A Fried, R Seidman, L Biederman, J AF Antshel, K. M. Faraone, S. V. Maglione, K. Doyle, A. Fried, R. Seidman, L. Biederman, J. TI Is adult attention deficit hyperactivity disorder a valid diagnosis in the presence of high IQ? SO PSYCHOLOGICAL MEDICINE LA English DT Article DE ADHD; impairment; intelligent; IQ ID QUALITY-OF-LIFE; OBSESSIVE-COMPULSIVE DISORDER; MGH LONGITUDINAL FAMILY; AGE-DEPENDENT DECLINE; DEFICIT/HYPERACTIVITY DISORDER; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; PRESCRIPTION STIMULANTS; PSYCHIATRIC COMORBIDITY; MEMORY CAPACITY AB Background. Because the diagnosis of attention deficit hyperactivity disorder (ADHD) in higher education settings is rapidly becoming a contentious issue, particularly among patients with high IQs, we sought to assess the validity of diagnosing ADHD in high-IQ adults and to further characterize the clinical features associated with their ADHD. Method. We operationalized high IQ as having a full-scale IQ >= 120. We identified 53 adults with a high IQ who did not have ADHD and 64 adults with a high IQ who met diagnostic criteria for ADHD. Groups did not differ on IQ, socio-economic status or gender. Results. High-IQ adults with ADHD reported a lower quality of life, had poorer familial and occupational functioning, and had more functional impairments, including more speeding tickets, accidents and arrests. Major depressive disorder, obsessive-compulsive disorder and generalized anxiety disorder diagnoses were higher in high-IQ adults with ADHD. All other psychiatric co-morbidities, including antisocial personality disorder and substance abuse, did not differ between the two high-IQ groups. ADHD was more prevalent in first-degree relatives of adults with ADHD relative to controls. Conclusions. Our data suggest that adults with ADHD and a high IQ display patterns of functional impairments, familiality and psychiatric co-morbiditles that parallel those found in the average-IQ adult ADHD population. C1 [Antshel, K. M.; Faraone, S. V.; Maglione, K.] Upstate Med Univ, SUNY, Dept Psychiat & Behav Sci, Syracuse, NY USA. [Doyle, A.; Fried, R.; Seidman, L.; Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Doyle, A.; Fried, R.; Seidman, L.; Biederman, J.] Harvard Univ, Sch Med, Boston, MA USA. RP Faraone, SV (reprint author), Upstate Med Univ, SUNY, Dept Psychiat & Behav Sci, Syracuse, NY USA. EM FaraoneS@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 69 TC 27 Z9 27 U1 1 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 AUG PY 2009 VL 39 IS 8 BP 1325 EP 1335 DI 10.1017/S0033291708004959 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 472XC UT WOS:000268165300011 PM 19105857 ER PT J AU Quintiliani, LM Stoddard, AM Ebbeling, CB Pereira, LK Sorensen, G AF Quintiliani, L. M. Stoddard, A. M. Ebbeling, C. B. Pereira, L. K. Sorensen, G. TI Associations of diet behaviours and intention to eat healthily with tobacco use among motor freight workers SO PUBLIC HEALTH LA English DT Article ID PHYSICAL-ACTIVITY; SMOKING STATUS C1 [Quintiliani, L. M.; Pereira, L. K.; Sorensen, G.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Soc Human Dev & Hlth,Ctr Community Based Res, Boston, MA 02115 USA. [Stoddard, A. M.] New England Res Inst, Ctr Stat Anal & Res, Watertown, MA 02172 USA. [Ebbeling, C. B.] Childrens Hosp, Div Endocrinol, Dept Pediat, Boston, MA 02115 USA. [Ebbeling, C. B.] Harvard Univ, Sch Med, Boston, MA USA. RP Quintiliani, LM (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Soc Human Dev & Hlth,Ctr Community Based Res, 44 Binney St,LW 703, Boston, MA 02115 USA. EM lisa_quintiliani@dfci.harvard.edu OI Quintiliani, Lisa/0000-0002-3328-6768 FU Centers for Disease Control and Prevention [5R01DP000099-03] FX Centers for Disease Control and Prevention (Grant Number: 5R01DP000099-03). NR 10 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0033-3506 J9 PUBLIC HEALTH JI Public Health PD AUG PY 2009 VL 123 IS 8 BP 565 EP 567 DI 10.1016/j.puhe.2009.06.017 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 504RJ UT WOS:000270634600008 PM 19646722 ER PT J AU Abujudeh, HH Kaewlai, R AF Abujudeh, Hani H. Kaewlai, Rathachai TI Radiology Failure Mode and Effect Analysis: What Is It? SO RADIOLOGY LA English DT Article ID HOSPITALIZED-PATIENTS; MEDICAL INJURIES; ADVERSE EVENTS; RISK ANALYSIS; SAFETY AB Proactive prevention of medical errors is critical in medical practice. Root cause analysis (RCA) is a conventional method used to deal with errors that result in an adverse event. However, RCA has several limitations. An analytic method for health care risk management, health care failure mode and effect analysis (FMEA), has been introduced relatively recently. Health care FMEA combines several existing analytic approaches into one simple tool with which to analyze a particular health care process, determine the risks associated with it, and develop corrective actions and outcome measures. The authors provide a brief history of health care FMEA, describe its validation process, and relate their experience with its use in a radiology department. (c) RSNA, 2009 C1 [Abujudeh, Hani H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND-213, Boston, MA 02114 USA. EM habujudeh@partners.org FU Bracco Diagnostics, Princeton, NJ FX From the Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, FND- 213, Boston, MA 02114. From the 2006 RSNA Annual Meeting. Received November 10, 2008; revision requested December 12; final revision received December 23; accepted January 26, 2009; final version accepted February 25. H. H. A. supported by Bracco Diagnostics, Princeton, NJ. Address correspondence to H. H. A. (e-mail: habujudeh@partners.org). NR 23 TC 14 Z9 15 U1 1 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2009 VL 252 IS 2 BP 544 EP 550 DI 10.1148/radiol.2522081954 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 482HQ UT WOS:000268875900030 PM 19703888 ER PT J AU Mori, S Hara, R Yanagi, T Sharp, GC Kumagai, M Asakura, H Kishimoto, R Yamada, S Kandatsu, S Kamada, T AF Mori, Shinichiro Hara, Ryusuke Yanagi, Takeshi Sharp, Gregory C. Kumagai, Motoki Asakura, Hiroshi Kishimoto, Riwa Yamada, Shigeru Kandatsu, Susumu Kamada, Tadashi TI Four-dimensional measurement of intrafractional respiratory motion of pancreatic tumors using a 256 multi-slice CT scanner SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Carbon beam; CT; Four-dimensional; Pancreas; Radiation therapy ID HEAVY-ION RADIOTHERAPY; CELL LUNG-CANCER; PERFORMANCE EVALUATION; DOSE-ESCALATION; THERAPY; RADIATION; IRRADIATION; MOVEMENT; SYSTEM; LIVER AB Purpose: To quantify pancreas and pancreatic tumor movement due to respiratory motion using volumetric cine CT images. Materials and methods: Six patients with pancreatic tumors were scanned in cine mode with a 256 multi-slice CT scanner under free breathing conditions. Gross tumor volume (GTV) and pancreas were manually contoured on the CT data set by a radiation oncologist. Intrafractional respiratory movement of the GTV and pancreas was calculated, and the results were compared between the respiratory ungated and gated phases, which is a 30% duty cycle around exhalation. Results: Respiratory-induced organ motion was observed mainly in the anterior abdominal side than the posterior side. Average GTV displacement (ungated/gated phases) was 0.7 mm/0.2 mm in both the left and right directions, and 2.5 mm/0.9 mm in the anterior, 0.1 mm/0 mm in the posterior, and 8.9 mm/2.6 mm in the inferior directions. Average pancreas center of mass displacement relative to that at peak exhalation was mainly in the inferior direction, at 9.6 mm in the ungated phase and 2.3 mm in the gated phase. Conclusions: By allowing accurate determination of the margin, quantitative analysis of tumor and pancreas displacement provides useful information in treatment planning in all radiation approaches for pancreatic tumors. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 92 (2009) 231-237 C1 [Mori, Shinichiro] Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 2638555, Japan. [Sharp, Gregory C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Asakura, Hiroshi] Accelerator Engn Corp, Chiba, Japan. RP Mori, S (reprint author), Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 2638555, Japan. EM shinshin@nirs.go.jp OI Mori, Shinichiro/0000-0002-0412-4399 NR 26 TC 43 Z9 44 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD AUG PY 2009 VL 92 IS 2 BP 231 EP 237 DI 10.1016/j.radonc.2008.12.015 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 484YZ UT WOS:000269088400012 PM 19211167 ER PT J AU Uomoto, JM Williams, RM AF Uomoto, Jay M. Williams, Rhonda M. TI Post-Acute Polytrauma Rehabilitation and Integrated Care of Returning Veterans: Toward a Holistic Approach SO REHABILITATION PSYCHOLOGY LA English DT Article DE Operation Enduring Freedom; Operation Iraqi Freedom; war; rehabilitation; brain injuries; stress disorders ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; OPERATION IRAQI FREEDOM; MENTAL-HEALTH PROBLEMS; MEDICALLY UNEXPLAINED SYMPTOMS; RANDOMIZED CONTROLLED-TRIAL; OF-THE-LITERATURE; PEER SUPPORT; VIETNAM VETERANS; SHELL-SHOCK AB Throughout the history of war, exposure to combat has been associated with clusters of physical and psychological symptoms labeled in various ways, from "hysteria" to "shell shock" in World War I to "polytrauma" in Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF). Objective: To describe the historical conceptualizations of combat injury and the ways they are relevant to developing current rehabilitation strategies, discuss the symptom complex presented by OEF/OIF veterans, and describe key elements and principles of holistic, integrated care for post-acute OEF/OIF veterans. Conclusions: A conceptualization of rehabilitation recognizing a final common pathway of functional disability and suffering is proposed, and both systematic and treatment-specific aspects at the core of a veteran-centered holistic approach are discussed. C1 [Uomoto, Jay M.] VA Puget Sound Hlth Care Syst, VISN VHA Polytrauma Network Site 20, Ctr Polytrauma Care, Rehabil Care Serv, Seattle, WA USA. [Williams, Rhonda M.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. RP Uomoto, JM (reprint author), VA Puget Sound Hlth Care Syst, VISN VHA Polytrauma Network Site 20, Ctr Polytrauma Care, Rehabil Care Serv, Seattle, WA USA. EM jay.uomoto@va.gov NR 84 TC 12 Z9 12 U1 2 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD AUG PY 2009 VL 54 IS 3 BP 259 EP 269 DI 10.1037/a0016907 PG 11 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 488SW UT WOS:000269371100003 PM 19702424 ER PT J AU Dausch, BM Saliman, S AF Dausch, Barbara M. Saliman, Sheila TI Use of Family Focused Therapy in Rehabilitation for Veterans With Traumatic Brain Injury SO REHABILITATION PSYCHOLOGY LA English DT Article DE family therapy; TBI; rehabilitation; veterans; Iraq ID RANDOMIZED CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; SPINAL-CORD INJURIES; BIPOLAR DISORDER; EXPRESSED EMOTION; COMBAT DEPLOYMENT; IRAQ WAR; INTERVENTION; CAREGIVERS AB Objective: Military personnel returning from Iraq and Afghanistan with traumatic brain injury (TBI) present with a complex array of stressors encountered during combat as well as upon re-entry, often with additional physical and mental health comorbidities. This requires an intensive approach to treatment that includes family intervention as a part of rehabilitation. There is a small but growing literature addressing the needs of families when a family member has sustained a TBI. An established treatment intervention for individuals with serious mental illness, such as family focused therapy (FFT), is uniquely suited to address the complexity of issues presented by returning military personnel, and may be adapted for moderate to severe TBI populations. In this article, we discuss the rationale for adapting this family intervention for this population and present a case vignette illustrating adaptations for TBI. Conclusions: The adaptation of an existing family intervention for a chronic condition that focuses on enhancing both individual and family functioning is a useful starting point. With further research to modify FFT for this unique population and establish feasibility, this approach may supplement existing models of family intervention. C1 [Dausch, Barbara M.; Saliman, Sheila] Denver Vet Affairs Med Ctr, Eastern Colorado Hlth Care Syst, Denver, CO 80220 USA. [Dausch, Barbara M.] Univ Colorado, Sch Med, Boulder, CO 80309 USA. RP Dausch, BM (reprint author), Denver Vet Affairs Med Ctr, Eastern Colorado Hlth Care Syst, 1055 Clermont St,116 Denver, Denver, CO 80220 USA. EM Barbara.Dausch@va.gov NR 54 TC 16 Z9 17 U1 6 U2 12 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD AUG PY 2009 VL 54 IS 3 BP 279 EP 287 DI 10.1037/a0016809 PG 9 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 488SW UT WOS:000269371100005 PM 19702426 ER PT J AU Dougherty, CM Thompson, EA AF Dougherty, Cynthia M. Thompson, Elaine A. TI Intimate Partner Physical and Mental Health After Sudden Cardiac Arrest and Receipt of an Implantable Cardioverter Defibrillator SO RESEARCH IN NURSING & HEALTH LA English DT Article DE sudden cardiac death; ICD; partner; psychological; physical health; description ID MYOCARDIAL-INFARCTION; SPOUSAL CAREGIVERS; ADJUSTMENT; QUALITY; PATIENT; ANXIETY; SUPPORT; FAMILY; IMPACT; TRIAL AB The purpose of this study was to describe the physical and mental health of the intimate Partners of persons receiving an implantable cardioverter defibrillator (ICD). A prospective longitudinal repeated measures design was used, with data collected at hospital discharge, and at 1, 3, 6, and 12 months after implantation. Intimate Partners' Physical health, symptoms, and depression significantly declined over the first year. Although anxiety was significantly reduced over time, it remained elevated in Partners after 1 year. The impact of implantation of the ICD on the intimate relationship and care demands was most dramatic at hospital discharge. Health care use was low throughout the year. Intimate partners could benefit from an intervention that would assist in their psychological adjustment and provide strategies for dealing with caregiving demands at home. (C) 2009 Wiley Periodicals, Inc. Res Nurs Health 32:432-442, 2009 C1 [Dougherty, Cynthia M.; Thompson, Elaine A.] Univ Washington, Sch Nursing, Psychosocial & Community Hlth, Seattle, WA 98195 USA. [Dougherty, Cynthia M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Dougherty, CM (reprint author), Univ Washington, Sch Nursing, Psychosocial & Community Hlth, Box 357266, Seattle, WA 98195 USA. FU National Institutes of Health; National Institute for Nursing Research [R03 NR008942] FX Contract grant sponsor: National Institutes of Health, National Institute for Nursing Research; Contract grant number: R03 NR008942. NR 40 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD AUG PY 2009 VL 32 IS 4 BP 432 EP 442 DI 10.1002/nur.20330 PG 11 WC Nursing SC Nursing GA 472RQ UT WOS:000268150100007 PM 19434648 ER PT J AU Leuckfeld, I Olsen, I Geiran, O Bjortuft, O Paster, BJ AF Leuckfeld, I. Olsen, I. Geiran, O. Bjortuft, O. Paster, B. J. TI The subgingival microflora in COPD and periodontitis SO RESPIRATORY MEDICINE LA English DT Meeting Abstract C1 [Leuckfeld, I.; Olsen, I.] Univ Oslo, Fac Dent, Inst Oral Biol, N-0316 Oslo, Norway. [Leuckfeld, I.; Bjortuft, O.] Univ Oslo, Rikshosp, Med Ctr, Dept Resp Med, N-0027 Oslo, Norway. [Geiran, O.] Univ Oslo, Rikshosp, Med Ctr, Dept Thorac & Cardiovasc Surg, N-0027 Oslo, Norway. [Paster, B. J.] Forsyth Inst, Dept Mol Genet, Boston, MA USA. [Paster, B. J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. EM inga.leuckfeld@rikshospitalet.no NR 0 TC 0 Z9 0 U1 1 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 AUG PY 2009 VL 103 BP S6 EP S6 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 472QY UT WOS:000268148300014 ER PT J AU Griffin, AMJ Caviedes, L Gilman, R Coronel, J Delgado, F Quispe, M Moore, DAJ AF Griffin, Anne M. J. Caviedes, Luz Gilman, Robert Coronel, Jorge Delgado, Freddy Quispe, MaryLuz Moore, David A. J. TI Field and laboratory preparedness: challenges to rolling out new multidrug-resistant tuberculosis diagnostics SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE Mycobacterium tuberculosis; tuberculosis, multidrug-resistant; health plan implementation; clinical laboratory techniques; Peru ID DRUG-SUSCEPTIBILITY ASSAY; MICROSCOPIC-OBSERVATION; MYCOBACTERIUM-TUBERCULOSIS; TB AB Objectives. In a pilot implementation project of the microscopic-observation drugs-usceptibility methodology, we conducted a process evaluation to identify health system and logistic challenges that need to be addressed in order to harness the benefits of rolling out promising new diagnostic tools for multidrug-resistant tuberculosis (MDRTB). Methods. Regional data relating to health system practices and performance related to the MDRTB diagnostic algorithm were collected at health center, local, and regional laboratories. Results. Parallel implementation of a new test and an existing method creates demands on funds, personnel, sample transport, and information systems in addition to new test startup costs. Obviating the need for primary culture at intermediate laboratories through direct drug susceptibility testing (DST) at the regional reference laboratory significantly reduces delay. Field application of well-defined national guidelines for DST is patchy. If fidelity to national guidelines were perfect, DST requests would increase more than 50-fold, with important implications for laboratory capacity. Conclusions. Implementing a new MDRTB diagnostic presents challenges to the laboratory environment, the existing DST process, and the application of national guidelines in peripheral clinics. Assessing each element can maximize efficient use of a new tool. Specifically, strengthening systems for transferring samples to the laboratory and delivering results to the requesting clinic in addition to investing in personnel and laboratory resources are integral to harnessing the benefits of high-performance new diagnostic tests and can bring added value to other programs in the health care system. C1 [Griffin, Anne M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Griffin, Anne M. J.] Mt Sinai Sch Med, New York, NY 10029 USA. [Caviedes, Luz; Gilman, Robert; Coronel, Jorge; Moore, David A. J.] Univ Peruana Cayetano Heredia, Lab Invest Enfermedades Infecciosas, Lima, Peru. [Gilman, Robert; Moore, David A. J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Gilman, Robert; Moore, David A. J.] Univ London Imperial Coll Sci Technol & Med, Wellcome Ctr Clin Trop Med, Dept Infect Dis & Immun, London, England. [Delgado, Freddy; Quispe, MaryLuz] Hosp Honorio Delgado, Programa TB, Direcc Salud, Arequipa, Peru. RP Griffin, AMJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM amjgriffin@gmail.com NR 12 TC 3 Z9 3 U1 0 U2 2 PU PAN AMER HEALTH ORGANIZATION PI WASHINGTON PA 525 23RD ST NW, WASHINGTON, DC 20037 USA SN 1020-4989 J9 REV PANAM SALUD PUBL JI Rev. Panam. Salud Publica PD AUG PY 2009 VL 26 IS 2 BP 120 EP 127 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 505HR UT WOS:000270683800004 PM 19814891 ER PT J AU Cheng, JW DeCaprio, JA Fluck, MM Schaffhausen, BS AF Cheng, Jingwei DeCaprio, James A. Fluck, Michele M. Schaffhausen, Brian S. TI Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE SV40; Polyoma; T antigen; p53; Retinoblastoma; Src; PI3 kinase; Shc ID RETINOBLASTOMA TUMOR-SUPPRESSOR; PROTEIN PHOSPHATASE 2A; INSULIN-RECEPTOR SUBSTRATE-1; PRB-RELATED PROTEINS; MIDDLE-T; MAMMARY-TUMORS; MEDIATED TRANSFORMATION; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSGENIC MICE; SIMIAN VIRUS-40 AB Simian Virus 40 (SV40) and Mouse Polyoma Virus (PY) are small DNA tumor viruses that have been used extensively to study cellular transformation. The SV40 early region encodes three tumor antigens, large T (LT), small T (ST) and 17KT that contribute to cellular transformation. While PY also encodes LT and ST, the unique middle T (MT) generates most of the transforming activity. SV40 IT mediated transformation requires binding to the tumor suppressor proteins Rb and p53 in the nucleus and ST binding to the protein phosphatase PP2A in the cytoplasm. SV40 IT also binds to several additional cellular proteins including p300, CBP, Cul7, IRS1, Bub1, Nbs1 and Fbxw7 that contribute to viral transformation. PY MT transformation is dependent on binding to PP2A and the Src family protein tyrosine kinases (PTK) and assembly of a signaling complex on cell membranes that leads to transformation in a manner similar to Her2/neu. Phosphorylation of MT tyrosine residues activates key signaling molecules including Shc/Grb2, PI3K and PLC gamma 1. The unique contributions of SV40 LT and ST and PY MT to cellular transformation have provided significant insights into our understanding of tumor suppressors, oncogenes and the process of oncogenesis. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Cheng, Jingwei; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cheng, Jingwei; DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cheng, Jingwei; DeCaprio, James A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [DeCaprio, James A.] Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. [Fluck, Michele M.] Michigan State Univ, Interdept Program Cell & Mol Biol, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Schaffhausen, Brian S.] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu; brian.schaffhausen@tufts.edu FU Public Health Service NIH [PO1-CA50661, RO1-CA34722, RO1-CA63113, RO1-CA93804, R01-CA29270] FX Constraints of space permit discussion of only some issues and citation of just a small fraction of the relevant literature. NR 123 TC 88 Z9 90 U1 1 U2 9 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD AUG PY 2009 VL 19 IS 4 BP 218 EP 228 DI 10.1016/j.semcancer.2009.03.002 PG 11 WC Oncology SC Oncology GA 468RS UT WOS:000267838300003 PM 19505649 ER PT J AU Reichardt, P Hogendoorn, PCW Tamborini, E Loda, M Gronchi, A Poveda, A Schoffski, P AF Reichardt, Peter Hogendoorn, Pancras C. W. Tamborini, Elena Loda, Massimo Gronchi, Alessandro Poveda, Andres Schoffski, Patrick TI Gastrointestinal Stromal Tumors I: Pathology, Pathobiology, Primary Therapy, and Surgical Issues SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Sarcomas and Gastrointestinal Stromal Tumors CY MAY 13-14, 2008 CL Milan, ITALY SP European Soc Med Oncol ID OF-FUNCTION MUTATIONS; BONE-SARCOMA-GROUP; EORTC-SOFT-TISSUE; IMATINIB MESYLATE; TYROSINE-KINASE; PHASE-II; C-KIT; ACQUIRED-RESISTANCE; DIFFERENTIAL-DIAGNOSIS; RESIDUAL DISEASE C1 [Schoffski, Patrick] Catholic Univ Louvain, Univ Hosp Leuven, Dept Gen Med Oncol, B-3000 Louvain, Belgium. [Schoffski, Patrick] Catholic Univ Louvain, Leuven Canc Inst, Expt Oncol Lab, B-3000 Louvain, Belgium. [Poveda, Andres] Inst Valenciano Oncol, Valencia, Spain. [Gronchi, Alessandro] Ist Nazl Tumori, Dept Surg, I-20133 Milan, Italy. [Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tamborini, Elena] Ist Nazl Tumori, IRCCS Fdn, Lab Expt Mol Pathol, I-20133 Milan, Italy. [Hogendoorn, Pancras C. W.] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands. [Reichardt, Peter] HELIOS Klinikum Bad Saarow, Sarcoma Ctr Berlin Brandenburg, Bad Saarow Pieskow, Germany. RP Schoffski, P (reprint author), Catholic Univ Louvain, Univ Hosp Leuven, Dept Gen Med Oncol, Herestr 49, B-3000 Louvain, Belgium. EM patrick.schoffski@uz.kuleuven.ac.be RI Tamborini, Elena/C-3307-2017; Hogendoorn, Pancras/H-5859-2015; OI Tamborini, Elena/0000-0002-3819-8687; Hogendoorn, Pancras/0000-0002-1513-8104; Gronchi, Alessandro/0000-0002-4703-3534 NR 55 TC 17 Z9 17 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2009 VL 36 IS 4 BP 290 EP 301 DI 10.1053/j.seminoncol.2009.06.002 PG 12 WC Oncology SC Oncology GA 482OW UT WOS:000268899600002 PM 19664490 ER PT J AU Benjamin, RS Debiec-Rychter, M Le Cesne, A Sleijfer, S Demetri, GD Joensuu, H Schoffski, P Poveda, A AF Benjamin, Robert S. Debiec-Rychter, Maria Le Cesne, Axel Sleijfer, Stefan Demetri, George D. Joensuu, Heikki Schoeffski, Patrick Poveda, Andres TI Gastrointestinal Stromal Tumors II: Medical Oncology and Tumor Response Assessment SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Sarcomas and Gastrointestinal Stromal Tumors CY MAY 13-14, 2008 CL Milan, ITALY SP European Soc Med Oncol ID BONE-SARCOMA-GROUP; EORTC-SOFT-TISSUE; POSITRON-EMISSION-TOMOGRAPHY; DYSFUNCTION WORKING GROUP; RECEPTOR TYROSINE KINASE; CHRONIC MYELOID-LEUKEMIA; IMATINIB MESYLATE; PHASE-II; DOSE IMATINIB; ADVANCED MALIGNANCIES C1 [Poveda, Andres] Inst Valenciano Oncol, Valencia 46009, Spain. [Schoeffski, Patrick] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium. [Schoeffski, Patrick] Katholieke Univ Leuven, Leuven Canc Inst, Expt Oncol Lab, Leuven, Belgium. [Joensuu, Heikki] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Sleijfer, Stefan] Erasmus Univ, Med Ctr, Dept Med Oncol, Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands. [Le Cesne, Axel] Inst Gustave Roussy, Villejuif, France. [Debiec-Rychter, Maria] Katholieke Univ Leuven, Dept Human Genet, Leuven, Belgium. [Benjamin, Robert S.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. RP Poveda, A (reprint author), Inst Valenciano Oncol, Prof Baguena 19, Valencia 46009, Spain. EM apoveda@fivo.org OI Joensuu, Heikki/0000-0003-0281-2507 NR 61 TC 22 Z9 25 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 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2009 VL 36 IS 4 BP 302 EP 311 DI 10.1053/j.seminoncol.2009.06.003 PG 10 WC Oncology SC Oncology GA 482OW UT WOS:000268899600003 PM 19664491 ER PT J AU Dei Tos, AP Wagner, AJ Modena, P Comandone, A Leyvraz, S AF Dei Tos, A. Paolo Wagner, Andrew J. Modena, Piergiorgio Comandone, Alessandro Leyvraz, Serge TI Epithelioid Soft Tissue Tumors SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Sarcomas and Gastrointestinal Stromal Tumors CY MAY 13-14, 2008 CL Milan, ITALY SP European Soc Med Oncol ID MALIGNANT RHABDOID TUMORS; FRENCH SARCOMA GROUP; NERVE SHEATH TUMOR; PART SARCOMA; IMMUNOHISTOCHEMICAL ANALYSIS; PROGNOSTIC-FACTORS; SINGLE INSTITUTION; GENE FUSION; PHASE-II; ANGIOSARCOMA C1 [Dei Tos, A. Paolo] Gen Hosp Treviso, Dept Pathol Anat, I-31100 Treviso, Italy. [Wagner, Andrew J.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Modena, Piergiorgio] Ist Nazl Tumori, Fdn IRCCS, Unit Mol Cytogenet UO5, I-20133 Milan, Italy. [Comandone, Alessandro] SC Oncol Osped Gradenigo, Turin, Italy. [Leyvraz, Serge] Univ Lausanne Hosp, Ctr Pluridisciplinaire Oncol, Lausanne, Switzerland. RP Dei Tos, AP (reprint author), Gen Hosp Treviso, Dept Pathol Anat, Piazza Osped 1, I-31100 Treviso, Italy. EM apdeitos@ulss.tv.it OI DEI TOS, ANGELO/0000-0002-1228-8940 NR 70 TC 14 Z9 15 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2009 VL 36 IS 4 BP 347 EP 357 DI 10.1053/j.seminoncol.2009.06.005 PG 11 WC Oncology SC Oncology GA 482OW UT WOS:000268899600007 PM 19664495 ER PT J AU Glantz, M Kesari, S Recht, L Fleischhack, G Van Horn, A AF Glantz, Michael Kesari, Santosh Recht, Lawrence Fleischhack, Gudrun Van Horn, Alexis TI Understanding the Origins of Gliomas and Developing Novel Therapies: Cerebrospinal Fluid and Subventricular Zone Interplay SO SEMINARS IN ONCOLOGY LA English DT Article ID NEURAL STEM-CELLS; ADULT MAMMALIAN BRAIN; COMPARATIVE GENOMIC HYBRIDIZATION; RECURSIVE PARTITIONING ANALYSIS; ETHYL-N-NITROSOUREA; GLIOBLASTOMA-MULTIFORME; GROWTH-FACTOR; NERVOUS-SYSTEM; CANCER; RADIOTHERAPY AB Glioblastoma multiforme (GBM), the most common malignant primary brain tumor in adults, carries a poor prognosis, with median survival generally less than 1 year. Although initial therapy often eradicates the bulk of the tumor, disease recurrence, usually within 2 cm of the original tumor, is almost inevitable. This may be due to a failure of current therapies to eradicate viable chemotherapy- and radiotherapy-resistan.t neoplastic progenitor cells, which may then repopulate tumors. An increasing body of preclinical data suggests that these cells may correspond to stem cells derived from the subventricular zone (SVZ), which migrate to tumor sites and contribute to glioma growth and recurrence. Therapeutic targeting of SVZ stem cell populations via cerebrospinal fluid (CSF)-directed therapy may provide a means for limiting tumor recurrence. This approach has proved successful in the treatment of medulloblastoma, another brain tumor thought to be derived from stem cells. We discuss the rationale and design considerations for a clinical trial to evaluate the efficacy of CSF-directed therapy for preventing GBM recurrence. Semin Oncol 36 (Suppl 2):S17-S24. (C) 2009 Published by Elsevier Inc. C1 [Glantz, Michael] Penn State Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA. [Kesari, Santosh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Recht, Lawrence] Stanford Univ, Sch Med, Stanford Canc Ctr, Stanford, CA 94305 USA. [Fleischhack, Gudrun] Univ Childrens Hosp, Dept Pediat Hematol Oncol, Bonn, Germany. [Van Horn, Alexis] Tufts Med Ctr, Boston, MA USA. RP Glantz, M (reprint author), Penn State Hershey Med Ctr, Dept Neurosurg, EC 110,30 Hope Dr,POB 859, Hershey, PA 17033 USA. EM mjg@massmed.org RI Kesari, Santosh/E-8461-2013 NR 58 TC 14 Z9 14 U1 1 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2009 VL 36 IS 4 BP S17 EP S24 DI 10.1053/j.seminoncol.2009.05.003 PG 8 WC Oncology SC Oncology GA 482OX UT WOS:000268899700003 PM 19660679 ER PT J AU Mimiaga, MJ Helms, DJ Reisner, SL Grasso, C Bertrand, T Mosure, DJ Weinstock, H McLean, C Mayer, KH AF Mimiaga, Matthew J. Helms, Donna J. Reisner, Sari L. Grasso, Chris Bertrand, Thomas Mosure, Debra J. Weinstock, Hillard McLean, Catherine Mayer, Kenneth H. TI Gonococcal, Chlamydia, and Syphilis Infection Positivity Among MSM Attending a Large Primary Care Clinic, Boston, 2003 to 2004 SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; HIV-INFECTION; MEN; SEX; GONORRHEA; TRANSMISSION; TRENDS AB Background: in the past decade, increases in syphilis and rectal gonorrhea have been reported among men who have sex with men (MSM) in the United States; however, limited sexually transmitted disease (STD) positivity data are available oil MSM who receive their healthcare from primary care or general medical clinics. The Current study sought to elucidate STD positivity in asymptomatic MSM seen at the largest primary care clinic for MSM in New England and to describe STD test positivity by reason for STD testing. Methods: As part of the Centers for Disease Control and Prevention's MSM Prevalence Monitoring Project, all medical visits between 2003 and 2004 (n = 21,927) among MSM attending Fenway Community Health (Boston) were reviewed. The prevalence of positive STD tests (chlamydia, gonorrhea, and syphilis reactivity) was determined and analyzed by demographic characteristics, HIV status, symptoms. and reason for testing. Results: Overall, 23.4% of MSM visits included STD testing during the observation period. Their mean age was 39 years (range: 18-65 years) 84% were white, 5% were black, and 5% were Hispanic. Sixty-five percent of MSM tested were asymptomatic with 7% of asymptomatic MSM testing positive for at least one STD. STD prevalence varied by reason for STD testing: 4.4% of MSM routinely screened had at least one STD, compared to 6.9% of MSM who reported having high risk sex in the preceding 3 months, and 17% of MSM reporting an exposure to an STD. Among all asymptomatic MSM tested, 1.0% had urethral gonorrhea: 1.7% had pharyngeal gonorrhea: 5.6% had rectal gonorrhea: 2.2% had urethral chlamydia: and 4.3% were seroreactive for syphilis. Conclusions: Rectal gonorrhea and syphilis seropositivity were frequently diagnosed in asymptomatic MSM; STD prevalence was highest in MSM tested due to an STD exposure or reporting high-risk Sex, underscoring the need to promote routine screening in high risk, MSM populations. C1 [Mimiaga, Matthew J.; Reisner, Sari L.; Grasso, Chris; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Epidemiol Unit, Boston, MA 02119 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Helms, Donna J.; Weinstock, Hillard] Ctr Dis Control & Prevent, Div STD Prevent, Atlanta, GA USA. [Bertrand, Thomas] Massachusetts Dept Publ Hlth, Boston, MA USA. [Mosure, Debra J.; McLean, Catherine] Ctr Dis Control & Prevent, Global AIDS Program, Atlanta, GA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Dept Infect Dis & Community Hlth, Providence, RI 02906 USA. RP Mimiaga, MJ (reprint author), Fenway Community Hlth, Fenway Inst, Epidemiol Unit, Prudential Tower,4th Floor,800 Boylston St, Boston, MA 02119 USA. EM mmimiaga@fenwayhealth.org NR 17 TC 31 Z9 31 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD AUG PY 2009 VL 36 IS 8 BP 507 EP 511 DI 10.1097/OLQ.0b013e3181a2ad98 PG 5 WC Infectious Diseases SC Infectious Diseases GA 476GD UT WOS:000268425900008 PM 19455081 ER PT J AU Tucker, JD Shah, S Jarell, AD Tsai, KY Zembowicz, A Kroshinsky, D AF Tucker, Joseph D. Shah, Sonali Jarell, Abel D. Tsai, Kenneth Y. Zembowicz, Artur Kroshinsky, Daniela TI Lues Maligna in Early HIV Infection Case Report and Review of the Literature SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYPHILIS AB Background: Lues maligna (also known as malignant syphilis or ulceronodular syphilis) is a rare dermatologic manifestation of syphilis more commonly seen in patients with HIV infection. The classic lesion of Iues maligna is an oval. papulopustular skin lesion with well demarcated borders sometimes covered with a lamellar crust, but myriad clinical presentations of this disease also exist. Goals: To report a presentation of Iues maligna in a patient with probable early HIV infection, emphasizing the diagnostic criteria and clinical manifestations of Iues maligna. Study Design: Case report of lues maligna in a patient with probable early HIV infection. Conclusions: As syphilis becomes more common in many developed regions. it is important to recognize even atypical presentations of this clinical entity. especially among individuals who have unecognized or early HIV infection. C1 [Tucker, Joseph D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Shah, Sonali] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Jarell, Abel D.; Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tsai, Kenneth Y.; Zembowicz, Artur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tucker, JD (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jtucker4@partners.org NR 12 TC 18 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD AUG PY 2009 VL 36 IS 8 BP 512 EP 514 DI 10.1097/OLQ.0b013e3181a2a946 PG 3 WC Infectious Diseases SC Infectious Diseases GA 476GD UT WOS:000268425900009 PM 19455078 ER PT J AU Mankin, HJ AF Mankin, Henry J. TI The current state of limb salvage surgery SO SKELETAL RADIOLOGY LA English DT Editorial Material ID OSTEOCHONDRAL ALLOGRAFTS; IMMUNOLOGICAL RESPONSES; FOLLOW-UP; BONE; TUMORS C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, 1122A Jackson Bldg, Boston, MA 02114 USA. EM hmankin@partners.org NR 14 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD AUG PY 2009 VL 38 IS 8 BP 733 EP 734 DI 10.1007/s00256-009-0728-4 PG 2 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 466LX UT WOS:000267664800001 PM 19526229 ER PT J AU Jerabek, SA Asnis, PD Bredella, MA Ouellette, HA Poon, SK Gill, TJ AF Jerabek, Seth A. Asnis, Peter D. Bredella, Miriam A. Ouellette, Hugue A. Poon, Steven K. Gill, Thomas J., IV TI Medial patellar ossification after patellar instability: a radiographic finding indicative of prior patella subluxation/dislocation SO SKELETAL RADIOLOGY LA English DT Article DE Patella; Instability; MPFL; Ossification; Imaging ID PATELLOFEMORAL LIGAMENT AB To describe the correlation between medial patellar ossification and prior patella subluxation and/or dislocation. A retrospective billing database search identified 544 patients who had been diagnosed with patellar instability over a 13-year period. One hundred twenty-eight patients met the inclusion criteria. After review by a staff orthopedic surgeon and two musculoskeletal radiologists, 28 patients were found to have medial patellar ossification. The size and location of medial patellar ossification was recorded. Of the 28 patients (20 males, eight females, age 13-66 years, mean 28 years) who were found to have medial patellar ossification, 22 had radiographs, 16 had magnetic resonance imaging, and ten had both. The medial patellar ossification ranged in size from 2 to 18 mm with an average of 6.8 mm. Twelve were located in the medial patellofemoral ligament (MPFL), 14 in the medial joint capsule, and two in both the MPFL and joint capsule. Twenty-seven of 28 patients had a single ossification, and one patient had two ossifications. The timing from injury to first imaging of the lesion ranged from 10 days to a chronic history (a parts per thousand yen35 years) of patellar instability. Medial patellar ossification correlates with a history of prior patella subluxation and/or dislocation. The medial ossification can be seen within the MPFL or the medial joint capsule, suggesting remote injury to these structures. The presence of this lesion will prompt physicians to evaluate for patellar instability. C1 [Jerabek, Seth A.] Harvard Combined Orthopaed Surg Residency Program, Boston, MA 02114 USA. [Asnis, Peter D.; Poon, Steven K.; Gill, Thomas J., IV] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Bredella, Miriam A.; Ouellette, Hugue A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Jerabek, SA (reprint author), Harvard Combined Orthopaed Surg Residency Program, 55 Fruit St,White 535, Boston, MA 02114 USA. EM sjerabek@partners.org NR 9 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD AUG PY 2009 VL 38 IS 8 BP 785 EP 790 DI 10.1007/s00256-008-0644-z PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 466LX UT WOS:000267664800007 PM 19205694 ER PT J AU Thannickal, TC Nienhuis, R Siegel, JM AF Thannickal, Thomas C. Nienhuis, Robert Siegel, Jerome M. TI Localized Loss of Hypocretin (Orexin) Cells in Narcolepsy Without Cataplexy SO SLEEP LA English DT Article DE Hypocretin; orexin; narcolepsy; cataplexy ID OLFACTORY DYSFUNCTION; PARKINSONS-DISEASE; SLEEP BEHAVIOR; EPIDEMIOLOGY; NEURONS AB Study Objectives: Narcolepsy with cataplexy is characterized by a loss of approximately 90% of hypocretin (Hcrt) neurons. However, more than a quarter of narcoleptics do not have cataplexy and have normal levels of hypocretin in their cerebrospinal fluid, raising the possibility that their disease is caused by unrelated abnormalities. In this study we examined hypocretin pathology in narcolepsy without cataplexy. Design: We examined postmortem brain samples, including the hypothalamus of 5 narcolepsy with cataplexy patients; one narcolepsy without cataplexy patient whose complete hypothalamus was available (patient 1); one narcolepsy without cataplexy patient with anterior hypothalamus available (patient 2); and 6 normal brains. The hypothalamic tissue was immunostained for Hcrt-1, melanin-concentrating hormone (MCH), and glial fibrillary acidic protein (GFAP). Measurements and Results: Neither of the narcolepsy without cataplexy patients had a loss of Hcrt axons in the anterior hypothalamus. The narcolepsy without cataplexy patient whose entire brain was available for study had an overall loss of 33% of hypocretin cells compared to normals, with maximal cell loss in the posterior hypothalamus. We found elevated levels of gliosis with GFAP staining, with levels increased in the posterior hypothalamic nucleus by (295%), paraventricular (211%), periventricular (123%), arcuate (126%), and lateral (72%) hypothalamic nuclei, but not in the anterior, dorsomedial, or dorsal hypothalamus. There was no reduction in the number of MCH neurons in either patient. Conclusions: Narcolepsy without cataplexy can be caused by a partial loss of hypocretin cells. C1 [Thannickal, Thomas C.; Nienhuis, Robert; Siegel, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, North Hills, CA USA. [Thannickal, Thomas C.; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Thannickal, Thomas C.; Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, VAGLAHS Sepulveda, Neurobiol Res 151A3,16111 Plummer St, North Hills, CA 91343 USA. EM jsiegel@ucla.edu FU Human Brain and Spinal Fluid Resource Center, VAGLAHS, Los Angeles [NS14610, HL41370, MH64109]; Medical Research Service of the Dept. of Veterans Affairs FX Tissues were obtained from the Human Brain and Spinal Fluid Resource Center, VAGLAHS, Los Angeles. Supported by NS14610, HL41370, MH64109 and the Medical Research Service of the Dept. of Veterans Affairs. A preliminary version of these findings was submitted on May 12, 2008, for presentation at the Society for Neuroscience Meeting.; The work was performed at Veterans Administration Greater Los Angeles Healthcare System, North Hills and U.C.L.A. NR 20 TC 76 Z9 78 U1 0 U2 6 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 AUG 1 PY 2009 VL 32 IS 8 BP 993 EP 998 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 477ZN UT WOS:000268557600006 PM 19725250 ER PT J AU Cannuscio, CC Weiss, EE Fruchtman, H Schroeder, J Weiner, J Asch, DA AF Cannuscio, Carolyn C. Weiss, Eve E. Fruchtman, Hannah Schroeder, Jeannette Weiner, Janet Asch, David A. TI Visual epidemiology: Photographs as tools for probing street-level etiologies SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; Urban health; Social epidemiology; Visual methods; Health disparities; Neighborhoods; Food environment; Violence; Social environment; Physical environment; Photovoice ID HEALTH INEQUALITIES; LAY EPIDEMIOLOGY; PHOTOVOICE; PLACE; DISCRIMINATION; ENVIRONMENT; PREVENTION; CONTEXT; FAMILY; ADULTS AB Epidemiologists and social scientists agree that place shapes health. But the model of "risk factor" epidemiology faces limits in explaining how neighborhoods, as complex systems, produce health or disease. This paper describes how visual methods can advance epidemiological inquiry. Drawing from the work of The Health of Philadelphia Photo-documentation Project (HOPPP), this paper asks the following question: how can visual methods inform the work of epidemiologists? The project was conducted in three contiguous neighborhoods that represent a steep socioeconomic gradient. Photographs served as a stimulus for probing the sources of health variation across neighborhoods. The project incorporated three visual data sources: 1) "outsider perspective" images gathered systematically by staff photographers on randomly sampled blocks; 2) "insider perspective" images taken by adult residents during their daily routines; and 3) collaborative images taken by staff photographers in partnership with local participants. During in-depth interviews, these photographs served as prompts to elicit residents' health concerns and beliefs regarding urban environmental causes of good and poor health ("street-level etiologies"). We found that visual methods generated etiologic insights regarding the production of urban health and illness. Photographs enabled systematic observation of urban neighborhoods by the research team; engaged urban residents as active agents in the search for the underlying causes of urban health disparities; and created a social bridge between researchers and urban residents. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Cannuscio, Carolyn C.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.; Schroeder, Jeannette] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.; Weiner, Janet; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Cannuscio, CC (reprint author), Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. EM cannusci@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X; Weiner, Janet/0000-0001-5810-5807 NR 41 TC 17 Z9 18 U1 2 U2 15 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 AUG PY 2009 VL 69 IS 4 BP 553 EP 564 DI 10.1016/j.socscimed.2009.06.013 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 489JR UT WOS:000269416900012 PM 19573966 ER PT J AU Evans, CT Hershow, RC Chin, A Foulis, PR Burns, SP Weaver, FM AF Evans, C. T. Hershow, R. C. Chin, A. Foulis, P. R. Burns, S. P. Weaver, F. M. TI Bloodstream infections and setting of onset in persons with spinal cord injury and disorder SO SPINAL CORD LA English DT Article DE bacteremia; spinal cord injuries; health care ID ACUTE REHABILITATION UNIT; ACQUIRED INFECTIONS; RESISTANT ORGANISMS; BACTEREMIA; EPIDEMIOLOGY; POPULATION; MORTALITY; VETERANS AB Study Design: A retrospective cohort study. Objective: Health-care-associated (HCA) bloodstream infection (BSI) has been shown to be a distinct epidemiologic category in the general adult population, but few studies have examined specific patient populations. The objective of this study was to assess characteristics associated with BSI that occurred in the hospital (hospital-acquired, HA BSI), from health-care contact outside the hospital (HCA BSI) or in the community (community-acquired, CA BSI) in veterans with spinal cord injury and disorder (SCI&D). Setting: Two United States Department of Veterans Affairs hospitals. Methods: All patients with SCI&D with a positive blood culture admitted to study hospitals over a 7-year period (1 October 1997 to 30 September 2004). Demographics, medical characteristics and causative organisms were collected. Results: Four hundred and thirteen episodes of BSI occurred in 226 patients, with a rate of 7.2 BSI episodes per 100 admissions: 267 (64.7%) were HA BSI, 110 (26.6%) were HCA BSI and 36 (8.7%) were CA BSI. Antibiotic resistance was more common in those with HA BSI (65.5%) compared with that in those with HCA (49.1%, P = 0.001) and CA BSI (22.2%, P<0.0001). Methicillin resistance in Staphylococcus aureus was highly prevalent; HA BSI (84.5%), HCA BSI (60.6%) and CA BSI (33.3%). Conclusion: HCA BSI comprises one-quarter of all BSIs in hospitalized patients with SCI&D. Although those with HCA and CA BSI share similarities, several differences in medical characteristics and causal microorganism are noted. Treatment and management strategies for HCA and CA infections need to vary. Spinal Cord (2009) 47, 610-615; doi: 10.1038/sc.2009.2; published online 24 February 2009 C1 [Evans, C. T.; Chin, A.; Weaver, F. M.] EJ Hines Jr VA Hosp 151H, Ctr Management Complex Chron Care, Dept Vet Affairs, Hines, IL 60141 USA. [Evans, C. T.; Weaver, F. M.] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. [Evans, C. T.; Hershow, R. C.] Univ Illinois, Sch Publ Hlth, Dept Epidemiol & Biostat, Chicago, IL USA. [Foulis, P. R.] James A Haley VA Hosp, Pathol Lab Serv, Tampa, FL USA. [Burns, S. P.] Univ Washington, Seattle, WA 98195 USA. [Burns, S. P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Weaver, F. M.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. RP Evans, CT (reprint author), EJ Hines Jr VA Hosp 151H, Ctr Management Complex Chron Care, Dept Vet Affairs, 5th Ave & Roosevelt Rd, Hines, IL 60141 USA. EM Charlesnika.Evans@va.gov FU Department of Veterans Affairs; Office of Research and Development; Health Services Research and Development Service FX This paper is based upon study supported by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service. NR 20 TC 6 Z9 6 U1 0 U2 0 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 AUG PY 2009 VL 47 IS 8 BP 610 EP 615 DI 10.1038/sc.2009.2 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 479TT UT WOS:000268684500008 PM 19238165 ER PT J AU Bauman, WA Schwartz, E Song, ISY Kirshblum, S Cirnigliaro, C Morrison, N Spungen, AM AF Bauman, W. A. Schwartz, E. Song, I. S. Y. Kirshblum, S. Cirnigliaro, C. Morrison, N. Spungen, A. M. TI Dual-energy X-ray absorptiometry overestimates bone mineral density of the lumbar spine in persons with spinal cord injury SO SPINAL CORD LA English DT Article DE spinal cord injury; bone mineral density; vertebral body; quantitative computerized tomography; dual-energy X-ray absorptiometry; degenerative joint disease ID QUANTITATIVE COMPUTED-TOMOGRAPHY; LOWER-EXTREMITY FRACTURES; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; CLINICAL-USE; OSTEOPOROSIS; DENSITOMETRY; DEMINERALIZATION; DIAGNOSIS; DISEASE AB Background: Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal or increased in persons with chronic spinal cord injury (SCI). Objective: To determine BMD of the L-spine by dual-energy X-ray absorptiometry (DXA) and quantitative computerized tomography (qCT) in men with chronic SCI compared with able-bodied controls. Design: Cross-sectional, comparative study. Setting: Clinical research unit, Veterans Affairs Medical Center, Bronx, NY, USA and Kessler Institute of Rehabilitation, West Orange, NJ, USA. Methods: Measurements of the L-spine were made in 20 men with SCI and compared with 15 able-bodied controls. The DXA images were acquired on a GE Lunar DPX-IQ. The qCT images of the L-spine were acquired on a Picker Q series computerized tomographic scanner. Results: The mean ages for the SCI and control groups were 44 +/- 13 vs 42 +/- 9 years, and the duration of injury of the group with SCI was 14 +/- 11 years. There were no significant differences between the SCI and control groups for L-spine DXA BMD (1.391 +/- 0.210 vs 1.315 +/- 0.178 g/m(2)) or for L-spine DXA T-score (1.471 +/- 1.794 vs 0.782 +/- 1.481). L-spine qCT BMD was significantly lower in the SCI compared with the control group (1.296 +/- 0.416 vs 1.572 +/- 0.382 g/m(2), P=0.05); the T-score approached significance (-1.838 +/- 1.366 vs -0.963 +/- 1.227, P=0.059). Subjects with moderate degenerative joint disease (DJD) had significantly higher T-scores by DXA than those without or with mild DJD. Conclusion: Individuals with SCI who have moderate to severe DJD may have bone loss of the L-spine that may be underestimated by DXA, reducing awareness of the risk of fracture. Spinal Cord (2009) 47, 628-633; doi: 10.1038/sc.2008.169; published online 20 January 2009 C1 [Bauman, W. A.; Schwartz, E.; Song, I. S. Y.; Cirnigliaro, C.; Morrison, N.; Spungen, A. M.] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Bauman, W. A.; Spungen, A. M.] James J Peters Vet Affairs Med Ctr, Med Serv, Bronx, NY 10468 USA. [Bauman, W. A.; Spungen, A. M.] James J Peters Vet Affairs Med Ctr, Spinal Cord Injury Serv, Bronx, NY 10468 USA. [Bauman, W. A.; Spungen, A. M.] James J Peters Vet Affairs Med Ctr, Res Serv, Bronx, NY 10468 USA. [Bauman, W. A.; Spungen, A. M.] Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. [Bauman, W. A.; Spungen, A. M.] Mt Sinai Med Ctr, Dept Rehabil Med, New York, NY 10029 USA. [Kirshblum, S.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, S.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP Bauman, WA (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov FU United Spinal Association (formally Eastern Paralyzed Veterans Association),; James J Peters Medical Center, Bronx, NY; Department of Veterans Affairs Rehabilitation Research & Development Service; Kessler Institute for Rehabilitation, West Orange, NJ,; Rehabilitation Research & Development (RRD) Service [B98-1452]; RR&D Center of Excellence for the Medical Consequences of Spinal Cord Injury [B2648C, B4162C] FX The authors wish to thank United Spinal Association (formally Eastern Paralyzed Veterans Association), The James J Peters Medical Center, Bronx, NY, the Department of Veterans Affairs Rehabilitation Research & Development Service, and the Kessler Institute for Rehabilitation, West Orange, NJ, for their support. This work was funded by a Rehabilitation Research & Development (RR&D) Service Merit Review entitled 'Bone Loss in Acute and Chronic Spinal Cord Injury' (#B98-1452) & RR&D Center of Excellence for the Medical Consequences of Spinal Cord Injury (#B2648C & B4162C). NR 25 TC 10 Z9 11 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 EI 1476-5624 J9 SPINAL CORD JI Spinal Cord PD AUG PY 2009 VL 47 IS 8 BP 628 EP 633 DI 10.1038/sc.2008.169 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 479TT UT WOS:000268684500011 PM 19153590 ER PT J AU Park, KP Rosell, A Foerch, C Xing, C Kim, WJ Lee, S Opdenakker, G Furie, KL Lo, EH AF Park, Kyung-Pil Rosell, Anna Foerch, Christian Xing, Changhong Kim, Woo Jean Lee, Seoul Opdenakker, Ghislain Furie, Karen L. Lo, Eng H. TI Plasma and Brain Matrix Metalloproteinase-9 After Acute Focal Cerebral Ischemia in Rats SO STROKE LA English DT Article DE cerebral ischemia; matrix metalloproteinase; stroke ID MATRIX-METALLOPROTEINASE EXPRESSION; HEMORRHAGIC TRANSFORMATION; REPERFUSION INJURY; CELL-DEATH; STROKE; MINOCYCLINE; GELATINASE; INHIBITION; DISRUPTION; BREAKDOWN AB Background and Purpose-Plasma levels of matrix metalloproteinase-9 (MMP-9) have been proposed to be a useful biomarker for assessing pathological events in brain. Here, we examined the temporal profiles of MMP-9 in blood and brain using a rat model of acute focal cerebral ischemia. Methods-Plasma and brain levels of MMP-2 and MMP-9 were quantified at 3, 6, 12, and 24 hours after permanent middle cerebral artery occlusion in male Sprague-Dawley rats. Infarct volumes at 24 hours were confirmed with 2,3,5-triphenyltetrazolium-chloride staining. Results-In plasma, zymographic bands were detected between 70 and 95 kDa corresponding to pro-MMP-2, pro-MMP-9, and activated MMP-9. A higher 135-kDa band was also seen that is likely to be NGAL-conjugated MMP-9. After ischemia, there were no significant changes in pro-MMP-2, but plasma levels of pro-MMP-9 steadily increased over the course of 24 hours. Activated MMP-9 levels in plasma were significantly elevated only at 24 hours. Plasma NGAL-MMP-9 complexes showed a transient elevation between 3 to 6 hours, after which levels decreased back down to pre-ischemic baselines. In brain homogenates, pro-MMP-2, pro-MMP-9, and activated MMP-9 were seen but no NGAL-MMP-9 bands were detected. Compared to the contralateral hemisphere, MMP-2 and MMP-9 levels in ischemic brain progressively increased over the course of 24 hours. Overall levels of MMP-9 in plasma and brain were significantly correlated, especially at 24 hours. Plasma levels of pro-MMP-9 at 24 hours were correlated with final infarct volumes. Conclusions-Elevated plasma levels of MMP-9 appear to be correlated with brain levels within 24 hours of acute cerebral ischemia in rats. Further investigation into clinical profiles of MMP-9 in acute stroke patients may be useful. (Stroke. 2009; 40: 2836-2842.) C1 [Park, Kyung-Pil; Rosell, Anna; Foerch, Christian; Xing, Changhong; Kim, Woo Jean; Lee, Seoul; Furie, Karen L.; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Park, Kyung-Pil; Rosell, Anna; Foerch, Christian; Xing, Changhong; Kim, Woo Jean; Lee, Seoul; Furie, Karen L.; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Park, Kyung-Pil] Pusan Natl Univ, Yangsan Hosp, Med Res Inst, Dept Neurol, Pusan, South Korea. [Opdenakker, Ghislain] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. RP Lo, EH (reprint author), Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM kppark@pusan.ac.kr; Lo@helix.mgh.harvard.edu OI Lee, Seoul/0000-0002-4594-1213; Park, Kyung-Pil/0000-0003-4952-3796 FU NIH [R37-NS37074, R01-NS48422, R01-NS56458, P01-NS55104, P50-NS51343]; Medical Research Institute, Pusan National University [2006-34] FX This study was supported in part by NIH grants R37-NS37074, R01-NS48422, R01-NS56458, P01-NS55104, and P50-NS51343, and grant 2006-34 from the Medical Research Institute, Pusan National University. NR 28 TC 50 Z9 58 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2009 VL 40 IS 8 BP 2836 EP 2842 DI 10.1161/STROKEAHA.109.554824 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 475UN UT WOS:000268387000029 PM 19556529 ER PT J AU Schaefer, PW Mui, K Kamalian, S Nogueira, RG Gonzalez, RG Lev, MH AF Schaefer, Pamela W. Mui, Kit Kamalian, Shahmir Nogueira, Raul G. Gonzalez, R. Gilberto Lev, Michael H. TI Avoiding "Pseudo-Reversibility" of CT-CBV Infarct Core Lesions in Acute Stroke Patients After Thrombolytic Therapy The Need for Algorithmically "Delay-Corrected" CT Perfusion Map Postprocessing Software SO STROKE LA English DT Article DE stroke management; CT perfusion AB Background and Purpose-Rarely, acute ischemic stroke (AIS) patients have pretreatment CT-CBV abnormalities larger than final infarct volumes. We sought to determine: (1) the prevalence of CT-CBV "reversibility" in AIS patients treated with thrombolytic therapy, and (2) whether the presumed tissue salvage of these CT-CBV lesions depends on the CTP software. Methods-We reviewed the admission CT-CBV maps (calculated with an algorithm sensitive to tracer arrival time) and follow-up images of 148 AIS patients who received thrombolytic therapy. When the follow-up infarct appeared smaller than the admission CT-CBV lesion, the CTP source images were reprocessed using "delay-correction" software (GE, CTP 4). Original and "delay-corrected" CT-CBV ischemic lesion volumes were compared to each other and follow-up infarct volumes using the Student t test. Results-11/148 (7.4%) patients had admission CT-CBV larger than follow-up lesions (mean difference -69.5 cc, range -146.0 to -14.0 cc; P<0.05). For all patients, the admission CT-CBV lesions were smaller on the delay-versus nondelay-corrected maps (mean difference -83.1, range -233 to -2 cc; P<0.05). Only 2 patients had delay-corrected CT-CBV lesions larger than follow-up infarctions, with a 12- to 17-cc difference in volume. 7/9 of the remaining patients had extracranial hemodynamic factors potentially delaying tracer arrival, including atrial fibrillation (AF; n = 4), congestive heart failure (CHF; n 4), or extracranial internal carotid artery (ICA) stenosis (n = 1). Conclusion-True "reversibility" of CT-CBV "core" lesions in AIS patients after thrombolytic therapy is rare, with small volumes of "salvaged" tissue. Pseudoreversibility of core lesions in standard CT-CBV maps can be avoided by using specific algorithmically optimized delay-correction software. Further investigation is warranted to determine whether this finding applies to algorithms provided by other vendors. (Stroke. 2009; 40: 2875-2878.) C1 [Schaefer, Pamela W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Gray 273A,55 Fruit St, Boston, MA 02114 USA. EM pschaefer@partners.org OI Kamalian, Shahmir/0000-0002-9640-8144 NR 6 TC 29 Z9 30 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2009 VL 40 IS 8 BP 2875 EP 2878 DI 10.1161/STROKEAHA.109.547679 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 475UN UT WOS:000268387000037 PM 19520995 ER PT J AU Hesketh, PJ Younger, J Sanz-Altamira, P Hayden, M Bushey, J Trainor, B Krentzin, M Nowd, P Arnaoutakis, K Hesketh, AM AF Hesketh, Paul J. Younger, Jerry Sanz-Altamira, Pedro Hayden, Melissa Bushey, Julie Trainor, Brian Krentzin, Michael Nowd, Peter Arnaoutakis, Konstantinos Hesketh, Ann M. TI Aprepitant as salvage antiemetic therapy in breast cancer patients receiving doxorubicin and cyclophosphamide SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Aprepitant; Breast cancer; Nausea; Vomiting; Antiemetic ID CHEMOTHERAPY-INDUCED NAUSEA; 5-HT3 RECEPTOR ANTAGONISTS; PLACEBO-CONTROLLED TRIAL; CISPLATIN-INDUCED EMESIS; DOUBLE-BLIND; CLINICAL-PRACTICE; ONDANSETRON; PREVENTION; PROPHYLAXIS; EFFICACY AB To assess the efficacy of adding aprepitant to a 5-HT(3) antagonist and dexamethasone as salvage antiemetic therapy for breast cancer patients receiving their initial cycle of an anthracycline and cyclophosphamide (AC) and failing to achieve complete control of emesis. Eligibility: breast cancer patients receiving their first cycle of AC. Treatment: standard dose of a 5-HT(3) antagonist and dexamethasone 8-10 mg IV/PO on day 1 prior to cycle 1 of AC and dexamethasone 4 mg bid on days 2 and 3. Patients without complete control (no emesis, no nausea, or rescue antiemetics) during cycle 1 could proceed to cycle 2. During cycle 2, patients received AC and identical antiemetics (except dexamethasone 4 mg qd on days 2 and 3) plus aprepitant 125 mg PO day 1 and 80 mg PO days 2 and 3. Primary endpoint: complete control, 0-120 h after chemotherapy. Sixty-two patients received cycle 1 of AC. Complete control cycle 1: 13 patients (21%; 95%CI, 12-33%). Of the 49 patients eligible for cycle 2, four elected not to continue on study. Of the 45 patients receiving cycle 2, 44 were evaluable. Complete control and complete response (no emesis, no rescue) for the 5-day study period improved from 0% to 18% (p = 0.14) and 7% to 36% (p = 0.02) on cycles 1 and 2, respectively. In breast cancer patients receiving AC, the addition of aprepitant to a 5-HT(3) antagonist and dexamethasone during cycle 2 of treatment improved antiemetic outcome. Although the improvement in the primary endpoint of complete control during cycle 2 was not significant, all secondary endpoints such as complete response and no emesis rates were significantly better during cycle 2. The extent of antiemetic control during cycle 2 was numerically inferior to the results achieved in a phase III trial employing aprepitant with cycle 1 of AC chemotherapy, suggesting that the preferred approach is to include aprepitant with the initial cycle of AC chemotherapy. C1 [Hesketh, Paul J.; Trainor, Brian; Krentzin, Michael; Nowd, Peter; Arnaoutakis, Konstantinos; Hesketh, Ann M.] Caritas St Elizabeths Med Ctr Boston, Boston, MA 02135 USA. [Younger, Jerry; Hayden, Melissa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sanz-Altamira, Pedro; Bushey, Julie] Caritas Holy Family Hosp, Methuen, MA USA. RP Hesketh, PJ (reprint author), Caritas St Elizabeths Med Ctr Boston, HOQ Room 223,736 Cambridge St, Boston, MA 02135 USA. EM phesketh@massmed.org FU Merck FX This investigation was supported in part by a grant from Merck. NR 25 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD AUG PY 2009 VL 17 IS 8 BP 1065 EP 1070 DI 10.1007/s00520-008-0545-7 PG 6 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 468OB UT WOS:000267827800004 PM 19066985 ER PT J AU Abolmaali, K Balakrishnan, A Stearns, AT Rounds, J Rhoads, DB Ashley, SW Tavakkolizadeh, A AF Abolmaali, Kamran Balakrishnan, Anita Stearns, Adam T. Rounds, Jan Rhoads, David B. Ashley, Stanley W. Tavakkolizadeh, Ali TI Circadian variation in intestinal dihydropyrimidine dehydrogenase (DPD) expression: A potential mechanism for benefits of 5FU chrono-chemotherapy SO SURGERY LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the Society-of-University-Surgeons/4th Annual Academic Surgical Congress CY FEB 03-06, 2009 CL Ft Myers, FL SP Soc Univ Surg, Assoc Acad Surg ID METASTATIC COLORECTAL-CANCER; MESSENGER-RNA EXPRESSION; SMALL-BOWEL TOXICITY; ENZYME-ACTIVITY; FOLINIC ACID; 5-FLUOROURACIL; CHRONOTHERAPY; FLUOROURACIL; OXALIPLATIN; LEUCOVORIN AB Background. 5 fluorouracil (5FU) is associated with significant GI side-effects. Randomized trials have shown a 50% reduction in severe diarrhea with chrono-chemotherapy versus conventional regimens at similar doses. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in 5FU breakdown. We hypothesized that DPD has a circadian expression Pattern, accounting for the reduced GI side effects of chrono-modulated 5FU therapy. Methods. Fifty-one rats were killed at 3-hourly intervals over 24 hours. DPD and thymidylate synthase (TS) mRNA in jejunal and colonic mucosa were measured using qRT-PCP, Cosinor analysis was used for statistical comparison. Results. There was a significant circadian rhythm in the DPD mRNA expression in jejunum (1.7-fold, P < .001) and colon (1.5 fold, P < .01), with a peak expression in early sleep phase, and a trough at mid-wake cycle. TS also followed a circadian rhythm in jejunal mucosa with a peak at early rest phase. Conclusion. This rhythm in DPD expression may explain the benefit of chrono-chemotherapy. The peak of DPD expression in sleep phase in rats corresponds to time for lower GI adverse effects in chrono-chemotherapy in human trials. We believe better understanding of this process allows development of novel approaches to optimize the timing of chemotherapy without the administrative challenges of chronotherapy. (Surgery 2009;146:269-73.) C1 [Abolmaali, Kamran; Balakrishnan, Anita; Stearns, Adam T.; Rounds, Jan; Rhoads, David B.; Ashley, Stanley W.; Tavakkolizadeh, Ali] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Abolmaali, Kamran; Balakrishnan, Anita; Stearns, Adam T.; Ashley, Stanley W.; Tavakkolizadeh, Ali] Harvard Univ, Sch Med, Boston, MA USA. [Rhoads, David B.] MassGen Hosp Children, Boston, MA USA. [Balakrishnan, Anita] Univ Liverpool, Div Gastroenterol, Sch Clin Sci, Liverpool L69 3BX, Merseyside, England. [Stearns, Adam T.] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. RP Tavakkolizadeh, A (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM atavakkoli@partners.org OI Stearns, Adam/0000-0003-4327-7360 FU NIDDK NIH HHS [P30 DK040561-14, P30 DK040561] NR 25 TC 9 Z9 11 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2009 VL 146 IS 2 BP 269 EP 273 DI 10.1016/j.surg.2009.05.005 PG 5 WC Surgery SC Surgery GA 483MY UT WOS:000268972200019 PM 19628084 ER PT J AU Alam, HB Shuja, F Butt, MU Duggan, M Li, YQ Zacharias, N Fukudome, EY Liu, BL deMoya, M Velmahos, GC AF Alam, Hasan B. Shuja, Fahad Butt, Muhammad U. Duggan, Michael Li, Yongqing Zacharias, Nikolaos Fukudome, Eugene Y. Liu, Baoling deMoya, Marc Velmahos, George C. TI Surviving blood loss without blood transfusion in a swine poly-trauma model SO SURGERY LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the Society-of-University-Surgeons/4th Annual Academic Surgical Congress CY FEB 03-06, 2009 CL Ft Myers, FL SP Soc Univ Surg, Assoc Acad Surg ID DIFFERENT RESUSCITATION STRATEGIES; HEMORRHAGIC-SHOCK; VALPROIC ACID; HISTONE DEACETYLASE; FLUID RESUSCITATION; THERAPEUTIC TARGET; MILITARY; COAGULOPATHY AB Background. We have demonstrated previously that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival in lethal models of hemorrhagic shock. This study investigated Whether VPA treatment would improve survival in a clinically relevant large animal model of poly-trauma/hemorrhagic shock, and whether the Protective effects are executed through the Akt survival pathway. Methods. Yorkshire swine were subjected to a poly-trauma protocol, including: (1) Pre-hospital phase-Femur fracture, 60% hemorrhage, 30 min of shock (mean arterial pressure [MAP]: 25-30 mmHg), and infusion of 154mM NaCl (3 x shed blood); (2) Early hospital phase A Grade V liver injury (simulating rupture of a previously contained hematoma) followed by liver packing; (3) Treatment/monitoring phase randomization to 3 treatment groups (n = 6-8/group): no treatment (control), fresh whole blood (FWB), and intravenous VPA (400 mg/kg, given during the pre-hospital phase). Animals, were monitored for 4 h, with survival being the primary endpoint. Liver tissue was subjected to Western blot analysis. Results. FWB (n = 6) and VPA treatments (n = 7) significantly increased survival (100% and 86%, respectively) compared to control group (n = 8) (25%). The protocol produced, significant anemia, (Hb < 6 g/dL) and lactic acidosis (lactate 3-5 mmol/L.). Acidosis improved after blood transfusion and worsened in the other two groups. VPA treatment increased phospho-Akt (activated), phospho-GSK-3 beta (Glycogen synthase kinase 3 beta), beta-catenin and Bcl-2 (B-cell leukemia/lymphoma. 2) protein levels, compared to control group (P = .01, .01, .03, and .02, respectively). There was no significant difference in the level of these proteins between the control and FWB groups. Conclusion. Treatment with VPA without blood transfusion improves early survival in a highly lethal poly-trauma and hemorrhagic shock model. The survival advantage is due not to improvement in resuscitation but to better tolerance of shock by the cells, in part due to the preservation of the Akt survival pathway. (Surgery 2009;146:325-33.) C1 [Alam, Hasan B.; Shuja, Fahad; Butt, Muhammad U.; Duggan, Michael; Li, Yongqing; Zacharias, Nikolaos; Fukudome, Eugene Y.; Liu, Baoling; deMoya, Marc; Velmahos, George C.] Harvard Univ, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Med Sch, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 26 TC 48 Z9 52 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2009 VL 146 IS 2 BP 325 EP 333 DI 10.1016/j.surg.2009.04.007 PG 9 WC Surgery SC Surgery GA 483MY UT WOS:000268972200027 PM 19628092 ER PT J AU Sheu, EG Oakes, SM Ahmadi-Yazdi, C Afnan, J Carroll, MC Moore, FD AF Sheu, Eric G. Oakes, Sean M. Ahmadi-Yazdi, Cyrus Afnan, Jalil Carroll, Michael C. Moore, Francis D., Jr. TI Restoration of Skeletal muscle ischemia-reperfusion injury in humanized immunodeficient mice SO SURGERY LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the Society-of-University-Surgeons/4th Annual Academic Surgical Congress CY FEB 03-06, 2009 CL Ft Myers, FL SP Soc Univ Surg, Assoc Acad Surg ID COMPLEMENT RECEPTOR TYPE-1; ISCHEMIA/REPERFUSION INJURY; NATURAL ANTIBODY; IGM; MODEL; ACTIVATION; IDENTIFICATION; DISEASE; CELLS AB Background. Ischemia anti reperfusion (I/R) of tissue provokes an inflammatory process that is highly dependent on circulating natural immunoglobulin M (IgM) and the complement cascade. In mice, a single IgM specificity produced by peritoneal B cells can initiate reperfusion injury. It is unknown whether humans express natural IgM with a similar specificity. It is also unknown whether Pathogenic IgM is produced solely from peritoneal B cells or can also be made by circulating B cells. Methods. Immunodeficient mice lacking endogenous immunoglobulin were used. Mice were reconstituted with 0.9% normal saline, human serum, or xenografted human peripheral blood lymphocytes (PBLs) and then subjected to tourniquet-induced hindlimb I/R. Serum human IgM and immunoglobulin G (IgG) were measured by enzyme-linked immunosorbent (ELISA) assay. Skeletal muscle was harvested for injury assessment by histology and for immunohistochemistry. Results. Immunodeficient mice were protected from skeletal muscle injury after hindlimb I/R. Transfer of human serum restored skeletal muscle damage. Rag2/gamma R-/- mice that were engrafted with human PBL (huPBL-SCID) had high levels of human IgM. huPBL-SCID mice developed significantly more skeletal muscle injury than control saline-treated mice (P <= .01) and human serum-reconstituted Rag2/gamma R-/- mice (P <= 0.01). Sham-treated huPBL-SCID mice had no muscle injury, demonstrating that human lymphocyte engraftment did not cause injury in the absence of ischemia. Deposition of human IgM was observed on injured but not sham-injured muscle. Conclusion. Human serum can initiate murine skeletal muscle I/R injury. Circulating human PBL may be a source of pathogenic IgM. The huPBL-SCID mouse may be a useful model to define the specificity of pathogenic human IgM and, to test therapeutics for I/R injury. (Surgery 2009;146:340-6.) C1 [Sheu, Eric G.; Oakes, Sean M.; Ahmadi-Yazdi, Cyrus; Afnan, Jalil; Moore, Francis D., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. RP Moore, FD (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM fmoore@partners.org FU NIGMS NIH HHS [P50 GM052585, P50GM052585, F32 GM084639, F32GM084639, P50 GM052585-13, P50 GM052585-15] NR 25 TC 6 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2009 VL 146 IS 2 BP 340 EP 346 DI 10.1016/j.surg.2009.06.010 PG 7 WC Surgery SC Surgery GA 483MY UT WOS:000268972200029 PM 19628094 ER PT J AU Baer, S Baddley, JW Gnann, JW Pappas, PG AF Baer, S. Baddley, J. W. Gnann, J. W. Pappas, P. G. TI Cryptococcal disease presenting as necrotizing cellulitis in transplant recipients SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE Cryptococcus; necrotizing fasciitis; necrotizing vasculitis; myositis; transplantation ID NEOFORMANS; VASCULITIS; FASCIITIS AB P>Disseminated cryptococcosis uncommonly presents with skin lesions in immunocompromised hosts. Necrotizing fasciitis, necrotizing vasculitis, myositis, or necrotizing soft tissue infection are even more rare presentations. We report 3 cases of cryptococcal necrotizing soft tissue infection, 2 in renal transplant patients, and 1 in a heart transplant patient, and discuss similar cases from the literature. Cryptococcus neoformans should be considered in the differential diagnosis of cellulitis or necrotizing soft tissue infections in immunocompromised patients. C1 [Baer, S.] Augusta VA Med Ctr, Augusta, GA 30904 USA. [Baer, S.] Med Coll Georgia, Dept Internal Med, Div Infect Dis, Augusta, GA 30912 USA. [Baddley, J. W.; Gnann, J. W.; Pappas, P. G.] Univ Alabama, Dept Internal Med, Div Infect Dis, Birmingham, AL USA. [Baddley, J. W.; Gnann, J. W.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Baer, S (reprint author), Augusta VA Med Ctr, 1 Freedom Way 235, Augusta, GA 30904 USA. EM sbaer@mcg.edu NR 19 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD AUG PY 2009 VL 11 IS 4 BP 353 EP 358 DI 10.1111/j.1399-3062.2009.00399.x PG 6 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 480EI UT WOS:000268714600014 PM 19422669 ER PT J AU Frese, J Hackstein, H Menzler, S Padberg, W Madsen, JC Hoerbelt, R AF Frese, Jan Hackstein, Holger Menzler, Stefan Padberg, Winfried Madsen, Joren C. Hoerbelt, Ruediger TI THE EFFECT OF INHIBITION OF INDIRECT T-CELL ACTIVATION ON CHRONIC REJECTION OF KIDNEY ALLOGRAFTS IN RATS SO TRANSPLANT INTERNATIONAL LA English DT Meeting Abstract C1 [Frese, Jan; Menzler, Stefan; Padberg, Winfried; Madsen, Joren C.; Hoerbelt, Ruediger] Univ Giessen, Dept Surg, Giessen, Germany. [Hackstein, Holger] Univ Giessen, Dept Immunol, Giessen, Germany. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD AUG PY 2009 VL 22 BP 126 EP 126 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 489AV UT WOS:000269392800468 ER PT J AU Meier, M Fricke, L Wong, WC Steinhoff, J Lehnert, H Kramer, J Nitschke, M AF Meier, Markus Fricke, Lutz Wong, Waichi Steinhoff, Juergen Lehnert, Hendrik Kramer, Jan Nitschke, Martin TI CLOSURE OF HIGH-VOLUME ARTERIOVENOUS FISTULAS RESCUES RENAL ALLOGRAFT FUNCTION IN PATIENTS WITH RIGHT HEART FAILURE. A RETROSPECTIVE ANALYSIS OF 6 PATIENTS SO TRANSPLANT INTERNATIONAL LA English DT Meeting Abstract C1 [Meier, Markus; Fricke, Lutz; Steinhoff, Juergen; Lehnert, Hendrik; Kramer, Jan; Nitschke, Martin] Med Univ Lubeck, Sch Med, Transplant Ctr, Med Clin 1, D-23538 Lubeck, Germany. [Wong, Waichi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD AUG PY 2009 VL 22 BP 183 EP 183 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 489AV UT WOS:000269392800696 ER PT J AU Fricke, L Meier, M Bode, W Wong, WC Lehnert, H Steinhoff, J Meier, M AF Fricke, Lutz Meier, Markus Bode, Wibke Wong, Waichi Lehnert, Hendrik Steinhoff, Juergen Meier, Markus TI LOW DOSE IMMUNOSUPPRESSION IS NOT SUFFICIENT TO AVOID ACUTE REJECTIONS IN OLD FOR OLD KIDNEY TRANSPLANT RECIPIENTS: A ONE YEAR PROSPECTIVE MULTICENTER RANDOMIZED CONTROLLED TRIAL SO TRANSPLANT INTERNATIONAL LA English DT Meeting Abstract C1 [Fricke, Lutz; Meier, Markus; Bode, Wibke; Lehnert, Hendrik; Steinhoff, Juergen; Meier, Markus] Univ Lubeck, Sch Med, Med Clin 1, Transplant Ctr, Lubeck, Germany. [Wong, Waichi] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD AUG PY 2009 VL 22 BP 190 EP 190 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 489AV UT WOS:000269392800723 ER PT J AU Huang, PL AF Huang, Paul L. TI eNOS, metabolic syndrome and cardiovascular disease SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID NITRIC-OXIDE SYNTHASE; DOUBLE-KNOCKOUT MICE; VASCULAR ENDOTHELIAL-CELLS; PROTEIN-KINASE AKT; INSULIN-RESISTANCE; MITOCHONDRIAL BIOGENESIS; ACCELERATED ATHEROSCLEROSIS; MICROVASCULAR DYSFUNCTION; PRIMARY PREVENTION; PROVISIONAL REPORT AB Large epidemiologic studies have established that diabetes, hyperlipidemia and obesity all increase the risk for cardiovascular disease. However, the precise mechanisms by which these metabolic disorders increase the propensity to develop atherosclerosis are not known. Recently, the concept of the metabolic syndrome - a constellation of conditions including obesity, hypertension, hyperlipidemia and insulin resistance - has received much attention. Studies on the metabolic syndrome might enable a better understanding of the underlying biological mechanisms that lead to cardiovascular disease. This review focuses on endothelial nitric oxide synthase and summarizes evidence that a reduction in the bioavailability of endothelium-derived nitric oxide serves as a key link between metabolic disorders and cardiovascular risk. C1 [Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM phuang1@partners.org FU NINDS NIH HHS [R01 NS033335, R01 NS033335-15] NR 88 TC 149 Z9 167 U1 2 U2 16 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD AUG PY 2009 VL 20 IS 6 BP 295 EP 302 DI 10.1016/j.tem.2009.03.005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 489HV UT WOS:000269412000006 PM 19647446 ER PT J AU Caviness, VS Nowakowski, RS Bhide, PG AF Caviness, Verne S., Jr. Nowakowski, Richard S. Bhide, Pradeep G. TI Neocortical neurogenesis: morphogenetic gradients and beyond SO TRENDS IN NEUROSCIENCES LA English DT Review ID CELL FATE SPECIFICATION; INTERMEDIATE PROGENITOR CELLS; CYCLIN-DEPENDENT KINASES; MURINE CEREBRAL WALL; RADIAL GLIAL-CELLS; NEURAL STEM-CELLS; PROLIFERATIVE EPITHELIUM; MAMMALIAN TELENCEPHALON; SUBVENTRICULAR ZONE; SEGMENTATION CLOCK AB Each of the five cellular layers of the cerebral neocortex is composed of a specific number of a single predominant 'class' of projection neuron. The projection neuron class is defined by its unique morphology and axonal projections to other areas of the brain. Precursor cell populations lining the embryonic lateral ventricles produce the projection neurons. The mechanisms regulating precursor cell proliferation also regulate total numbers of neurons produced at specific developmental periods and destined to a specific neocortical layer. Because the newborn neurons migrate relatively long distances to reach their final layer destinations, it is often assumed that the mechanisms governing acquisition of neuronal-class-specific characteristics, many of which become evident after neuron production, are independent of the mechanisms governing neuron production. We review evidence that suggests that the two mechanisms might be linked via operations of Notch1 and p27(Kip1) molecules known to regulate precursor cell proliferation and neuron production. C1 [Caviness, Verne S., Jr.; Bhide, Pradeep G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Nowakowski, Richard S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. RP Caviness, VS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM caviness@helix.mgh.harvard.edu RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670; Bhide, Pradeep/0000-0003-4236-9415 FU NIDA NIH HHS [R01 DA020796, R01 DA020796-04]; NINDS NIH HHS [P30 NS045776, P30 NS045776-06A17807, R01 NS012005-33, R01 NS043426, R01 NS043426-05] NR 85 TC 44 Z9 45 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD AUG PY 2009 VL 32 IS 8 BP 443 EP 450 DI 10.1016/j.tins.2009.05.003 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 489HW UT WOS:000269412100004 PM 19635637 ER PT J AU Rudolph, JL Sorond, FA Pochay, VE Haime, M Treanor, P Crittenden, MD Babikian, VL AF Rudolph, James L. Sorond, Farzaneh A. Pochay, Val E. Haime, Miguel Treanor, Patrick Crittenden, Michael D. Babikian, Viken L. TI CEREBRAL HEMODYNAMICS DURING CORONARY ARTERY BYPASS GRAFT SURGERY: THE EFFECT OF CAROTID STENOSIS SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 32nd International Stroke Conference CY FEB 07-08, 2007 CL San Francisco, CA DE Transcranial Doppler; Carotid stenosis; Cardiac surgery; Cerebral perfusion ID TRANSCRANIAL DOPPLER SONOGRAPHY; BLOOD-FLOW AUTOREGULATION; VELOCITY; ENDARTERECTOMY; OCCLUSION; HUMANS AB Carotid stenosis is a frequent coexisting condition in patients undergoing coronary artery bypass graft (CABG) surgery,. The impact of carotid stenosis on cerebral perfusion is not fully understood. The purpose of this study was to determine the impact of carotid stenosis on cerebral blood flow velocity in patients undergoing CABG. Seventy-three patients undergoing CABG were prospectively recruited and underwent preoperative Duplex carotid ultrasound to evaluate the degree of carotid stenosis. Intraoperatively, transcranial Doppler ultrasound was used to record the mean flow velocity (MFV) within the bilateral middle cerebral arteries. In addition, during the period of cardiopulmonary bypass, regulators of cerebral hemodynamics such as hematocrit, partial pressure of carbon dioxide and temperature were recorded. The ipsilateral middle cerebral artery mean How velocity was compared in arteries with and without carotid stenosis using a repeated measures analysis. Seventy-three patients underwent intraoperative monitoring during CABG and 30% (n = 22) had carotid stenosis. Overall, MFV rose throughout the duration of CABG including when the patient was on cardiopulmonary bypass. However, there was no significant MFV difference between those arteries with and without stenosis (F = 1.2, p = .21). Further analysis during cardiopulmonary bypass, demonstrated that hemodilution and partial pressure of carbon dioxide may play a role in cerebral autoregulation during CABG. Carotid stenosis did not impact mean cerebral blood flow velocity during CABG. The cerebrovascular regulatory process appears to be largely intact during CABG. (E-mail: jrudolph@partners.org) Published by Elsevier Inc. oil behalf of World Federation for Ultrasound in Medicine & Biology. C1 [Rudolph, James L.] Ctr Geriatr Res Educ & Clin, Boston, MA USA. [Pochay, Val E.; Babikian, Viken L.] VA Boston Healthcare Syst, Dept Neurol, Boston, MA USA. [Haime, Miguel; Treanor, Patrick] VA Boston Healthcare Syst, Dept Cardiac Surg, Boston, MA USA. [Sorond, Farzaneh A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Crittenden, Michael D.] St Louis VA Med Ctr, Dept Surg, Div Cardiac Surg, St Louis, MO USA. [Babikian, Viken L.] Boston Univ, Med Ctr, Dept Neurol, Boston, MA USA. [Rudolph, James L.; Sorond, Farzaneh A.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VABHS GRECC JP-182,150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU NIA NIH HHS [AG08812, Z01 AG000294, AG000294, AG030967, R03 AG029861-02, K23 AG030967, AG029861, P60 AG008812, K23 AG030967-01A1, K12 AG000294, R03 AG029861] NR 27 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD AUG PY 2009 VL 35 IS 8 BP 1235 EP 1241 DI 10.1016/j.ultrasmedbio.2009.04.008 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 481BR UT WOS:000268782100001 PM 19540657 ER PT J AU Kiernan, TJ Taqueti, V Crevensten, G Yan, BP Slovut, DP Jaff, MR AF Kiernan, Thomas J. Taqueti, Viviany Crevensten, Gwen Yan, Bryan P. Slovut, David P. Jaff, Michael R. TI Correlates of carotid stenosis in patients undergoing coronary artery bypass grafting - a case control study SO VASCULAR MEDICINE LA English DT Article DE carotid arteries; carotid artery diseases; carotid stenosis; cerebral artery ID CARDIAC-SURGERY; RISK-FACTORS; STROKE RISK; DISEASE AB Carotid duplex ultrasonography (DUS) is routinely performed prior to coronary artery bypass graft surgery (CABG) on all patients > 65 years old because of the reported associated risk of finding concomitant carotid artery stenosis. Identifying risk factors that correlate with severe carotid stenosis may result in more cost-effective screening for patients with asymptomatic carotid artery disease prior to CABG. We performed a retrospective study to identify risk factors for significant carotid artery disease in patients scheduled to undergo CABG between March 2005 and March 2008 at the Massachusetts General Hospital. Patients with carotid stenosis >= 70% identified by DUS (n = 50) were matched by age and sex to control patients who had < 50% stenosis (n = 50). Data were analyzed using the chi-squared test or analysis of variance as appropriate. Logistic regression was used to examine multi-variate correlates of carotid stenosis. A total of 643 patients were screened to arrive at the patient cohorts described below. This produced a prevalence of 7.7% for significant (> 70%) carotid disease. The patient cohorts were predominantly male with no significant difference in the incidence of diabetes, hypertension, extent of coronary artery disease (CAD) (i.e. left main coronary artery disease (LMCA) and one, two-, or three-vessel CAD) or lipid abnormalities in the two groups. Univariate analysis identified the presence of peripheral arterial disease (PAD, p = 0.001), a cervical bruit (p < 0.0001), a prior neurological event (p = 0.020), and the presence of an abdominal aortic aneurysm (AAA; p = 0.046) as significant predictors of = 70% internal carotid artery stenosis. Logistic regression analysis revealed that the presence of a carotid bruit (p = 0.0068) and PAD (p = 0.0194) were associated with an increased risk of significant carotid artery disease. In conclusion, the presence of a carotid bruit or PAD predicts an increased likelihood of significant carotid artery disease in patients undergoing CABG. Unlike previous studies, LMCA or extent of CAD did not correlate with significant carotid artery disease. Using these predictive models, a prospective outcomes trial is required to validate these criteria. C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Vasc Ctr,Sect Vasc Med, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Vasc Ctr,Sect Vasc Med, Boston, MA 02114 USA. EM mjaff@partners.org RI Yan, Bryan/P-5928-2015 NR 27 TC 12 Z9 13 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD AUG 1 PY 2009 VL 14 IS 3 BP 233 EP 237 DI 10.1177/1358863X08101643 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 478DP UT WOS:000268568300006 PM 19651673 ER PT J AU Patel, PM Eisenberg, J Islam, MA Maree, AO Rosenfield, KA AF Patel, Pranav M. Eisenberg, Jonathan Islam, M. Ashequl Maree, Andrew O. Rosenfield, Kenneth A. TI Percutaneous revascularization of persistent renal artery in-stent restenosis SO VASCULAR MEDICINE LA English DT Article DE peripheral vascular diseases; renal artery; renal artery obstruction; stents ID CUTTING BALLOON ANGIOPLASTY; ENDOVASCULAR BRACHYTHERAPY; RENOVASCULAR DISEASE; ILIAC ARTERY; STENOSIS; GRAFT; ANEURYSM; TRIAL; INTERVENTION; IMPLANTATION AB Percutaneous renal artery stenting is a common means of treating atherosclerotic renal artery stenosis. However, renal artery restenosis remains a frequent problem. The optimal treatment of restenosis has not been established and may involve percutaneous renal artery angioplasty or deployment of a second stent. Other modalities include cutting balloon angioplasty, repeat stenting with drug-eluting stents or endovascular brachytherapy. Most recently, use of polytetrafluoroethylene (PTFE)-covered stents may offer a new and innovative way to treat recurrent renal artery stenosis. We describe a case in a patient who initially presented with renal insufficiency and multi-drug hypertension in the setting of severe bilateral renal artery stenosis. Her renal artery stenosis was initially successfully treated by percutaneous deployment of bilateral bare metal renal artery stents. After initial improvement of her hypertension and renal insufficiency, both parameters declined and follow-up duplex evaluation confirmed renal artery in-stent restenosis. Owing to other medical co-morbidities she was felt to be a poor surgical candidate and was subsequently treated first with bilateral cutting balloon angioplasty and second with drug-eluting stent deployment. Each procedure was associated with initial improvement of renal function and blood pressure control, which then later deteriorated with the development of further significant in-stent restenosis. It was then decided to treat the restenosis using PTFE-covered stents. At 12 months of follow-up, the blood pressure had remained stable and renal function had normalized. The covered stents remained free of any significant neointimal tissue or obstruction. C1 [Patel, Pranav M.; Eisenberg, Jonathan; Islam, M. Ashequl; Maree, Andrew O.; Rosenfield, Kenneth A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Cambridge, MA 02138 USA. RP Patel, PM (reprint author), Univ Calif Irvine, Div Cardiol, 101 City Dr S,Rte 81,Bldg 53,Rm 100, Orange, CA 92868 USA. EM pranavp@uci.edu NR 39 TC 10 Z9 10 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD AUG 1 PY 2009 VL 14 IS 3 BP 259 EP 264 DI 10.1177/1358863X08100386 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 478DP UT WOS:000268568300009 PM 19651676 ER PT J AU Slovut, DP AF Slovut, David P. TI Screening renal angiography as a routine part of cardiac catheterization: a reappraisal SO VASCULAR MEDICINE LA English DT Editorial Material ID ATHEROSCLEROTIC RENOVASCULAR DISEASE; CHRONIC KIDNEY-DISEASE; EVALUATION PROGRAM KEEP; 4-YEAR FOLLOW-UP; ARTERY STENOSIS; CARDIOVASCULAR-DISEASE; CORONARY-ANGIOGRAPHY; STENT REVASCULARIZATION; CLINICAL CARDIOLOGY; VASCULAR-DISEASE C1 [Slovut, David P.] N Shore Med Ctr, Dept Vasc Med, Salem, MA 01970 USA. [Slovut, David P.] N Shore Med Ctr, Dept Cardiol, Salem, MA 01970 USA. [Slovut, David P.] Massachusetts Gen Hosp, Dept Vasc Med, Salem, MA USA. RP Slovut, DP (reprint author), N Shore Med Ctr, Dept Vasc Med, 81 Highland Ave, Salem, MA 01970 USA. EM david.slovut@mssm.edu NR 39 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD AUG 1 PY 2009 VL 14 IS 3 BP 271 EP 275 DI 10.1177/1358863X09104225 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 478DP UT WOS:000268568300011 PM 19651678 ER PT J AU Ruangchira-urai, R Mark, EJ AF Ruangchira-urai, Ruchira Mark, Eugene J. TI Lymphangiomatoid pattern in diffuse malignant mesothelioma of the pleura: a report of six cases SO VIRCHOWS ARCHIV LA English DT Article DE Lymphangiomatoid; Diffuse malignant mesothelioma ID PERITONEAL MESOTHELIOMA; DIFFERENTIAL-DIAGNOSIS; MORPHOLOGIC SPECTRUM; CELL MESOTHELIOMA; YOUNG FEMALES; FEATURES; VARIANT AB The multiplicity of epithelioid and mesenchymal forms of diffuse malignant mesothelioma includes patterns that may mimic another process. Identification of the multiplicity of patterns may help in the diagnosis of diffuse malignant mesothelioma. One pattern that has not been described is lymphangiomatoid. We observed six cases with ovoid or elongated or irregular anastomosing vascular-like spaces lined by flattened cells simulating lymphangioma. The luminal spaces could contain proteinaceous material simulating lymph but not erythrocytes. The cells lining the spaces were mesothelial by immunohistochemical staining. The lymphangiomatoid areas never constituted more than 40% of the area of the tumor on the slides. When seen in more solid areas of tumor, the lymphangiomatoid structures generally did not produce diagnostic difficulty. However, when seen at the edge of solid tumor or forming an irregular nodule or invading into adjacent adipose tissue, these lymphangiomatoid structures could be confusing. All six patients had been exposed to asbestos either by occupation or by spousal exposure. Three patients received chemotherapy. One patient died of diffuse malignant mesothelioma of the pleura. C1 [Ruangchira-urai, Ruchira; Mark, Eugene J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ruangchira-urai, Ruchira] Mahidol Univ, Siriraj Hosp, Dept Pathol, Bangkok 10700, Thailand. RP Mark, EJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM emark@partners.org 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 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD AUG PY 2009 VL 455 IS 2 BP 143 EP 148 DI 10.1007/s00428-009-0806-y PG 6 WC Pathology SC Pathology GA 483XW UT WOS:000269007700006 PM 19618209 ER PT J AU Li, JH Chian, RJ Ay, I Celia, SA Kashi, BB Tamrazian, E Matthews, JC Remington, MP Pepinsky, RB Fishman, PS Brown, RH Francis, JW AF Li, Jianhong Chian, Ru-Ju Ay, Ilknur Celia, Samuel A. Kashi, Brenda B. Tamrazian, Eric Matthews, Jonathan C. Remington, Mary P. Pepinsky, R. Blake Fishman, Paul S. Brown, Robert H., Jr. Francis, Jonathan W. TI Recombinant GDNF: Tetanus toxin fragment C fusion protein produced from insect cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Recombinant protein; GDNF; Tetanus toxin fragment C; Fusion protein; Insect cells; Ganglioside binding; PhosphoAkt ID NEUROTROPHIC FACTOR; MOTOR-NEURONS; DELIVERY; BINDING; GLYCOSYLATION; EXPRESSION; TRANSPORT; SURVIVAL; RECEPTOR; SYSTEM AB Glial cell line-derived neurotrophic factor (GDNF) has potent survival-promoting effects on CNS motor neurons in experimental animals. Its therapeutic efficacy in humans, however, may have been limited by poor bioavailability to the brain and spinal cord. With a view toward improving delivery of GDNF to CNS motor neurons in vivo, we generated a recombinant fusion protein comprised of rat GDNF linked to the non-toxic, neuron-binding fragment of tetanus toxin. Recombinant GDNF:TFC produced from insect cells was a soluble homodimer like wild-type GDNF and was bi-functional with respect to GDNF and TTC activity. Like recombinant rat GDNF, the fusion protein increased levels of immunoreactive phosphoAkt in treated NB41A3-hGFR alpha-1 neuroblastoma cells. Like TTC, GDNF:TTC bound to immobilized ganglioside GT1b in vitro with high affinity and selectivity. These results Support further testing of recombinant GDNF:TTC as a non-viral vector to improve delivery of GDNF to brain and spinal Cord in vivo. (C) 2009 Elsevier Inc. All rights reserved. C1 [Li, Jianhong; Chian, Ru-Ju; Ay, Ilknur; Celia, Samuel A.; Kashi, Brenda B.; Tamrazian, Eric; Matthews, Jonathan C.; Brown, Robert H., Jr.; Francis, Jonathan W.] Massachusetts Gen Hosp, Dept Neurol, Cecil B Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. [Remington, Mary P.; Fishman, Paul S.] Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA. [Pepinsky, R. Blake] Biogenldec Inc, Cambridge Ctr 14, Cambridge, MA 02142 USA. [Fishman, Paul S.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Francis, JW (reprint author), Massachusetts Gen Hosp, Dept Neurol, Cecil B Day Lab Neuromuscular Res, Bldg 114,l6th St,Room 3003, Charlestown, MA 02129 USA. EM jwfrancisby@gmail.com RI li, jianhong/D-3483-2009 FU National Institute of Neurological Disorders and Stroke FX We thank Dr. Konrad Miatkowski from Biogenldec for his technical advice on production of recombinant proteins from insect cells. NB41A3-hGFR alpha-1 neuroblastoma cells were obtained from Biogenldec. Recombinant human GDNF expressed in E. coli was a generous gift from Amgen, Inc. Our work was supported by the National Institute of Neurological Disorders and Stroke (J.W.F., RJ.C., S.A.C., R.H.B.; RO1 NS038679), the Muscular Dystrophy Association (J.W.F., J.L.), the ALS Therapy Alliance (R.H.B., J.W.F., B.B.K., J.L., RJ.C.), Project ALS (R.H.B., J.W.F.) and AviTx, Inc. (R.H.B., J.W.F.). NR 21 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 31 PY 2009 VL 385 IS 3 BP 380 EP 384 DI 10.1016/j.bbrc.2009.05.079 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 459YP UT WOS:000267149800017 PM 19465006 ER PT J AU Kao, SY AF Kao, Shyan-Yuan TI Rescue of alpha-synuclein cytotoxicity by insulin-like growth factors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Parkinson disease; alpha-Synuclein; Insulin-like growth factor 1; Protein aggregation ID SPINOCEREBELLAR ATAXIA TYPE-1; PARKINSONS-DISEASE; LEWY BODIES; RAT MODEL; GENE; MUTATIONS; NEURODEGENERATION; DEMENTIA; NEUROTOXICITY; COMPONENT AB While Mutation of alpha-Synuclein is a Cause of autosomal-dominant Parkinson's disease (PD), it is still elusive as to how alpha-synuclein is involved in the pathogenesis of PD. Here, we show that dopamine-dependent accumulation of alpha-synuclein in Cultured cells results in apoptosis. Furthermore, activation of insulin-like growth factor 1 (IGF-1) pathway can rescue alpha-synuclein toxicity and suppress alpha-synuclein aggregation through the activation of PI3K/Akt pathways. These results suggest the therapeutic potential of IGF-1 pathway in Parkinson disease. (C) 2009 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Kao, SY (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM shyan-yuan_kao@meei.harvard.edu NR 30 TC 15 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 31 PY 2009 VL 385 IS 3 BP 434 EP 438 DI 10.1016/j.bbrc.2009.05.089 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 459YP UT WOS:000267149800027 PM 19470380 ER PT J AU Kruse, GR Barbour, R Heimer, R Shaboltas, AV Toussova, OV Hoffman, IF Kozlov, AP AF Kruse, Gina Rae Barbour, Russell Heimer, Robert Shaboltas, Alla V. Toussova, Olga V. Hoffman, Irving F. Kozlov, Andrei P. TI Drug choice, spatial distribution, HIV risk, and HIV prevalence among injection drug users in St. Petersburg, Russia SO HARM REDUCTION JOURNAL LA English DT Article ID METHAMPHETAMINE USE; DETERMINANTS; TRANSMISSION; IMPULSIVITY; EPIDEMIC AB Background: The HIV epidemic in Russia has been driven by the unsafe injection of drugs, predominantly heroin and the ephedrine derived psychostimulants. Understanding differences in HIV risk behaviors among injectors associated with different substances has important implications for prevention programs. Methods: We examined behaviors associated with HIV risk among 900 IDUs who inject heroin, psychostimulants, or multiple substances in 2002. Study participants completed screening questionnaires that provided data on sociodemographics, drug use, place of residence and injection- and sex-related HIV risk behaviors. HIV testing was performed and prevalence was modeled using general estimating equation (GEE) analysis. Individuals were clustered by neighborhood and disaggregated into three drug use categories: Heroin Only Users, Stimulant Only Users, and Mixed Drug Users. Results: Among Heroin Only Users, younger age, front/backloading of syringes, sharing cotton and cookers were all significant predictors of HIV infection. In contrast, sharing needles and rinse water were significant among the Stimulant Only Users. The Mixed Drug Use group was similar to the Heroin Only Users with age, front/back loading, and sharing cotton significantly associated with HIV infection. These differences became apparent only when neighborhood of residence was included in models run using GEE. Conclusion: The type of drug injected was associated with distinct behavioral risks. Risks specific to Stimulant Only Users appeared related to direct syringe sharing. The risks specific to the other two groups are common to the process of sharing drugs in preparation to injecting. Across the board, IDUs could profit from prevention education that emphasizes both access to clean syringes and preparing and apportioning drug with these clean syringes. However, attention to neighborhood differences might improve the intervention impact for injectors who favor different drugs. C1 [Heimer, Robert] Yale Univ, Sch Publ Hlth, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Barbour, Russell; Heimer, Robert] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [Kruse, Gina Rae] Baylor Coll Med, Houston, TX 77030 USA. [Shaboltas, Alla V.] St Petersburg State Univ, Fac Psychol, St Petersburg, Russia. [Shaboltas, Alla V.; Toussova, Olga V.; Kozlov, Andrei P.] Biomed Ctr, St Petersburg, Russia. [Hoffman, Irving F.] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA. [Kruse, Gina Rae] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Heimer, R (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol & Publ Hlth, POB 208034,60 Coll St, New Haven, CT 06520 USA. EM grkruse@gmail.com; russellbarbour@gmail.com; robert.heimer@yale.edu; alla@biomed.spb.ru; toussova@biomed.spb.ru; hoffmani@med.unc.edu; contact@biomed.spb.ru RI Kozlov, Andrei/H-2117-2016; OI Kozlov, Andrei/0000-0003-4611-1534; Shaboltas, Alla/0000-0002-1966-6924 FU FIC NIH HHS [U2R TW006893]; NIMH NIH HHS [P30 MH062294] NR 32 TC 12 Z9 12 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7517 J9 HARM REDUCT J JI Harm Reduct. J. PD JUL 31 PY 2009 VL 6 AR 22 DI 10.1186/1477-7517-6-22 PG 7 WC Substance Abuse SC Substance Abuse GA 542XR UT WOS:000273533100001 PM 19646255 ER PT J AU Parmar, K D'Andrea, A Niedernhofer, LJ AF Parmar, Kalindi D'Andrea, Alan Niedernhofer, Laura J. TI Mouse models of Fanconi anemia SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE Interstrand crosslinks; Gene targeting; Mouse models; Genome instability; Tumors; Stem cells ID HEMATOPOIETIC STEM-CELLS; NECROSIS-FACTOR-ALPHA; DOUBLE-STRAND BREAKS; GROUP-A GENE; HOMOLOGY-DIRECTED REPAIR; FANCD2 KNOCKOUT MICE; NUCLEAR RAD51 FOCI; IN-VIVO INFUSION; WILD-TYPE CELLS; GROUP-C AB Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway a, response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability. (C) 2009 Elsevier B.V. All rights reserved. C1 [Niedernhofer, Laura J.] Univ Pittsburgh, Sch Med, Dept Mol Genet & Microbiol, Pittsburgh, PA 15213 USA. [Parmar, Kalindi; D'Andrea, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Niedernhofer, Laura J.] Pittsburgh Canc Inst, Pittsburgh, PA 15213 USA. RP Niedernhofer, LJ (reprint author), Univ Pittsburgh, Sch Med, Dept Mol Genet & Microbiol, 5117 Ctr Ave,Hillman Canc Ctr,Res Pavil 2-6, Pittsburgh, PA 15213 USA. EM niedernhofer@upmc.edu FU Ellison Medical Foundation [AG-NS-0303-05]; NIEHS [R01 ES016714]; NIH [U19AI067751] FX L.J.N. is supported by The Ellison Medical Foundation (AG-NS-0303-05) and NIEHS (R01 ES016714). K.P. and A.D.D. were supported by NIH grant U19AI067751. NR 91 TC 53 Z9 55 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUL 31 PY 2009 VL 668 IS 1-2 BP 133 EP 140 DI 10.1016/j.mrfmmm.2009.03.015 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 484LN UT WOS:000269046500012 PM 19427003 ER PT J AU Muller, LUW Williams, DA AF Mueller, Lars U. W. Williams, David A. TI Finding the needle in the hay stack: Hematopoietic stem cells in Fanconi anemia SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE Fanconi anemia; HSC; Gene therapy; Bone marrow failure ID COLONY-STIMULATING FACTOR; DOSE G-CSF; SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW-TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; BLOOD CD34(+) CELLS; RETROVIRAL GENE MARKING; SEVERE APLASTIC-ANEMIA; NECROSIS-FACTOR-ALPHA; HUMAN SOMATIC-CELLS AB Fanconi anemia is a rare bone marrow failure and cancer predisposition syndrome. Childhood onset of aplastic anemia is one of the hallmarks of this condition. Supportive therapy in the form of blood products, androgens, and hematopoietic growth factors may boost blood counts temporarily. However, allogeneic hematopoietic stem cell transplantation (HSCT) currently remains the only curative treatment option for the hematologic manifestations of Fanconi anemia (FA). Here we review current clinical and pre-clinical strategies for treating hematopoietic stem cell (HSC) failure, including the experience with mobilizing and collecting CD34+ hematopoietic stem and progenitor cells as target cells for somatic gene therapy, the current state of FA gene therapy trials, and future prospects for cell and gene therapy. (C) 2009 Elsevier B.V. All rights reserved. C1 [Mueller, Lars U. W.; Williams, David A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med,Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Mueller, Lars U. W.; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mueller, Lars U. W.; Williams, David A.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Williams, DA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med,Div Pediat Hematol Oncol, 300 Longwood Ave,Karp 08125-4, Boston, MA 02115 USA. EM DAWilliams@childrens.harvard.edu FU St. Baldrick's Foundation; NIH [R01 HL081499, DK074310] FX This work was supported by a fellowship grant from the St. Baldrick's Foundation (to L.U.W.M.) and NIH R01 HL081499 and DK074310 (to D.A.W.). NR 106 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUL 31 PY 2009 VL 668 IS 1-2 BP 141 EP 149 DI 10.1016/j.mrfmmm.2009.03.010 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 484LN UT WOS:000269046500013 PM 19508850 ER PT J AU Russom, A Gupta, AK Nagrath, S Di Carlo, D Edd, JF Toner, M AF Russom, Aman Gupta, Amit K. Nagrath, Sunitha Di Carlo, Dino Edd, Jon F. Toner, Mehmet TI Differential inertial focusing of particles in curved low-aspect-ratio microchannels SO NEW JOURNAL OF PHYSICS LA English DT Article ID CONTINUOUS-FLOW SEPARATION; MICROFLUIDIC DEVICE; POISEUILLE FLOW; CELLS; MIGRATION; FILTER; SPHERE; SIZE AB Microfluidic-based manipulation of particles is of great interest due to the insight it provides into the physics of hydrodynamic forces. Here, we study a particle-size-dependent phenomenon based on differential inertial focusing that utilizes the flow characteristics of curved, low aspect ratio (channel width >> height), microfluidic channels. We report the emergence of two focusing points along the height of the channel (z-plane), where different sized particles are focused and ordered in evenly spaced trains at correspondingly different lateral positions within the channel cross-section. We applied the system for continuous ordering and separation of suspension particles. C1 [Russom, Aman] Shriners Hosp Children, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Russom, A (reprint author), Shriners Hosp Children, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. EM aman@kth.se RI Russom, Aman/B-1675-2012; OI Russom, Aman/0000-0002-0242-358X FU National Institute of Health [P41 EB-002503] FX This work was supported by the National Institute of Health (P41 EB-002503). Octavio Hurtado is acknowledged for help with microfabrication and we thank Ramin Haghgooie for discussions. NR 29 TC 67 Z9 68 U1 1 U2 41 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1367-2630 J9 NEW J PHYS JI New J. Phys. PD JUL 31 PY 2009 VL 11 AR 075025 DI 10.1088/1367-2630/11/7/075025 PG 9 WC Physics, Multidisciplinary SC Physics GA 479YW UT WOS:000268699200012 PM 20862272 ER PT J AU Swirski, FK Nahrendorf, M Etzrodt, M Wildgruber, M Cortez-Retamozo, V Panizzi, P Figueiredo, JL Kohler, RH Chudnovskiy, A Waterman, P Aikawa, E Mempel, TR Libby, P Weissleder, R Pittet, MJ AF Swirski, Filip K. Nahrendorf, Matthias Etzrodt, Martin Wildgruber, Moritz Cortez-Retamozo, Virna Panizzi, Peter Figueiredo, Jose-Luiz Kohler, Rainer H. Chudnovskiy, Aleksey Waterman, Peter Aikawa, Elena Mempel, Thorsten R. Libby, Peter Weissleder, Ralph Pittet, Mikael J. TI Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites SO SCIENCE LA English DT Article ID BLOOD-VESSELS; BONE-MARROW; RECEPTOR; SUBSETS; CCR2; HETEROGENEITY; RECRUITMENT; MACROPHAGES; MIGRATION; ORIGIN AB A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation. C1 [Swirski, Filip K.; Nahrendorf, Matthias; Etzrodt, Martin; Wildgruber, Moritz; Cortez-Retamozo, Virna; Panizzi, Peter; Figueiredo, Jose-Luiz; Kohler, Rainer H.; Chudnovskiy, Aleksey; Waterman, Peter; Aikawa, Elena; Mempel, Thorsten R.; Weissleder, Ralph; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Swirski, Filip K.; Nahrendorf, Matthias; Etzrodt, Martin; Wildgruber, Moritz; Cortez-Retamozo, Virna; Panizzi, Peter; Figueiredo, Jose-Luiz; Kohler, Rainer H.; Chudnovskiy, Aleksey; Waterman, Peter; Aikawa, Elena; Mempel, Thorsten R.; Weissleder, Ralph; Pittet, Mikael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Etzrodt, Martin] Univ Lausanne, Fac Biol & Med, CH-1015 Lausanne, Switzerland. [Mempel, Thorsten R.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Mempel, Thorsten R.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Libby, Peter] Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu; rweissleder@mgh.harvard.edu; mpittet@mgh.harvard.edu RI Etzrodt, Martin/P-3325-2015; OI Etzrodt, Martin/0000-0003-1928-3904; Panizzi, Peter/0000-0003-0141-8807 FU NIH [U01 HL080731, P50 CA86355, R24 CA69246, U54 CA126515, P01 A154904, 1R01HL095612]; MGH-Center for Systems Biology; AHA [SDG 0835623D] FX This work was supported in part by NIH grants U01 HL080731, P50 CA86355, R24 CA69246, U54 CA126515, and P01 A154904 to RW, MGH Center for Systems Biology to MJP, AHA SDG 0835623D to MN, and NIH grant 1R01HL095612 to FKS. The authors thank U. von Andrian for critical assessment of the manuscript, A. Luster for providing Ccr2 mice, D. Erle, A. Barcak, and C. Eisley for microarray hybridization and data analysis, M. Waring for sorting cells, A. Moseman for helpful discussion and feedback with parabiosis experiments, and A. Newton, C. Siegel, N. Sergeyev, and Y. Iwamoto for technical assistance. MIAME minimum information about a microarray experiment compliant expression data have been deposited under accession no. GSE14850. This work is dedicated to the memory of Marc Henri Pittet. NR 27 TC 757 Z9 782 U1 3 U2 61 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 31 PY 2009 VL 325 IS 5940 BP 612 EP 616 DI 10.1126/science.1175202 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 477BY UT WOS:000268493000051 PM 19644120 ER PT J AU Vardiman, JW Thiele, J Arber, DA Brunning, RD Borowitz, MJ Porwit, A Harris, NL Le Beau, MM Hellstrom-Lindberg, E Tefferi, A Bloomfield, CD AF Vardiman, James W. Thiele, Juergen Arber, Daniel A. Brunning, Richard D. Borowitz, Michael J. Porwit, Anna Harris, Nancy Lee Le Beau, Michelle M. Hellstrom-Lindberg, Eva Tefferi, Ayalew Bloomfield, Clara D. TI The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes SO BLOOD LA English DT Article; Proceedings Paper CT Myeloid-Clinical-Advistory-Committed Meeting 2007 CY FEB, 2007 CL Chicago, IL SP SPIE ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; BALANCED CHROMOSOME-ABERRATIONS; ACQUIRED APLASTIC-ANEMIA; TRANSIENT MYELOPROLIFERATIVE DISORDER; INDEPENDENT PROGNOSTIC RELEVANCE; ACUTE UNDIFFERENTIATED LEUKEMIA; MYELODYSPLASTIC SYNDROMES MDS; ACUTE BIPHENOTYPIC LEUKEMIA; TYROSINE KINASE JAK2 AB Recently the World Health Organization (WHO), in collaboration with the European Association for Haematopathology and the Society for Hematopathology, published a revised and updated edition of the WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissues. The 4th edition of the WHO classification incorporates new information that emerged from scientific and clinical studies in the interval since the publication of the 3rd edition in 2001, and includes new criteria for the recognition of some previously described neoplasms as well as clarification and refinement of the defining criteria for others. It also adds entities-some defined principally by genetic features-that have only recently been characterized. In this paper, the classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes. (Blood. 2009; 114: 937-951) C1 [Vardiman, James W.] Univ Chicago Hosp, Dept Pathol, Chicago, IL 60637 USA. [Thiele, Juergen] Univ Cologne, Inst Pathol, D-5000 Cologne, Germany. [Arber, Daniel A.] Stanford Univ, Dept Pathol, Med Ctr, Stanford, CA 94305 USA. [Brunning, Richard D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Borowitz, Michael J.] Johns Hopkins Med Inst, Dept Pathol & Oncol, Baltimore, MD 21205 USA. [Porwit, Anna] Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden. [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Harris, Nancy Lee] Harvard Univ, Sch Med, Boston, MA USA. [Le Beau, Michelle M.] Univ Chicago Hosp, Hematol Oncol Sect, Chicago, IL 60637 USA. [Hellstrom-Lindberg, Eva] Karolinska Univ Hosp, Dept Med, Stockholm, Sweden. [Tefferi, Ayalew] Mayo Clin, Div Hematol, Rochester, MN USA. [Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Vardiman, JW (reprint author), Univ Chicago Hosp, Dept Pathol, 5841 S Maryland Ave,MC0008, Chicago, IL 60637 USA. EM james.vardiman@uchospitals.edu NR 119 TC 1714 Z9 1875 U1 13 U2 101 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 30 PY 2009 VL 114 IS 5 BP 937 EP 951 DI 10.1182/blood-2009-03-209262 PG 15 WC Hematology SC Hematology GA 477BH UT WOS:000268491100007 PM 19357394 ER PT J AU Tosello, V Mansour, MR Barnes, K Paganin, M Sulis, ML Jenkinson, S Allen, CG Gale, RE Linch, DC Palomero, T Real, P Murty, V Yao, XP Richards, SM Goldstone, A Rowe, J Basso, G Wiernik, PH Paietta, E Pieters, R Horstmann, M Meijerink, JPP Ferrando, AA AF Tosello, Valeria Mansour, Marc R. Barnes, Kelly Paganin, Maddalena Sulis, Maria Luisa Jenkinson, Sarah Allen, Christopher G. Gale, Rosemary E. Linch, David C. Palomero, Teresa Real, Pedro Murty, Vundavalli Yao, Xiaopan Richards, Susan M. Goldstone, Anthony Rowe, Jacob Basso, Giuseppe Wiernik, Peter H. Paietta, Elisabeth Pieters, Rob Horstmann, Martin Meijerink, Jules P. P. Ferrando, Adolfo A. TI WT1 mutations in T-ALL SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; GAMMA-SECRETASE INHIBITORS; DENYS-DRASH SYNDROME; WILMS-TUMOR; GENE-MUTATIONS; CELL LEUKEMIA; UBIQUITIN LIGASE; SUPPRESSOR; ABNORMALITIES AB The molecular mechanisms involved in disease progression and relapse in T-cell acute lymphoblastic leukemia (T-ALL) are poorly understood. We used single nucleotide polymorphism array analysis to analyze paired diagnostic and relapsed T-ALL samples to identify recurrent genetic alterations in T-ALL. This analysis showed that diagnosis and relapsed cases have common genetic alterations, but also that relapsed samples frequently lose chromosomal markers present at diagnosis, suggesting that relapsed T-ALL emerges from an ancestral clone different from the major leukemic population at diagnosis. In addition, we identified deletions and associated mutations in the WT1 tumor suppressor gene in 2 of 9 samples. Subsequent analysis showed WT1 mutations in 28 of 211 (13.2%) of pediatric and 10 of 85 (11.7%) of adult T-ALL cases. WT1 mutations present in T-ALL are predominantly heterozygous frame-shift mutations resulting in truncation of the C-terminal zinc finger domains of this transcription factor. WT1 mutations are most prominently found in T-ALL cases with aberrant rearrangements of the oncogenic TLX1, TLX3, and HOXA transcription factor oncogenes. Survival analysis demonstrated that WT1 mutations do not confer adverse prognosis in pediatric and adult T-ALL. Overall, these results identify the presence of WT1 mutations as a recurrent genetic alteration in T-ALL. (Blood. 2009; 114: 1038-1045) C1 [Tosello, Valeria; Barnes, Kelly; Sulis, Maria Luisa; Palomero, Teresa; Real, Pedro; Murty, Vundavalli; Ferrando, Adolfo A.] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. [Mansour, Marc R.; Jenkinson, Sarah; Allen, Christopher G.; Gale, Rosemary E.; Linch, David C.] UCL, Dept Haematol, Inst Canc, London, England. [Paganin, Maddalena; Basso, Giuseppe] Univ Padua, Dept Pediat, Hematooncol Lab, Padua, Italy. [Sulis, Maria Luisa; Ferrando, Adolfo A.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. [Palomero, Teresa; Ferrando, Adolfo A.] Columbia Univ, Dept Pathol, Med Ctr, New York, NY 10027 USA. [Real, Pedro] Ctr Invest Biomed, Andalusian Stem Cell Bank, Granada, Spain. [Yao, Xiaopan] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Richards, Susan M.] Radcliffe Infirm, Clin Trial Serv Unit, Oxford OX2 6HE, England. [Goldstone, Anthony] Univ Coll London Hosp, London, England. [Rowe, Jacob] Technion Israel Inst Technol, Haifa, Israel. [Rowe, Jacob] Rambam Med Ctr, Haifa, Israel. [Wiernik, Peter H.; Paietta, Elisabeth] Montefiore Med Ctr N, Bronx, NY USA. [Wiernik, Peter H.; Paietta, Elisabeth] New York Med Coll, New York, NY USA. [Pieters, Rob; Meijerink, Jules P. P.] Erasmus MC Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Rotterdam, Netherlands. [Pieters, Rob] Dutch Childhood Oncol Grp, The Hague, Netherlands. [Horstmann, Martin] Univ Hosp Hamburg Eppendorf, Clin Pediat Hematol & Oncol, Hamburg, Germany. [Horstmann, Martin] German Cooperat Study Grp Childhood Acute Lymphob, Hamburg, Germany. RP Ferrando, AA (reprint author), Columbia Univ, Inst Canc Genet, 1130 St Nicholas Ave,Rm 505A, New York, NY 10032 USA. EM af2196@columbia.edu RI Real, Pedro/K-2994-2014; Ferrando, Adolfo /Q-7026-2016; Meijerink, Jules/D-4393-2017; OI Real, Pedro/0000-0001-7968-5353; Meijerink, Jules/0000-0002-6860-798X; Allen, Christopher/0000-0002-5310-0529; BASSO, GIUSEPPE/0000-0002-2634-9302; Tosello, Valeria/0000-0001-9560-340X FU National Institutes of Health [R01CA120196, R01CA129382, CA114737, CA02111]; ECOG's Leukemia Tissue Bank; WOLF Foundation; Leukemia & Lymphoma Society [1287-08, 6237-08]; Charlotte Geyer Foundation; Cancer Research Institute; Swim Across America Foundation; Golfers Against Cancer Foundation; Leukemia Research Fund; Medical Research Council of Great Britain; Fondo de Investigacion Sanitaria [CD07/00033]; Leukemia & Lymphoma Society Scholar; Alex's Lemonade Stand Foundation FX A complete list of the DCOG and the German COALL participants can be found in the supplemental Appendix. NR 49 TC 63 Z9 63 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 30 PY 2009 VL 114 IS 5 BP 1038 EP 1045 DI 10.1182/blood-2008-12-192039 PG 8 WC Hematology SC Hematology GA 477BH UT WOS:000268491100018 PM 19494353 ER PT J AU Hideshima, T Ikeda, H Chauhan, D Okawa, Y Raje, N Podar, K Mitsiades, C Munshi, NC Richardson, PG Carrasco, RD Anderson, KC AF Hideshima, Teru Ikeda, Hiroshi Chauhan, Dharminder Okawa, Yutaka Raje, Noopur Podar, Klaus Mitsiades, Constantine Munshi, Nikhil C. Richardson, Paul G. Carrasco, Ruben D. Anderson, Kenneth C. TI Bortezomib induces canonical nuclear factor-kappa B activation in multiple myeloma cells SO BLOOD LA English DT Article ID PROTEASOME INHIBITOR PS-341; KINASE-BETA INHIBITOR; IN-VIVO; BONE-MARROW; DOWN-REGULATION; IKK-BETA; GROWTH; PHOSPHORYLATION; CYTOTOXICITY; APOPTOSIS AB Bortezomib is a proteasome inhibitor with remarkable preclinical and clinical antitumor activity in multiple myeloma (MM) patients. The initial rationale for its use in MM was inhibition of nuclear factor (NF)-kappa B activity by blocking proteasomal degradation of inhibitor of kappa B alpha (I kappa B alpha). Bortezomib inhibits inducible NF-kappa B activity; however, its impact on constitutive NF-kappa B activity in MM cells has not yet been defined. In this study, we demonstrate that bortezomib significantly down-regulated I kappa B alpha expression and triggered NF-kappa B activation in MM cell lines and primary tumor cells from MM patients. Importantly, no inhibition of p65 ( RelA) nuclear translocation was recognized after bortezomib treatment in a murine xenograft model bearing human MM cells. Bortezomib-induced NF-kappa B activation was mediated via the canonical pathway. Moreover, other classes of proteasome inhibitors also induced I kappa B alpha down-regulation associated with NF-kappa B activation. Molecular mechanisms whereby bortezomib induced I kappa B alpha down-regulation were further examined. Bortezomib triggered phosphorylation of I kappa B kinase (IKK beta) and its upstream receptor-interacting protein 2, whereas IKK beta inhibitor MLN120B blocked bortezomib-induced I kappa B alpha down-regulation and NF-kappa B activation, indicating receptor-interacting protein 2/IKK beta signaling plays crucial role in bortezomib-induced NF-kappa B activation. Moreover, IKK beta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappa B activity in MM cells. (Blood. 2009; 114: 1046-1052) C1 [Hideshima, Teru; Ikeda, Hiroshi; Chauhan, Dharminder; Okawa, Yutaka; Raje, Noopur; Podar, Klaus; Mitsiades, Constantine; Richardson, Paul G.; Carrasco, Ruben D.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU National Institutes of Health [SPORE IP50 CA10070, PO-1 CA78378, RO-1 CA 50947] FX This study is supported by National Institutes of Health SPORE IP50 CA10070, PO-1 CA78378, and RO-1 CA 50947 grants; the Multiple Myeloma Research Foundation (to T. H., D. C., N.R., and C. M.); and the LeBow Family Fund to Cure Myeloma (to K. C. A.). NR 41 TC 195 Z9 202 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 30 PY 2009 VL 114 IS 5 BP 1046 EP 1052 DI 10.1182/blood-2009-01-199604 PG 7 WC Hematology SC Hematology GA 477BH UT WOS:000268491100019 PM 19436050 ER PT J AU Weintraub, D Hoops, S Shea, JA Lyons, KE Pahwa, R Driver-Dunckley, ED Adler, CH Potenza, MN Miyasaki, J Siderowf, AD Duda, JE Hurtig, HI Colcher, A Horn, SS Stem, MB Voon, V AF Weintraub, Daniel Hoops, Staci Shea, Judy A. Lyons, Kelly E. Pahwa, Rajesh Driver-Dunckley, Erika D. Adler, Charles H. Potenza, Marc N. Miyasaki, Janis Siderowf, Andrew D. Duda, John E. Hurtig, Howard I. Colcher, Amy Horn, Stacy S. Stem, Matthew B. Voon, Valerie TI Validation of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; impulse control disorders; dopamine dysregulation syndrome; punding; pathological gambling ID HEDONISTIC HOMEOSTATIC DYSREGULATION; DOPAMINE AGONISTS; PREVALENCE; BEHAVIOR; ASSOCIATION AB As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson's disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 Compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored. The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling = 0.95, sexual behavior = 0.97, buying = 0.87, eating = 0.88, punding = 0.78, hobbyism = 0.93, walkabout = 0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling = 0.95, sexual behavior = 0.96, buying = 0.87, eating = 0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96 and 94%, respectively. Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management. (C) 2009 Movement Disorder Society C1 [Weintraub, Daniel; Hoops, Staci] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel; Siderowf, Andrew D.; Duda, John E.; Hurtig, Howard I.; Colcher, Amy; Horn, Stacy S.; Stem, Matthew B.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel; Duda, John E.; Stem, Matthew B.] Philadelphia Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. [Shea, Judy A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Shea, Judy A.] Philadelphia Vet Affairs Med, CHERP, Philadelphia, PA USA. [Lyons, Kelly E.; Pahwa, Rajesh] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. [Driver-Dunckley, Erika D.; Adler, Charles H.] Mayo Clin Scottsdale, Dept Neurol, Scottsdale, AZ USA. [Potenza, Marc N.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Miyasaki, Janis] Univ Toronto, Div Neurol, Toronto, ON, Canada. [Voon, Valerie] NINDS, Bethesda, MD 20892 USA. RP Weintraub, D (reprint author), 3615 Chestnut St,Room 330, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu OI Miyasaki, Janis/0000-0002-6372-6007 FU NIDA NIH HHS [R01 DA019039, R01 DA019039-05]; NIMH NIH HHS [K23 MH067894, K23 MH067894-05] NR 31 TC 133 Z9 134 U1 3 U2 13 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL 30 PY 2009 VL 24 IS 10 BP 1461 EP 1467 DI 10.1002/mds.22571 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 478UK UT WOS:000268613600006 PM 19452562 ER PT J AU Finkel, T Deng, CX Mostoslavsky, R AF Finkel, Toren Deng, Chu-Xia Mostoslavsky, Raul TI Recent progress in the biology and physiology of sirtuins SO NATURE LA English DT Review ID PANCREATIC BETA-CELLS; SIRT1 REGULATES APOPTOSIS; CALORIE RESTRICTION; DEACETYLASE SIRT1; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; INSULIN-SECRETION; LIFE-SPAN; TRANSCRIPTION FACTORS; LYSINE ACETYLATION AB The sirtuins are a highly conserved family of NAD(+)-dependent enzymes that regulate lifespan in lower organisms. Recently, the mammalian sirtuins have been connected to an ever widening circle of activities that encompass cellular stress resistance, genomic stability, tumorigenesis and energy metabolism. Here we review the recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long we live. C1 [Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Finkel, Toren] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. [Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU NIH; Ellison Medical Foundation; Sidney Kimmel Cancer Research Foundation; V Foundation FX We apologize to our colleagues for being unable to cite all appropriate references owing to space limitations. Highlighted references are a subjective appraisal of some of the most interesting manuscripts published in the last year. We are grateful to I. Rovira for help with figures. This work was supported by NIH Intramural funds (T. F, C.-X. D.), The Ellison Medical Foundation (T. F.), The Sidney Kimmel Cancer Research Foundation (R. M.) and the V Foundation (R. M.). NR 84 TC 679 Z9 703 U1 11 U2 110 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 30 PY 2009 VL 460 IS 7255 BP 587 EP 591 DI 10.1038/nature08197 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 476PK UT WOS:000268454300041 PM 19641587 ER PT J AU Sperling, RA LaViolette, PS O'Keefe, K O'Brien, J Rentz, DM Pihlajamaki, M Marshall, G Hyman, BT Selkoe, DJ Hedden, T Buckner, RL Becker, JA Johnson, KA AF Sperling, Reisa A. LaViolette, Peter S. O'Keefe, Kelly O'Brien, Jacqueline Rentz, Dorene M. Pihlajamaki, Maija Marshall, Gad Hyman, Bradley T. Selkoe, Dennis J. Hedden, Trey Buckner, Randy L. Becker, J. Alex Johnson, Keith A. TI Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons without Dementia SO NEURON LA English DT Article ID MILD COGNITIVE IMPAIRMENT; PRECLINICAL ALZHEIMERS-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; RESTING-STATE NETWORKS; PITTSBURGH COMPOUND-B; HIPPOCAMPAL ACTIVATION; MODE NETWORK; PARIETAL DEACTIVATION; CINGULATE CORTEX; CEREBRAL-CORTEX AB Alzheimer's disease (AD) has been associated with functional alterations in a distributed network of brain regions linked to memory function, with a recent focus on the cortical regions collectively known as the default network. Posterior components of the default network, including the precuneus and posterior cingulate, are particularly vulnerable to early deposition of amyloid beta-protein, one of the hallmark pathologies of AD. In this study, we use in vivo amyloid imaging to demonstrate that high levels of amyloid deposition are associated with aberrant default network functional magnetic resonance imaging (fMRI) activity in asymptomatic and minimally impaired older individuals, similar to the pattern of dysfunction reported in AD patients. These findings suggest that amyloid pathology is linked to neural dysfunction in brain regions supporting memory function and provide support for the hypothesis that cognitively intact older individuals with evidence of amyloid pathology may be in early stages of AD. C1 [Sperling, Reisa A.; O'Keefe, Kelly; O'Brien, Jacqueline; Rentz, Dorene M.; Pihlajamaki, Maija; Marshall, Gad; Selkoe, Dennis J.; Johnson, Keith A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Sperling, Reisa A.; Rentz, Dorene M.; Marshall, Gad; Hyman, Bradley T.; Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [LaViolette, Peter S.; Buckner, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Hedden, Trey; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Hedden, Trey; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Sperling, Reisa A.; LaViolette, Peter S.; Hedden, Trey; Buckner, Randy L.] Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Buckner, Randy L.; Becker, J. Alex; Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Sperling, RA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu FU National Institute on Aging [R01AG027435]; Massachusetts Alzheimer's Disease Research Center [P50AG005134]; Anonymous Medical Foundation; Howard Hughes Medical Institute; Alzheimer's Association FX We thank Mary Foley, Larry White, and the Athinoula A. Martinos Center MRI Core for assistance with MRI imaging. The Massachusetts General Hospital Molecular Imaging PET Core provided assistance with PiB PET amyloid imaging. Bill Klunk and Chef Mathis from the University of Pittsburgh generously provided expertise in PiB imaging and analyses. We thank the Massaschuseffs Alzheimer's Disease Research Center (ADRC) and Sarah Rastegar for assistance with subject recruitment. We thank Meghan Frey, Elisha Eng, and Lauren Olson for assistance with neuropsychological testing. We thank Bill Klunk, Brad Dickerson, Akram Bakkour, Deborah Blacker, Ali Atri, and Patrizia Vannini for assistance with analyses and insightful comments. This work was supported by the National Institute on Aging R01AG027435 (R.A.S. and K.A.J.), the Massachusetts Alzheimer's Disease Research Center P50AG005134 (R.A.S., K.A.J., B.T.H., D.J.S.), an Anonymous Medical Foundation (R.A.S.), the Howard Hughes Medical Institute (R.L.B.), and the Alzheimer's Association (R.A.S.). Dr. Keith Johnson has consulted for GE Healthcare, who holds the commercial licensing and distribution rights for PiB PET imaging. NR 73 TC 422 Z9 430 U1 7 U2 48 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL 30 PY 2009 VL 63 IS 2 BP 178 EP 188 DI 10.1016/j.neuron.2009.07.003 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 479IS UT WOS:000268653500007 PM 19640477 ER PT J AU Stone, JH Caruso, PA Deshpande, V AF Stone, John H. Caruso, Paul A. Deshpande, Vikram TI Chronic sclerosing sialadenitis (IgG4-associated chronic sclerosing sialadenitis, Kuttner's tumor).A Woman with Painful Swelling of the Neck SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AUTOIMMUNE PANCREATITIS; SJOGRENS-SYNDROME; SUBMANDIBULAR-GLAND; DISEASE; CHOLANGITIS; PROGNOSIS; LYMPHOMA; FIBROSIS; COMPLEX C1 [Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. [Caruso, Paul A.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Radiol, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Pathol, Boston, MA 02114 USA. [Stone, John H.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Caruso, Paul A.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. NR 31 TC 23 Z9 25 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 30 PY 2009 VL 361 IS 5 BP 511 EP 518 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 476LW UT WOS:000268443900013 PM 19641208 ER PT J AU Elenko, MP Szostak, JW van Oijen, AM AF Elenko, Mark P. Szostak, Jack W. van Oijen, Antoine M. TI Single-Molecule Imaging of an in Vitro-Evolved RNA Aptamer Reveals Homogeneous Ligand Binding Kinetics SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DYNAMICS; GTP AB Many studies of RNA folding and catalysis have revealed conformational heterogeneity, metastable folding intermediates, and long-lived states with distinct catalytic activities. We have developed a single-molecule imaging approach for investigating the functional heterogeneity of in vitro-evolved RNA aptamers. Monitoring the association of fluorescently labeled ligands with individual RNA aptamer molecules has allowed us to record binding events over the course of multiple days, thus providing sufficient statistics to quantitatively define the kinetic properties at the single-molecule level. T. he ligand binding kinetics of the highly optimized RNA aptamer studied here displays a remarkable degree of uniformity and tack of memory. Such homogeneous behavior is quite different from the heterogeneity seen in previous single-molecule studies of naturally derived RNA and protein enzymes. The single-molecule methods we describe may be of use in analyzing the distribution of functional molecules in heterogeneous evolving populations or even in unselected samples of random sequences. C1 [van Oijen, Antoine M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Elenko, Mark P.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP van Oijen, AM (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM antoine_van_oijen@hms.harvard.edu OI van Oijen, Antoine/0000-0002-1794-5161 FU Howard Hughes Medical Institute NR 14 TC 23 Z9 23 U1 3 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 29 PY 2009 VL 131 IS 29 BP 9866 EP + DI 10.1021/ja901880v PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 475WM UT WOS:000268395000004 PM 19572753 ER PT J AU Dal-Bianco, JP Aikawa, E Bischoff, J Guerrero, JL Handschumacher, MD Sullivan, S Johnson, B Titus, JS Iwamoto, Y Wylie-Sears, J Levine, RA Carpentier, A AF Dal-Bianco, Jacob P. Aikawa, Elena Bischoff, Joyce Guerrero, J. Luis Handschumacher, Mark D. Sullivan, Suzanne Johnson, Benjamin Titus, James S. Iwamoto, Yoshiko Wylie-Sears, Jill Levine, Robert A. Carpentier, Alain TI Active Adaptation of the Tethered Mitral Valve Insights Into a Compensatory Mechanism for Functional Mitral Regurgitation SO CIRCULATION LA English DT Article; Proceedings Paper CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc DE echocardiography; mitral valve; valves ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; IN-VITRO; EXTRACELLULAR-MATRIX; INTERSTITIAL-CELLS; COLLAGEN-SYNTHESIS; ENDOTHELIAL-CELLS; MARFAN-SYNDROME; CUSHION TISSUE AB Background-In patients with left ventricular infarction or dilatation, leaflet tethering by displaced papillary muscles frequently induces mitral regurgitation, which doubles mortality. Little is known about the biological potential of the mitral valve (MV) to compensate for ventricular remodeling. We tested the hypothesis that MV leaflet surface area increases over time with mechanical stretch created by papillary muscle displacement through cell activation, not passive stretching. Methods and Results-Under cardiopulmonary bypass, the papillary muscle tips in 6 adult sheep were retracted apically short of producing mitral regurgitation to replicate tethering without confounding myocardial infarction or turbulence. Diastolic leaflet area was quantified by 3-dimensional echocardiography over 61 +/- 6 days compared with 6 unstretched sheep MVs. Total diastolic leaflet area increased by 2.4 +/- 1.3 cm(2) (17 +/- 10%) from 14.3 +/- 1.9 to 16.7 +/- 1.9 cm(2) (P = 0.006) with stretch with no change in the unstretched valves despite sham open heart surgery. Stretched MVs were 2.8 times thicker than normal (1.18 +/- 0.14 versus 0.42 +/- 0.14 mm; P < 0.0001) at 60 days with an increased spongiosa layer. Endothelial cells (CD31(+)) coexpressing alpha-smooth muscle actin were significantly more common by fluorescent cell sorting in tethered versus normal leaflets (41 +/- 19% versus 9 +/- 5%; P = 0.02), indicating endothelial-mesenchymal transdifferentiation. alpha-Smooth muscle actin-positive cells appeared in the atrial endothelium, penetrating into the interstitium, with increased collagen deposition. Thickened chordae showed endothelial and subendothelial alpha-smooth muscle actin. Endothelial-mesenchymal transdifferentiation capacity also was demonstrated in cultured MV endothelial cells. Conclusions-Mechanical stresses imposed by papillary muscle tethering increase MV leaflet area and thickness, with cellular changes suggesting reactivated embryonic developmental pathways. Understanding such actively adaptive mechanisms can potentially provide therapeutic opportunities to augment MV area and reduce ischemic mitral regurgitation. (Circulation. 2009; 120:334-342.) C1 [Dal-Bianco, Jacob P.; Handschumacher, Mark D.; Levine, Robert A.] Harvard Univ, Cardiac Ultrasound Lab, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guerrero, J. Luis; Sullivan, Suzanne; Johnson, Benjamin; Titus, James S.] Harvard Univ, Surg Cardiovasc Lab, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bischoff, Joyce; Wylie-Sears, Jill] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Bischoff, Joyce] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Aikawa, Elena; Iwamoto, Yoshiko] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Aikawa, Elena; Iwamoto, Yoshiko] Harvard Univ, Sch Med, Charlestown, MA USA. [Carpentier, Alain] Pompidou Hosp, Dept Cardiovasc Surg, Paris, France. [Carpentier, Alain] INSERM, U633, Paris, France. [Dal-Bianco, Jacob P.; Aikawa, Elena; Bischoff, Joyce; Levine, Robert A.; Carpentier, Alain] Fdn Leducq, Paris, France. RP Levine, RA (reprint author), Harvard Univ, Cardiac Ultrasound Lab, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 5068, Boston, MA 02114 USA. EM rlevine@partners.org OI Bischoff, Joyce/0000-0002-6367-1974 FU NHLBI NIH HHS [K24 HL67434, R01 HL038176, R01 HL038176-14, R01 HL38176, K24 HL067434, K24 HL067434-08] NR 51 TC 83 Z9 89 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 28 PY 2009 VL 120 IS 4 BP 334 EP + DI 10.1161/CIRCULATIONAHA.108.846782 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 475RG UT WOS:000268377500011 PM 19597052 ER PT J AU Cantley, LC AF Cantley, Lewis C. TI Lewis C. Cantley SO CURRENT BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM lcantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 28 PY 2009 VL 19 IS 14 BP R540 EP R541 DI 10.1016/j.cub.2009.06.010 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 477PE UT WOS:000268530200003 PM 19655422 ER PT J AU Weinrauch, LA Lewis, EF AF Weinrauch, Larry A. Lewis, Eldrin F. TI Aiming for the Best Control of Glycemia in Patients With Heart Failure and Type 2 Diabetes The "Sweet Spot" SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE diabetes; heart failure; glycosylated hemoglobin; HbA1c; prognosis ID BLOOD-GLUCOSE CONTROL; ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL PATIENTS; COMPLICATIONS; OUTCOMES; THERAPY AB Glycemic control has been a key target of therapy for patients with diabetes. In addition to the control of symptoms, it has been proposed that the potential reduction of additional morbidity and mortality represented another rationale for glycemic control. It has been assumed that physiologic perturbations associated with inadequate metabolic glucose control would be improved by restoration of normalized metabolism. In patients with type 1 (insulinopenic) diabetes mellitus, studies have indeed demonstrated significant microvascular (but less macrovascular) benefit when euglycemia as measured by glycosylated hemoglobin A1c (HbA1c) is approached with multiple daily insulin injections (1,2). C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Mt Auburn Hosp, Cambridge, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Weinrauch, LA (reprint author), 521 Mt Auburn St, Watertown, MA 02472 USA. EM lweinrauch@hms.harvard.edu OI Weinrauch, Larry/0000-0003-1357-9528 NR 16 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 28 PY 2009 VL 54 IS 5 BP 429 EP 431 DI 10.1016/j.jacc.2009.05.014 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 475BG UT WOS:000268329900008 PM 19628118 ER PT J AU Kreslavsky, T Savage, AK Hobbs, R Gounari, F Bronson, R Pereira, P Pandolfi, PP Bendelac, A von Boehmer, H AF Kreslavsky, Taras Savage, Adam K. Hobbs, Robin Gounari, Fotini Bronson, Roderick Pereira, Pablo Pandolfi, Pier Paolo Bendelac, Albert von Boehmer, Harald TI TCR-inducible PLZF transcription factor required for innate phenotype of a subset of gamma delta T cells with restricted TCR diversity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE agonist selection; innate T cells; transgenes ID ALPHA-BETA; LINEAGE FATE; SELECTION; REPERTOIRE; THYMOCYTES; MICE; PRECURSORS; RESPONSES; EXPRESS; THYMUS AB Some gamma delta and alpha beta T lymphocytes exhibit an "innate" phenotype associated with rapid cytokine responses. The PLZF transcription factor is essential for the innate phenotype of NKT cells. This report shows that PLZF is likewise responsible for the innate, NKT-like phenotype of V gamma 1+V delta 6.3/V delta 6.4+ cells. TCR cross-linking induced PLZF expression in all polyclonal immature gamma delta thymocytes, suggesting that agonist selection might be required for PLZF induction. Transgenic expression of V gamma 1V delta 6.4 TCR was sufficient to support the development of large numbers of PLZF+ T cells, further supporting the importance of the TCR for PLZF induction. Interestingly, expression of this TCR transgene led to the development of spontaneous dermatitis. C1 [Kreslavsky, Taras; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Lymphocyte Biol, Boston, MA 02115 USA. [Hobbs, Robin; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Dept Pathol & Med, Beth Israel Deaconess Canc Ctr,Canc Genet Program, Boston, MA USA. [Bronson, Roderick] Harvard Univ, Sch Med, Rodent Histopathol Lab, Boston, MA USA. [Savage, Adam K.; Bendelac, Albert] Univ Chicago, Comm Immunol, Dept Pathol, Howard Hughes Med Inst, Chicago, IL 60637 USA. [Gounari, Fotini] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Pereira, Pablo] Inst Pasteur, Unite Dev Lymphocytes, Paris, France. [Pereira, Pablo] INSERM, U668, Paris, France. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Lymphocyte Biol, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Pereira, Pablo/M-7224-2014; OI Hobbs, Robin/0000-0002-3853-2614 FU National Institutes of Health [R01 A145846, R01 A151378] FX We thank J.C. Zuniga-Pflucker (University of Toronto, Toronto) for providing reagents and G. Turchinovich, A. Krueger, M. Gleimer, and C. Daniel for helpful discussions. We are grateful to V. Schmidt for technical assistance. We thank the National Institutes of Health tetramer core facility for preparation of CD1d tetramer. These studies were supported by National Institutes of Health Grants R01 A145846 and R01 A151378. NR 37 TC 114 Z9 114 U1 0 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 JUL 28 PY 2009 VL 106 IS 30 BP 12453 EP 12458 DI 10.1073/pnas.0903895106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 476KV UT WOS:000268440200046 PM 19617548 ER PT J AU Lee, H Yoon, TJ Figueiredo, JL Swirski, FK Weissleder, R AF Lee, Hakho Yoon, Tae-Jong Figueiredo, Jose-Luiz Swirski, Filip K. Weissleder, Ralph TI Rapid detection and profiling of cancer cells in fine-needle aspirates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microfluidics; nanoparticle; nuclear magnetic resonance ID MAGNETIC-RESONANCE; TUMOR-CELLS; NANOPARTICLES; PROTEIN; DIAGNOSIS; SURFACE; SENSOR; NANOCRYSTALS; MACROPHAGES; TECHNOLOGY AB There is a growing need for fast, highly sensitive and quantitative technologies to detect and profile unaltered cells in biological samples. Technologies in current clinical use are often time consuming, expensive, or require considerable sample sizes. Here, we report a diagnostic magnetic resonance (DMR) sensor that combines a miniaturized NMR probe with targeted magnetic nanoparticles for detection and molecular profiling of cancer cells. The sensor measures the transverse relaxation rate of water molecules in biological samples in which target cells of interest are labeled with magnetic nanoparticles. We achieved remarkable sensitivity improvements over our prior DMR prototypes by synthesizing new nanoparticles with higher transverse relaxivity and by optimizing assay protocols. Wedetected as few as 2 cancer cells in 1-mu L sample volumes of unprocessed fine-needle aspirates of tumors and profiled the expression of several cellular markers in <15 min. C1 [Lee, Hakho; Yoon, Tae-Jong; Figueiredo, Jose-Luiz; Swirski, Filip K.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NCI NIH HHS [U54-CA119349, U54 CA119349]; NHLBI NIH HHS [U01 HL080731, U01-HL080731] NR 38 TC 113 Z9 113 U1 0 U2 34 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 JUL 28 PY 2009 VL 106 IS 30 BP 12459 EP 12464 DI 10.1073/pnas.0902365106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 476KV UT WOS:000268440200047 PM 19620715 ER PT J AU Hoffman, KE McCarthy, EP Recklitis, CJ Ng, AK AF Hoffman, Karen E. McCarthy, Ellen P. Recklitis, Christopher J. Ng, Andrea K. TI Psychological Distress in Long-term Survivors of Adult-Onset Cancer Results From a National Survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol ID QUALITY-OF-LIFE; BONE-MARROW TRANSPLANTATION; HODGKINS-DISEASE SURVIVORS; ACUTE-LEUKEMIA SURVIVORS; SERIOUS MENTAL-ILLNESS; BREAST-CANCER; CHILDHOOD-CANCER; FOLLOW-UP; HEALTH; CHEMOTHERAPY AB Background: As advances in cancer screening and treatment increase the number of long-term cancer survivors, it is important to understand the long-term psychological sequelae of the cancer experience. Methods: The 4636 respondents who identified themselves as survivors of adult-onset cancer of 5 years or more and 122 220 respondents who were never diagnosed as having cancer were identified in the 2002 to 2006 National Health Interview Survey. The primary outcome in this population-based study was serious psychological distress (SPD) defined as a K6 scale (a validated screening tool for mental illness) score of 13 or more. Results: Among survivors, the median age at diagnosis was 50 years, the age at interview was 66 years, and the time since diagnosis was 12 years. The prevalence of SPD was significantly higher among long-term cancer survivors than among respondents who were never diagnosed as having cancer (5.6% vs 3.0%; P < .001). After adjustment for clinical and sociodemographic variables (age, sex, race, relationship status, educational attainment, insurance status, comorbidities, smoking history, and ability to perform instrumental activities of daily living), survivors remained significantly more likely to experience SPD (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.7). After adjustment for other clinical and sociodemographic variables, long-term survivors who were younger, were unmarried, had less than a high school education, were uninsured, had more comorbidities, or had difficulty performing instrumental activities of daily living were more likely to experience SPD. Conclusions: Long-term survivors of adult-onset cancer are at increased risk for psychological distress. This study identifies several clinical and sociodemographic factors associated with SPD that may help target high-risk survivors for psychological screening and support. C1 [Hoffman, Karen E.; Ng, Andrea K.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Hoffman, Karen E.] Harvard Radiat Oncol Program, Boston, MA USA. [McCarthy, Ellen P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. [Recklitis, Christopher J.] Dept Pediat, Boston, MA USA. [McCarthy, Ellen P.; Recklitis, Christopher J.; Ng, Andrea K.] Harvard Univ, Sch Med, Boston, MA USA. RP Hoffman, KE (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM khoffman1@partners.org NR 73 TC 79 Z9 80 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 27 PY 2009 VL 169 IS 14 BP 1274 EP 1281 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 475PT UT WOS:000268373000004 PM 19636028 ER PT J AU Nathan, DM Zinman, B Cleary, PA Backlund, JYC Genuth, S Miller, R Orchard, TJ AF Nathan, David M. Zinman, Bernard Cleary, Patricia A. Backlund, Jye-Yu C. Genuth, Saul Miller, Rachel Orchard, Trevor J. CA DCCT EDIC Res Grp TI Modern-Day Clinical Course of Type 1 Diabetes Mellitus After 30 Years' Duration The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications and Pittsburgh Epidemiology of Diabetes Complications Experience (1983-2005) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PITTSBURGH EPIDEMIOLOGY; INTENSIVE TREATMENT; NATURAL-HISTORY; IDDM PATIENTS; FOLLOW-UP; RETINOPATHY; NEPHROPATHY; TRIAL; PROGRESSION; DISEASE AB Background: Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM. Methods: An analysis of the cumulative incidence of long-term complications was performed. The DCCT (1983-1993) assigned patients to conventional or intensive therapy. Since 1993, the DCCT has been observational, and intensive therapy was recommended for all patients. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study is an observational study of patients with T1DM from Allegheny County, Pennsylvania. The study population comprised the DCCT T1DM cohort (N = 1441) and a subset of the EDC cohort (n = 161) selected to match DCCT entry criteria. In the DCCT, intensive therapy aimed for a near-normal glycemic level with 3 or more daily insulin injections or an insulin pump. Conventional therapy, with 1 to 2 daily insulin injections, was not designed to achieve specific glycemic targets. Main outcome measures included the incidences of proliferative retinopathy, nephropathy (albumin excretion rate >300 mg/24 h, creatinine level >= 2 mg/dL [to convert to micromoles per liter, multiply by 88.4], or renal replacement), and cardiovascular disease. Results: After 30 years of diabetes, the cumulative incidences of proliferative retinopathy, nephropathy, and cardiovascular disease were 50%, 25%, and 14%, respectively, in the DCCT conventional treatment group, and 47%, 17%, and 14%, respectively, in the EDC cohort. The DCCT intensive therapy group had substantially lower cumulative incidences (21%, 9%, and 9%) and fewer than 1% became blind, required kidney replacement, or had an amputation because of diabetes during that time. Conclusion: The frequencies of serious complications in patients with T1DM, especially when treated intensively, are lower than that reported historically. Trial Registration: clinicaltrials. gov Identifiers: NCT00360815 and NCT00360893 C1 [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Diabet Unit, Dept Med, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Zinman, Bernard] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Cleary, Patricia A.; Backlund, Jye-Yu C.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Genuth, Saul] Case Western Reserve Univ, Dept Med, Sch Med, Cleveland, OH 44106 USA. [Miller, Rachel; Orchard, Trevor J.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Diabet Unit, Dept Med, 50 Staniford St,Ste 340, Boston, MA 02114 USA. EM dnathan@partners.org RI Zinman, Bernard/E-7266-2013 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK 034818]; National Eye Institute; National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical and Translation Science Centers Program; National Center for Research Resources; Genentech through a Cooperative Research and Development Agreement FX The DCCT/EDIC project is supported by contracts with the Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases; the National Eye Institute; the National Institute of Neurological Disorders and Stroke; the General Clinical Research Centers Program; and the Clinical and Translation Science Centers Program, National Center for Research Resources; and by Genentech through a Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Contributors of free or discounted supplies and/or equipment include Lifescan, Roche, Aventis, Eli Lilly, OmniPod, Can-Am, B-D, Animas, Medtronic, Medtronic Minimed, Bayer (donation one time in 2008), and Omron. The EDC is supported by grant DK 034818 from the National Institute of Diabetes and Kidney Diseases. NR 31 TC 230 Z9 240 U1 2 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 27 PY 2009 VL 169 IS 14 BP 1307 EP 1316 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 475PT UT WOS:000268373000009 ER PT J AU Steinman, MA Rosenthal, GE Landefeld, CS Bertenthal, D Kaboli, PJ AF Steinman, Michael A. Rosenthal, Gary E. Landefeld, C. Seth Bertenthal, Daniel Kaboli, Peter J. TI Agreement Between Drugs-to-Avoid Criteria and Expert Assessments of Problematic Prescribing SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med ID INAPPROPRIATE MEDICATION USE; EMERGENCY-DEPARTMENT VISITS; NURSING-HOME RESIDENTS; BEERS CRITERIA; ELDERLY PATIENTS; CONSENSUS PANEL; OLDER-ADULTS; QUALITY; OUTCOMES; EVENTS AB Background: Drugs-to-avoid criteria are commonly used to evaluate prescribing quality in elderly persons. However, few studies have evaluated the concordance between these criteria and individualized patient assessments as measures of problem prescribing. Methods: We used data on 256 outpatients from the Iowa City VA Medical Center who were 65 years or older and taking 5 or more medications. After a comprehensive patient interview, a study team composed of a physician and a pharmacist recommended that certain drugs be discontinued, substituted, or reduced in dose. We evaluated the degree to which drugs considered potentially inappropriate by the drugs-to-avoid criteria of Beers et al and Zhan et al (hereinafter, Beers criteria and Zhan criteria) were also considered problematic by the study team, and vice versa. Results: In the study cohort, 256 patients were using 3678 medications. The physician-pharmacist team identified 563 drugs (15%) as problematic, while 214 drugs (6%) were flagged as potentially inappropriate by the Beers criteria and 91 drugs (2.5%) were flagged as potentially inappropriate using the Zhan criteria. The kappa statistics for concordance between drugs-to-avoid criteria and expert assessments were 0.10 to 0.14, indicating slight agreement between these measures. Sixty-one percent of drugs identified as potentially inappropriate by the Beers criteria and 49% of drugs flagged by the Zhan criteria were not judged to be problematic by the expert reviewers. Correspondence between drugs-to-avoid criteria and expert assessment varied widely across different types of drugs. Conclusions: Drugs-to-avoid criteria have limited power to differentiate between drugs and patients with and without prescribing problems identified on individualized expert review. Although these criteria are useful as guides for initial prescribing decisions, they are insufficiently accurate to use as stand-alone measures of prescribing quality. C1 [Steinman, Michael A.; Landefeld, C. Seth; Bertenthal, Daniel] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Steinman, Michael A.; Landefeld, C. Seth] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Rosenthal, Gary E.; Kaboli, Peter J.] Iowa City VA Healthcare Syst, Ctr Res Implementat Innovat Strategies Practice, Iowa City, IA USA. [Rosenthal, Gary E.; Kaboli, Peter J.] Univ Iowa, Dept Internal Med, Div Gen Internal Med, Iowa City, IA 52242 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Box 181G,4150 Clement St, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU AHRQ HHS [U18 HS016094]; NIA NIH HHS [1K23AG030999, AG 00912, AG 10418, K07 AG000912, K23 AG030999, K23 AG030999-01A1, Z01 AG000912]; PHS HHS [5 U18 HSO16094] NR 30 TC 32 Z9 33 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 27 PY 2009 VL 169 IS 14 BP 1326 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 475PT UT WOS:000268373000011 PM 19636035 ER PT J AU Hamrah, P Haskova, Z Taylor, AW Zhang, Q Ksander, BR Dana, MR AF Hamrah, Pedram Haskova, Zdenka Taylor, Andrew W. Zhang, Qiang Ksander, Bruce R. Dana, M. Reza TI Local Treatment With Alpha-Melanocyte Stimulating Hormone Reduces Corneal Allorejection SO TRANSPLANTATION LA English DT Article DE Alpha-melanocyte-stimulating hormone; Neuropeptide; Corneal transplantation; Dendritic cells; Allograft rejection ID NF-KAPPA-B; EXPERIMENTAL HEART-TRANSPLANTATION; ENDOTOXIN-INDUCED UVEITIS; DENDRITIC CELLS; INFLAMMATORY AGENTS; GENE-EXPRESSION; AQUEOUS-HUMOR; T-CELLS; MSH; RECEPTORS AB Background. Corneal grafting is by far the most common form of transplantation. Many grafts suffer from immune rejection and current therapies are associated with many side effects, requiring more effective and safe therapies. alpha-Melanocyte stimulating hormone (alpha-MSH) is a neuropeptide that suppresses host inflammatory defense mechanisms. The purpose of this study was to determine the role of local therapy with a-MSH on corneal allograft survival, and the mechanisms by which it may influence graft outcome. Methods. Orthotopic corneal transplantation was performed, with recipients receiving subconjunctival alpha-MSH or sham injections twice weekly. Grafts were followed up for 70 days, and graft inflammation/opacification was compared between the two groups in a masked fashion. Graft infiltration and ocular gene expression of select inflammatory cytokines was evaluated at different timepoints. Additionally, allospecific delayed-type hypersensitivity was compared among the groups 3 weeks posttransplantation. Results. Results showed a significant increase in corneal graft survival in alpha-MSH-treated recipients compared with controls. Although 75% of allografts in alpha-MSH-treated hosts survived at 70 days, 43% survived in controls (P=0.04). Graft infiltration studies demonstrated a significant decrease in the number of mononuclear and polymorphonuclear cells in a-MSH-treated mice compared with controls at days 7 and 14 after transplantation. Furthermore, allospecific delayed-type hypersensitivity and gene expression of interferon-gamma and interleukin-2 showed a significantly reduced expression in a-MSH-treated mice compared with controls. Conclusions. This study provides for the first time, in vivo evidence that treatment with local alpha-MSH may significantly reduce allorejection of orthotopic transplants. C1 [Hamrah, Pedram; Haskova, Zdenka; Taylor, Andrew W.; Zhang, Qiang; Ksander, Bruce R.; Dana, M. Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. [Hamrah, Pedram; Dana, M. Reza] Harvard Univ, Sch Med, Cornea Serv, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02114 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu OI Taylor, Andrew/0000-0002-0330-8591 FU National Institutes of Health [R01-EY-012963]; Massachusetts Lions Eye Research Fund; M.R.D. FX This work was supported by grant R01-EY-012963 from the National Institutes of Health, a research grant from the Massachusetts Lions Eye Research Fund, and a Research to Prevent Blindness Physician-Scientist Merit Award (M.R.D.). NR 45 TC 6 Z9 6 U1 0 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 JUL 27 PY 2009 VL 88 IS 2 BP 180 EP 187 DI 10.1097/TP.0b013e3181ac11ea PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 475RK UT WOS:000268377900006 PM 19623012 ER EF