FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Thygesen, LC Wu, K Gronbaek, M Fuchs, CS Willett, WC Giovannucci, E AF Thygesen, Lau Caspar Wu, Kana Gronbaek, Morten Fuchs, Charles S. Willett, Walter C. Giovannucci, Edward TI Alcohol intake and colorectal cancer - A comparison of approaches for including repeated measures of alcohol consumption SO EPIDEMIOLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; RECTAL-CANCER; COLON-CANCER; RISK; COHORT; MEN; VALIDITY; FOLATE; TIME AB Background: In numerous studies, alcohol intake has been found to be positively associated with colorectal cancer risk. However, the majority of studies included only one exposure measurement, which may bias the results if long-term intake is relevant. Methods: We compared different approaches for including repeated measures of alcohol intake among 47,432 US men enrolled in the Health Professionals Follow-up Study. Questionnaires including questions on alcohol intake had been completed in 1986, 1990, 1994, and 1998. The outcome was incident colorectal cancer during follow-up from 1986 to 2002. Results: During follow-up, 868 members of the cohort experienced colorectal cancer. Baseline, updated, and cumulative average alcohol intakes were positively associated with colorectal cancer, with only minor differences among the approaches. These results support moderately increased risk for intake >30 g/d and weaker increased risk for lower intake. The hazard ratio for baseline alcohol intake was 1.07 (95% confidence interval = 1.02-1.11) per 10 g/d increase, which was similar for updated and cumulative average alcohol intake. Consistent moderate and high alcohol intake showed increased risk, and the relative risk decreased slightly with longer latency time. Alcohol frequency was positively associated with cancer risk among men with alcohol intake above 15 g/d. Conclusions: Alcohol intake was positively associated with colorectal cancer, with minor differences among analytic approaches (which may be attributable to low intraindividual variation during follow-up). C1 [Thygesen, Lau Caspar; Gronbaek, Morten] Natl Publ Hlth Inst, Alcohol Res Ctr, DK-1399 Copenhagen, Denmark. [Thygesen, Lau Caspar; Wu, Kana; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fuchs, Charles S.; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Med, Dept Med, Channing Lab, Cambridge, MA 02138 USA. [Fuchs, Charles S.; Willett, Walter C.; Giovannucci, Edward] Brigham & Womens Hosp, Cambridge, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Thygesen, LC (reprint author), Natl Publ Hlth Inst, Alcohol Res Ctr, Oster Farimagsgade 5, DK-1399 Copenhagen, Denmark. EM lct@niph.dk OI Thygesen, Lau/0000-0001-8375-5211 FU NCI NIH HHS [CA55075] NR 37 TC 22 Z9 23 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2008 VL 19 IS 2 BP 258 EP 264 DI 10.1097/EDE.0b013e31816339e0 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265ZU UT WOS:000253401400015 PM 18300715 ER PT J AU Bautista, JF Kelly, JA Harley, JB Gray-McGuire, C AF Bautista, Jocelyn F. Kelly, Jennifer A. Harley, John B. Gray-McGuire, Courtney TI Addressing genetic heterogeneity in complex disease: Finding seizure genes in systemic lupus erythematosus SO EPILEPSIA LA English DT Article DE linkage; lupus; seizures; genetic; covariates ID REVISED CRITERIA; LINKAGE; CLASSIFICATION; MODEL AB Complex genetic disease is inherently difficult to study due to an imperfect relationship between genotype and phenotype. One important reason for this imperfect relationship is genetic heterogeneity, the occurrence of different genetic factors underlying the same clinical syndrome. One method of addressing genetic heterogeneity is covariate-based linkage analysis, which allows the use of additional phenotypic features to define genetically distinct subsets of patients. Systemic lupus erythematosus (SLE) is one example of a complex genetic disease affecting multiple organ systems including the central nervous system. We report here the use of covariate-based linkage analysis to detect a potential genetic locus on chromosome 15 influencing the development of seizures in individuals with SLE. The use of covariates increases the power to detect linkage in the presence of genetic heterogeneity. C1 [Bautista, Jocelyn F.] Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. [Kelly, Jennifer A.; Harley, John B.] Oklahoma Med Res Fdn, Arthritis & Immunol Res Program, Oklahoma City, OK USA. [Harley, John B.] Univ Oklahoma, Dept Med, Oklahoma City, OK USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Gray-McGuire, Courtney] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Bautista, JF (reprint author), Cleveland Clin Fdn, Dept Neurol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM bautisj@ccf.org FU NCRR NIH HHS [RR020143, RR03655, RR03655-15]; NIAID NIH HHS [AI24717, AI31584]; NIAMS NIH HHS [AR 048940, AR-6-2277, P30 AR053483, AR-5-2221, AR42460, AR049084] NR 7 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR PY 2008 VL 49 IS 3 BP 527 EP 530 DI 10.1111/j.1528-1167.2007.01453.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 266ZP UT WOS:000253477800021 PM 18070094 ER PT J AU Ellis, C Egede, LE AF Ellis, Charles Egede, Leonard E. TI Racial/ethnic differences in stroke awareness among veterans SO ETHNICITY & DISEASE LA English DT Article DE stroke; ethnicity; health disparities; survey research; health education ID AMERICAN-HEART-ASSOCIATION; RISK-FACTOR SURVEY; WARNING SIGNS; ISCHEMIC-STROKE; RACIAL DISPARITIES; UNITED-STATES; KNOWLEDGE; CARE; POPULATION; EMERGENCY AB Objectives: To examine racial/ethnic differences in stroke recognition and knowledge of appropriate first action if someone was having a stroke. Methods: We examined data from 36,150 veterans from the 2003 Behavioral Risk Factor ICIT Surveillance System (BRFSS). Respondents indicated recognition of five stroke warning signs/symptoms and first action they would take if someone were having a stroke. Multiple logistic regression was used to assess the independent effect of race/ethnicity on stroke recognition and appropriate first action, controlling for relevant covariates. Results: Most respondents recognized at least one warning sign: 96% recognized sudden confusion or trouble speaking; 97% recognized sudden facial, arm, or leg weakness; 88% recognized sudden vision loss; 94% recognized sudden trouble walking; and 80% recognized sudden headache; 86% recognized calling 911 as the appropriate first action. However, only 17% recognized all five warning signs/symptoms, and only 15% recognized all five warning signs/symptoms and would call 911 as the first action. In multivariate models with Whites as reference, Hispanics (OR .34, 95% Cl .22-.51) and Others (OR .68, 95% Cl .50-.92) were less likely to recognize all five stroke warning signs/ symptoms. Hispanics (OR .37, 95% Cl.24-.58) and Others (OR .68, 95% Cl .48-.96) were less likely to recognize all five warning signs/ symptoms and call 911 as the first action. Conclusions: Most veterans recognize individual stroke warning signs, but very few recognize all five and would take appropriate action to call 911 in the event of a stroke. Low rates of stroke recognition and taking appropriate action are more pronounced in racial/ethnic minority veterans. C1 [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dsipar Res, Charleston, SC 29425 USA. [Ellis, Charles] Med Univ S Carolina, Dept Rehabil Sci, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Ctr Hlth Dsipar Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu NR 36 TC 9 Z9 9 U1 0 U2 1 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SPR PY 2008 VL 18 IS 2 BP 198 EP 203 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286YH UT WOS:000254882200013 PM 18507274 ER PT J AU Bush, AI Curtain, CC AF Bush, Ashley I. Curtain, Cyril C. TI Twenty years of metallo-neurobiology: where to now? SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Review ID AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; OXIDATIVE DAMAGE; BINDS COPPER; IN-VIVO; ZINC; PROTEIN; NEUROTOXICITY AB The redox active transition metals Cu2+ and Fe3+ have been proposed as important factors in the neuropathology of Alzheimer's disease (AD) and other neurodegenerative diseases. The field that has been called metallo-neurobiology has expanded greatly in the last 20 years. Although there is much experimental evidence on various aspects of the interaction between these metals and the molecular and supramolecular components of the neuropil and the structural biology of metal binding, we are far from fully understanding the part this interaction plays in the normal CNS and in neurodegeneration. This understanding is needed if we are to move beyond the promising, but semi-empirical, approaches to therapies of these diseases based on metal attenuation. C1 [Curtain, Cyril C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Curtain, Cyril C.] Univ Melbourne, Mol Biol & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia. [Bush, Ashley I.] Mental Hlth Res Inst Victoria, Oxidat Disorders Lab, Parkville, Vic 3052, Australia. [Curtain, Cyril C.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Curtain, CC (reprint author), Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. EM ccurtain@unimelb.edu.au RI Bush, Ashley/A-1186-2007; OI Bush, Ashley/0000-0001-8259-9069; Curtain, Cyril/0000-0001-6955-320X NR 39 TC 37 Z9 37 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD MAR PY 2008 VL 37 IS 3 BP 241 EP 245 DI 10.1007/s00249-007-0228-1 PG 5 WC Biophysics SC Biophysics GA 267RC UT WOS:000253525900002 PM 17994233 ER PT J AU Pang, PS Cleland, JGF Teerlink, JR Collins, SP Lindsell, CJ Sopko, G Peacock, WF Fonarow, GC Aldeen, AZ Kirk, JD Storrow, AB Tavares, M Mebazaa, A Roland, E Massie, BM Maisel, AS Komajda, M Filippatos, G Gheorghiade, M AF Pang, Peter S. Cleland, John G. F. Teerlink, John R. Collins, Sean P. Lindsell, Christopher J. Sopko, George Peacock, W. Frank Fonarow, Gregg C. Aldeen, Amer Z. Kirk, J. Douglas Storrow, Alan B. Tavares, Miguel Mebazaa, Alexandre Roland, Edmond Massie, Barry M. Maisel, Alan S. Komajda, Michel Filippatos, Gerasimos Gheorghiade, Mihai CA Acute Heart Failure Syndromes Int TI A proposal to standardize dyspnoea measurement in clinical trials of acute heart failure syndromes: the need for a uniform approach SO EUROPEAN HEART JOURNAL LA English DT Article DE heart failure; clinical trials; dyspnoea ID RANDOMIZED CONTROLLED-TRIALS; NATRIURETIC PEPTIDE; TEZOSENTAN; NESIRITIDE; OUTCOMES; DIAGNOSIS; DESIGN; RISK; ANTAGONIST; RATIONALE AB Dyspnoea is the most common presenting symptom amongst patients with acute heart failure syndromes (AHFS). It is distressing to patients and therefore an important target for treatment in clinical practice, clinical trials, and for regulatory approval of novel agents. Despite its importance as a treatment target, no consensus exists on how to assess dyspnoea in this setting. There is a considerable uncertainty about the reproducibility of the various instruments used to measure dyspnoea, their ability to reflect changes in symptoms and whether they accurately reflect the patient's experience. Little attempt has been made to ensure consistent implementation with respect to patients' posture during assessment or timing in relationship to therapy. There is also limited understanding of how rapidly and completely dyspnoea responds to standard therapy. A standardized method with which to assess dyspnoea is required for clinical trials of AHFS in order to ensure uniform collection of data on a key endpoint. We propose the Provocative Dyspnoea Assessment, a method of measurement that combines sequential dyspnoea provocation by positioning and walking with a dyspnoea self assessment using a five-point Likert scale, to yield a final Dyspnoea Severity Score. This proposed tool requires detailed validation but has face validity for the uniform assessment of dyspnoea. C1 [Cleland, John G. F.; Aldeen, Amer Z.] Univ Hull, Castle Hill Hosp, Dept Cardiol, Kingston Upon Hull, Yorks, England. [Pang, Peter S.; Aldeen, Amer Z.] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Collins, Sean P.; Lindsell, Christopher J.] Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA. [Sopko, George] Natl Inst Hlth, Bethesda, MD USA. [Peacock, W. Frank] Cleveland Clin, Dept Emergency Med, Cleveland, OH 44106 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. [Kirk, J. Douglas] Univ Calif Davis, Med Ctr, Dept Emergency Med, Sacramento, CA 95817 USA. [Storrow, Alan B.] Vanderbilt Univ, Med Ctr, Dept Emergency Med, Nashville, TN USA. [Tavares, Miguel] Hosp Geral Santo Antonio, Dept Anesthesiol & Crit Care, Oporto, Portugal. [Mebazaa, Alexandre] Hop Lariboisiere, Dept Anesthesiol & Crit Care Med, F-75475 Paris, France. [Roland, Edmond] Agcy Francaise Secur Sanit Prod Sante, Paris, France. [Maisel, Alan S.] Univ Calif San Diego, Vet Affairs San Diego Hlth Care Syst, Dept Med, Div Cardiol, San Diego, CA 92103 USA. [Komajda, Michel] Univ Paris 06, Dept Cardiol, Paris, France. [Komajda, Michel] Hop La Pitie Salpetriere, Paris, France. [Filippatos, Gerasimos] Athens Univ Hosp, Heart Failure Unit, Dept Cardiol, Attikon, Greece. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA. RP Cleland, JGF (reprint author), Univ Hull, Castle Hill Hosp, Dept Cardiol, Kingston Upon Hull, Yorks, England. EM j.g.cleland@hull.ac.uk RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; OI Lindsell, Christopher/0000-0002-3297-2811; Cleland, John/0000-0002-1471-7016 NR 37 TC 75 Z9 76 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAR PY 2008 VL 29 IS 6 BP 816 EP 824 DI 10.1093/eurheartj/ehn048 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278NL UT WOS:000254293500021 PM 18310669 ER PT J AU Wilson, PWF Meigs, JB AF Wilson, Peter W. F. Meigs, James B. TI Risk of type 2 diabetes mellitus and coronary heart disease: a pivotal role for metabolic factors SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article DE coronary artery disease; diabetes mellitus; insulin resistance ID INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; ADULTS; IMPACT AB Prediction of the development of type 2 diabetes mellitus (T2DM) and coronary heart disease has considered a large number of factors that may have important effects on risk. Data from recent publications of the Framingham Heart Study are reviewed from the perspective of how metabolic factors contribute to increased risk for T2DM, coronary heart disease, and vascular disease. Persons with impaired fasting glucose or impaired glucose tolerance were found to have increased risk of coronary artery calcification, left ventricular hypertrophy among women, and augmented risk to develop coronary artery disease events. The metabolic syndrome risk factor burden and fasting insulin were also shown to affect the risk of developing future T2DM. Risk estimation for the development of T2DM showed that each of the five metabolic syndrome traits (increased waist girth, elevated blood pressure, low high density lipoprotein (HDL)cholesterol, high triglycerides, and impaired fasting glucose) were important predictors for the development of T2DM in middle-aged men and women. Both T2DM and coronary heart disease are consequences of persons with elevated blood glucose levels, insulin resistance, and an increasing burden of metabolic syndrome traits. C1 [Wilson, Peter W. F.] Emory Univ, Sch Med, EPICORE, Atlanta, GA 30306 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wilson, PWF (reprint author), Emory Univ, Sch Med, EPICORE, Suite 1 N,1256 Briarcliff Rd, Atlanta, GA 30306 USA. EM peter.wf.wilson@emory.edu NR 10 TC 2 Z9 2 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD MAR PY 2008 VL 10 IS B BP B11 EP B15 DI 10.1093/eurheartj/sum043 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278OW UT WOS:000254297200003 ER PT J AU Baron, JH Sonnenberg, A AF Baron, Jeremy Hugh Sonnenberg, Amnon TI Hospital admissions and primary care attendances for nonulcer dyspepsia, reflux oesophagitis and peptic ulcer in Scotland 1981-2004 SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE deprivation; duodenal ulcer; dyspepsia; gastric ulcer; gastro-oesophageal reflux disease; Helicobacter pylori; social class; time trends ID DUODENAL-ULCER; DISEASE; PREVALENCE; MORTALITY; SYMPTOMS; OBESITY; TRENDS AB Aim The aim of this study was to assess the recent time trends of oesophageal disorders, nonulcer dyspepsia, gastric and duodenal ulcer in the light of such risk factors as age, sex, deprivation and urban versus rural residence. Methods The Scottish National Health Service provided diagnostic data on all admissions to all Scottish hospitals from 1981 to 2004 and patient visits to general practitioners (GP) from 1998 to 2004. Results In the last quarter of a century in Scotland, there were sevenfold increases in annual hospitalizations for dyspepsia (from 900 to 6000 per million population) and for oesophageal disorders (from 500 to 3700). Annual hospitalisations for gastric and duodenal ulcer changed from 590 to 1100 and from 1400 to 1130 per million population, respectively. The variation of hospital admissions for dyspepsia among various Scottish regions closely matched the variation of deprivation among them. GP contacts for dyspepsia (27600 per million population) and oesophageal disorders (10000) were common compared with relatively infrequent contacts for gastric ulcer (500) and duodenal ulcer (11200). Dyspepsia showed a rise of GP contacts with increasing scores of deprivation. This rise occurred similarly among urban and rural residents and applied to data for each individual year between 1998 until 2004. None of the other diagnoses showed any clear-cut correlation with grade of deprivation. Conclusion Gastric and duodenal ulcer are relatively rare causes for hospital admission as well as outpatient physician visits. Their former predominant role in upper gastrointestinal disease has been replaced by gastro-oesophageal reflux disease and nonulcer dyspepsia, both increasing sevenfold in the last quarter of a century. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Baron, Jeremy Hugh] New York & Imperial Coll, Mt Sinai Sch Med, London, England. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW,US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 29 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD MAR PY 2008 VL 20 IS 3 BP 180 EP 186 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 325ZP UT WOS:000257628000006 PM 18301297 ER PT J AU Liguori, A Fiorito, C Balestrieri, ML Crimi, E Bruzzese, G Williams-Ignarro, S D'Amora, M Sommese, L Grimaldi, V Minucci, PB Giovane, A Farzati, B Ignarro, LJ Napoli, C AF Liguori, Antonio Fiorito, Carmela Balestrieri, Maria Luisa Crimi, Ettore Bruzzese, Giuseppe Williams-Ignarro, Sharon D'Amora, Maurizio Sommese, Linda Grimaldi, Vincenzo Minucci, Pellegrino Biagio Giovane, Alfonso Farzati, Bartolomeo Ignarro, Louis J. Napoli, Claudio TI Functional impairment of hematopoietic progenitor cells in patients with coronary heart disease SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE coronary heart disease; progenitor cells; stem cells ID NITRIC-OXIDE SYNTHASE; CIRCULATING ENDOTHELIAL-CELLS; LEFT-VENTRICULAR FUNCTION; SOUTH ASIAN MEN; BONE-MARROW; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; NEOVASCULARIZATION CAPACITY; OXIDATIVE STRESS; STEM-CELLS AB The circulating form of endothelial progenitors cells (EPCs) are derivated from bone marrow (BM)-derived hematopoietic stem cells (HSCs). Enhanced mobilization of EPCs was shown to be linked to cardiac diseases. This study investigated whether reduced EPC levels in advanced coronary heart disease (CHD) are secondary to a functional exhaustion of HSCs in the BM or to reduced mobilization. Number and functional properties of EPCs were assessed in 15 healthy controls, and 40 patients with CHD. The colony-forming unit (CFU) capacity of BM-derived mononuclear cells and the CD34(+) HSC number were examined in four healthy volunteers, and 15 CHD patients. EPC number was reduced in CHD patients (P < 0.01 vs. controls). Moreover, the migratory capacity was significantly impaired in EPCs of CHD patients (P < 0.05 vs. controls). On multivariate analysis, CHD was an independent predictor of functional EPC impairment. CFUs were reduced in CHD patients (59.6 +/- 21.2 vs. 75.4 +/- 25.8 in controls, P < 0.05). CHD was also predictor of impaired CFU capacity. In this small clinical study, CHD is associated with selective impairment of HSC function in the BM and in the peripheral blood, which may contribute to impairment of cardiac function. C1 [Liguori, Antonio; Bruzzese, Giuseppe; D'Amora, Maurizio] Hosp Pellegrini ASL NA1, Dept Cardiol CCU, Naples, Italy. [Fiorito, Carmela; Sommese, Linda; Grimaldi, Vincenzo; Minucci, Pellegrino Biagio; Farzati, Bartolomeo; Napoli, Claudio] Univ Naples Federico 2, Dept Gen Pathol, Div Clin Pathol, Naples, Italy. [Fiorito, Carmela; Sommese, Linda; Grimaldi, Vincenzo; Minucci, Pellegrino Biagio; Farzati, Bartolomeo; Napoli, Claudio] Univ Naples Federico 2, Excellence Res Ctr Cardiovasc Dis, Naples, Italy. [Fiorito, Carmela] IRCCS Multimedia, Milan, Italy. [Balestrieri, Maria Luisa] Univ Naples Federico 2, Dept Biochem & Biophys, Naples, Italy. [Crimi, Ettore] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Williams-Ignarro, Sharon] Univ Calif Los Angeles, David Geffen Sch Med, Div Anesthesiol, Los Angeles, CA 90095 USA. [Ignarro, Louis J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Balestrieri, ML (reprint author), Univ Naples 2, Dept Biochem & Biophys, Sch Med 1, Via Costantinopoli 16, I-80138 Naples, Italy. EM marialuisa.balestrieri@unina2.it OI Giovane, Alfonso/0000-0002-2508-2597; Napoli, Claudio/0000-0002-5455-555X NR 38 TC 24 Z9 25 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD MAR PY 2008 VL 80 IS 3 BP 258 EP 264 DI 10.1111/j.1600-0609.2007.01007.x PG 7 WC Hematology SC Hematology GA 263YI UT WOS:000253252000010 PM 18081701 ER PT J AU Raymond, SB Skoch, J Hills, ID Nesterov, EE Swager, TM Bacskai, BJ AF Raymond, Scott B. Skoch, Jesse Hills, Ivory D. Nesterov, Evgueni E. Swager, Timothy M. Bacskai, Brian J. TI Smart optical probes for near-infrared fluorescence imaging of Alzheimer's disease pathology SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Optical probes; Fluorescence imaging; Alzheimer's disease; Near-infrared AB Purpose Near-infrared fluorescent probes for amyloid-beta (A beta) are an exciting option for molecular imaging in Alzheimer's disease research and may translate to clinical diagnostics. However, A beta-targeted optical probes often suffer from poor specificity and slow clearance from the brain. We are designing smart optical probes that emit characteristic fluorescence signal only when bound to A beta. Methods We synthesized a family of dyes and tested A beta-binding sensitivity with fluorescence spectroscopy and tissue-staining. Results Select compounds exhibited A beta-dependent changes in fluorescence quantum yield, lifetime, and emission spectra that may be imaged microscopically or in vivo using new lifetime and spectral fluorescence imaging techniques. Conclusion Smart optical probes that turn on when bound to A beta will improve amyloid detection and may enable quantitative molecular imaging in vivo. C1 [Raymond, Scott B.; Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. [Skoch, Jesse] Univ Colorado, Dept Pharmacol, Denver, CO 80262 USA. [Skoch, Jesse] Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. [Nesterov, Evgueni E.] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. [Hills, Ivory D.; Swager, Timothy M.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Hills, Ivory D.; Swager, Timothy M.] MIT, Inst Soldier Nanotechnol, Cambridge, MA 02139 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org RI Swager, Timothy/H-7459-2012; OI Swager, Timothy/0000-0002-3577-0510; Raymond, Scott/0000-0001-7008-8974 FU NIH [EB00768, AG026240]; US Army through the Institute for Soldier Nanotechnologies [DAAD-19-02-D-0002]; NDSEG fellowship; Harvard University Ashford fellowship; [T32 EB001680] FX This work was supported by NIH EB00768 and AG026240 (BJB) and the US Army through the Institute for Soldier Nanotechnologies, DAAD-19-02-D-0002 (TMS). S. B. Raymond was supported with the NDSEG fellowship, the Harvard University Ashford fellowship, and T32 EB001680. NR 30 TC 46 Z9 49 U1 2 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD MAR PY 2008 VL 35 SU 1 BP S93 EP S98 DI 10.1007/s00259-007-0708-7 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V28OR UT WOS:000208690600013 PM 18236039 ER PT J AU d'Othee, BJ Siebert, U Cury, R Jadvar, H Dunn, EJ Hoffmann, U AF d'Othee, Bertrand Janne Siebert, Uwe Cury, Ricardo Jadvar, Hossein Dunn, Edward J. Hoffmann, Udo TI A systematic review on diagnostic accuracy of CT-based detection of significant coronary artery disease SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Review DE coronary disease; imaging; computed tomography; meta-analysis ID SPIRAL COMPUTED-TOMOGRAPHY; ELECTRON-BEAM CT; STABLE ANGINA-PECTORIS; NONINVASIVE DETECTION; CARDIAC-CATHETERIZATION; HIGH-RISK; ANGIOGRAPHY; STENOSES; EXPERIENCE; RESOLUTION AB Objectives: Systematic review of diagnostic accuracy of contrast enhanced coronary computed tomography (CE-CCT). Background: Noninvasive detection of coronary artery stenosis (CAS) by CE-CCT as an alternative to catheter-based coronary angiography (CCA) may improve patient management. Methods: Forty-one articles published between 1997 and 2006 were included that evaluated native coronary arteries for significant stenosis and used CE-CCT as diagnostic test and CCA as reference standard. Study group characteristics, study methodology and diagnostic outcomes were extracted. Pooled summary sensitivity and specificity of CE-CCT were calculated using a random effects model (1) for all coronary segments, (2) assessable segments, and (3) per patient. Results: The 41 studies totaled 2515 patients (75% males; mean age: 59 years, CAS prevalence: 59%). Analysis of all coronary segments yielded a sensitivity of 95% (80%, 89%, 86%, 98% for electron beam CT, 4/8-slice, 16-slice and 64-slice MDCT, respectively) for a specificity of 85% (77%, 84%, 95%,91%). Analysis limited to segments deemed assessable by CT showed sensitivity of 96% (86%, 85%,98%,97%) for a specificity of 95% (90%, 96%, 96%, 96%). Per patient, sensitivity was 99% (90%, 97%, 99%, 98%) and specificity was 76% (59%, 81%, 83%, 92%). Heterogeneity was quantitatively important but not explainable by patient group characteristics or study methodology. Conclusions: Current diagnostic accuracy of CE-CCT is high. Advances in CT technology have resulted in increases in diagnostic accuracy and proportion of assessable coronary segments. However, per patient, accuracy may be lower and CT may have more limited clinical utility in populations at high risk for CAD. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [d'Othee, Bertrand Janne] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02215 USA. [Siebert, Uwe; Cury, Ricardo; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02215 USA. [Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & Hlth Technol As, Innsbruck, Austria. [Jadvar, Hossein] Univ So Calif, Keck Sch Med, Dept Radiol, Los Angeles, CA 90033 USA. [Dunn, Edward J.] Vet Hlth Adm, Natl Ctr Patient Safety, Ann Arbor, MI USA. RP d'Othee, BJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave,W-CC-385, Boston, MA 02215 USA. EM bjanne@bidmc.harvard.edu; uwe.siebert@umit.at; rcury@partners.org; jadvar@usc.edu; edward.dunn@med.va.gov; uhoffman@partners.org RI Janne d'Othee, Bertrand/E-8467-2010 NR 60 TC 79 Z9 81 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2008 VL 65 IS 3 BP 449 EP 461 DI 10.1016/j.ejrad.2007.05.003 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 282VM UT WOS:000254595300016 PM 17590554 ER PT J AU Tagashira, H Arakawa, K Yoshimoto, M Mochizuki, T Murase, K Yoshida, H AF Tagashira, Hiroyuki Arakawa, Kenji Yoshimoto, Masahiro Mochizuki, Teruhito Murase, Kenya Yoshida, Hiroyuki TI Improvement of lung abnormality detection in computed radiography using multi-objective frequency processing: Evaluation by receiver operating characteristics (ROC) analysis SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE lung cancer; computed radiography; multi-objective frequency processing; ROC analysis ID CHEST RADIOGRAPHS; TEXTURE AB Computed radiography (CR) has been shown to have relatively low sensitivity for detection of pulmonary nodules. This poor sensitivity precludes its use as a screening modality despite the low cost, low dose and wide distribution of devices. The purpose of this study was to apply multi-objective frequency processing (MFP) to CR images and to evaluate its usefulness for diagnosing subtle lung abnormalities. Fifty CR images with simulated subtle lung abnormalities were obtained from 50 volunteers. Each image was processed with MFP. We cut chest images. The chest image was divided into two rights and left. A total of 200 half-chest images (100 MFP-processed images and 100 MFP-unprocessed images) were prepared. Five radiologists participated in this study. ROC analyses demonstrated that the detection rate of simulated subtle lung abnormalities on the CR images was significantly better with MFP (Az = 0.8508) than without MFP (Az = 0.7925). The CR images processed with MFP could be useful for diagnosing subtle lung abnormalities. In conclusion, MFP appears to be useful for increasing the sensitivity and specificity in the detection of pulmonary nodules, ground-glass opacity (GGO) and reticular shadow. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Tagashira, Hiroyuki; Arakawa, Kenji; Yoshimoto, Masahiro; Mochizuki, Teruhito] Ehime Univ Hosp, Radiol Ctr, Toon, Ehime 7910295, Japan. [Tagashira, Hiroyuki; Murase, Kenya] Osaka Univ, Grad Sch Med, Dept Med Phys & Engn, Suita, Osaka 5650871, Japan. [Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tagashira, H (reprint author), Ehime Univ Hosp, Radiol Ctr, 454 Shitsukawa, Toon, Ehime 7910295, Japan. EM syourin@swallow.m.ehime-u.ac.jp NR 12 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2008 VL 65 IS 3 BP 473 EP 477 DI 10.1016/j.ejrad.2007.04.017 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 282VM UT WOS:000254595300019 PM 17540526 ER PT J AU Simon, NM McNamara, K Chow, CW Maser, RS Papakostas, GI Pollack, MH Nierenberg, AA Fava, M Wong, KK AF Simon, N. M. McNamara, K. Chow, C. W. Maser, R. S. Papakostas, G. I. Pollack, M. H. Nierenberg, A. A. Fava, M. Wong, K. K. TI A detailed examination of cytokine abnormalities in Major Depressive Disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cytokines; inflammation; depression; major depressive disorder; stress; cardiovascular ID CORONARY-HEART-DISEASE; PROINFLAMMATORY CYTOKINES; CLINICAL DEPRESSION; RISK; WOMEN; MEN; INTERLEUKIN-6; PATHOGENESIS; INFLAMMATION; CHEMOKINES AB Recent technological advances offer an opportunity to further elucidate the complex cytokine network in Major Depressive Disorder (MDD). Twenty cytokines were simultaneously assessed in 49 individuals with MDD and 49 age and gender matched controls. Multiple pro-inflammatory and two anti-inflammatory cytokines were significantly elevated in the MDD sample, including an antidepressant naive subset. These data support a generalized chronic inflammatory state in MDD, and implicate additional cytokines and chemokines previously linked to cardiovascular disease. (c) 2007 Elsevier B.V. and ECNP. All rights reserved. C1 [Simon, N. M.; Chow, C. W.; Papakostas, G. I.; Pollack, M. H.; Nierenberg, A. A.; Fava, M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Simon, N. M.; Chow, C. W.; Papakostas, G. I.; Pollack, M. H.; Nierenberg, A. A.; Fava, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [McNamara, K.; Maser, R. S.; Wong, K. K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,185 Cambridge St,Suite 2200,185, Boston, MA 02114 USA. EM NSIMON@Partners.org RI Maser, Richard/B-2970-2012; Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [R10 MH056057, R10 MH056057-03, R10 MH56058] NR 28 TC 123 Z9 126 U1 5 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 2008 VL 18 IS 3 BP 230 EP 233 DI 10.1016/j.euroneuro.2007.06.004 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 265AA UT WOS:000253330300009 PM 17681762 ER PT J AU Reich, O Bachmann, A Choi, B Collins, E De La Rossette, JJMCH Gomez, SF Muir, G Tabatabaei, S Woo, H AF Reich, O. Bachmann, A. Choi, B. Collins, E. De La Rossette, J. J. M. C. H. Gomez, Sanche F. Muir, G. Tabatabaei, S. Woo, H. CA IGLU TI International multicentre experience of the greenlight HPS120Wlaser in patients with symptomatic BPH SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Meeting Abstract C1 [Reich, O.] Univ Munich, Dept Urol, Munich, Germany. [Bachmann, A.] Univ Basel Hosp, Dept Urol, CH-4031 Basel, Switzerland. [Choi, B.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY USA. California Urol Serv, Dept Urol, San Francisco, CA USA. [De La Rossette, J. J. M. C. H.] Univ Amsterdam, Acad Med Ctr, Dept Urol, NL-1012 WX Amsterdam, Netherlands. [Gomez, Sanche F.] Inst Adv Urol Surg, Dept Urol, Madrid, Spain. [Muir, G.] Kings Coll Hosp London, Dept Urol, London, England. [Tabatabaei, S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Woo, H.] Weastmed Univ Hosp, Dept Urol, Sydney, NSW, Australia. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD MAR PY 2008 VL 7 IS 3 MA 527 BP 202 EP 202 DI 10.1016/S1569-9056(08)60523-0 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 272DQ UT WOS:000253839800520 ER PT J AU Stemberg, N Sartor, OA Petrylak, OP Witjes, F Bodrogi, I Harper, P James, N Demkov, T Eymard, JC Wirth, M AF Stemberg, N. Sartor, O. A. Petrylak, O. P. Witjes, F. Bodrogi, I Harper, P. James, N. Demkov, T. Eymard, J-C Wirth, M. TI Satraplatin (S) increases progression-free survival (PFS) and delays pain progression in patients (PTS) with hormone refractory prostate cancer (HRPC) that have progressed after prior docetaxel SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Meeting Abstract C1 [Stemberg, N.] San Camillo Forlanini Hosp, Dept Med Oncol, Rome, Italy. [Sartor, O. A.] Dana Farber Canc Inst, Dept Genitouiary Oncol, Boston, MA 02115 USA. [Petrylak, O. P.] Columbia Presbyterian Med Ctr, Dept Med Oncol, New York, NY 10032 USA. [Witjes, F.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Bodrogi, I] Natl Inst Oncol, Dept Oncol, Budapest, Hungary. [Harper, P.] Guys & St Thomas Hosp, Dept Med Oncol, London SE1 9RT, England. [James, N.] Queen Elizabeth Hosp, Dept Clin Oncol, Birmingham B15 2TH, W Midlands, England. [Demkov, T.] Maria Sklosdowska Curie Mem Canc Ctr, Dept Oncol, Warsaw, Poland. [Eymard, J-C] Inst Jean Godinoi, Dept Oncol, F-51056 Reims, France. [Wirth, M.] Carl Gustav Carus Univ Hosp, Dept Urol, Dresden, Germany. RI Witjes, Fred/N-9665-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD MAR PY 2008 VL 7 IS 3 MA 638 BP 230 EP 230 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 272DQ UT WOS:000253839801038 ER PT J AU Oudard, S Motzer, RJ Michaelson, MD Hutson, TE Tomczak, P Bukowski, RM Rixie, O Negrier, S Kim, ST Chen, J Figlin, RA AF Oudard, S. Motzer, R. J. Michaelson, M. D. Hutson, T. E. Tomczak, P. Bukowski, R. M. Rixie, O. Negrier, S. Kim, S. T. Chen, J. Figlin, R. A. TI Sunitinib as first-line treatment for metastatic renal cell carcinoma (MRCC): Updated results and analysis of prognostic factors from a phase III randomised trial SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Meeting Abstract C1 [Oudard, S.] Hop Europeen Georges Pompidou, Serv Canc Med, Paris, France. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hutson, T. E.] Baylor Sammons Canc Ctr, Texas Oncol, Dallas, TX USA. [Tomczak, P.] Klin Onkol Oddzial Chemiotherapii, Poznan, Poland. [Bukowski, R. M.] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH USA. [Rixie, O.] Hop La Pitie Salpetriere, Paris, France. [Negrier, S.] Cent Leon Berard, Lyon, France. [Kim, S. T.; Chen, J.] Pfizer Global Res & Dev, La Jolla, CA USA. [Figlin, R. A.] City Hope Comprehens Canc Ctr, Los Angeles, CA 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 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD MAR PY 2008 VL 7 IS 3 MA 698 BP 245 EP 245 DI 10.1016/S1569-9056(08)60696-X PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 272DQ UT WOS:000253839801100 ER PT J AU Gomez, SF Muir, G Bachmann, A Choi, B Collins, E De La Rosette, J Reich, O Tabatabei, S Woo, H AF Gomez, Sancha F. Muir, G. Bachmann, A. Choi, B. Collins, E. De La Rosette, J. Reich, O. Tabatabei, S. Woo, H. CA IGLU TI Green light HPS laser prostatectomy: Recommendations on surgical technique SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Meeting Abstract C1 [Gomez, Sancha F.] Inst Cirugia Urol Avanzada, Dept Urol, Madrid, Spain. [Muir, G.] Kings Coll Hosp, Dept Urol, London, England. [Bachmann, A.] Univ Basel Hosp, Dept Urol, CH-4031 Basel, Switzerland. [Choi, B.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY USA. [Collins, E.] Calif Urol Serv, Dept Urol, San Francisco, CA USA. [De La Rosette, J.] Univ Amsterdam, Acad Med Ctr, Dept Urol, Amsterdam, Netherlands. [Reich, O.] Univ Munich, Dept Urol, Munich, Germany. [Tabatabei, S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Woo, H.] Univ Sydney, Westmead Hosp, Dept Urol, Sydney, NSW 2006, Australia. 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 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD MAR PY 2008 VL 7 IS 3 MA V15 BP 332 EP 332 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 272DQ UT WOS:000253839801430 ER PT J AU Barton, JJS Pandita, M Thakkar, K Goff, DC Manoach, DS AF Barton, Jason J. S. Pandita, Manisha Thakkar, Katy Goff, Donald C. Manoach, Dara S. TI The relation between antisaccade errors, fixation stability and prosaccade errors in schizophrenia SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE antisaccade; fixation; prosaccade; schizophrenia; inhibition ID SACCADIC EYE-MOVEMENTS; BIOLOGICAL RELATIVES; SMOOTH-PURSUIT; VOLUNTARY CONTROL; TASK-PERFORMANCE; VISUAL FIXATION; WORKING-MEMORY; ANTI-SACCADES; PRO-SACCADES; ABNORMALITIES AB Whether antisaccade errors in schizophrenia are due to defects in implementing saccadic inhibition or difficulty in generating novel responses is uncertain. We investigated whether antisaccade errors were related to difficulty in inhibiting saccades when subjects were asked to maintain steady fixation, a situation that does not require a novel response. We examined the ocular motor data of 15 schizophrenia subjects and 16 healthy subjects. We assessed fixation in two situations: first, during the period before target onset during each saccadic trial, and second, during fixation trials that were interspersed with saccadic trials. We found that schizophrenia subjects had higher rates of fixation losses than control subjects in both situations. Second, both in healthy and schizophrenia subjects, antisaccade error rate was positively correlated with the frequency of fixation losses in the preparatory period of saccadic trials, but not with the frequency of fixation losses during fixation trials. Third, antisaccade errors were more likely to occur in trials with unstable fixation than in trials with stable fixation. Last, antisaccade error rate was also correlated with prosaccade error rate. We conclude that antisaccade errors are related to difficulties with implementing inhibitory control in the saccadic system. However, the finding of a correlation between the error rates for antisaccades and prosaccades suggests that this is not specifically concerned with inhibiting the automatic prosaccade, but a more general deficit in implementing goal-oriented behavior. C1 [Barton, Jason J. S.] VGH Eye Care Ctr, Neuroophthalmol Sect D, Vancouver, BC V5Z 3N9, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Neurol Ophthalmol & Visual Sci, Vancouver, BC, Canada. [Barton, Jason J. S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Pandita, Manisha; Thakkar, Katy; Goff, Donald C.; Manoach, Dara S.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA USA. [Pandita, Manisha; Thakkar, Katy; Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Barton, JJS (reprint author), VGH Eye Care Ctr, Neuroophthalmol Sect D, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada. EM jasonbarton@shaw.ca RI Barton, Jason/A-6362-2012; OI Thakkar, Katharine/0000-0002-0026-2030 FU NCRR NIH HHS [P41-RR14075]; NIMH NIH HHS [R01 MH67720] NR 58 TC 7 Z9 8 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAR PY 2008 VL 186 IS 2 BP 273 EP 282 DI 10.1007/s00221-007-1235-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 277AB UT WOS:000254183700008 PM 18057921 ER PT J AU Pukkila-Worley, R Mylonakis, E AF Pukkila-Worley, Read Mylonakis, Eleftherios TI Epidemiology and management of cryptococcal meningitis: developments and challenges SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE amphotericin B; Cryptococcus gattii; Cryptococcus neoformans; fluconazole; fungal infection; HIV infection; posaconazole; voriconazole ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; RECONSTITUTION INFLAMMATORY SYNDROME; B LIPID COMPLEX; ORGAN TRANSPLANT RECIPIENTS; PLACEBO-CONTROLLED TRIAL; IN-VITRO SUSCEPTIBILITY; AMPHOTERICIN-B; IMMUNE RECONSTITUTION; INTRACRANIAL-PRESSURE AB The significance of cryptococcal infection as a cause of human disease has dramatically evolved in recent: years. The objective of this study was to outline the worldwide significance of cryptococcosis and review developments in the management of cryptococcal meningitis. Cryptococcus neoformans var. grubii remains an important cause of disease, particularly in hosts with acquired immunosuppression. Cryptococcus gattii, on the other hand, infects hosts with seemingly normal immune systems and a recent dramatic outbreak in a new ecologic environment highlights the emerging clinical significance of this fungal pathogen. The introduction of new antifungal agents and the adoption of strategies for controlling elevated intracranial pressure in cryptococcal meningitis have added to our therapeutic options. However, the mortality from this infection remains unacceptably high and we are faced with the specific challenges in the management of this disease. C1 [Pukkila-Worley, Read; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIAID NIH HHS [T32 AI007061, K08AI63084] NR 69 TC 43 Z9 48 U1 1 U2 15 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD MAR PY 2008 VL 9 IS 4 BP 551 EP 560 DI 10.1517/14656566.9.4.551 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 277CF UT WOS:000254189600005 PM 18312157 ER PT J AU Schrader, KA Masciari, S Boyd, N Wiyrick, S Kaurah, P Senz, J Burke, W Lynch, HT Garber, JE Huntsman, DG AF Schrader, Kasmintan A. Masciari, Serena Boyd, Niki Wiyrick, Sara Kaurah, Pardeep Senz, Janine Burke, Wylie Lynch, Henry T. Garber, Judy E. Huntsman, David G. TI Hereditary diffuse gastric cancer: association with lobular breast cancer SO FAMILIAL CANCER LA English DT Article DE hereditary diffuse gastric cancer (HDGC); diffuse gastric cancer; E-cadherin mutation; CDH1 mutation; lobular breast cancer; screening; prophylactic total gastrectomy ID E-CADHERIN GENE; GERMLINE MUTATIONS; CDH1 MUTATIONS; BETA-CATENIN; CARCINOMA; FAMILIES; CARRIERS; BRCA2; EXPRESSION; TUMOR AB Hereditary diffuse gastric cancer (HDGC) has been shown to be caused by germline mutations in the gene CDH1 located at 16q22.1, which encodes the cell-cell adhesion molecule, E-cadherin. Not only does loss of expression of E-cadherin account for the morphologic differences between intestinal and diffuse gastric cancer (DGC) variants, but it also appears to lead to distinct cellular features which appear to be common amongst related cancers that have been seen in the syndrome. As in most hereditary cancer syndromes, multiple organ sites may be commonly affected by cancer, in HDGC, lobular carcinoma of the breast (LBC) and possibly other organ sites have been shown to be associated with the familial cancer syndrome. Given the complexity of HDGC, not only with regard to the management of the DGC risk, but also with regard to the risk for other related cancers, such as LBC, a multi-disciplinary approach is needed for the management of individuals with known CDH1 mutations. C1 [Schrader, Kasmintan A.; Garber, Judy E.; Huntsman, David G.] Univ British Columbia, British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 1L3, Canada. [Schrader, Kasmintan A.; Boyd, Niki; Kaurah, Pardeep; Huntsman, David G.] British Columbia Canc Agcy, Hereditary Canc Program, Vancouver, BC V5Z 4E6, Canada. [Masciari, Serena; Garber, Judy E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wiyrick, Sara] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Wiyrick, Sara] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Burke, Wylie] Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. [Lynch, Henry T.] Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. RP Huntsman, DG (reprint author), Univ British Columbia, British Columbia Canc Agcy, Dept Pathol & Lab Med, 600 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM dhuntsma@bccancer.bc.ca NR 91 TC 51 Z9 52 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9600 J9 FAM CANCER JI Fam. Cancer PD MAR PY 2008 VL 7 IS 1 BP 73 EP 82 DI 10.1007/s10689-007-9172-6 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 267RR UT WOS:000253527400010 PM 18046629 ER PT J AU Cho, CH Parashurama, N Park, EYH Suganuma, K Nahniias, Y Park, J Tilles, AW Berthiaume, F Yarmush, ML AF Cho, Cheul H. Parashurama, Natesh Park, Eric Y. H. Suganuma, Kazuhiro Nahniias, Yaakov Park, Jaesung Tilles, Arno W. Berthiaume, FranCois Yarmush, Martin L. TI Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure SO FASEB JOURNAL LA English DT Article DE coculture; endoderm; animal model; bioartificial liver device ID IN-VITRO DIFFERENTIATION; DEFINITIVE ENDODERM; GROWTH-FACTOR; HEPATIC DIFFERENTIATION; SANDWICH CONFIGURATION; BIOARTIFICIAL LIVER; COLLAGEN SANDWICH; ENDOTHELIAL-CELLS; CONTROLLED-TRIAL; GENE-EXPRESSION AB One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. While embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. Here we describe a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. Mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiated and proliferated into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17, and AFP and could be further differentiated into hepatocyte-like cells, demonstrating hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells.-Cho, C. H., Parashurama, N., Park, E. Y. H., Sugamuna, K, Nahmias, Y., Park, J., Tilles, A. W., Berthiaume, F., Yarmush, M. L. Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Dept Surg, Boston, MA 02114 USA. RP Tilles, AW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM arno-tilles@hms.harvard.edu; ireis@sbi.org RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X FU NIDDK NIH HHS [K08 DK066040, K18 DK076819, P30 DK040561, P30 DK040561-12, R01 DK43371] NR 61 TC 44 Z9 48 U1 2 U2 7 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 MAR PY 2008 VL 22 IS 3 BP 898 EP 909 DI 10.1096/fj.06-7764com PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 276LQ UT WOS:000254143700028 PM 17942827 ER PT J AU El Jamali, A Valente, AJ Lechleiter, JD Gamez, MJ Pearson, DW Nauseef, WM Clark, RA AF El Jamali, Amina Valente, Anthony J. Lechleiter, James D. Gamez, Maria J. Pearson, Doran W. Nauseef, William M. Clark, Robert A. TI Novel redox-dependent regulation of NOX5 by the tyrosine kinase c-Abl SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE NADPH oxidase; NOX5; hydrogen peroxide; signaling; c-Abl; superoxide; calcium; free radicals ID NF-KAPPA-B; HYDROGEN-PEROXIDE; GROWTH-FACTORS; HEMATOPOIETIC-CELLS; ENDOTHELIAL-CELLS; MYC EXPRESSION; ANGIOTENSIN-II; NADPH OXIDASES; DNA-SYNTHESIS; ACTIVATION AB We investigated the mechanism of H(2)O(2) activation of the Ca(2+)-regulated NADPH oxidase NOX5. H(2)O(2) induced a transient, dose-dependent increase in superoxide production in K562 cells expressing NOX5. Confocal studies demonstrated that the initial calcium influx generated by H(2)O(2) is amplified by a feedback mechanism involving NOX5-dependent superoxide production and H(2)O(2). H(2)O(2) NOX5 activation was inhibited by extracellular Ca(2+) chelators, a pharmacological inhibitor of c-Abl, and overexpression of kinase-dead c-Abl. Transfected kinase-active GFP-c-Abl colocalized with vesicular sites of superoxide production in a Ca(2+)-dependent manner. In contrast to H(2)O(2), the Ca(2+) ionophore ionomycin induced NOX5 activity independent of c-Abl. Immunoprecipitation of cell lysates revealed that active GFP-c-Abl formed oligomers with endogenous c-Abl and that phosphorylation of both proteins was increased by H(2)O(2) treatment. Furthermore, H(2)O(2)-induced NOX5 activity correlated with increased localization of c-Abl to the membrane fraction, and NOX5 proteins could be coimmunoprecipitated with GFP-Abl proteins. Our data demonstrate for the first time that NOX5 is activated by c-Abl through a Ca(2+)-mediated, redox-dependent signaling pathway and suggest a functional association between NOX5 NADPH oxidase and c-Abl. (c) 2007 Elsevier Inc. All rights reserved. C1 [El Jamali, Amina; Valente, Anthony J.; Gamez, Maria J.; Pearson, Doran W.; Clark, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [El Jamali, Amina; Valente, Anthony J.; Lechleiter, James D.; Gamez, Maria J.; Pearson, Doran W.; Clark, Robert A.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Lechleiter, James D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Nauseef, William M.] Univ Iowa, Dept Med, Inflammat Program, Iowa City, IA 52241 USA. [Nauseef, William M.] Vet Adm Med Ctr, Iowa City, IA 52241 USA. RP El Jamali, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM AkoulouzeBik@uthscsa.edu FU BLRD VA [I01 BX000513]; NCI NIH HHS [P30 CA 054174, P30 CA054174]; NIA NIH HHS [P30 AG 013319, R01 AG019519, P01 AG019316, AG 019519, P01 AG 019316, P30 AG013319]; NIAID NIH HHS [R37 AI020866, R56 AI034879, R01 AI034879, R01 AI020866-18, AI 034879, AI 020866, R01 AI020866] NR 47 TC 52 Z9 52 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 1 PY 2008 VL 44 IS 5 BP 868 EP 881 DI 10.1016/j.freeradbiomed.2007.11.020 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 265OI UT WOS:000253369000013 PM 18160052 ER PT J AU Chatelain, D Brevet, M Fuks, D Yzet, T Verhaeghe, P Regimbeau, JM Lauwers, G Sevestre, H AF Chatelain, D. Brevet, M. Fuks, D. Yzet, T. Verhaeghe, P. Regimbeau, J. -M. Lauwers, G. Sevestre, H. TI Inflammatory fibroid polyp, a rare tumor of the appendix SO GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE LA French DT Article ID GASTROINTESTINAL-TRACT; MYOFIBROBLASTIC TUMORS; PSEUDOTUMORS AB We report the rare occurence of an inflammatory fibroid polyp of the appendix. The lesion was diagnosed in a 33-year-old woman presenting with abdominal pain, fever and localized tenderness in right iliac fossa on abdominal palpation. CT-scan showed an 8 cm appendiceal mass and a laparoscopic appendectomy was consequently performed. On microscopic examination, the tumor consisted of spindle cells dispersed in a loose fibromyxoid stroma containing numerous blood cells and inflammatory cells with abundant eosinophils. On immunohistochemistry, the spindle tumor cells were positive for vimentin, fascin and focally for CD34 and CD35. They were negative for smooth muscle actin, desmin, CD21, CD23, CD117 and S100 protein. Inflammatory fibroid polyp is a rare benign mesenchymal tumor of the gastrointestinal tract rarely reported in the appendix. This tumor shares some common pathologic features with the myofibroblatic inflammatory tumor but they are two different entities. The pathogenesis of this tumor remains unclear but fascin and CD35 immunoreactivity of the tumor cells suggests a probable dendritic cell origin. (C) 2008 Elsevier Masson SAS. Tous droits reserves. C1 [Chatelain, D.; Brevet, M.; Sevestre, H.] CHU Amiens, Serv Anat Pathol, F-80054 Amiens 1, France. [Fuks, D.; Verhaeghe, P.; Regimbeau, J. -M.] CHU Amiens, Serv Chirurg Digest, F-80054 Amiens, France. [Yzet, T.] Serv Radiol, F-80054 Amiens 1, France. [Lauwers, G.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. RP Chatelain, D (reprint author), CHU Amiens, Serv Anat Pathol, Pl Victor Pauchet, F-80054 Amiens 1, France. EM chatelain.denis@chu-amiens.fr NR 13 TC 2 Z9 2 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0399-8320 J9 GASTROEN CLIN BIOL JI Gastroenterol. Clin. Biol. PD MAR PY 2008 VL 32 IS 3 BP 274 EP 277 DI 10.1016/j.gcb.2007.07.003 PN 1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 308XB UT WOS:000256422900016 PM 18353580 ER PT J AU Kaplan, GG Mccarthy, EP Ayanian, JZ Korzenik, J Hodin, R Sands, BE AF Kaplan, Gilaad G. Mccarthy, Ellen P. Ayanian, John Z. Korzenik, Joshua Hodin, Richard Sands, Bruce E. TI Impact of hospital volume on postoperative morbidity and mortality following a colectomy for ulcerative colitis SO GASTROENTEROLOGY LA English DT Article ID POUCH-ANAL ANASTOMOSIS; INFLAMMATORY-BOWEL-DISEASE; TERTIARY CARE CENTER; RESTORATIVE PROCTOCOLECTOMY; OPERATIVE MORTALITY; SUBTOTAL COLECTOMY; ADMINISTRATIVE DATA; CANCER-SURGERY; COMPLICATIONS; EXPERIENCE AB Background&Aims: Postoperative morbidity and mortality following a colectomy for ulcerative colitis (UC) has been primarily reported from tertiary care referral centers that perform a high volume of operations; however, the postoperative outcomes among nonselected hospitals are not known. We set out to evaluate postoperative morbidity and mortality using a nationally representative database and to determine the factors that influenced outcomes. Methods: We analyzed the 1995-2005 Nationwide Inpatient Sample to identify 7108 discharges for UC patients who underwent a total abdominal colectomy. The effects of hospital volume on postoperative morbidity and mortality were evaluated in logistic regression models adjusting for demographic and clinical factors. Results: Postoperative mortality and morbidity rates were 2.3% and 30.8%, respectively. Most operations were performed in low-volume hospitals that had an increased risk of death (adjusted odds ratio [aOR], 2.42; 95% confidence interval [CI]: 1.26-4.63). In-hospital mortality was increased in patients who were admitted emergently (aOR, 5.40; 95% CI: 3.48-8.40), aged 60-80 years (aOR, 8.70; 95% CI: 3.30-22.92), and those with Medicaid (aOR, 4.29; 95% CI: 2.13-8.66). Emergently admitted UC patients whose surgery was performed 6 days after their admission had significantly increased likelihood of in-hospital death (aOR, 2.12; 95% CI: 1.13-3.97). Conclusions: Postoperative mortality was lowest in hospitals that performed the highest volume of operations. Increasing the proportion of total colectomies performed in high-volume hospitals may improve clinical outcomes for patients with UC. C1 [Kaplan, Gilaad G.] Univ Calgary, Inflammatory Bowel Dis Clin, Calgary, AB, Canada. [Mccarthy, Ellen P.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. [Ayanian, John Z.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Med, Boston, MA USA. [Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. [Korzenik, Joshua; Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Korzenik, Joshua; Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Korzenik, Joshua; Sands, Bruce E.] MGH Crohns & Colitis Ctr, Boston, MA USA. [Hodin, Richard] Harvard Univ, Sch Med, Boston, MA USA. [Hodin, Richard] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Kaplan, GG (reprint author), Univ Calgary, Inflammatory Bowel Dis Clin, Calgary, AB, Canada. OI Kaplan, Gilaad/0000-0003-2719-0556 NR 50 TC 116 Z9 117 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2008 VL 134 IS 3 BP 680 EP 687 DI 10.1053/j.gastro.2008.01.004 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 272DA UT WOS:000253838000009 PM 18242604 ER PT J AU Lewis, JD Lichtenstein, GR Deren, JJ Sands, BE Hanauer, SB Katz, JA Lashner, B Present, DH Chuai, S Ellenbergr, JH Nessel, L Wu, GD AF Lewis, James D. Lichtenstein, Gary R. Deren, Julius J. Sands, Bruce E. Hanauer, Stephen B. Katz, Jeffrey A. Lashner, Bret Present, Daniel H. Chuai, Shaokun Ellenbergr, Jonas H. Nessel, Lisa Wu, Gary D. CA Rosigiltazone Ulcerative Colitis TI Rosiglitazone for active ulcerative colitis: A randomized placebo-controlled trial SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; QUALITY-OF-LIFE; PPAR-GAMMA; 5-AMINOSALICYLIC ACID; MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; ANTIDIABETIC AGENTS; GENE-EXPRESSION; CROHNS-DISEASE; RECEPTOR-GAMMA AB Background&Aims: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferatoractivated receptors (PPAR gamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC). Methods: This multicenter, randomized, double-blind, placebocontrolled clinical trial compared the efficacy of rosightazone (Avandia; GlaxoSmithKhne, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>= 2-point reduction) at week 12. Clinical remission (Mayo score <= 2), endoscopic remission, and quality of life were secondary outcomes. Results: After 12 weeks of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo achieved clinical response (P = .04). Remission was achieved in 9 patients (17%) treated with rosightazone and I patient (2%) treated with placebo (P = .01). Endoscopic remission was uncommon in either treatment arm (8% rosiglitazone vs 2% placebo; P = .34). Clinical improvement was evident as early as 4 weeks after beginning treatment (P = .049). Quality of life was improved significantly at week 8 (P = .01), but not at week 4 (P = .48) or week 12 (P = .14). Serious adverse events were rare. Conclusions: Rosightazone was efficacious in the treatment of mild to moderately active UC. C1 [Lewis, James D.; Lichtenstein, Gary R.; Deren, Julius J.; Wu, Gary D.] Univ Penn, Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Lewis, James D.; Chuai, Shaokun; Ellenbergr, Jonas H.; Nessel, Lisa] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lewis, James D.; Lichtenstein, Gary R.; Deren, Julius J.; Wu, Gary D.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Lewis, James D.; Chuai, Shaokun; Ellenbergr, Jonas H.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hanauer, Stephen B.] Univ Chicago, Chicago, IL 60637 USA. [Katz, Jeffrey A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Lashner, Bret] Cleveland Clin, Cleveland, OH 44106 USA. [Present, Daniel H.] Mt Sinai Sch Med, New York, NY USA. RP Lewis, JD (reprint author), Univ Penn, Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [DK059961, R01 DK059961, R01 DK059961-05] NR 40 TC 120 Z9 123 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 MAR PY 2008 VL 134 IS 3 BP 688 EP 695 DI 10.1053/j.gastro.2007.12.012 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 272DA UT WOS:000253838000010 PM 18325386 ER PT J AU Karagiannides, I Torres, D Tseng, YH Bowe, C Carvalho, E Espinoza, D Pothoulakis, C Kokkotou, E AF Karagiannides, Iordanes Torres, Daniel Tseng, Yu-Hua Bowe, Collin Carvalho, Eugenia Espinoza, Daniel Pothoulakis, Charalabos Kokkotou, Efi TI Substance P as a novel anti-obesity target SO GASTROENTEROLOGY LA English DT Article ID CLOSTRIDIUM-DIFFICILE TOXIN; TACHYKININ NK1 RECEPTOR; LOCOMOTOR-ACTIVITY; UNITED-STATES; OBESITY; ANTAGONIST; INFLAMMATION; RESPONSES; PEPTIDE; RATS AB Background & Aims: Substance P (SP) is an 11-amino acid peptide that belongs to the tachykinin family of peptides. SP acts in the brain and in the periphery as a neuropeptide, neurotransmitter, and hormone affecting diverse physiologic pathways, mainly via its high-affinity neurokinin-1 receptor (NK-1R). Its presence in the hypothalamus and other areas of the brain that regulate feeding as well as in the stomach and small intestine prompted us to investigate its role on appetite control and energy balance. Methods: CJ 012,255 (CJ), a SP antagonist that binds to NK-1R, was injected into lean, diet-induced obese (DIO), and genetically obese (ob/ob) mice, and its effects on body weight, adiposity, and insulin sensitivity were investigated. Results: CJ administration prevented weight gain and accumulation of fat after 2 weeks of high-fat feeding, whereas similar CJ treatment in obese mice (following 3 months of high-fat diet) resulted in weight loss, reduction in adiposity, and improvement of insulin sensitivity, in part because of inhibition of food intake. The effects of SP in the control of energy balance are, at least in part, leptin independent because CJ treatment was also effective in leptin-deficient mice. Peripheral SP administration resulted in a mild, dose-dependent increase in food intake, evident 3 hours post-SP injection. Conclusions: CJ reduces appetite and promotes weight loss in mice. We speculate that NK-1R antagonists, already tested in clinical trials for various diseases, may represent a potential target against obesity. C1 [Karagiannides, Iordanes; Torres, Daniel; Bowe, Collin; Carvalho, Eugenia; Espinoza, Daniel; Pothoulakis, Charalabos; Kokkotou, Efi] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, Boston, MA 02115 USA. [Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. [Pothoulakis, Charalabos; Kokkotou, Efi] Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. RP Karagiannides, I (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, Boston, MA 02115 USA. OI Corkey, Barbara/0000-0002-5467-1630; Carvalho, Eugenia/0000-0001-6264-3632 FU NIDDK NIH HHS [P30 DK046200, 5 P30 DK 46200-15, P30 DK040561, P30 DK040561-12, P30 DK046200-15, R01 DK047343, R01 DK047343-14, R01 DK056690] NR 47 TC 27 Z9 32 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2008 VL 134 IS 3 BP 747 EP 755 DI 10.1053/j.gastro.2007.12.032 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 272DA UT WOS:000253838000016 PM 18325388 ER PT J AU Lin, W Weinberg, EM Tai, AW Peng, LF Brockman, MA Kim, KA Kim, SS Borges, CB Shao, RX Chung, RT AF Lin, Wenyu Weinberg, Ethan M. Tai, Andrew W. Peng, Lee F. Brockman, Mark A. Kim, Kyung-Ah Kim, Sun Suk Borges, Carolina B. Shao, Run-Xuan Chung, Raymond T. TI HIV increases HCV replication in a TGF-beta 1-dependent manner SO GASTROENTEROLOGY LA English DT Article ID HEPATITIS-C VIRUS; CHEMOKINE RECEPTORS; HUMAN HEPATOCYTES; LIVER-DISEASE; IN-VITRO; EXPRESSION; INFECTION; BETA; SUPPRESSION; ACTIVATION AB Background & Aims: Human immunodeficiency virus (HIV) coinfection increases hepatitis C virus (HCV)-related progression of hepatic fibrosis, increases HCV persistence, and decreases response rates to interferon-based anti-HCV therapy. It has remained unclear how HIV, a nonhepatotropic virus, accelerates the progression of liver disease by HCV. Methods: We explored the possibility that circulating HIV and/or its proteins contribute to the pathogenesis of HCV through engagement of extracellular coreceptors on hepatocytes. Results: In this study, we found that inactivated HIV or gp120 increases HCV replication and enhances HCV-regulated transforming growth factor (TGF)-beta 1 expression in both a replicon and an infectious model of HCV. This proviral effect of HIV and gp120 on HCV replication is neutralized by antibodies to CCR5 or CXCR4. However, HIV and gp120 did not alter type I interferon-mediated signaling in these HCV models, indicating that HIV regulates HCV replication through an alternative mechanism. Interestingly, we found that human TGF-beta 1 also enhanced HCV replication. The effect of HIV on HCV replication was blocked by a neutralizing antibody to TGF-beta 1, indicating that its effects on HCV replication are TGF-beta 1 dependent. Conclusions: These results suggest a novel mechanism by which HIV not only enhances HCV replication but also contributes to progression of hepatic fibrosis. C1 [Lin, Wenyu; Weinberg, Ethan M.; Tai, Andrew W.; Peng, Lee F.; Kim, Kyung-Ah; Kim, Sun Suk; Borges, Carolina B.; Shao, Run-Xuan; Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02115 USA. [Brockman, Mark A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RP Lin, W (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02115 USA. FU NIAID NIH HHS [AI069939-01] NR 34 TC 73 Z9 75 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2008 VL 134 IS 3 BP 803 EP 811 DI 10.1053/j.gastro.2008.01.005 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 272DA UT WOS:000253838000021 PM 18325393 ER PT J AU McCormick, BA AF McCormick, Beth A. TI Using Salmonella enterica serotype typhimurium to model intestinal fibrosis SO GASTROENTEROLOGY LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; DIFFERENTIAL EXPRESSION; GROWTH-FACTOR; MOUSE COLON; FIBROGENESIS; SURGERY C1 [McCormick, Beth A.] Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. [McCormick, Beth A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu NR 22 TC 3 Z9 3 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 MAR PY 2008 VL 134 IS 3 BP 872 EP 875 DI 10.1053/j.gastro.2008.01.019 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 272DA UT WOS:000253838000027 PM 18242605 ER PT J AU Sonnenberg, A Amorosi, SL Lacey, MJ Lieberman, DA AF Sonnenberg, Amnon Amorosi, Stacey L. Lacey, Michael J. Lieberman, David A. TI Patterns of endoscopy in the United States: analysis of data from the Centers for Medicare and Medicaid Services and the National Endoscopic Database SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLORECTAL-CANCER; PEPTIC-ULCER; HEALTH-CARE; COLONOSCOPY; DISEASE; TRENDS; DISPARITIES; POPULATION; COMMUNITY; INSURANCE AB Background: Patterns of GI endoscopy are influenced by the underlying epidemiology of GI disease, as well as by policy and practice guidelines. Objective: To compare practice patterns of GI endoscopy between two large national databases of the United States. Design: Descriptive database analysis. Setting: A 5% sample of the entire U.S. Medicare population (Centers for Medicare and Medicaid Services, CMS data files) and endoscopic data repository of U.S. gastroenterology practices (Clinical Outcomes Research Initiative, CORI database) from 1999 to 2003. Patients: The study population included 1,121,215 Medicare and 635,573 CORI patients undergoing various types of GI endoscopy. Interventions: EGD, colonoscopy, and flexible sigmoidoscopy. Main Outcome Measurements: Patient demographics, endoscopic diagnoses, time trends of diagnoses. Results: A colonoscopy was the most common endoscopic procedure performed (CMS 53%, CORI 58%), followed by an EGD (37%, 32%), and a flexible sigmoidoscopy (10%, 10%). In the CMS data, women accounted for 59% of the EGDs, 57% of the colonoscopies, and 56% of the flexible sigmoidoscopies, and in the CORI data, the corresponding numbers were 57%, 55%, and 54%, respectively. Compared with their distribution in the U.S. census population, nonwhite patients in both databases under-went relatively more EGDs and fewer colonoscopies. The most common upper-GI diagnosis was GERD, followed by GI bleeding, gastric ulcer, and duodenal ulcer. The most common lower-GI diagnosis was colorectal polyp. Over the period of 1999 to 2003, the rates of colorectal cancer diagnosed with colonoscopy declined. Limitations: Only a limited amount of information about individual patients was retrievable from the electronic databases. Conclusions: A colonoscopy is now the most common endoscopic procedure in the United States. Women undergo both upper and lower endoscopic procedures more often than men. Nonwhite patients are underrepresented in the use of colonoscopy relative to the prevalence of nonwhite persons in the U.S. population. Increased use of a colonoscopy for colon screening and surveillance has been associated with a decreased rate of cancer diagnosis. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Boston Sci Corp, Natick, MA USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Veterans Hosp Rd, Portland, OR 97239 USA. FU NIDDK NIH HHS [U01-DK057132-06A1] NR 23 TC 65 Z9 67 U1 1 U2 4 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 MAR PY 2008 VL 67 IS 3 BP 489 EP 496 DI 10.1016/j.gie.2007.08.041 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270WL UT WOS:000253750800018 PM 18179793 ER PT J AU Morasco, BJ Dobscha, SK AF Morasco, Benjamin J. Dobscha, Steven K. TI Prescription medication misuse and substance use disorder in VA primary care patients with chronic pain SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE chronic pain; opiates; medication misuse; substance use disorder; primary care ID CHRONIC NONMALIGNANT PAIN; MEDICALLY ILL PATIENTS; CHRONIC NONCANCER PAIN; ABUSE SCREENING-TEST; OPIOID THERAPY; METHADONE-MAINTENANCE; MUSCULOSKELETAL PAIN; BACK-PAIN; ADDICTION; PREVALENCE AB Objective: The goal of this paper was to examine the relationship between history of substance use disorder (SUD) and self-reported prescription medication misuse in 127 primary care patients who receive opioid medications for treatment of chronic pain. Method: Participants completed measures of pain location, pain intensity, disability due to pain, and misuse of prescription medications. Other measures included demographic characteristics, psychiatric symptomatology and quality of life. Results: Seventy-eight percent of participants reported at least one indicator of medication misuse in the prior year. After adjusting for age and clinical factors (pain severity, depression severity, current alcohol or substance use disorder), participants with SUD history were significantly more likely than participants without SUD history to report borrowing pain medications from others (OR=6.62, 95% CI=1.430.7) and requesting an early refill of pain medication (OR=3.86, 95% 0=1.5-9.6). Conclusions: Misuse of prescription medications is a concern among primary care patients with chronic pain. Participants with a lifetime history of SUD are more likely to endorse some aberrant medication;related behaviors. Patients with SUD histories should be carefully evaluated for medication misuse potential and may require more intense assessment and follow-up. Published by Elsevier Inc. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97219 USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Dobscha, Steven K.] Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Phys & Mental D, Portland, OR 97219 USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97219 USA. EM benjamin.morasco@va.gov NR 47 TC 49 Z9 50 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAR-APR PY 2008 VL 30 IS 2 BP 93 EP 99 DI 10.1016/j.genhosppsych.2007.12.004 PG 7 WC Psychiatry SC Psychiatry GA 270WK UT WOS:000253750700001 PM 18291290 ER PT J AU Leibowitz, RQ Jeffreys, MD Copeland, LA Noel, PH AF Leibowitz, Ruth Q. Jeffreys, Matthew D. Copeland, Laurel A. Noel, Polly H. TI Veterans' disclosure of trauma to healthcare providers SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE trauma; PTSD; disclosure; health communication ID POSTTRAUMATIC-STRESS-DISORDER; ADMINISTERED PTSD SCALE; MENTAL-HEALTH; FEMALE VETERANS; HELP-SEEKING; SYMPTOMS; ASSOCIATION; DEPRESSION; ANXIETY; ABUSE AB Objective: The purpose of this study is to gain a better understanding of patients' trauma disclosure to health professionals. Method: A convenience sample of 173 veterans in outpatient treatment for posttraumatic stress disorder (PTSD) in the Veterans Health Administration completed surveys querying trauma history, reasons for trauma disclosure and perceived provider responses. Results: For half of the participants, a healthcare provider was the first person to whom they disclosed. Reasons were primarily external, such as pressure from others. Although 72% were glad to disclose, 45% perceived at least one negative provider response. Conclusion: Patients disclose to a wide range of provider types and perceive varied responses. Providers' awareness of the need to be sensitive to trauma disclosure could facilitate treatment for PTSD. Published by Elsevier Inc. C1 [Leibowitz, Ruth Q.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Jeffreys, Matthew D.] S Texas Vet Hlth Care Syst, Dept Psychiat, San Antonio, TX 78229 USA. [Jeffreys, Matthew D.; Copeland, Laurel A.; Noel, Polly H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Copeland, Laurel A.] S Texas Vet Hlth Care Syst, VERDICT HSR&D, San Antonio, TX 78229 USA. [Noel, Polly H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Leibowitz, RQ (reprint author), Vet Adm Med Ctr, Portland Div, POB 1034 P3MHDC, Portland, OR 97207 USA. EM Dr.Leibq@hotmail.com OI Copeland, Laurel/0000-0002-9478-0209 NR 22 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAR-APR PY 2008 VL 30 IS 2 BP 100 EP 103 DI 10.1016/j.genhosppsych.2007.11.004 PG 4 WC Psychiatry SC Psychiatry GA 270WK UT WOS:000253750700002 PM 18291291 ER PT J AU Graham, DSC Vyse, TJ Fortin, PR Montpetit, A Cai, YC Lim, S McKenzie, T Farwell, L Rhodes, B Chad, L Hudson, TJ Sharpe, A Terhorst, C Greenwood, CMT Wither, J Rioux, JD AF Graham, D. S. Cunninghame Vyse, T. J. Fortin, P. R. Montpetit, A. Cai, Y-C Lim, S. McKenzie, T. Farwell, L. Rhodes, B. Chad, L. Hudson, T. J. Sharpe, A. Terhorst, C. Greenwood, C. M. T. Wither, J. Rioux, J. D. CA CaNIOS GenES Investigators TI Association of LY9 in UK and Canadian SLE families SO GENES AND IMMUNITY LA English DT Article DE SLE; LY9; SLAMF7; genetic association and T cells ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; GENOME SCAN; SLAM; MICE; CHROMOSOME-1; MOLECULES; GENES; CELLS AB Systemic lupus erythematosus (SLE) is a complex disease trait of unknown aetiology. Genome-wide linkage studies in human SLE identified several linkage regions, including one at 1q23, which contains multiple susceptibility genes, including the members of the signalling lymphocyte activation molecule (SLAM) locus. In mice there is a syntenic linkage region, Sle1. The SLAM genes are functionally related cell-surface receptors, which regulate signal transduction of cells in the immune system. Family-based association study in UK and Canadian SLE families identified variants in the promoter and coding region of SLAMF7 and LY9 contributing to SLE disease susceptibility. The strongest association was from rs509749, in exon 8 of LY9 (P = 0.00209). rs509749 encodes a Val/Met nonsynonymous change in amino acid 602 in the cytoplasmic domain of LY9. In the parents and affected individuals from the Canadian SLE families, the risk allele of rs509049 skews the T-cell population by increasing the number of CD8+ memory T cells, while decreasing the proportion of CD4+ naive T cells and activated T cells. Since rs509749 lies within the consensus binding site for SAP/SH2D1a, which influences downstream signalling events from LY9, the mechanism for increased CD8+ memory T cells may include differential binding SAP/SH2D1a to the cytoplasmic domain of LY9. C1 [Graham, D. S. Cunninghame; Vyse, T. J.; Rhodes, B.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Hammersmith Hosp, Sect Mol Genet & Pheumatol, London W12 ONN, England. [Fortin, P. R.] Univ Hlth Network, Toronto Western Hosp, Ctr Prognosis Studies Rheumat Dis, Univ Toronto Lupus Clin, Toronto, ON, Canada. [Fortin, P. R.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Chad, L.; Hudson, T. J.] McGill Univ, Montreal, PQ, Canada. [Chad, L.; Hudson, T. J.] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Chad, L.; Hudson, T. J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Cai, Y-C; McKenzie, T.] Univ Hlth Network, Toronto Western Hosp, Res Inst, Toronto, ON, Canada. [Lim, S.; Greenwood, C. M. T.] Hosp Sick Children, Res Inst, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Farwell, L.; Rioux, J. D.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Farwell, L.; Rioux, J. D.] Harvard Univ, Cambridge, MA 02138 USA. [Sharpe, A.] Harvard Univ, Sch Med, NRB 837, Boston, MA 02115 USA. [Terhorst, C.] Harvard Univ, Inst Med, Div Immunol, BIDMC, Boston, MA 02115 USA. [Wither, J.] Arthritis Ctr Excellence, Toronto, ON, Canada. [Wither, J.] Univ Hlth Network, Toronto Western Hosp, Res Inst, Div Genet & Dev, Toronto, ON, Canada. [Wither, J.] Univ Toronto, Dept Med & Immunol, Toronto, ON, Canada. [Rioux, J. D.] Univ Montreal, Montreal, PQ, Canada. [Rioux, J. D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. RP Graham, DSC (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Hammersmith Hosp, Sect Mol Genet & Pheumatol, Hammersmith Campus,1st Floor J Block,Room 118-119, London W12 ONN, England. EM deborah.cunninghame-graham@imperial.ac.uk RI Vyse, Tim/G-3887-2011; Rioux, John/A-9599-2015; OI Rioux, John/0000-0001-7560-8326; Peschken, Christine/0000-0002-4269-5213 NR 32 TC 41 Z9 41 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD MAR PY 2008 VL 9 IS 2 BP 93 EP 102 DI 10.1038/sj.gene.6364453 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 271VA UT WOS:000253815600002 ER PT J AU Swanson, KD Winter, JM Reis, M Bentires-Alj, M Greulich, H Grewal, R Hruban, RH Yeo, CJ Yassin, Y Lartchouk, O Montgomery, K Whitman, SP Caligiuri, MA Loh, ML Gilliland, DG Look, AT Kucherlapati, R Kern, SE Meyerson, M Neel, BG AF Swanson, Kenneth D. Winter, Jordan M. Reis, Marcelo Bentires-Alj, Mohamed Greulich, Heidi Grewal, Rupinder Hruban, Ralph H. Yeo, Charles J. Yassin, Yosuf Lartchouk, Oleg Montgomery, Kate Whitman, Susan P. Caligiuri, Michael A. Loh, Mignon L. Gilliland, D. Gary Look, A. Thomas Kucherlapati, Raju Kern, Scott E. Meyerson, Matthew Neel, Benjamin G. TI SOSI mutations are rare in human malignancies: Implications for Noonan syndrome patients SO GENES CHROMOSOMES & CANCER LA English DT Article ID HEREDITARY GINGIVAL FIBROMATOSIS; FACIO-CUTANEOUS SYNDROME; OF-FUNCTION MUTATIONS; RAS GENE-MUTATIONS; EGF RECEPTOR; MYELOMONOCYTIC LEUKEMIA; LUNG ADENOCARCINOMA; GERMLINE MUTATIONS; PROSTATE-CANCER; HUMAN-BREAST AB Germ line gain-of-function mutations in several members of the RAS/ERK pathway, including PTPNII, KRAS, and RAFI cause the autosomal dominant genetic disorder Noonan Syndrome (NS). INS patients are at increased risk of leukemia/myeloproliferative disease and possibly some solid tumors, such as neuroblastoma. Recently, SOSI gain of function mutations have also been shown to cause NS. Somatic PTPNII, KRAS, and RAFI mutations occur (although at different frequencies) in a variety of sporadic neoplasms, but whether SOSI mutations are associated with human cancer has not been evaluated. We sequenced DNA from a total of 810 primary malignancies, including pancreatic, lung, breast, and colon carcinomas, and acute myelogenous leukemia, as well as several neuroblastorna cell lines. From this large, diverse series, missense SOSI mutations were identified in a single pancreatic tumor, one lung adenocarcinoma, and a T-cell acute lymphoblastic leukemia cell line. Our findings suggest that SOSI is not a significant human oncogene in most cancers. Furthermore, NS patients with SOSI mutations may not be at increased risk of developing cancer. (c) 2007 Wiley-Liss, Inc. C1 [Swanson, Kenneth D.; Bentires-Alj, Mohamed; Neel, Benjamin G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Swanson, Kenneth D.; Bentires-Alj, Mohamed; Neel, Benjamin G.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Prog, Boston, MA 02215 USA. [Winter, Jordan M.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Surg, Baltimore, MD USA. [Kern, Scott E.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [Reis, Marcelo] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA. [Greulich, Heidi; Grewal, Rupinder; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Greulich, Heidi; Grewal, Rupinder; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Greulich, Heidi; Grewal, Rupinder; Yassin, Yosuf; Lartchouk, Oleg; Montgomery, Kate; Kucherlapati, Raju; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Greulich, Heidi; Grewal, Rupinder; Meyerson, Matthew] Broad Inst Harvard, Cambridge, MA USA. [Greulich, Heidi; Grewal, Rupinder; Meyerson, Matthew] MIT, Cambridge, MA 02139 USA. [Hruban, Ralph H.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Yeo, Charles J.] Thomas Jefferson Univ, Dept Surg, Philadelphia, PA 19107 USA. [Yassin, Yosuf; Lartchouk, Oleg; Montgomery, Kate; Kucherlapati, Raju] Harvard Partners Ctr Genet & Genom, Boston, MA USA. [Whitman, Susan P.; Caligiuri, Michael A.] Ohio State Univ, Div Hematol Oncol, Dept Internal Med, Coll Med & Publ Hlth, Columbus, OH 43210 USA. [Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Gilliland, D. Gary] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Look, A. Thomas] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Cambridge, MA 02138 USA. RP Swanson, KD (reprint author), 77 Ave,Louis Pasteur NRB 1030, Boston, MA 02115 USA. EM kswanson@bidmc.harvard..edu RI Meyerson, Matthew/E-7123-2012; Reis, Marcelo/H-9370-2012; Mohamed, Bentires-Alj/F-4484-2015 OI Reis, Marcelo/0000-0002-4706-1041; Mohamed, Bentires-Alj/0000-0001-6344-1127 FU NCI NIH HHS [CA62924, CA84301, K22 CA113557, P01 CA 108631, R01 CA116020, CA016058-30, R37CA49152]; NICHD NIH HHS [HD47863]; NIDDK NIH HHS [T32-DK007713] NR 54 TC 17 Z9 19 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 2008 VL 47 IS 3 BP 253 EP 259 DI 10.1002/gec.20527 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 256XX UT WOS:000252764300008 PM 18064648 ER PT J AU Levasseur, DN Wang, J Dorschner, MO Stamatoyannopoulos, JA Orkin, SH AF Levasseur, Dana N. Wang, Jianlong Dorschner, Michael O. Stamatoyannopoulos, John A. Orkin, Stuart H. TI Oct4 dependence of chromatin structure within the extended Nanog locus in ES cells SO GENES & DEVELOPMENT LA English DT Article DE Nanog; Oct4; chromatin; reprogramming; self renewal ID EMBRYONIC STEM-CELLS; SELF-RENEWAL; HUMAN GENOME; MOUSE EPIBLAST; CTCF; GENE; TRANSCRIPTION; PLURIPOTENCY; EXPRESSION; INSULATOR AB Embryonic stem (ES) cells offer insight into early developmental fate decisions, and their controlled differentiation may yield vast regenerative potential. The molecular determinants supporting ES cell self-renewal are incompletely understood. The homeodomain proteins Nanog and Oct4 are essential for mouse ES cell self-renewal. Using a high-throughput approach, we discovered DNaseI hypersensitive sites and potential regulatory elements along a 160-kb region of the genome that includes GDF3, Dppa3, and Nanog. We analyzed gene expression, chromatin occupancy, and higher-order chromatin structure throughout this gene locus and found that expression of the reprogramming factor Oct4 is required to maintain its integrity. C1 [Levasseur, Dana N.; Wang, Jianlong; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Levasseur, Dana N.; Wang, Jianlong; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Dorschner, Michael O.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu FU Howard Hughes Medical Institute; NHGRI NIH HHS [U01HG003161]; NIGMS NIH HHS [R01GM071923] NR 29 TC 67 Z9 68 U1 0 U2 4 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 MAR 1 PY 2008 VL 22 IS 5 BP 575 EP 580 DI 10.1101/gad.1606308 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 271HK UT WOS:000253779300002 PM 18283123 ER PT J AU Kang, HM Zaitlen, NA Wade, CM Kirby, A Heckerman, D Daly, MJ Eskin, E AF Kang, Hyun Min Zaitlen, Noah A. Wade, Claire M. Kirby, Andrew Heckerman, David Daly, Mark J. Eskin, Eleazar TI Efficient control of population structure in model organism association mapping SO GENETICS LA English DT Article ID RESTRICTED MAXIMUM-LIKELIHOOD; QUANTITATIVE TRAIT LOCI; INBRED MOUSE STRAINS; LINEAR MIXED MODELS; PAIRWISE RELATEDNESS; VARIANCE-COMPONENTS; AVERAGE INFORMATION; MOLECULAR MARKERS; ANIMAL-MODELS; RATIO TESTS AB Genomewide association mapping in model organisms such as inbred mouse strains is a promising approach for the identification of risk factors related to human diseases. However, genetic association studies in inbred model organisms are confronted by the problem of complex population structure among strains. This induces inflated false positive rates, which cannot be corrected using standard approaches applied in human association studies such as genomic control or structured association. Recent studies demonstrated that mixed models successfully correct for the genetic relatedness in association mapping in maize and Arabidopsis panel data sets. However, the currently available mixed-model methods suffer froth computational inefficiency. In this article, we propose a new method, efficient mixed-model association (EMMA), which corrects for population structure and genetic relatedness in model organism association mapping. Our method takes advantage of the specific nature of the optimization problem in applying mixed models for association snapping, which allows us to substantially increase the computational speed and reliability of the results. We applied EMMA to in silico whole-genome association mapping of inbred mouse strains involving hundreds of thousands of SNPs, in addition to Arabidopsis and maize data sets. We also performed extensive simulation studies to estimate the statistical power of EMMA under various SNP effects, varying degrees of population structure, and differing numbers of multiple measurements per strain. Despite the fruited power of inbred mouse association mapping due to the limited number of available inbred strains, we are able to identify significantly associated SNPs, which fall into known QTL or genes identified through previous studies while avoiding an inflation of false positives. An R package implementation and webserver of our EMMA method are publicly available. C1 [Eskin, Eleazar] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. [Kang, Hyun Min] Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA. [Zaitlen, Noah A.] Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USA. [Wade, Claire M.; Kirby, Andrew; Daly, Mark J.] Harvard Univ, Broad Inst, Boston, MA 02141 USA. MIT, Boston, MA 02141 USA. [Wade, Claire M.; Kirby, Andrew; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Heckerman, David] Microsoft Res, Redmond, WA 98052 USA. RP Eskin, E (reprint author), Univ Calif Los Angeles, Dept Comp Sci, Mail Code 1596,3532-J Boelter Hall, Los Angeles, CA 90095 USA. EM eeskin@cs.ucla.edu RI Eskin, Eleazar/J-9187-2012; OI Eskin, Eleazar/0000-0003-1149-4758; Wade, Claire/0000-0003-3413-4771 FU NCRR NIH HHS [C06 RR017588, P41 RR008605, P41 RR08605]; NHLBI NIH HHS [1K25HL080079, K25 HL080079] NR 61 TC 553 Z9 563 U1 8 U2 88 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 2008 VL 178 IS 3 BP 1709 EP 1723 DI 10.1534/genetics.107.080101 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 287MQ UT WOS:000254921600050 PM 18385116 ER PT J AU Johnson, DS Li, W Gordon, DB Bhattacharjee, A Curry, B Ghosh, J Brizuela, L Carroll, JS Brown, M Flicek, P Koch, CM Dunham, I Bieda, M Xu, XQ Farnham, PJ Kapranov, P Nix, DA Gingeras, TR Zhang, XM Holster, H Jiang, N Green, RD Song, JS Mccuine, SA Anton, E Nguyen, L Trinklein, ND Ye, Z Ching, K Hawkins, D Ren, B Scacheri, PC Rozowsky, J Karpikov, A Euskirchen, G Weissman, S Gerstein, M Snyder, M Yang, A Moqtaderi, Z Hirsch, H Shulha, HP Fu, YT Weng, ZP Struhl, K Myers, RM Lieb, JD Liu, XS AF Johnson, David S. Li, Wei Gordon, D. Benjamin Bhattacharjee, Arindam Curry, Bo Ghosh, Jayati Brizuela, Leonardo Carroll, Jason S. Brown, Myles Flicek, Paul Koch, Christoph M. Dunham, Ian Bieda, Mark Xu, Xiaoqin Farnham, Peggy J. Kapranov, Philipp Nix, David A. Gingeras, Thomas R. Zhang, Xinmin Holster, Heather Jiang, Nan Green, Roland D. Song, Jun S. Mccuine, Scott A. Anton, Elizabeth Nguyen, Loan Trinklein, Nathan D. Ye, Zhen Ching, Keith Hawkins, David Ren, Bing Scacheri, Peter C. Rozowsky, Joel Karpikov, Alexander Euskirchen, Ghia Weissman, Sherman Gerstein, Mark Snyder, Michael Yang, Annie Moqtaderi, Zarmik Hirsch, Heather Shulha, Hennady P. Fu, Yutao Weng, Zhiping Struhl, Kevin Myers, Richard M. Lieb, Jason D. Liu, X. Shirley TI Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets SO GENOME RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; GENOME-WIDE ANALYSIS; CONTROL MAQC PROJECT; HUMAN-CELLS; MICROARRAYS; SITES; PLATFORMS; 1-PERCENT; SEQUENCE; ELEMENTS AB The most widely used method for detecting genome-wide protein-DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first objective analysis of tiling array platforms, amplification procedures, and signal detection algorithms in a simulated ChIP-chip experiment. Mixtures of human genomic DNA and "spike-ins" comprised of nearly 100 human sequences at various concentrations were hybridized to four tiling array platforms by eight independent groups. Blind to the number of spike-ins, their locations, and the range of concentrations, each group made predictions of the spike-in locations. We found that microarray platform choice is not the primary determinant of overall performance. In fact, variation in performance between labs, protocols, and algorithms within the same array platform was greater than the variation in performance between array platforms. However, each array platform had unique performance characteristics that varied with tiling resolution and the number of replicates, which have implications for cost versus detection power. Long oligonucleotide arrays were slightly more sensitive at detecting very low enrichment. On all platforms, simple sequence repeats and genome redundancy tended to result in false positives. LM-PCR and WGA, the most popular sample amplification techniques, reproduced relative enrichment levels with high fidelity. Performance among signal detection algorithms was heavily dependent on array platform. The spike-in DNA samples and the data presented here provide a stable benchmark against which future ChIP platforms, protocol improvements, and analysis methods can be evaluated. C1 [Moqtaderi, Zarmik; Hirsch, Heather; Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Johnson, David S.; Anton, Elizabeth; Nguyen, Loan; Myers, Richard M.] Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA. [Li, Wei; Song, Jun S.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gordon, D. Benjamin; Bhattacharjee, Arindam; Curry, Bo; Ghosh, Jayati; Brizuela, Leonardo] Agilent Technol, Santa Clara, CA 95051 USA. [Carroll, Jason S.] Cambridge Res Inst, Canc Res UK, Cambridge CB2 0RE, England. [Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Flicek, Paul; Koch, Christoph M.; Dunham, Ian] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England. [Bieda, Mark; Xu, Xiaoqin; Farnham, Peggy J.] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA. [Bieda, Mark; Xu, Xiaoqin; Farnham, Peggy J.] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. [Kapranov, Philipp; Gingeras, Thomas R.] Affymetrix Inc, Santa Clara, CA 95051 USA. [Nix, David A.] Huntsman Canc Inst, HCI Bio Informat, Salt Lake City, UT 84112 USA. [Zhang, Xinmin; Holster, Heather; Jiang, Nan; Green, Roland D.] Roche NimbleGen Inc, Madison, WI 53719 USA. [Mccuine, Scott A.] Whitehead Inst, Cambridge, MA 02142 USA. [Trinklein, Nathan D.] SwitchGear Gen, Menlo Pk, CA 94025 USA. [Ye, Zhen; Ching, Keith; Hawkins, David; Ren, Bing] Univ Calif San Diego, Ludwig Inst Canc Res, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Scacheri, Peter C.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Rozowsky, Joel; Karpikov, Alexander; Gerstein, Mark; Snyder, Michael] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Euskirchen, Ghia; Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Weissman, Sherman] Yale Univ, Dept Genet, New Haven, CT 06520 USA. [Yang, Annie] Genentech Inc, San Francisco, CA 94080 USA. [Moqtaderi, Zarmik; Hirsch, Heather; Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Shulha, Hennady P.; Weng, Zhiping] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Fu, Yutao; Weng, Zhiping] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Lieb, Jason D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Lieb, Jason D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. RP Struhl, K (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM kevin_struhl@hms.harvard.edu; Myers@shgc.stanford.edu; jlieb@bio.unc.edu; xsliu@jimmy.harvard.edu RI Li, Wei/A-8544-2009; OI Gingeras, Thomas/0000-0001-9106-3573; Brown, Myles/0000-0002-8213-1658; Dunham, Ian/0000-0003-2525-5598; Flicek, Paul/0000-0002-3897-7955; Koch, Christof/0000-0001-6482-8067; Rozowsky, Joel/0000-0002-3565-0762; Farnham, Peggy/0000-0003-4469-7914 FU NHGRI NIH HHS [1R01 HG004069-01, R01 HG004069, R01 HG004069-02] NR 32 TC 108 Z9 110 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 2008 VL 18 IS 3 BP 393 EP 403 DI 10.1101/gr.7080508 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 271CO UT WOS:000253766700005 PM 18258921 ER PT J AU Brockmeyer, AD Hughes, L Lee, E Groshen, S Del Priore, G Duggan, BD Cliby, WA Chi, DS Gershenson, DM Penson, RT Zempolich, K Roman, LD Dubeau, L AF Brockmeyer, A. D. Hughes, L. Lee, E. Groshen, S. Del Priore, G. Duggan, B. D. Cliby, W. A. Chi, D. S. Gershenson, D. M. Penson, R. T. Zempolich, K. Roman, L. D. Dubeau, L. TI Telomerase activity in peritoneal washings is a prognostic indicator in patients who achieve complete clinical response after first-line chemotherapy for ovarian carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Brockmeyer, A. D.; Hughes, L.; Lee, E.; Groshen, S.; Roman, L. D.; Dubeau, L.] Univ So Calif, Los Angeles, CA 90089 USA. [Del Priore, G.] NYU, New York, NY USA. [Duggan, B. D.] Scripps Hlth, La Jolla, CA USA. [Cliby, W. A.] Mayo Clin, Rochester, MN USA. [Cliby, W. A.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Gershenson, D. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Penson, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zempolich, K.] Univ Utah, Ctr Hlth Sci, Salt Lake City, UT 84112 USA. NR 0 TC 0 Z9 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 BP S118 EP S118 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200269 ER PT J AU Chapman, E Venkat, P Ko, E Orezzoli, JP Del Carmen, M AF Chapman, E. Venkat, P. Ko, E. Orezzoli, J. P. Del Carmen, M. TI Use of multimedia as an educational tool to improve human papillomavirus vaccine acceptability SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Chapman, E.; Ko, E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Venkat, P.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Orezzoli, J. P.; Del Carmen, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 318 BP S139 EP S140 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200320 ER PT J AU Matulonis, U Richard, P Campos, S Bryan, J Lee, J Kendal, D Krasner, C Berlin, S Roche, M Duska, L Pereira, L Horowitz, N AF Matulonis, U. Richard, P. Campos, S. Bryan, J. Lee, J. Kendal, D. Krasner, C. Berlin, S. Roche, M. Duska, L. Pereira, L. Horowitz, N. TI Phase II study of carboplatin and pemetrexed for the treatment of platinum-sensitive recurrent ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Matulonis, U.; Campos, S.; Bryan, J.; Lee, J.; Berlin, S.; Pereira, L.; Horowitz, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richard, P.; Kendal, D.; Krasner, C.; Roche, M.; Duska, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 50 BP S23 EP S24 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200052 ER PT J AU McGuire, W Matulonis, U Hirte, H Husain, A Chiang, A Aghajanian, C Hawtin, R Goldberg, Z AF McGuire, W. Matulonis, U. Hirte, H. Husain, A. Chiang, A. Aghajanian, C. Hawtin, R. Goldberg, Z. TI A phase 2 trial of SNS-595 in women with platinum-refractory epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [McGuire, W.] Weinberg Canc Ctr, Baltimore, MD USA. [Matulonis, U.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hirte, H.] Juravinski Canc Ctr, Hamilton, ON, Canada. [Husain, A.] Stanford Univ, Stanford, CA 94305 USA. [Chiang, A.; Aghajanian, C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hawtin, R.; Goldberg, Z.] Sunesis Pharmaceut, San Francisco, CA USA. NR 0 TC 0 Z9 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 290 BP S128 EP S128 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200292 ER PT J AU Orezzoli, JP Russell, AH Oliva, E Eichhorn, J Del Carmen, MG Fuller, AF AF Orezzoli, J. P. Russell, A. H. Oliva, E. Eichhorn, J. Del Carmen, M. G. Fuller, A. F. TI Endometriosis as a prognostic factor in clear cell cancer of the ovary SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Orezzoli, J. P.; Russell, A. H.; Del Carmen, M. G.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Oliva, E.; Eichhorn, J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fuller, A. F.] Winchester Hosp Reg Canc Ctr, Winchester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 340 BP S148 EP S149 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200342 ER PT J AU Hirshfeld-Becker, DR Masek, B Henin, A Blakely, LR Rettew, DC Dufton, L Segool, N Biederman, J AF Hirshfeld-Becker, Dina R. Masek, Bruce Henin, Aude Blakely, Lauren Raezer Rettew, David C. Dufton, Lynette Segool, Natasha Biederman, Joseph TI Cognitive-behavioral intervention with young anxious children SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE behavioral inhibition; childhood anxiety disorders; cognitive-behavioral therapy ID RANDOMIZED CLINICAL-TRIAL; ANXIETY DISORDERS; PANIC DISORDER; FOLLOW-UP; PRESCHOOL-CHILDREN; CHILDHOOD ANXIETY; MAJOR DEPRESSION; SOCIAL ANXIETY; HIGH-RISK; EXPRESSED EMOTION AB Despite evidence that preschool and early elementary school-age children can present with anxiety disorders that may put them at risk for later psychopathology and dysfunction, the cognitive-behavioral protocols available for treating anxiety in children have been tested almost exclusively in older children. However, there could be benefits to treating children earlier, before anxiety disorders begin to impair their social and academic development. This report discusses the adaptations necessary in providing cognitive-behavioral therapy to young anxious children and describes a manualized, cognitive-behavioral intervention, with child and parent components, that was piloted openly in nine families with children aged 4 to 7 years - each of whom had multiple risk factors for developing anxiety disorders, and most of whom had already presented with anxiety disorders. Eight of the nine children were judged "much" or "very much improved" at postintervention on number of anxiety diagnoses, number of DSM-IV anxiety symptoms, and ability to cope with feared situations. Cases are presented to illustrate the way that cognitive-behavioral therapy can be conducted with youngsters in this age range. Whereas randomized, controlled trials are needed to confirm the efficacy of this manualized treatment, our experience suggests that cognitive-behavioral protocols for anxiety can be adapted and successfully implemented with young children. C1 Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, 185 Alewife Brook Pkwy,Suite 2100, Cambridge, MA 02138 USA. EM dhirshfeld@partners.org FU NIMH NIH HHS [K08 MH-001538-05] NR 84 TC 27 Z9 27 U1 4 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2008 VL 16 IS 2 BP 113 EP 125 DI 10.1080/10673220802073956 PG 13 WC Psychiatry SC Psychiatry GA 288QH UT WOS:000255000400005 PM 18415883 ER PT J AU Koski, G AF Koski, Greg TI Tipping point, over the top, or just noncompliance as usual? SO HASTINGS CENTER REPORT LA English DT Article C1 [Koski, Greg] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Koski, Greg] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Koski, G (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 4 TC 2 Z9 2 U1 0 U2 1 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAR-APR PY 2008 VL 38 IS 2 BP 27 EP 29 DI 10.1353/hcr.2008.0023 PG 3 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 282JM UT WOS:000254563800014 PM 18457226 ER PT J AU Joffe, S Miller, FG AF Joffe, Steven Miller, Franklin G. TI Bench to bedside - Mapping the moral terrain of clinical research SO HASTINGS CENTER REPORT LA English DT Article ID PLACEBO-CONTROLLED TRIALS; THERAPEUTIC MISCONCEPTION; CARE RESPONSIBILITIES; MEDICAL RESEARCHERS; ETHICAL FRAMEWORK; RANDOMIZED-TRIAL; BREAST-CANCER; EQUIPOISE; CRITIQUE; INVESTIGATOR C1 [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Boston, MA 02115 USA. [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [K01-CA096872] NR 75 TC 55 Z9 56 U1 1 U2 3 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAR-APR PY 2008 VL 38 IS 2 BP 30 EP 42 DI 10.1353/hcr.2008.0019 PG 13 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 282JM UT WOS:000254563800015 PM 18457227 ER PT J AU Silvia, KA Ozanne, EM Sepucha, KR AF Silvia, Kerry A. Ozanne, Elissa M. Sepucha, Karen R. TI Implementing breast cancer decision aids in community sites: barriers and resources SO HEALTH EXPECTATIONS LA English DT Article DE clinical care; community; decision aids; early stage breast cancer; feasibility; implementation ID PREFERENCES; CARE AB Objective To assess the feasibility of implementing four patient decision aids (PtDAs) for early stage breast cancer treatment decisions into routine clinical care in community settings. Background There is very limited information available about implementing decision aids into routine clinical practice and most of this information is based on academic centres; more information is needed about implementing them into routine clinical practice in community settings. Design Structured individual interviews. Setting and participants Providers from 12 sites, including nine community hospitals, a community oncology centre and two academic centres. Main outcome measures Usage data, barriers to and resources for implementing the PtDAs. Results Nine of the 12 sites were using the PtDAs with patients. All of the sites were lending the PtDAs to patients, usually without a formal sign-out system. The keys to successful implementation included nurses' and social workers' interest in distributing the PtDAs and the success of the lending model. Barriers that limited or prevented sites from using the PtDA included a lack of physician support, a lack of an organized system for distributing the PtDAs and nurses' perceptions about patients' attitude towards participation in decision making. Conclusions It is feasible to implement PtDAs for early stage breast cancer into routine clinical care in community settings, even with few resources available. C1 [Sepucha, Karen R.] Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. [Silvia, Kerry A.] Suffolk Univ, Boston, MA 02114 USA. [Ozanne, Elissa M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Silvia, KA (reprint author), Massachusetts Gen Hosp, Hlth Decis Res Unit, 50 Staniford St,Suite 936, Boston, MA 02114 USA. EM ksepucha@partners.org NR 20 TC 28 Z9 28 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD MAR PY 2008 VL 11 IS 1 BP 46 EP 53 DI 10.1111/j.1369-7625.2007.00477.x PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 262AJ UT WOS:000253121100006 PM 18275401 ER PT J AU Williamson, RE Darrow, KN Giersch, ABS Resendes, BL Huang, M Conrad, GW Chen, ZY Liberman, MC Morton, CC Tasheva, ES AF Williamson, Robin E. Darrow, Keith N. Giersch, Anne B. S. Resendes, Barbara L. Huang, Mingqian Conrad, Gary W. Chen, Zheng-Yi Liberman, M. Charles Morton, Cynthia C. Tasheva, Elena S. TI Expression studies of osteoglycin/mimecan (OGN) in the cochlea and auditory phenotype of Ogn-deficient mice SO HEARING RESEARCH LA English DT Article DE mimecan/osteoglycin; proteoglycan; hearing loss ID RECESSIVE ALPORT SYNDROME; PROGRESSIVE HEARING-LOSS; COL4A5 COLLAGEN GENE; AUTOSOMAL-DOMINANT; INNER-EAR; STICKLER-SYNDROME; OSTEOGENESIS IMPERFECTA; NONSYNDROMIC DEAFNESS; MENIERES-DISEASE; CDNA LIBRARY AB Genes involved in the hearing process have been identified through both positional cloning efforts following genetic linkage studies of families with heritable deafness and by candidate gene approaches based on known functional properties or inner ear expression. The latter method of gene discovery may employ a tissue- or organ-specific approach. Through characterization of a human fetal cochlear cDNA library, we have identified transcripts that are preferentially and/or highly expressed in the cochlea. High expression in the cochlea may be suggestive of a fundamental role for a transcript in the auditory system. Herein we report the identification and characterization of a transcript from the cochlear cDNA library with abundant cochlear expression and unknown function that was subsequently determined to represent osteoglycin (OGN). Ogn-deficient mice, when analyzed by auditory brainstem response and distortion product otoacoustic emissions, have normal hearing thresholds. (C) 2007 Elsevier B.V. All rights reserved. C1 [Giersch, Anne B. S.; Resendes, Barbara L.; Morton, Cynthia C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Williamson, Robin E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Darrow, Keith N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Darrow, Keith N.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA USA. [Morton, Cynthia C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Chen, Zheng-Yi] Massachusetts Gen Hosp, Ctr Nervous Syst Repair, Neurol Serv, Boston, MA 02114 USA. [Conrad, Gary W.] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. [Tasheva, Elena S.] Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA. RP Morton, CC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, NRB 160,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cmorton@partners.org FU NEI NIH HHS [EY13395, R01 EY013395]; NIDCD NIH HHS [P30 DC005209, P30 DC5209, R01 DC003402-04, R01 DC003402-06, R01 DC003402-08, F31 DC005712, R01 DC06908, R01 DC04546, R01 DC03402, R01 DC0188, R01 DC006908, R01 DC004546, R01 DC003402-07, R01 DC003402-05, R01 DC003402-03, R01 DC003402, R01 DC000188-27, R01 DC000188, F32 DC00405, F32 DC000405]; NIGMS NIH HHS [P01 GM061354] NR 46 TC 10 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2008 VL 237 IS 1-2 BP 57 EP 65 DI 10.1016/j.heares.2007.12.006 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 289IU UT WOS:000255049000005 PM 18243607 ER PT J AU Napoli, C Balestrieri, ML Sica, V Lerman, LO Crimi, E De Rosa, G Schiano, C Servillo, L D'Armiento, FP AF Napoli, Claudio Balestrieri, Maria Luisa Sica, Vincenzo Lerman, Lilach O. Crimi, Ettore De Rosa, Gaetano Schiano, Concetta Servillo, Luigi D'Armiento, Francesco P. TI Beneficial effects of low doses of red wine consumption on perturbed shear stress-induced atherogenesis SO HEART AND VESSELS LA English DT Article DE polyphenol; red wine; antioxidant; shear stress; endothelial progenitor cell ID E-DEFICIENT MICE; NITRIC-OXIDE SYNTHASE; CORONARY-ARTERY-DISEASE; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; HYPERCHOLESTEROLEMIC MICE; CARDIOVASCULAR-DISEASE; TRANS-RESVERATROL; N-ACETYLCYSTEINE; ATHEROSCLEROSIS AB Moderate wine intake is associated with a reduced risk of morbidity and mortality from cardiovascular disease. Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases also the endothelial expression of oxidation-sensitive responsive genes (such as ELK-1 and p-JUN). This study evaluates the effects of chronic consumption of red wine on perturbed shear stress-induced atherogenesis. Results indicated that chronic treatment with red wine significantly attenuated the activation of redox-sensitive genes (ELK-1 and p-JUN) and increased endothelial nitric oxide synthase (eNOS) expression (which was decreased by perturbed shear stress) in cultured human coronary endothelial cells (EC) and in atherosclerosis-prone areas of hypercholesterolemic mice. Oral administration of red wine to hypercholesterolemic mice reduced significantly the progression of atherosclerosis. Moreover, short-term supplementation with red wine to C57BL/6J mice significantly increased upregulation of aortic eNOS and SIRT1 expression induced by physical training. These findings establish that administration of low doses of red wine can attenuate the proatherogenic effects induced by perturbed shear stress in vitro and in vivo. This evidence may have implications for the prevention of atherosclerotic lesion progression and its clinical manifestations. C1 [Napoli, Claudio; Sica, Vincenzo; Schiano, Concetta] Univ Naples 2, Div Clin Pathol, Dept Gen Pathol, Sch Med 1, I-80138 Naples, Italy. [Napoli, Claudio] Univ Naples 2, Sch Med 1, Div Clin Pathol, Excellence Res Ctr Cardiovasc Dis, Naples, Italy. [Napoli, Claudio] Boston Univ, Evans Dept Med, Boston, MA 02215 USA. [Balestrieri, Maria Luisa; Servillo, Luigi] Univ Naples 2, Dept Chem Biol & Phys, Naples, Italy. [Lerman, Lilach O.] Mayo Clin & Mayo Fdn, Div Hypertens, Rochester, MN 55905 USA. [Crimi, Ettore] Univ Novara, Dept Anesthesiol, Novara, Italy. [Crimi, Ettore] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. [De Rosa, Gaetano; D'Armiento, Francesco P.] Univ Naples Federico 2, Dept Human Pathol, Naples, Italy. RP Napoli, C (reprint author), Univ Naples 2, Div Clin Pathol, Dept Gen Pathol, Sch Med 1, Complesso S Andrea Dame,Via L de Crecchio 7, I-80138 Naples, Italy. EM claudio.napoli@unina2.it OI D'ARMIENTO, Francesco Paolo/0000-0002-1391-6451; DE ROSA, Gaetano/0000-0002-3635-5853; Napoli, Claudio/0000-0002-5455-555X; Schiano, Concetta/0000-0002-2570-6910 NR 54 TC 25 Z9 25 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0910-8327 J9 HEART VESSELS JI Heart Vessels PD MAR PY 2008 VL 23 IS 2 BP 124 EP 133 DI 10.1007/s00380-007-1015-8 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 285DE UT WOS:000254756700009 PM 18389338 ER PT J AU Reddy, VY Neuzi, P d'AviLa, A Laragy, M Malchano, ZJ Kralovec, S Kim, SJ Ruskin, JN AF Reddy, Vivek Y. Neuzi, Petr d'AviLa, Andre Laragy, Margaret Malchano, Zachary J. Kralovec, Stepan Kim, Steven J. Ruskin, Jeremy N. TI Balloon catheter ablation to treat paroxysmal atrial fibrillation: What is the level of pulmonary venous isolation? SO HEART RHYTHM LA English DT Article DE catheter ablation; balloon catheter; cryoablation; laser; focused ultrasound; electroanatomical mapping; atria[ fibrillation ID CIRCUMFERENTIAL ULTRASOUND ABLATION; VEIN ANTRUM ISOLATION; LONG-TERM; SYSTEM AB BACKGROUND Unlike the initial balloon ablation catheters that were designed to deliver ablation Lesions within the pulmonary veins (PVs), the current balloon prototypes are fashioned to deliver lesions at the PV ostia. OBJECTIVE Using etectroanatomical mapping, this study evaluates the actual location of ablation Lesions generated by cryobased, laser-based, or uttrasound-based balloon catheters. METHODS In a total of 14 patients with paroxysmal atrial fibrillation, PV isolation was performed using either a cryoballoon catheter (8 patients), Laser catheter (4 patients) or ultrasound balloon catheter (2 patients). Patients underwent preprocedural computed tomographic/magnetic resonance imaging. An intracardiac ultrasound catheter was used to aid in positioning the balloon catheter at the PV ostium/antrum. In all patients, sinus rhythm bipolar voltage amplitude maps (using either CARTO with computed tomographic/magnetic resonance image integration or NavX mapping) were generated at baseline and after electrical PV isolation as confirmed by use of a circular mapping catheter. RESULTS Eectrical isolation was achieved in 100% of the PVs. Electroanatomical mapping revealed that after ablation with any of the 3 balloon catheters, the extent of isolation included the tubular portions of each PV to the Level of the PV ostia. However, the PV antral portions were Left Largely unablated with all 3 balloon technologies. CONCLUSION Using the current generation of balloon ablation catheters, electrical isolation occurs at the level of the PV ostia, but the antral regions are Largely unablated. C1 [Reddy, Vivek Y.; Neuzi, Petr; d'AviLa, Andre; Laragy, Margaret; Malchano, Zachary J.; Kralovec, Stepan; Ruskin, Jeremy N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Reddy, Vivek Y.; d'AviLa, Andre; Laragy, Margaret; Malchano, Zachary J.; Ruskin, Jeremy N.] Homolka Hosp, Dept Cardiol, Prague, Czech Republic. [Kim, Steven J.] St Jude Med Inc, Minnetonka, MN USA. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St,GRB-109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; FU NHLBI NIH HHS [HL68064] NR 23 TC 60 Z9 63 U1 0 U2 0 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 MAR PY 2008 VL 5 IS 3 BP 353 EP 360 DI 10.1016/j.hrthm.2007.11.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 273WE UT WOS:000253961900004 PM 18313591 ER PT J AU Ellinor, PT MacRae, CA AF Ellinor, Patrick T. MacRae, Caum A. TI Ion channel mutations in AF: Signal or noise? SO HEART RHYTHM LA English DT Editorial Material ID OF-FUNCTION MUTATION; FAMILIAL ATRIAL-FIBRILLATION; SCN5A MUTATION; KCNQ1; RISK; GENE C1 [Ellinor, Patrick T.; MacRae, Caum A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM pellinor@partners.org NR 16 TC 17 Z9 17 U1 0 U2 1 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 MAR PY 2008 VL 5 IS 3 BP 436 EP 437 DI 10.1016/j.hrthm.2008.01.014 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 273WE UT WOS:000253961900018 PM 18313603 ER PT J AU Fontana, RJ Goodman, ZD Dienstag, JL Bonkovsky, HL Naishadham, D Sterling, RK Su, GL Ghosh, M Wright, EC AF Fontana, Robert J. Goodman, Zachary D. Dienstag, Jules L. Bonkovsky, Herbert L. Naishadham, Deepa Sterling, Richard K. Su, Grace L. Ghosh, Mita Wright, Elizabeth C. CA HALT-C Trial Grp TI Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C SO HEPATOLOGY LA English DT Article ID IMAGE-ANALYSIS; HYALURONIC-ACID; VIRUS-INFECTION; CIRRHOSIS; DISEASE; EVOLUTION; QUANTIFICATION; VARIABILITY; PROGRESSION; INTERFERON AB This study determined the utility of a panel of serum fibrosis markers along with routine laboratory tests in estimating the likelihood of histological cirrhosis in a cohort of prior nonresponders with chronic hepatitis C. The relationship between serum markers and quantitative hepatic collagen content was also determined. Liver biopsy samples from 513 subjects enrolled in the HALT-C trial were assigned Ishak fibrosis scores. The collagen content of 386 sirius-red stained, nonfragmented biopsy samples was quantified using computerized morphometry. Serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), amino-terminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA), and YKL-40 levels were determined using commercially available assays. Sixty-two percent of patients had noncirrhotic fibrosis (Ishak stage 2-4) whereas 38% had cirrhosis (Ishak stage 5,6). Multivariate analysis identified a 3-variable model (HA, TIMP-1, and platelet count) that had an area under the receiver operating curve (AUROC) of 0.81 for estimating the presence of cirrhosis. This model was significantly better than that derived from the cirrhosis discriminant score (AUROC 0.70), the AST-to-platelet ratio (AUROC 0.73), and a prior model developed in HALT-C patients (AUROC 0.79). Multivariate analysis demonstrated that the serum fibrosis markers correlated substantially better with Ishak fibrosis scores than with the log hepatic collagen content (AUROC 0.84 versus 0.72). Conclusion: A 3-variable model consisting of serum HA, TIMP-1, and platelet count was better than other published models in identifying cirrhosis in HALT-C Trial subjects. The stronger correlation of the serum markers with Ishak scores suggests that serum fibrosis markers reflect the pattern of fibrosis more closely than the quantity of hepatic collagen. C1 [Fontana, Robert J.; Ghosh, Mita] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Goodman, Zachary D.] Armed Forces Inst Pathol, Washington, DC 20306 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept 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. [Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Sterling, Richard K.] Virginia Commonwealth Univ Hlth Syst, Hepatol Sect, Richmond, VA USA. [Su, Grace L.] Ann Arbor Vet Adm Hlth Ctr, Ann Arbor, MI USA. [Wright, Elizabeth C.] NIDDK, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Fontana, RJ (reprint author), Univ Michigan, Sch Med, Dept Internal Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. EM rfontana@umich.edu FU NCRR NIH HHS [M01RR-06192, M01RR-01066, M01RR-00065]; NIDDK NIH HHS [N01-DK-9-2319, N01-DK-9-2328, N01-DK-9-2326, N01-DK-9-2323] NR 41 TC 97 Z9 100 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2008 VL 47 IS 3 BP 789 EP 798 DI 10.1002/hep.22099 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270CZ UT WOS:000253698900005 PM 18175357 ER PT J AU Swain, RS Tihan, T Horvai, AE Di Vizio, D Loda, M Burger, PC Scheithauer, BW Kim, GE AF Swain, Rebecca S. Tihan, Tarik Horvai, Andrew E. Di Vizio, Dolores Loda, Massimo Burger, Peter C. Scheithauer, Bernd W. Kim, Grace E. TI Inflammatory myofibroblastic tumor of the central nervous system and its relationship to inflammatory pseudotumor SO HUMAN PATHOLOGY LA English DT Article DE inflammatory myofibroplastic tumor; inflammatory pseudotumorl; central nervous system; plasma cell granuloma ID PLASMA-CELL GRANULOMA; ANAPLASTIC LYMPHOMA KINASE; EPSTEIN-BARR-VIRUS; OF-THE-LITERATURE; HUMAN-HERPESVIRUS-8; FIBROSARCOMA; OVEREXPRESSION; CHILDREN; 2P23; ALK1 AB Inflammatory myofibroblastic tumor (IMT) is a distinctive spindle cell lesion and occurs primarily in soft tissue. Recent evidence suggests a neoplastic nature, although historically, both neoplastic and nonneoplastic processes were combined in this category. Originally described as a nonneoplastic process, the term inflammatory pseudotumor (IP) has been used synonymously with IMT. IMTs have been linked to ALK gene (2p23) rearrangements, and some have suggested an association with the human herpesvirus 8 (HHV-8). IMT in the central nervous system (CNS) is rare, its characteristics are poorly defined, and its relation to similar tumors at other sites is unclear. To better characterize IMT within the CNS, we studied clinicopathologic features of 6 IMTs and compared them with 18 nonneoplastic lesions originally classified as IP. The IMT group consisted of 2 male and 4 female patients with a median age of 29 years. Of the six IMTs, 5 occurred within the cerebral hemispheres, and one was in the posterior fossa. All tumors were composed of neoplastic spindle cells and a variable amount of inflammatory infiltrate. Eighteen IPs included in this study consisted of predominantly inflammatory masses occasionally seen in the setting of systemic diseases. Only I IMT and none of the IPs recurred during the follow-up period. Four IMTs had either ALK protein overexpression or 2p23 rearrangement, and 1 case demonstrated both. None of the IPs were positive for ALK. Neither IMT nor IP cases demonstrated HHV-8 expression. We suggest that IMT in the CNS is distinct from the nonneoplastic IP, and distinguishing IMT from nonneoplastic lesions should enable better decisions for patient management. (c) 2008 Elsevier Inc. All rights reserved. C1 [Swain, Rebecca S.; Tihan, Tarik; Horvai, Andrew E.; Kim, Grace E.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Di Vizio, Dolores; Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burger, Peter C.] Johns Hopkins Univ, Baltimore, MD 21287 USA. [Scheithauer, Bernd W.] Mayo Clin, Rochester, MN 55905 USA. RP Tihan, T (reprint author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. EM Larik.tihan@ucsf.edu NR 31 TC 40 Z9 43 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 2008 VL 39 IS 3 BP 410 EP 419 DI 10.1016/j.humpath.2007.07.012 PG 10 WC Pathology SC Pathology GA 267IU UT WOS:000253503500014 PM 18261625 ER PT J AU Nery, FG Monkul, ES Hatch, JP Fonseca, M Zunta-Soares, GB Frey, BN Bowden, CL Soares, JC AF Nery, Fabiano G. Monkul, Emel S. Hatch, John P. Fonseca, Manoela Zunta-Soares, Giovana B. Frey, Benicio N. Bowden, Charles L. Soares, Jair C. TI Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE bipolar disorder; bipolar depression; randomized-controlled trials; anti-inflammatory agents; cyclooxygenase-2 inhibitors; celecoxib ID ANTIDEPRESSANT TREATMENT; MAJOR DEPRESSION; RATING-SCALE; CYCLOOXYGENASE-2; INHIBITION; BRAIN; SCHIZOPHRENIA; THERAPY; PROSTAGLANDIN-E2; AUGMENTATION AB Objective To investigate whether the cox-2 inhibitor celecoxib has antidepressant effects in bipolar disorder (BD) patients during depressive or mixed phases. Methods We studied 28 DSM-IV BD patients who were experiencing a depressive or mixed episode and were on a stable dose of a mood stabilizer or atypical antipsychotic medication. Subjects were randomized to receive 6 weeks of double-blind placebo or celecoxib (400 mg/day) treatment. Current mood stabilizer or antipsychotic medication remained at the same doses during the trial. Results Intention-to-treat analysis showed that the patients receiving celecoxib had lower Hamilton Depression Rating Scale (HamD) scores after 1 week of treatment compared to the patients receiving placebo, but this difference was not statistically significant (p=0.09). The improvement in the first week of treatment was statistically significant when the analysis included only the subjects who completed the full 6-week trial (p=0.03). The two groups did not differ significantly on depressive or manic symptoms from the second week until the end of the trial. Celecoxib was well tolerated with the exception of two subjects who dropped out of the study due to rash. Conclusions Our findings suggest that adjunctive treatment with celecoxib may produce a rapid-onset antidepressant effect in BD patients experiencing depressive or mixed episodes. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Nery, Fabiano G.; Monkul, Emel S.; Hatch, John P.; Fonseca, Manoela; Frey, Benicio N.; Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Nery, Fabiano G.; Monkul, Emel S.; Fonseca, Manoela] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Nery, Fabiano G.] Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat,Bipolar Disorder Res Program, Sao Paulo, Brazil. [Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. [Frey, Benicio N.] Univ Fed Rio Grande do Sul, Dept Biochem, Porto Alegre, RS, Brazil. [Frey, Benicio N.] Hosp Clin Porto Alegre, Bipolar Disorders Program, Porto Alegre, RS, Brazil. [Zunta-Soares, Giovana B.; Soares, Jair C.] Univ N Carolina, Sch Med, Ctr Excellence Res & Treatment Bipolar Disorders, Dept Psychiat, Chapel Hill, NC 27599 USA. RP Soares, JC (reprint author), Univ N Carolina, Sch Med, UNC Ctr Excellence Res & Treatment Bipolar Disord, Dept Psychiat, 10616 Neurosci Hosp,CB 7160, Chapel Hill, NC 27599 USA. EM jsoares@med.unc.edu FU NCRR NIH HHS [RR-20571, M01-RR-01346] NR 36 TC 139 Z9 146 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD MAR PY 2008 VL 23 IS 2 BP 87 EP 94 DI 10.1002/hup.912 PG 8 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 282VY UT WOS:000254596500002 PM 18172906 ER PT J AU Baldessarini, RJ Perry, R Pike, J AF Baldessarini, Ross J. Perry, Richard Pike, James TI Factors associated with treatment nonadherence among US bipolar disorder patients SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE adherence; adverse effects; bipolar disorder; long-term treatment; prophylaxis; maintenance ID MEDICATION ADHERENCE; LITHIUM TREATMENT; MOOD DISORDERS; COSTS; HOSPITALIZATION; SCHIZOPHRENIA; NONCOMPLIANCE; PROPHYLAXIS; POPULATION; THERAPY AB Objective Since sustained treatment-adherence is often problematic and may limit clinical outcomes among bipolar disorder (BPD) patients, we sought risk factors to guide clinical prediction of nonadherence. Methods Data were from a 2005 US national sample providing questionnaire responses by 131 randomly selected prescribing psychiatrists and their adult BPD patients. We contrasted demographic and clinical factors in treatment-adherent versus nonadherent patients (strictly defined as missing >= 1 dose within 10 days) in univariate analyses followed by multivariate logistic-regression modeling. Results Of 429 DSM-IV BPD patients (79% type-I; 62% women; 17% minorities), 34% reported missing >= 1 dose of psychotropic medication within 10 days, 20% missed entire daily doses at least once, and only 2.5% missed all doses for 10 days. However, their prescribing psychiatrists considered only 6% as treatment-nonadherent. Factors significantly associated with nonadherence in multivariate modeling ranked: alcohol-dependence > youth > greater affective morbidity > various side effects >= comorbid obsessive-compulsive disorder >= recovering from mania-hypomania. Unrelated were sex, diagnostic subtype, and other comorbidities. Since most patients received >= 2 psychotropics, potential relationships between treatment-complexity and adherence were obscured. Conclusions Prevalent treatment-nonadherence among American BPD patients, and striking underestimation of the problem by prescribing clinicians may encourage increasingly complex treatment-regimens of untested value, but added expense, risk of adverse effects, and uncertain impact on treatment-adherence itself. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Hosp, Psychopharmacol Program & Int Consortium Bipolar, Boston, MA 02114 USA. [Perry, Richard; Pike, James] Adelphi Grp, Bollington, Cheshire, England. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. EM rjb@mclean.org NR 69 TC 81 Z9 83 U1 3 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD MAR PY 2008 VL 23 IS 2 BP 95 EP 105 DI 10.1002/hup.908 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 282VY UT WOS:000254596500003 PM 18058849 ER PT J AU Simpson, R AF Simpson, Richard TI Making better decisions SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID INFORMATION; JUDGMENTS; ACCURACY; OUTCOMES; CHOICE; PROBABILITY; CONFIDENCE; STRATEGIES; BIAS C1 VA Pittsburgh Healthcare, Human Engn Labs, Pittsburgh, PA 15260 USA. RP Simpson, R (reprint author), VA Pittsburgh Healthcare, Human Engn Labs, Pittsburgh, PA 15260 USA. EM ris20@pitt.edu NR 35 TC 2 Z9 3 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD MAR-APR PY 2008 VL 27 IS 2 BP 23 EP 28 DI 10.1109/EMB.200790794 PG 6 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 277NT UT WOS:000254220900006 PM 18463018 ER PT J AU Seibel, EJ Carroll, RE Dominitz, JA Johnston, RS Melville, CD Lee, CM Seitz, SM Kimmey, MB AF Seibel, Eric J. Carroll, Robert E. Dominitz, Jason A. Johnston, Richard S. Melville, C. David Lee, Cameron M. Seitz, Steven M. Kimmey, Michael B. TI Tethered capsule endoscopy, a low-cost and high-performance alternative technology for the screening of esophageal cancer and Barrett's esophagus SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE biomedical image processing; biomedical imaging; cancer; medical diagnosis; optical imaging ID HIGH-GRADE DYSPLASIA; INTESTINAL METAPLASIA; ADENOCARCINOMA; ESOPHAGOSCOPY; DIAGNOSIS; PATTERNS; UTILITY; SYSTEM AB Esophageal cancer is currently the fastest growing cancer in the United States. To help combat the recent rise in morbidity, our laboratory has developed a low-cost tethered capsule endoscope system (TCE) aimed at improving early detection of esophageal cancer. The TCE contains a resonant fiberoptic laser scanner (1.6 mm O.D.) which fits into 6.4-mm easy-to-swallow capsule at the distal tip. The tethered portion contains a single mode optical fiber multiplexed to three laser diodes at the proximal end. This design offers two main advantages over current endoscope technology. First, because of its small size, the TCE can be swallowed with minimal patient discomfort, thereby obviating sedation. Second, by imaging via directed laser light, the TCE is strategically positioned to employ several burgeoning laser-based diagnostic technologies, such as narrow-band, hyperspectral, and fluorescence imaging. It is believed that the combination of such imaging techniques with novel biomarkers of dysplasia will greatly assist in identifying precancerous; conditions such as Barrett's esophagus (BE). As the probe is swallowed, the fiber scanner captures high resolution, wide-field color images of the gastroesophageal junction (500 lines at 0.05-mm resolution) currently at 15-Hz frame rate. Video images are recorded as the capsule is slowly retracted by its tether. Accompanying software generates panoramic images from the video output by mosaicing individual frames to aid in pattern recognition. This initial report describes the rationale for the unique TCE system design, results from preliminary testing in vitro and in vivo, and discussion on the merits of this new platform technology as a basis for developing a low-cost screening program for esophageal cancer. C1 [Seibel, Eric J.] Univ Washington, Dept Mech Engn, Human Photon Lab, Seattle, WA 98195 USA. [Dominitz, Jason A.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Seitz, Steven M.] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. [Kimmey, Michael B.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Seibel, EJ (reprint author), Univ Washington, Dept Mech Engn, Human Photon Lab, Box 352600, Seattle, WA 98195 USA. EM eseibel@u.washington.edu; carroll@eecs.berkeley.edu; jason.dominitz@va.gov; rsj3@u.washington.edu; dmelvill@u.washington.edu; lee101@u.washington.edu; seitz@cs.washington.edu; kimmey@u.washington.edu OI Dominitz, Jason/0000-0002-8070-7086 FU NCI NIH HHS [R21CA110184] NR 33 TC 37 Z9 39 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 2008 VL 55 IS 3 BP 1032 EP 1042 DI 10.1109/TBME.2008.915680 PG 11 WC Engineering, Biomedical SC Engineering GA 270PX UT WOS:000253733800020 PM 18334395 ER PT J AU Aubin, PM Cowley, MS Ledoux, WR AF Aubin, Patrick M. Cowley, Matthew S. Ledoux, William R. TI Gait simulation via a 6-DOF parallel robot with iterative learning control SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE gait simulation; iterative learning control; kinematics; kinetics; prosthetics ID CADAVER MODEL; STANCE PHASE; IN-VITRO AB We have developed a robotic gait simulator (RGS) by lever-aging a 6-degree of freedom parallel robot, with the goal of overcoming three significant challenges of gait simulation, including: 1) operating at near physiologically correct velocities; 2) inputting full scale ground reaction forces; and 3) simulating motion in all three planes (sagittal, coronal and transverse). The robot will eventually be employed with cadaveric specimens, but as a means of exploring the capability of the system, we have first used it with a prosthetic foot. Gait data were recorded from one transtibial amputee using a motion analysis system and force plate. Using the same prosthetic foot as the subject, the RGS accurately reproduced the recorded kinematics and kinetics and the appropriate vertical ground reaction force was realized with a proportional iterative learning controller. After six gait iterations the controller reduced the root mean square (RMS) error between the simulated and in situ vertical ground reaction force to 35 N during a 1.5 s simulation of the stance phase of gait with a prosthetic foot. This paper addresses the design, methodology and validation of the novel RGS. C1 [Aubin, Patrick M.; Cowley, Matthew S.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, VA RR&D Ctr Excellence Limb Loss Prevent & Prosth, Seattle, WA 98108 USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. [Aubin, Patrick M.] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, VA RR&D Ctr Excellence Limb Loss Prevent & Prosth, 1660 S Columbian Way,MS 151, Seattle, WA 98108 USA. EM paubin@u.washington.edu; matthew.cowley@comcast.net; wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 6 TC 21 Z9 23 U1 3 U2 11 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 2008 VL 55 IS 3 BP 1237 EP 1240 DI 10.1109/TBME.2007.908072 PG 4 WC Engineering, Biomedical SC Engineering GA 270PX UT WOS:000253733800046 PM 18334421 ER PT J AU Keator, DB Grethe, JS Marcus, D Ozyurt, B Gadde, S Murphy, S Pieper, S Greve, D Notestine, R Bockholt, HJ Papadopoulos, P AF Keator, David B. Grethe, J. S. Marcus, D. Ozyurt, B. Gadde, S. Murphy, Sean Pieper, S. Greve, D. Notestine, R. Bockholt, H. J. Papadopoulos, P. CA BIRN Funct BIRN Morphometry BIRN Coordinating TI A national human neuroimaging collaboratory enabled by the Biomedical Informatics Research Network (BIRN) SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE Biomedical Informatics Research Network (BIRN); cyberinfrastructure; database; data grid; Extensible Markup Language (XML); Extensible Markup Language (XML)-based clinical experiment data exchange schema (XCEDE); Extensible Neuroimaging Archive Toolkit (XNAT); globus; high intensity discharge (RID); informatics; magnetic resonance imaging (MRI); neuroimage; storage resources broker (SRB) AB The aggregation of imaging, clinical, and behavioral data from multiple independent institutions and researchers presents both a great opportunity for biomedical research as well as a formidable challenge. Many research groups have well-established data collection and analysis procedures, as well as data and metadata format requirements that are particular to that group. Moreover, the types of data and metadata collected are quite diverse, including image, physiological, and behavioral data, as well as descriptions of experimental design, and preprocessing and analysis methods. Each of these types of data utilizes a variety of software tools for collection, storage, and processing. Furthermore sites are reluctant to release control over the distribution and access to the data and the tools. To address these needs, the Biomedical Informatics Research Network (BIRN) has developed a federated and distributed infrastructure for the storage, retrieval, analysis, and documentation of biomedical imaging data. The infrastructure consists of distributed data collections hosted on dedicated storage and computational resources located at each participating site, a federated data management system and data integration environment, an Extensible Markup Language (XML) schema for data exchange, and analysis pipelines, designed to leverage both the distributed data management environment and the available grid computing resources. C1 [Keator, David B.] Univ Calif Irvine, Irvine, CA 92697 USA. [Grethe, J. S.; Ozyurt, B.; Notestine, R.; Papadopoulos, P.] Univ Calif San Diego, San Diego, CA 92093 USA. [Marcus, D.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Gadde, S.] Duke Univ, Durham, NC 27708 USA. [Murphy, Sean] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA 02115 USA. [Pieper, S.] Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. [Greve, D.] Massachusetts Gen Hosp, Dept Radiol, Ctr Magnet Resonance Imaging, Boston, MA 02115 USA. [Bockholt, H. J.] Med Invest Neurodev Disorders MIND Inst, Albuquerque, NM 87131 USA. NIH, Natl Ctr Res Resources, Biomed Informat Res Network, Bethesda, MD 20892 USA. RP Keator, DB (reprint author), Univ Calif Irvine, Irvine, CA 92697 USA. EM dbkeator@uci.edu; jgrethe@ncmir.ucsd.edu; dmarcus@npg.wustl.edu; iozyurt@ucsd.edu; gadde@biac.duke.edu; pieper@bwh.harvard.edu; greve@nmr.mgh.harvard.edu; RNotestine@ucsd.edu; jbockholt@themindinstitute.org; phil@sdsc.edu OI Grethe, Jeffrey/0000-0001-5212-7052 FU NCRR NIH HHS [U24 RR021992, U24 RR021992-02] NR 21 TC 59 Z9 59 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD MAR PY 2008 VL 12 IS 2 BP 162 EP 172 DI 10.1109/TITB.2008.917893 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 272DW UT WOS:000253840600005 PM 18348946 ER PT J AU Tang, SC Clement, GT AF Tang, Sai Chun Clement, Gregory T. TI A harmonic cancellation technique for an ultrasound transducer excited by a switched-mode power converter (vol 55, pg 359, 2008) SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Correction C1 [Tang, Sai Chun; Clement, Gregory T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Tang, SC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM sct@bwh.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD MAR PY 2008 VL 55 IS 3 BP 738 EP 738 DI 10.1109/TUFFC.2008.700 PG 1 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 276CI UT WOS:000254118500022 ER PT J AU Evans, CT LaVela, SL Weaver, FM Priebe, M Sandford, P Niemiec, P Miskevics, S Parada, JP AF Evans, Charlesnika T. LaVela, Sherri L. Weaver, Frances M. Priebe, Michael Sandford, Paul Niemiec, Pamela Miskevics, Scott Parada, Jorge P. TI Epidemiology of hospital-acquired infections in veterans with spinal cord injury and disorder SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 16th Annual Conference of the Society-for-Healthcare-Epidemiology-of-America CY MAR 18-21, 2006 CL Chicago, IL SP Soc Healthcare Epidemiol Amer ID INTENSIVE-CARE UNITS; NOSOCOMIAL INFECTIONS; REHABILITATION UNIT; CDC DEFINITIONS; SURVEILLANCE; PATHOGENS; LENGTH; IMPACT; STAY; COST AB Objective. To describe the epidemiology of hospital-acquired infections (HAIs) in veterans with spinal cord injury and disorder (SCI&D). Design. Retrospective medical record review. Setting. Midwestern Department of Veterans Affairs spinal cord injury center. Participants. A total of 226 patients with SCI&D hospitalized at least once during a 2-year period (October 1, 2001, through September 30, 2003). Results. A total of 549 hospitalizations were included in the analysis (mean duration of hospitalization, 33.7 days); an HAI occurred during 182 (33.2%) of these hospitalizations. A total of 657 HAIs occurred during 18,517 patient-days in the hospital ( incidence rate, 35.5 HAIs per 1,000 patient-days). Almost half of the 226 patients had at least 1 HAI; the mean number of HAIs among these patients was 6.0 HAIs per patient. The most common HAIs were urinary tract infection (164 [25.0%]of the 657 HAIs; incidence rate, 8.9 cases per 1,000 patient-days), bloodstream infection (111 [16.9%]; incidence rate, 6.0 cases per 1,000 patient-days), and bone and joint infection (103 [15.7%]; incidence rate, 5.6 cases per 1,000 patient-days). The most common culture isolates were gram-positive bacteria (1,082 [45.6%] of 2,307 isolates), including Staphylococcus aureus, and gram-negative bacteria (1,033 [43.6%] of isolates), including Pseudomonas aeruginosa. Multivariable regression demonstrated that predictors of HAI were longer length of hospital stay (P=.002), community-acquired infection (P=.007), and use of a urinary invasive device (P =.01) or respiratory invasive device (P =.04). Conclusions. The overall incidence of HAIs in persons with SCI&D was higher than that reported for other populations, confirming the increased risk of HAI in persons with spinal cord injury. The increased risk associated with longer length of stay and with community-acquired infection suggests that strategies are needed to reduce the duration of hospitalization and to effectively treat community-acquired infection, to decrease infection rates. There is significant room for improvement in reducing the incidence of HAIs in this population. C1 [Evans, Charlesnika T.; LaVela, Sherri L.; Weaver, Frances M.; Miskevics, Scott; Parada, Jorge P.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care,Dept Vet Affair, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. [Niemiec, Pamela] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Infect Control Sect, Hines, IL 60141 USA. [LaVela, Sherri L.] Univ Illinois, Ctr Res Hlth & Aging, Chicago, IL USA. [Weaver, Frances M.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Weaver, Frances M.] Northwestern Univ, Inst Hlth Serv & Policy Res, Chicago, IL 60611 USA. [Parada, Jorge P.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Priebe, Michael] Mayo Clin, Rochester, MN USA. [Sandford, Paul] Med Coll Wisconsin, Clement J Zablocki Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Milwaukee, WI 53226 USA. RP Evans, CT (reprint author), Edward J Hines Jr Vet Affairs Hosp 151H, 5th Ave & Roosevelt Rd,POB 5000,Room D302, Hines, IL 60141 USA. EM Charlesnika.Evans@va.gov NR 32 TC 27 Z9 28 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAR PY 2008 VL 29 IS 3 BP 234 EP 242 DI 10.1086/527509 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 271VO UT WOS:000253817000006 PM 18248306 ER PT J AU Gasink, LB Singer, K Fishman, NO Holmes, WC Weiner, MG Bilker, WB Lautenbach, E AF Gasink, Leanne B. Singer, Karyn Fishman, Neil O. Holmes, William C. Weiner, Mark G. Bilker, Warren B. Lautenbach, Ebbing TI Contact isolation for infection control in hospitalized patients: Is patient satisfaction affected? SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; PSYCHOLOGICAL IMPACT AB The effects of contact isolation on patient satisfaction are unknown. We performed a cross-sectional survey and found that most patients lack education and knowledge regarding isolation but feel that it improves their care. In multivariable analysis, isolated patients were not less satisfied with inpatient care than were nonisolated patients. C1 [Gasink, Leanne B.; Singer, Karyn; Fishman, Neil O.; Lautenbach, Ebbing] Univ Penn, Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Holmes, William C.; Weiner, Mark G.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Holmes, William C.; Bilker, Warren B.; Lautenbach, Ebbing] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Dept Med, Philadelphia, PA 19104 USA. [Gasink, Leanne B.; Holmes, William C.; Bilker, Warren B.; Lautenbach, Ebbing] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Holmes, William C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Gasink, LB (reprint author), Hosp Univ Penn, 3400 Spruce St,3 Silverstein Pavilion,Suite E, Philadelphia, PA 19104 USA. EM leanne.gasink@uphs.upenn.edu FU NIAID NIH HHS [T32 AI055435] NR 10 TC 30 Z9 30 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAR PY 2008 VL 29 IS 3 BP 275 EP 278 DI 10.1086/527508 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 271VO UT WOS:000253817000012 PM 18205528 ER PT J AU Rasche, V Mansour, M Reddy, V Singh, JP Qureshi, A Manzke, R Sokka, S Ruskin, J AF Rasche, Volker Mansour, Moussa Reddy, Vivek Singh, Jagmeet P. Qureshi, Answer Manzke, Robert Sokka, Sham Ruskin, Jeremy TI Fusion of three-dimensional X-ray angiography and three-dimensional echocardiography SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article AB Objective Cardiovascular intervention guidance requires knowledge of heart function relative to its blood supply or venous drainage. Functional and vascular anatomic data are usually generated on different imaging systems, so fusion of the data is necessary to simultaneously visualize the results for intervention planning and guidance. The objective of this work is to establish the feasibility of fusing volumetric ultrasound (U/S) data with three-dimensional (3D) X-ray imaging data for visualization of cardiac morphology, function and coronary venous drainage. Methods Temporally resolved U/S volume data was registered with the 3D reconstruction of vascular structures derived from X-ray modeling and reconstruction. U/S image registration was obtained by optical tracking fiducial markers with simultaneous X-ray imaging. The proposed technique was applied to phantom data for accuracy assessment of the registration process and to biventricular pacemaker implantation as clinical example. Results Fusion of U/S data with 3D X-ray reconstruction data produced an RMS registration error below 2 mm. Conclusion Preliminary clinical feasibility of U/S-derived data synchronously with X-ray derived 3D coronary venography was established. This technique can be applied for fusion of functional U/S data with 3D anatomic X-ray data of the coronary veins during a biventricular pacemaker implantation procedures. C1 [Rasche, Volker] Univ Ulm, Dept Internal Med 2, D-89069 Ulm, Germany. [Rasche, Volker] Philips Med Syst, Bothell, WA USA. [Mansour, Moussa; Reddy, Vivek; Singh, Jagmeet P.; Ruskin, Jeremy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Qureshi, Answer] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Manzke, Robert; Sokka, Sham] Philips Res North Amer, Clin Sites Res, Briacliff Manor, NY USA. RP Rasche, V (reprint author), Univ Ulm, Dept Internal Med 2, Robert Koch Str 8, D-89069 Ulm, Germany. EM Volker.Rasche@uniklinik-ulm.de RI Rasche, Volker/P-6523-2016 OI Rasche, Volker/0000-0001-8844-3583 NR 28 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD MAR PY 2008 VL 2 IS 5 BP 293 EP 303 DI 10.1007/s11548-007-0142-0 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZU UT WOS:000208989900006 ER PT J AU Growdon, WB Lopez-Varela, E Littell, R Oliva, E Seiden, M Krasner, C Lee, H Fuller, A AF Growdon, W. B. Lopez-Varela, E. Littell, R. Oliva, E. Seiden, M. Krasner, C. Lee, H. Fuller, A. TI Extent of extracranial disease is a powerful predictor of survival in patients with brain metastases from gynecological cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE brain metastasis; gynecological malignancy; retrospective cohort; survival ID EPITHELIAL OVARIAN-CARCINOMA; ENDOMETRIAL CARCINOMA; RADIATION-THERAPY; PROGNOSTIC-FACTORS; RADIOSURGERY; CHEMOTHERAPY AB Central nervous system metastasis from gynecological malignancy is a rare phenomenon that has been described in the past 30 years. The objective of this study is to analyze the treatment modalities and prognostic factors for brain metastases from gynecological tumors that predict prolonged survival. A retrospective chart and pathology review of 47 patients diagnosed with a gynecological tumor with brain metastasis in 1994-2004 was performed. Thirty patients had undergone initial diagnosis and treatment at our institution, and 17 patients were referred following primary treatment at an outside institution. Adjusted Chi-square, Kaplan-Meier survival estimates, log-rank tests, and Cox regression analysis were utilized for statistical analysis of the total cohort. Of the 3146 patients with newly diagnosed gynecological cancer in this 10-year period, 30 developed brain metastasis demonstrating an incidence of 0.95%. Overall median survival from the time of diagnosis of brain metastasis was 7.5 months (95% CI 4-15, range 9 days-64 months) and 40% survival at 1 year. Multivariate analysis revealed evidence of extracranial disease at time of metastasis diagnosis predicted decreased survival (hazard ratio 6.207), while papillary serous histology (hazard ratio 0.42), and use of any chemotherapy (hazard ratio 0.24) predicted longer survival. No other patient or tumor characteristics were found to be independent prognostic indicators affecting survival. Despite the ominous prognosis associated with the development of brain metastasis, these retrospective data suggest that multimodal therapy with whole brain radiation therapy, chemotherapy, and surgical resection of metastases in selected patients without evidence of extracranial and with solitary or multiple lesions can prolong survival. C1 [Growdon, W. B.; Lopez-Varela, E.; Littell, R.; Seiden, M.; Krasner, C.; Fuller, A.] Massachusetts Gen Hosp, Div Gynecol Oncol, Ctr Canc, Boston, MA 02114 USA. [Oliva, E.] Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. [Lee, H.] Massachusetts Gen Hosp, Div Clin Biostat, Boston, MA 02114 USA. RP Fuller, A (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Yawkey Ctr Outpatient Care, 32 Fruit St, Boston, MA 02114 USA. EM afuller@partners.org NR 23 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAR-APR PY 2008 VL 18 IS 2 BP 262 EP 268 DI 10.1111/j.1525-1438.2007.01011.x PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 272VA UT WOS:000253887300009 PM 17587320 ER PT J AU Losina, E Figueroa, P Duncan, J Divi, N Wolf, LL Hirschhorn, LR Robertson, M Harvey, K Whorms, S Freedberg, KA Gebre, Y AF Losina, Elena Figueroa, Peter Duncan, Jacqueline Divi, Nomita Wolf, Lindsey L. Hirschhorn, Lisa R. Robertson, Minnette Harvey, Kevin Whorms, Sheldon Freedberg, Kenneth A. Gebre, Yitades TI HIV morbidity and mortality in Jamaica: analysis of national surveillance data, 1993-2005 SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; AIDS; morbidity; mortality; Jamaica; Caribbean ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATURAL-HISTORY; DISEASE PROGRESSION; INFECTION; AIDS; PROPHYLAXIS; PREDICTORS; AFRICA; UGANDA; ADULTS AB Objectives: Pre-antiretroviral therapy (ART) HIV-related survival and timing of HIV identification have not been reported from the Caribbean. Using Jamaican national surveillance data, we estimated overall, AIDS-free, and AIDS survival, identified factors influencing HIV-retated mortatity, and examined factors associated with late HIV/AIDS identification. Methods: The Jamaican HIV/AIDS tracking system (HATS) national surveillance data included timing of first positive HIV test, stage at identification, date of AIDS diagnosis, and death. We estimated overall and AIDS-free survival by initial stage, using a proportional hazard model to identify factors associated with worse survival, and logistic regression to examine factors related to later case identification. Results: Of 10 674 reported HIV cases, 48% were asymptomatic, 14% symptomatic, and 38% first reported with AIDS. Five-year AIDS-free survival was 77% for asymptomatic persons and 63% for symptomatic. Median survival after AIDS diagnosis was 1.02 years. Age, number of opportunistic diseases, and initial stage were strongly associated with mortality. Older age, drug use, and sex with a commercial sex worker were associated with later identification. Conclusions: In the pre-ART era, over one-third of HIV-infected persons in Jamaica were first identified with advanced disease. This highlights the need for earlier diagnosis as ART programs roll out in the Caribbean. (c) 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 [Losina, Elena; Divi, Nomita; Wolf, Lindsey L.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med & Infect Dis, Boston, MA 02114 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Figueroa, Peter; Duncan, Jacqueline; Robertson, Minnette; Harvey, Kevin; Whorms, Sheldon] Jamaican Minist Hlth, Kingston, Jamaica. [Hirschhorn, Lisa R.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Harvard Ctr AIDS Res, Div AIDS, Boston, MA 02115 USA. [Gebre, Yitades] WHO, Pan Amer Hlth Org, Bahamas & Turks & Caicos Cty Off, Nassau, Bahamas. RP Losina, E (reprint author), Massachusetts Gen Hosp, Div Gen Med & Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM elosina@partners.org FU NIAID NIH HHS [K25 AI050436-04, R01 AI058736-04, K24 AI062476, P30 AI060354, K25 AI050436, K25 AI50436, P30 AI060354-03, K25 AI050436-05, R01 AI058736, K24 AI062476-04] NR 30 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD MAR PY 2008 VL 12 IS 2 BP 132 EP 138 DI 10.1016/j.ijid.2007.05.002 PG 7 WC Infectious Diseases SC Infectious Diseases GA 272IW UT WOS:000253854100007 PM 17706448 ER PT J AU Weingart, SN Hamrick, HE Tutkus, S Carbo, A Sands, DZ Tess, A Davis, RB Bates, DW Phillips, RS AF Weingart, Saul N. Hamrick, Hope E. Tutkus, Sharon Carbo, Alexander Sands, Daniel Z. Tess, Anjala Davis, Roger B. Bates, David W. Phillips, Russell S. TI Medication safety messages for patients via the web portal: The MedCheck intervention SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Internet; adverse effects; medical errors; patient-physician relations; communication ID RANDOMIZED CONTROLLED-TRIAL; HOSPITALIZED-PATIENTS; PRIMARY-CARE; EXPERIENCE; SYMPTOMS; ALERTS AB Objective: Communication failures account for many adverse drug events (ADEs) in adult primary care. Improving patient-physician communication may improve medication safety. Accordingly, the goal of this study was to learn whether electronic medication safety messages directed to patients can improve communication about medications and identify ADEs. Design: We studied adult patients enrolled in a patient Internet portal at three primary care practices affiliated with a teaching hospital. MedCheck, a medication safety application, sent patients a secure electronic message 10 days after they received a new or changed prescription. MedCheck asked if the patient had filled the prescription or experienced medication-related problems, and then forwarded the patient's response to their primary care physician. Measurements: We selected a stratified random sample of 267 subjects from 1821 patients who received and opened a MedCheck message from April 2001 to June 2002. We reviewed subjects' medical records for three months following their first MedCheck message. We analyzed patient and clinician response rates and times, examined patient-clinician communication about medications, and identified ADEs. Results: Patients opened 79% of MedCheck messages and responded to 12%; 77% responded within 1 day. Patients often identified problems filling their prescriptions (48%), problems with drug effectiveness (12%), and medication symptoms (10%). Clinicians responded to 68% of patients' messages; 93% answered within 1 week. Clinicians often supplied or requested information (19%), or made multiple recommendations (15%). Patients experienced 21 total ADEs; they reported 17 electronically. Conclusion: Patients and physicians responded promptly to patient-directed electronic medication messages, identifying and addressing medication -related problems including ADEs. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. [Weingart, Saul N.; Hamrick, Hope E.; Tutkus, Sharon; Carbo, Alexander; Sands, Daniel Z.; Tess, Anjala; Davis, Roger B.; Phillips, Russell S.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Weingart, Saul N.; Carbo, Alexander; Sands, Daniel Z.; Tess, Anjala; Davis, Roger B.; Bates, David W.; Phillips, Russell S.] Harvard Univ, Sch Med, Boston, MA USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 44 Binney St, Boston, MA 02115 USA. EM saul_weingart@dfci.harvard.edu FU AHRQ HHS [1 K08 HS 11644] NR 16 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD MAR PY 2008 VL 77 IS 3 BP 161 EP 168 DI 10.1016/j.ijmedinf.2007.04.007 PG 8 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 270DR UT WOS:000253700800002 PM 17581772 ER PT J AU Sharma, N Thomas, S Ho, L Reyes, DC AF Sharma, Naresh Thomas, Sunil Ho, Lap Reyes, Dillenia C. TI Immunomodulation with glatiramer acetate prevents long-term inflammatory pain SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE cyclooxygenase; fractalkine; glatiramer acetate; pain ID PROINFLAMMATORY CYTOKINE EXPRESSION; DORSAL-ROOT GANGLIA; CYCLOOXYGENASE INHIBITORS; NEUROTROPHIC FACTOR; NERVE INJURY; SPINAL-CORD; T-CELLS; RECEPTOR; FRACTALKINE; ACTIVATION AB The potential application of glatiramer acetate (GA) therapy as a safe pharmacological treatment for the attenuation or prevention of long-term inflammatory pain in a rat model was explored. Peripheral inflammatory pain was induced by an injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paw. Genome-wide DNA microarray studies were used to survey molecular mechanisms involved in long-term GA analgesic responses. Administration of a single or double subcutaneous injection of GA before, or immediately after, intraplantar injection of pro-inflarnmatory CFA significantly attenuated allodynia and hyperalgesic pain responses up to similar to 3 weeks after CFA treatment. These beneficial effects of GA immunization therapy coincided with the attenuation of expression of the chemotactic fractalkine chemokine (CX3CL 1) in the dorsal horn of the lumbar spinal cord (L4-L5) in response to CFA treatment, assessed by DNA microarray and confirmed immunocytochemically (ICC). This study is consistent with the hypothesis that a novel mechanism through which GA immunization therapy may beneficially influence long-term allodynia and hyperalgesia is through central regulation of fractalkine-mediated responses. C1 [Sharma, Naresh; Thomas, Sunil; Reyes, Dillenia C.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ho, Lap] James J Peters Vet Affairs Med Ctr, Geriat Res & Clin Ctr, Bronx, NY USA. RP Sharma, N (reprint author), Mt Sinai Sch Med, Dept Psychiat, E Bldg,Room 10-70 1 Levy Pl, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu NR 25 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PD MAR PY 2008 VL 118 IS 3 BP 433 EP 453 DI 10.1080/00207450701849018 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 270KV UT WOS:000253720600010 PM 18300014 ER PT J AU Tzika, AA AF Tzika, A. Aria TI Proton magnetic resonance spectroscopic imaging as a cancer biomarker for pediatric brain tumors (Review) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Review DE cancer biomarkers; nuclear magnetic resonance; diagnostic imaging; magnetic resonance spectroscopic imaging ID H-1 MR SPECTROSCOPY; IN-VIVO; THYMIDINE KINASE; NMR-SPECTROSCOPY; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; NEURAL-NETWORKS; GENE-THERAPY; VOLUME MRI; CELL-CYCLE AB Magnetic resonance (MR) techniques offer a noninvasive, non-irradiating yet sensitive approach to diagnose and monitor cancer, which encompasses diverse processes affecting various aspects of pathophysiology. Techniques such as MR spectroscopy (MRS) have been developed and applied to monitor the metabolic aspects of cancer. Given that cancer is such a variable disease, biomarkers identified using MRS represent a promising advance and may suggest appropriate therapy, especially when diagnostic biopsies are not feasible. This article will focus on proton MRS, which appears to be the most promising MR method and is complementary to existing diagnostic methods that may be used to characterize and monitor cancer processes. We further focus on applying the MRS technology to pediatric brain tumors, the leading cause of pediatric cancer mortality. C1 [Tzika, A. Aria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA. RP Tzika, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu NR 86 TC 8 Z9 8 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 2008 VL 32 IS 3 BP 517 EP 526 PG 10 WC Oncology SC Oncology GA 267KJ UT WOS:000253507600001 PM 18292928 ER PT J AU Zerpa, N Pabon, R Wide, A Gavidia, M Medina, M Caceres, JL Capaldo, J Baker, M Noya, O AF Zerpa, Noraida Pabon, Rosalba Wide, Albina Gavidia, Magda Medina, Mehudi Luis Caceres, Jose Capaldo, Jacinta Baker, Meghan Noya, Oscar TI Evaluation of the OptiMAL (R) test for diagnosis of malaria in Venezuela SO INVESTIGACION CLINICA LA English DT Article DE OptiMAL (R); Plasmodium falciparum; Plasmodium vivax; parasitaemia ID PLASMODIUM-FALCIPARUM MALARIA; MIXED INFECTIONS; RAPID TEST; VIVAX; PERFORMANCE; PCR; IDENTIFICATION; MICROSCOPY; PARASITES; ASSAY AB We evaluated the OptiMAL (R) rapid dipstick test by comparing it with the conventional standard thick-blood film method, for the detection of malaria in two groups of individuals from different Venezuelan endemic areas. One of the groups consisted of individuals with malaria-like symptoms (n = 113) and the other of asymptomatic individuals (n = 89). The classical microscopy analysis of these populations determined that 67.5% were infected with P. vivax, 31.3% with P. falciparum, and 1.2% with mixed infections. The OptiMAL (R) test showed 96.4% sensitivity, 100% specificity, 100% positive predictive value, 97.5% negative predictive value and optimal concordance (kappa = 0.97), capable of detecting any malaria infection in the evaluated population. However, these parameters were lower when the parasitaemia was :5 300 parasites/mu L. Freezing of the samples did not affect the sensitivity and specificity of the test. We concluded that this rapid malaria test is sensitive and specific for rapid diagnosis of malaria in the field and it is a complement to conventional microscopy. C1 [Zerpa, Noraida] Fdn Inst Estudios Avanzados IDEA, Ctr Biociencias, Sartenejas, Belize. [Pabon, Rosalba; Capaldo, Jacinta; Noya, Oscar] Cent Univ Venezuela, Lab Estudios Malaria IAESP Arnoldo Gabaldon, Caracas, Venezuela. [Wide, Albina; Noya, Oscar] Cent Univ Venezuela, Catedra Parasitol, Escuela Med Luis Razetti, Fac Med, Caracas, Venezuela. [Gavidia, Magda; Medina, Mehudi] Univ Carabobo, Minist Salud, Direcc Gen Salud Ambiental, Maracay, Venezuela. [Luis Caceres, Jose] Univ Carabobo, Fac Ciencias Salud, Maracay, Venezuela. [Baker, Meghan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baker, Meghan] Brigham & Womens Hosp, Dept Infect Dis, Boston, MA 02115 USA. RP Zerpa, N (reprint author), Fdn Inst Estudios Avanzados IDEA, Ctr Biociencias, Caracas, Venezuela. EM norazerpa@yahoo.com FU Ministry of Health and Social Development MSDS; Rural Endemic Services from Bolivar and Sucre; DiaMed SA, Cressier sur Morat, Switzerland; FONACIT FX We thanks the Ministry of Health and Social Development MSDS, and the Rural Endemic Services from Bolivar and Sucre states for allowing access and given support to this study. We also thanks, the Francesco Vitanza Research Center from Tumeremo, Bolivar State, where some assays were carried out. Partial support for travel expenses was provided by DiaMed SA, Cressier sur Morat, Switzerland. The presentation of these results in national and international meetings was sponsored by FONACIT. NR 26 TC 5 Z9 6 U1 1 U2 4 PU INST INVESTIGACION CLINICA PI MARACAIBO PA APARTADO 23, MARACAIBO 4001-A, VENEZUELA SN 0535-5133 J9 INVEST CLIN JI Invest. Clin. PD MAR PY 2008 VL 49 IS 1 BP 93 EP 101 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 344MY UT WOS:000258932900009 PM 18524335 ER PT J AU Saravanan, C Cao, ZY Kumar, J Qiu, JZ Plaut, AG Newburg, DS Panjwani, N AF Saravanan, Chandrassegar Cao, Zhiyi Kumar, Janardan Qiu, Jiazhou Plaut, Andrew G. Newburg, David S. Panjwani, Noorjahan TI Milk components inhibit Acanthamoeba-induced cytopathic effect SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MANNOSE-BINDING PROTEIN; CONTACT-LENS WEAR; IN-VITRO; KERATITIS; CASTELLANII; IGA; ADHERENCE; EPIDEMIOLOGY; PATHOGENESIS; VIRULENCE AB PURPOSE. Acanthamoebae provoke a vision-threatening corneal infection known as Acanthamoeba keratitis (AK). It is thought that Acanthamoeba-specific IgA antibodies present in mucosal secretions such as human tears, milk, and saliva provide protection against infection by inhibiting the adhesion of parasites to host cells. The goal of the present study was to determine whether human mucosal secretions have the potential to provide protection against the Acanthamoeba-induced cytopathic effect (CPE) by an additional mechanism that is independent of IgA. METHODS. Breast milk was used as a model of human mucosal secretions. In vitro CPE assays were used to examine the CPE inhibitory effect of IgA-depleted milk and various milk fractions obtained by gel filtration. The activity of amebic proteinases was examined by zymography. RESULTS. IgA-depleted milk inhibited the Acanthamoeba-induced CPE in a concentration-dependent manner. Milk proteins were separated into four major fractions (F1-F4) by gel filtration. Of these four fractions, CPE inhibitory activity was detected largely in fraction F3. In contrast, fractions F1, F2, and F4 lacked CPE inhibitory activity. Moreover, fraction F3, but not F1, F2, or F4, inhibited amebic proteinases. CONCLUSIONS. These data, in conjunction with published findings showing that amebic proteinases are responsible for the induction of Acanthamoeba CPE, led us to propose that human mucosal secretions have the potential to provide protection against Acanthamoeba-induced CPE by an additional mechanism that is independent of IgA and that involves the inhibition of cytotoxic proteinases of amebae. C1 [Saravanan, Chandrassegar; Cao, Zhiyi; Kumar, Janardan; Panjwani, Noorjahan] Tufts Univ, Sch Med, Dept Ophthalmol, Ctr Vis Res, Boston, MA 02111 USA. [Saravanan, Chandrassegar; Cao, Zhiyi; Kumar, Janardan; Panjwani, Noorjahan] Tufts Univ, Sch Med, Dept Ophthalmol, New England Eye Ctr, Boston, MA 02111 USA. [Saravanan, Chandrassegar; Panjwani, Noorjahan] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Anat & Cell Biol, Boston, MA 02111 USA. [Qiu, Jiazhou; Plaut, Andrew G.] Tufts Univ New England Med Ctr, Boston, MA USA. [Newburg, David S.] Massachusetts Gen Hosp, Program Glycobiol Pediat Gastroenterol & Nutr, Charlestown, MA USA. RP Panjwani, N (reprint author), Tufts Univ, Sch Med, Dept Ophthalmol, Ctr Vis Res, 136 Harrison Ave, Boston, MA 02111 USA. EM noorjahan.panjwani@tufts.edu FU NEI NIH HHS [EY09349]; NICHD NIH HHS [HD13021]; NIDCR NIH HHS [DE15844]; NIDDK NIH HHS [DK40561]; PHS HHS [DKP30-34928, EYP30-13078] NR 38 TC 3 Z9 4 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2008 VL 49 IS 3 BP 1010 EP 1015 DI 10.1167/iovs.07-1130 PG 6 WC Ophthalmology SC Ophthalmology GA 271TZ UT WOS:000253812900026 PM 18326724 ER PT J AU Menke, MN Feke, GT McMeel, JW Treon, SP AF Menke, Marcel N. Feke, Gilbert T. McMeel, J. Wallace Treon, Steven P. TI Effect of plasmapheresis on hyperviscosity-related retinopathy and retinal hemodynamics in patients with Waldenstrom's macroglobulinemia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MICROCIRCULATION; MANIFESTATIONS; MANAGEMENT; VISCOSITY AB PURPOSE. Waldenstrom's macroglobulinemia (WM) is characterized by an overproduction of immunoglobulin M (IgM), which can lead to a hyperviscosity syndrome (HVS) and HVS-related retinopathy. Plasmapheresis is known to reduce serum viscosity (SV) and IgM levels. The purpose of this study was to investigate the effects of plasmapheresis on HVS-related retinopathy and retinal hemodynamic parameters in patients with WM. METHODS. Nine patients with HVS due to WM were studied. SV and plasma IgM levels were measured before and after plasmapheresis treatment. The patients were evaluated for HVS-related retinopathy, and hemodynamic changes in a major temporal retinal vein by laser Doppler, before and after plasmapheresis. RESULTS. Plasmapheresis resulted in significant reductions in serum IgM (46.5% +/- 18.0%, mean +/- SD; P = 0.0009) and SV (44.7% +/- 17.3%, P = 0.002). HVS-related retinopathy improved in all patients after plasmapheresis. After treatment, the venous diameter decreased in each patient by an average of 15.3% +/- 5.8% (P = 0.0001). A significant (P = 0.0004) 55.2% +/- 22.5% increase in retinal venous blood speed accompanied the decreases in diameter. There was no significant change in the retinal blood flow rate after treatment. The percentage decreases in SV in the patients were significantly correlated with the percentage decreases in venous blood column diameter (P = 0.031, R-2 = 0.51). CONCLUSIONS. HVS triggers a distinctive retinopathy with a central retinal vein occlusion (CRVO)-like appearance. However, the retinal blood flow is not decreased as in CRVO, but remains at normal levels. Plasmapheresis is effective in reversing HVS-related retinopathy and in reducing abnormal venous dilatation. C1 [Menke, Marcel N.; Feke, Gilbert T.; McMeel, J. Wallace] Schepens Retina Associates Fdn, Boston, MA 02215 USA. [Menke, Marcel N.; Feke, Gilbert T.] Harvard Univ, Sch Med, Div Ophthalmol, Dept Surg, Boston, MA 02115 USA. [McMeel, J. Wallace] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Feke, GT (reprint author), Schepens Retina Associates Fdn, 1 Autumn St,6th Floor, Boston, MA 02215 USA. EM feke@schepens.com NR 19 TC 19 Z9 20 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2008 VL 49 IS 3 BP 1157 EP 1160 DI 10.1167/iovs.07-1254 PG 4 WC Ophthalmology SC Ophthalmology GA 271TZ UT WOS:000253812900046 PM 18326744 ER PT J AU Rockl, KSC Witczak, CA Goodyear, LJ AF Roeckl, Katja S. C. Witczak, Carol A. Goodyear, Laurie J. TI Signaling mechanisms in skeletal muscle: Acute responses and chronic adaptations to exercise SO IUBMB LIFE LA English DT Review DE skeletal muscle; AMPK; glucose uptake; training adaptation; exercise ID ACTIVATED PROTEIN-KINASE; INDUCED MITOCHONDRIAL BIOGENESIS; FATTY-ACID OXIDATION; GLUCOSE-TRANSPORT; CONTRACTILE ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; COACTIVATOR PGC-1; FIBER COMPOSITION; ENZYME-ACTIVITY; AS160 PHOSPHORYLATION AB Physical activity elicits physiological responses in skeletal muscle that result in a number of health benefits, in particular in disease states, such as type 2 diabetes. An acute bout of exercise/muscle contraction improves glucose homeostasis by increasing skeletal muscle glucose uptake, while chronic exercise training induces alterations in the expression of metabolic genes, such as those involved in muscle fiber type, mitochondrial biogenesis, or glucose transporter 4 (GLUT4) protein levels. A primary goal of exercise research is to elucidate the mechanisms that regulate these important metabolic and transcriptional events in skeletal muscle. In this review, we briefly summarize the current literature describing the molecular signals underlying skeletal muscle responses to acute and chronic exercise. The search for possible exercise/contraction-stimulated signaling proteins involved in glucose transport, muscle fiber type, and mitochondrial biogenesis is ongoing. Further research is needed because full elucidation of exercise-mediated signaling pathways would represent a significant step toward the development of new pharmacological targets for the treatment of metabolic diseases such as type 2 diabetes. (C) 2008 IUBMB. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02115 USA. EM laurie.goodyear@joslin.harvard.edu FU NIAMS NIH HHS [F32 AR051663-02, R01 AR045670, R01 AR045670-10, R01AR45670, F32AR051663, F32 AR051663]; NIDDK NIH HHS [P30 DK036836, P30 DK036836-21, R01 DK068626, R01DK068626, R01 DK068626-04, DK36836] NR 103 TC 98 Z9 103 U1 2 U2 20 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAR PY 2008 VL 60 IS 3 BP 145 EP 153 DI 10.1002/iub.21 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273SB UT WOS:000253950900001 PM 18380005 ER PT J AU O'Gara, P Sugeng, L Lang, R Sarano, M Hung, J Raman, S Fischer, G Carabello, B Adams, D Vannan, M AF O'Gara, Patrick Sugeng, Lissa Lang, Roberto Sarano, Maurice Hung, Judy Raman, Subha Fischer, Gregory Carabello, Blase Adams, David Vannan, Mani TI The Role of Imaging in Chronic Degenerative Mitral Regurgitation SO JACC-CARDIOVASCULAR IMAGING LA English DT Article AB Chronic degenerative mitral regurgitation (MR) is a complex problem, which requires an integrated assessment of etiology, pathophysiology, and severity to enable informed clinical decision-making. A multidisciplinary approach is required, with input from the clinician, imager, and surgeon. This review begins with a discussion of essential echocardiographic and surgical mitral valve (MV) anatomy, which dictates suitability for repair when indicated. The echocardiographic and Doppler principles, which underlie the quantitation of MR severity, are summarized in the next section, followed by a critical examination of left ventricular systolic function in this disorder. A brief discussion of the important role of imaging in the developing field of percutaneous MV repair is included. The methodical and objective noninvasive assessment of degenerative MR herein reviewed is intended to help guide management decisions for patients with this challenging valve lesion. (J Am Coll Cardiol Img 2008; 1: 221-37) (C) 2008 by the American College of Cardiology Foundation C1 [Vannan, Mani] Ohio State Univ, DHLRI, Med Ctr, Columbus, OH 43210 USA. [O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Fischer, Gregory; Adams, David] Mt Sinai Med Ctr, New York, NY 10029 USA. [Sugeng, Lissa; Lang, Roberto] Univ Chicago Hosp, Chicago, IL 60637 USA. [Sarano, Maurice] Mayo Clin, Rochester, MN USA. [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carabello, Blase] Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Vannan, M (reprint author), Ohio State Univ, DHLRI, Med Ctr, 473 W 12th Ave,Suite 200, Columbus, OH 43210 USA. EM mani.vannan@osumc.edu NR 29 TC 36 Z9 37 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAR PY 2008 VL 1 IS 2 BP 221 EP 237 DI 10.1016/j.jcmg.2008.01.011 PG 17 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V13EI UT WOS:000207649700014 PM 19356431 ER PT J AU Justman, JE Hoover, DR Shi, Q Tan, T Anastos, K Tien, PC Cole, SR Hyman, C Karim, R Weber, K Grinspoon, S AF Justman, Jessica E. Hoover, Donald R. Shi, Qiuhu Tan, Tianren Anastos, Kathryn Tien, Phyllis C. Cole, Stephen R. Hyman, Charles Karim, Roksana Weber, Kathleen Grinspoon, Steven TI Longitudinal anthropometric patterns among HIV-infected and HIV-uninfected women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE anthropometrics; HIV; waist-to-hip ratio; women ID ACTIVE ANTIRETROVIRAL THERAPY; WAIST CIRCUMFERENCE; INTERAGENCY HIV; HIV-1-INFECTED PATIENTS; FAT DISTRIBUTION; UNITED-STATES; RISK-FACTORS; WEIGHT-GAIN; OBESITY; HEALTH AB Introduction: Previous studies suggest that indicators of central adiposity such as waist-to-hip ratio (WHR) and waist circumference may be altered by HIV infection, antiretroviral treatment, or both. Methods: Waist and hip circumference and body mass index (BMI) were measured among participants of the Women's Interagency HIV Study semiannually from 1999 to 2004. Generalized linear models evaluated longitudinal patterns of these measures and associations with demographic and clinical characteristics. Results: WHR was significantly larger, whereas BMI and waist and hip circumference were significantly smaller at almost all I I semiannual visits among 942 HIV-infected women compared with 266 HIV-uninfected women. Among HIV-uninfected women, mean waist and hip circumference and BMI increased over the 5-year study period (waist: +4.1 cm or 4.4%, hip: +3.76 cm or 3.5%, and BMI +2.43 kg/m(2) or 8.2%), whereas WHR remained stable. Among the HIV-infected women, waist and hip circumference, BMI, and WHR did not significantly change. Independent predictors of smaller BMI among HIV-infected women included white race, hepatitis C virus seropositivity, current smoking, higher viral load, and lower CD4 cell count. Independent predictors of larger WHR among HIV-infected women included age, white and other non-African American race, higher CD4 cell count, and protease inhibitor (PI) use. Use of a highly active antiretroviral therapy (HAART) regimen was not an independent predictor of BMI or WHR. Conclusions: HIV-infected women had higher WHRs compared with HIV-uninfected women, despite lower BMIs and waist and hip measurements. BMI and waist and hip circumference increased over 5 years among the HIV-uninfected women but remained stable in the HIV-infected women. Among HIV-infected women, PI use was associated with a larger WHR, although HAART use itself was not appreciably associated with BMI or WHR. C1 [Justman, Jessica E.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Justman, Jessica E.] Columbia Univ, Dept Med, New York, NY 10032 USA. [Hoover, Donald R.] Rutgers State Univ, Dept Stat, Piscataway, NJ USA. [Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA. [Shi, Qiuhu] New York Med Coll, Sch Publ Hlth, Valhalla, NY 10595 USA. [Tan, Tianren] Data Solut LLC, Bronx, NY USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cole, Stephen R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Hyman, Charles] SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. [Karim, Roksana] Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Weber, Kathleen] John H Stroger Hosp Cook Cty, Chicago, IL USA. [Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA USA. RP Justman, JE (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St,Room 714, New York, NY 10032 USA. EM jj2l58@columbia.edu FU NCRR NIH HHS [M01-RR-00083, M01 RR000071, M01 RR000079, M01 RR000083, M01-RR-00071, M01-RR-00079]; NIAID NIH HHS [K23 AI066943, K23 AI066943-05, U01 AI031834, U01 AI034989, U01 AI034993, U01 AI034994, U01 AI035004, U01 AI042590, U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590]; NICHD NIH HHS [U01 HD032632, U01-HD-32632] NR 39 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2008 VL 47 IS 3 BP 312 EP 319 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 271XD UT WOS:000253821100007 PM 18197125 ER PT J AU Walkup, J Blank, MB Gonzalez, JS Safren, S Schwartz, R Brown, L Wilson, I Knowlton, A Lombard, F Grossman, C Lyda, K Schumacher, JE AF Walkup, James Blank, Michael B. Gonzalez, Jeffrey S. Safren, Steven Schwartz, Rebecca Brown, Larry Wilson, Ira Knowlton, Amy Lombard, Frank Grossman, Cynthia Lyda, Karen Schumacher, Joseph E. TI The impact of mental health and substance abuse factors on HIV prevention and treatment SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 1st National Scientific Meeting of the Social-and-Behavioral-Science-Research-Network CY MAR 27-28, 2006 CL Atlanta, GA SP Social & Behav Sci Res Network ID INFECTED MEDICAID BENEFICIARIES; ACTIVE ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; UNITED-STATES; USE DISORDERS; PSYCHIATRIC-DISORDERS; DEPRESSIVE SYMPTOMS; RISK BEHAVIORS; SEXUAL RISK; ILLNESS AB The convergence of HIV, substance abuse (SA), and mental illness (MI) represents a distinctive challenge to health care providers, policy makers, and researchers. Previous research with the mentally ill and substance-abusing populations has demonstrated high rates of psychiatric and general medical comorbidity. Additionally, persons living with HIV/AIDS have dramatically elevated rates of MI and other physical comorbidities. This pattern of co-occurring conditions has been described as a syndemic. Syndemic health problems occur when linked health problems involving 2 or more afflictions interact synergistically and contribute to the excess burden of disease in a population. Evidence for syndemics arises when health-related problems cluster by person, place, or time. This article describes a research agenda for beginning to understand the complex relations among MI, SA, and HIV and outlines a research agenda for the Social and Behavioral Science Research Network in these areas. C1 [Walkup, James] Rutgers State Univ, Inst Hlth Hlth Care Policy, New Brunswick, NJ USA. [Walkup, James] Rutgers State Univ, Grad Sch Appl & Profess Psychol, New Brunswick, NJ USA. [Blank, Michael B.] Univ Penn, Sch Med, Dept Psychiat, Ctr Mental Hlth Policy, Philadelphia, PA 19104 USA. [Blank, Michael B.] Univ Penn, Sch Med, Dept Psychiat, Res Serv, Philadelphia, PA 19104 USA. [Gonzalez, Jeffrey S.; Safren, Steven; Schwartz, Rebecca] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Safren, Steven] Fenway Community Hlth, Boston, MA USA. [Schwartz, Rebecca] SUNY Stony Brook, Downstate Med Ctr, New York, NY USA. [Brown, Larry] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Bradley Hasbro Childrens Res Ctr, Providence, RI 02903 USA. [Wilson, Ira] Tufts Univ New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Knowlton, Amy] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Lombard, Frank] Duke Univ, Ctr Hlth Policy, Durham, NC USA. [Grossman, Cynthia] NIMH, NIH, Bethesda, MD 20892 USA. [Lyda, Karen] Univ Colorado, Univ Colorado Hosp, Infect Dis Grp Practice, Denver, CO 80202 USA. [Schumacher, Joseph E.] Univ Alabama, Ctr AIDS Res, Div Prevent Med, Birmingham, AL USA. RP Walkup, J (reprint author), Rutgers State Univ, Inst Hlth Hlth Care Policy, 30 Coll Ave, New Brunswick, NJ USA. EM jamie.walkup@gmail.com RI walkup, james/E-5041-2012; Walkup, James/E-5047-2012 FU AHRQ HHS [U18-HS016097-01]; NIMH NIH HHS [R01-MH058984] NR 52 TC 50 Z9 50 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2008 VL 47 SU 1 BP S15 EP S19 DI 10.1097/QAI.0b013e3181605b26 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 271XE UT WOS:000253821200004 PM 18301129 ER PT J AU Merchant, SN Mckenna, MJ Adams, JC Nadol, JB Fayad, J Gellibolian, R Linthicum, FH Ishiyama, A Lopez, I Ishiyama, G Baloh, R Platt, C AF Merchant, Saumil N. Mckenna, Michael J. Adams, Joe C. Nadol, Joseph B., Jr. Fayad, Jose Gellibolian, Robert Linthicum, Fred H., Jr. Ishiyama, Akira Lopez, Ivan Ishiyama, Gail Baloh, Robert Platt, Christopher TI Human temporal bone consortium for research resource enhancement SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Editorial Material ID 3-DIMENSIONAL VIRTUAL MODEL; INNER-EAR; VESTIBULAR DYSFUNCTION; COCHLEAR IMPLANTS; HISTOPATHOLOGY; DFNA9; PATHOLOGY; DEAFNESS; HEARING; PATIENT C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fayad, Jose; Gellibolian, Robert; Linthicum, Fred H., Jr.; Lopez, Ivan] House Ear Res Inst, Los Angeles, CA 90057 USA. [Ishiyama, Akira; Lopez, Ivan; Ishiyama, Gail; Baloh, Robert] Univ Calif Los Angeles, Los Angeles, CA 90057 USA. [Platt, Christopher] Natl Tech Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM saumil_merchant@meei.harvard.edu OI Lopez, Ivan/0000-0001-5205-7293 FU NIDCD NIH HHS [U24 DC008559-02, U24 DC008559] NR 23 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD MAR PY 2008 VL 9 IS 1 BP 1 EP 4 DI 10.1007/s10162-008-0111-5 PG 4 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 275CA UT WOS:000254048300001 PM 18247091 ER PT J AU Braunstein, EM Crenshaw, EB Morrow, BE Adams, JC AF Braunstein, Evan M. Crenshaw, E. Bryan, III Morrow, Bernice E. Adams, Joe C. TI Cooperative function of Tbx1 and Brn4 in the periotic mesenchyme is necessary for cochlea formation SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE inner ear; genetic interaction; Mondini dysplasia ID INNER-EAR MORPHOGENESIS; OTIC CAPSULE; HEARING-LOSS; CELL-PROLIFERATION; MAMMALIAN COCHLEA; MONDINI-DYSPLASIA; SONIC HEDGEHOG; MOUSE MODEL; DEAFNESS; DFN3 AB The T-box transcription factor TBX1 has been identified as the major gene responsible for the etiology of velocardicifacial syndrome/DiGeorge syndrome (VCFS/DGS). Conductive hearing loss occurs in a majority of patients with this syndrome, while sensorineural deafness has also been reported in some cases. Mutations in POU3F4/BRN4, a POU domain transcription factor, cause DFN3, an X-linked non-syndromic form of deafness characterized by mixed conductive and sensorineural hearing loss. Inactivation of the murine orthologues of these genes causes similar defects to those seen in humans and has provided excellent models for the study of inner ear development. Tbx1 and Brn4 are expressed in the mesenchymal cells surrounding the otic vesicle and have been shown to play roles in cochlear outgrowth. Furthermore, expression of Brn4 is reduced in Tbx1 null mutants, suggesting a possible genetic interaction between these genes. To test whether Tbx1 and Brn4 function in a common pathway, mice mutant for both genes were generated and analyzed for inner ear defects. Brn4-;Tbx1+/- mutants displayed a significant reduction in the number of turns of the cochlea compared to Brn4- or Tbx1+/- mice. In addition, Brn4-;Tbx1+/- mice displayed structural defects in the apical cochlea indicative of Mondini dysplasia found in patients with either VCFS/DGS or DFN3. These data establish a genetic interaction between Tbx1 and Brn4 relevant to human disease and indicate a function of these genes in signaling from the periotic mesenchyme to the otic vesicle to direct proper coiling of the cochlear duct. C1 [Braunstein, Evan M.; Morrow, Bernice E.] Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. [Crenshaw, E. Bryan, III] Childrens Hosp Philadelphia, Mammalian Neurogenet Grp, Ctr Childhood Commun, Philadelphia, PA 19104 USA. [Crenshaw, E. Bryan, III] Univ Penn, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Adams, Joe C.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Morrow, BE (reprint author), Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM morrow@aecom.yu.edu FU NIDCD NIH HHS [DC008239-02, DC05186-03, F30 DC008239, P30 DC005209, R01 DC005186]; NIGMS NIH HHS [T32 GM007288] NR 32 TC 34 Z9 36 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD MAR PY 2008 VL 9 IS 1 BP 33 EP 43 DI 10.1007/s10162-008-0110-6 PG 11 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 275CA UT WOS:000254048300004 PM 18231833 ER PT J AU Oesterle, EC Campbell, S Taylor, RR Forge, A Hume, CR AF Oesterle, Elizabeth C. Campbell, Sean Taylor, Ruth R. Forge, Andrew Hume, Clifford R. TI Sox2 and Jagged1 expression in normal and drug-damaged adult mouse inner ear SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Review DE ototoxicity; aminoglycoside; cochlea; vestibular; supporting cell; hair cell ID HAIR CELL REGENERATION; AVIAN AUDITORY EPITHELIUM; CALCIUM-BINDING PROTEINS; EMBRYONIC STEM-CELLS; GROWTH-FACTOR-ALPHA; K-CL COTRANSPORTER; SENSORY EPITHELIA; ETHACRYNIC-ACID; STRIA VASCULARIS; HEARING-LOSS AB Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for non-sensory cells within the sensory receptor epithelia. The present study delineates a protocol to drug damage the adult mouse auditory epithelium (organ of Corti) in situ and uses this protocol to investigate Sox2 and Jagged1 expression in damaged inner ear sensory epithelia. In other tissues, the transcription factor Sox2 and a ligand member of the Notch signaling pathway, Jagged1, are involved in regenerative processes. Both are involved in early inner ear development and are expressed in developing support cells, but little is known about their expressions in the adult. We describe a nonsurgical technique for inducing hair cell damage in adult mouse organ of Corti by a single high-dose injection of the aminoglycoside kanamycin followed by a single injection of the loop diuretic furosemide. This drug combination causes the rapid death of outer hair cells throughout the cochlea. Using immunocytochemical techniques, Sox2 is shown to be expressed specifically in support cells in normal adult mouse inner ear and is not affected by drug damage. Sox2 is absent from auditory hair cells, but is expressed in a subset of vestibular hair cells. Double-labeling experiments with Sox2 and calbindin suggest Sox2-positive hair cells are Type II. Jagged1 is also expressed in support cells in the adult ear and is not affected by drug damage. Sox2 and Jagged1 may be involved in the maintenance of support cells in adult mouse inner ear. C1 [Oesterle, Elizabeth C.; Campbell, Sean; Hume, Clifford R.] Univ Washington, Dept Otolaryngol Head & Neck Surg, Virginia Merrill Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. [Taylor, Ruth R.; Forge, Andrew] UCL Ear Inst, Ctr Auditory Res, London WC1X 8EE, England. [Hume, Clifford R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Oesterle, EC (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Virginia Merrill Bloedel Hearing Res Ctr, CHDD CD176 Box 357923, Seattle, WA 98195 USA. EM oesterle@u.washington.edu FU Action on Hearing Loss [G27]; NICHD NIH HHS [P30 HD002274, P30HD002274]; NIDCD NIH HHS [P30 DC004661, P30DC04661, R01 DC003944, R01DC03944] NR 139 TC 98 Z9 102 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD MAR PY 2008 VL 9 IS 1 BP 65 EP 89 DI 10.1007/s10162-007-0106-7 PG 25 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 275CA UT WOS:000254048300006 PM 18157569 ER PT J AU Gupta, RS Zhang, XY Sharp, LK Shannon, JJ Weiss, KB AF Gupta, Ruchi S. Zhang, Xingyou Sharp, Lisa K. Shannon, John J. Weiss, Kevin B. TI Geographic variability in childhood asthma prevalence in Chicago SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; children; disparities; neighborhood variability; asthma prevalence ID SCHOOL-AGE-CHILDREN; INNER-CITY ASTHMA; HOUSE-DUST MITE; SOCIOECONOMIC-STATUS; AIR-POLLUTION; BIRTH-COHORT; ENVIRONMENTAL EXPOSURE; LOGISTIC-REGRESSION; ALLERGEN EXPOSURE; TOBACCO-SMOKE AB Background: Childhood asthma prevalence has been shown to be higher in urban communities overall without an understanding of differences by neighborhood. Objective: To characterize the geographic variability of childhood asthma prevalence among neighborhoods in Chicago. Methods: Asthma screening was conducted among children attending 105 Chicago schools as part of the Chicago Initiative to Raise Asthma Health Equity. Additional child information included age, sex, race/ethnicity, and household members with asthma. Surveys were geocoded and linked with neighborhoods. Neighborhood information on race, education, and income was based on 2000 census data. Bivariate and multilevel analyses were performed. Results: Of the 48,917 surveys, 41,255 (84.3%) were geocoded into 287 neighborhoods. Asthma prevalence among all children was 12.9%. Asthma rates varied among neighborhoods from 0% to 44% (interquartile range, 8% to 24%). Asthma prevalence (mean, SD, range) in predominantly black neighborhoods (19.9, +/- 7, 4% to 44%) was higher than in predominantly white neighborhoods (11.4, +/- 4.7, 2% to 30%) and predominantly Hispanic neighborhoods (12.1, +/- 6.8, 0% to 29%). Although sex, age, household members with asthma, and neighborhood income significantly affected asthma prevalence, they did not explain the differences seen between neighborhoods. Race explained a significant proportion (about 80%) but not all of this variation. Conclusion: Childhood asthma prevalence varies widely by neighborhood within this urban environment. Adjacent areas in Chicago were identified with significantly different asthma prevalence. A better understanding of the effect of neighborhood characteristics may lend insight into potential interventions to reduce childhood asthma. C1 [Gupta, Ruchi S.] Childrens Mem Hosp, Smith Child Hlth Res Program, Chicago, IL 60614 USA. [Gupta, Ruchi S.; Weiss, Kevin B.] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. [Weiss, Kevin B.] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA. [Zhang, Xingyou] Amer Acad Family Phys, Policy Studies Family Med & Primary Care, Robert Graham Ctr, Washington, DC USA. [Sharp, Lisa K.] Univ Illinois, Sect Hlth Promot, Dept Med, Chicago, IL 60680 USA. [Shannon, John J.] Cook Cty Hosp, Dept Med, Div Pulm & Crit Care Med, Chicago, IL 60612 USA. [Weiss, Kevin B.] US Dept Vet Affairs, Midwest Ctr Hlth Serv & Policy Res, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Gupta, RS (reprint author), Childrens Mem Hosp, Smith Child Hlth Res Program, 2300 Childrens Plaza,Box 157, Chicago, IL 60614 USA. EM r-gupta@northwestern.edu FU NHLBI NIH HHS [5U01 HL072478-05]; NICHD NIH HHS [K12 HD052902] NR 55 TC 43 Z9 44 U1 6 U2 11 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 MAR PY 2008 VL 121 IS 3 BP 639 EP 645 DI 10.1016/j.jaci.2007.11.036 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 273GR UT WOS:000253918900015 PM 18243285 ER PT J AU Hamilos, DL Yamin, M Holbrook, E Busaba, N Gray, S Powell, KJ Harold, R Sridhar, A AF Hamilos, D. L. Yamin, M. Holbrook, E. Busaba, N. Gray, S. Powell, K. J. Harold, R. Sridhar, A. TI Secondhand cigarette smoke may combine with common respiratory viruses to trigger exaggerated inflammation in CRS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Hamilos, D. L.; Yamin, M.; Powell, K. J.; Harold, R.; Sridhar, A.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Holbrook, E.; Busaba, N.; Gray, S.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 MAR PY 2008 VL 121 IS 3 MA LB23 BP 796 EP 797 DI 10.1016/j.jaci.2008.01.059 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 273GR UT WOS:000253918900076 ER PT J AU Dusek, JA Hibberd, PL Buczynski, B Chang, BH Dusek, KC Johnston, JM Wohlhueter, AL Benson, H Zusman, RM AF Dusek, Jeffery A. Hibberd, Patricia L. Buczynski, Beverly Chang, Bei-Hung Dusek, Kathryn C. Johnston, Jennifer M. Wohlhueter, Ann L. Benson, Herbert Zusman, Randall M. TI Stress management versus lifestyle modification on Systolic hypertension and medication elimination: A randomized trial SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; HIGH BLOOD-PRESSURE; RELAXATION RESPONSE; STOP HYPERTENSION; AFRICAN-AMERICANS; NATIONAL-HEALTH; CLINICAL-TRIAL; PLACEBO; PREVALENCE; PREVENTION AB Isolated systolic hypertension is common in the elderly, but decreasing systolic blood pressure (SBP) without lowering diastolic blood pressure (DBP) remains a therapeutic challenge. Although stress management training, in particular eliciting the relaxation response, reduces essential hypertension its efficacy in treating isolated systolic hypertension has not been evaluated. We conducted a double-blind, randomized trial comparing 8 weeks of stress management, specifically relaxation response training (61 patients), versus lifestyle modification (control, 61 patients). Inclusion criteria were >= 55 years, SBP 140-159 mm Hg, DBP < 90 mm Hg, and at least two antihypertensive medications. The primary outcome measure was change in SBP after 8 weeks. Patients who achieved SBP < 140 mm Hg and >= 5 mm Hg reduction in SBP were eligible for 8 additional weeks of training with supervised medication elimination. SBP decreased 9.4 (standard deviation [SD] 11.4) and 8.8 (SD 13.0) mm Hg in relaxation response and control groups, respectively (both ps < 0.0001) without group difference (p = 0.75). DBP decreased 1.5 (SD 6.2) and 2.4 (SD 6.9) mm Hg (p = 0.05 and 0.01, respectively) without group difference (p = 0.48). Forty-four (44) in the relaxation response group and 36 in the control group were eligible for supervised antihypertensive medication elimination. After controlling for differences in characteristics at the start of medication elimination, patients in the relaxation response group were more likely to successfully eliminate an antihypertensive medication (odds ratio 4.3, 95% confidence interval 1.2-15.9, p = 0.03). Although both groups had similar reductions in SBP, significantly more participants in the relaxation response group eliminated an antihypertensive medication while maintaining adequate blood pressure control. C1 [Buczynski, Beverly; Zusman, Randall M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Sect Hypertens & Vasc Med,Cardiol Div,Med Serv, Boston, MA 02114 USA. [Dusek, Jeffery A.; Hibberd, Patricia L.; Chang, Bei-Hung; Dusek, Kathryn C.; Johnston, Jennifer M.; Wohlhueter, Ann L.; Benson, Herbert] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Dusek, Jeffery A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Dusek, Jeffery A.; Dusek, Kathryn C.; Johnston, Jennifer M.; Wohlhueter, Ann L.; Benson, Herbert] Mind Body Med Inst, Chestnut Hill, MA USA. [Hibberd, Patricia L.; Benson, Herbert] Tufts Univ, Sch Med, Dept Publ Hlth & Family Med, Boston, MA 02111 USA. [Chang, Bei-Hung] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Zusman, RM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Sect Hypertens & Vasc Med,Cardiol Div,Med Serv, 55 Fruit St,Yawkey Ctr 5B-5800, Boston, MA 02114 USA. EM rzusman@partners.org OI Dusek, Jeffery/0000-0001-9581-0564 FU NCCDPHP CDC HHS [R01 DP000339]; NCCIH NIH HHS [K24AT003683]; PHS HHS [H75/CCH 123424, H75/CCH 19124] NR 33 TC 27 Z9 29 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD MAR PY 2008 VL 14 IS 2 BP 129 EP 138 DI 10.1089/acm.2007.0623 PG 10 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 282PU UT WOS:000254580500006 PM 18315510 ER PT J AU Darouiche, RO Mansouri, MD Gawande, PV Madhyastha, S AF Darouiche, Rabih O. Mansouri, Mohammad D. Gawande, Purushottam V. Madhyastha, Srinivasa TI Efficacy of combination of chlorhexidine and protamine sulphate against device-associated pathogens SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE device-related infections; antimicrobial activity; Escherichia coli ID STAPHYLOCOCCUS-AUREUS; SURGICAL IMPLANTS; BIOFILM FORMATION; URINARY CATHETER; CONTROLLED TRIAL; IN-VIVO; INFECTIONS; INHIBITION; BACTERIA; CELLS AB Objectives: The objectives of this study were to examine: (i) the potential in vitro synergy of combining protamine sulphate (PS) with chlorhexidine (CHX); (ii) the in vitro spectrum and durability of antimicrobial activity of CHX + PS-coated catheters; and (iii) the in vivo efficacy of CHX + PS-coated catheters in comparison with silver-hydrogel-coated and uncoated catheters. Methods: The potential synergistic antimicrobial and antibiofilm activities of CHX and PS were investigated in vitro by the MIC and biofilm assays. The spectrum and durability of antimicrobial activity of CHX + PS-coated catheters were studied in vitro by using a serial plate transfer method. The in vivo efficacy of CHX + PS-coated catheters was assessed in a rabbit model against Escherichia coli. Results: In vitro studies showed that the combination of CHX + PS has a synergistic inhibitory effect on E. coli and provides a significant synergistic antibiofilm and antimicrobial activity against E. coli, Pseudomonas aeruginosa and Staphylococcus epidermidis. Furthermore, catheters coated with CHX + PS provided a broad-spectrum and enduring in vitro antimicrobial activity over a 10 day period. The in vivo efficacy study demonstrated that subcutaneously implanted CHX + PS-coated catheters in rabbits are significantly less likely to become colonized (2/28 = 7%) than either silver-hydrogel-coated (25/28 = 89%; P < 0.001) or uncoated catheters (18/28 = 64%; P < 0.001) by E. coli. Conclusions: The synergistic, broad-spectrum and durable in vitro activity of the CHX + PS combination and the robust in vivo efficacy of catheters coated with this unique composition encourage clinical evaluation of this innovative approach. C1 [Darouiche, Rabih O.; Mansouri, Mohammad D.] Michael E Debakey Vet Affairs Med Ctr, Ctr Prostheses Infect & Infect Dis Sect, Houston, TX 77030 USA. [Darouiche, Rabih O.; Mansouri, Mohammad D.] Baylor Coll Med, Houston, TX 77030 USA. [Gawande, Purushottam V.; Madhyastha, Srinivasa] Kane Biotech Inc, Winnipeg, MB R3T 6C6, Canada. RP Darouiche, RO (reprint author), Michael E Debakey Vet Affairs Med Ctr, Ctr Prostheses Infect & Infect Dis Sect, Houston, TX 77030 USA. EM rdarouiche@aol.com RI Gawande, Purushottam/C-5487-2014 OI Gawande, Purushottam/0000-0001-8675-9293 NR 37 TC 35 Z9 35 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAR PY 2008 VL 61 IS 3 BP 651 EP 657 DI 10.1093/jac/dkn006 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 267DX UT WOS:000253490800028 PM 18258612 ER PT J AU Haller, J Hyde, D Deliolanis, N de Kleine, R Niedre, M Ntziachristos, V AF Haller, Jodi Hyde, Damon Deliolanis, Nikolaos de Kleine, Ruben Niedre, Mark Ntziachristos, Vasilis TI Visualization of pulmonary inflammation using noninvasive fluorescence molecular imaging SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE in vivo small animal imaging; molecular tomography; cysteine proteases ID POSITRON-EMISSION-TOMOGRAPHY; LYSOSOMAL CYSTEINE PROTEASES; INDUCED LUNG INJURY; TRANSGENE EXPRESSION; EPITHELIAL-CELLS; GENE-EXPRESSION; EMERGING ROLES; MONOMERIC RED; SMALL ANIMALS; IN-VIVO AB The ability to visualize molecular processes and cellular regulators of complex pulmonary diseases such as asthma, chronic obstructive pulmonary disease ( COPD), or adult respiratory distress syndrome ( ARDS), would aid in the diagnosis, differentiation, therapy assessment and in small animal-based drug-discovery processes. Herein we report the application of normalized transillumination and fluorescence molecular tomography (FMT) for the noninvasive quantitative imaging of the mouse lung in vivo. We demonstrate the ability to visualize and quantitate pulmonary response in a murine model of LPS-induced airway inflammation. Twenty-four hours prior to imaging, BALB/c female mice were injected via tail vein with 2 nmol of a cathepsin-sensitive activatable fluorescent probe ( excitation: 750 nm; emission: 780 nm) and 2 nmol of accompanying intravascular agent ( excitation: 674 nm; emission: 694 nm). Six hours later, the mice were anesthetized with isoflurane and administered intranasal LPS in sterile 0.9% saline in 25 mu l aliquots ( one per nostril). Fluorescence molecular imaging revealed the in vivo profile of cysteine protease activation and vascular distribution within the lung typifying the inflammatory response to LPS insult. Results were correlated with standard in vitro laboratory tests ( Western blot, bronchoalveolar lavage or BAL analysis, immunohistochemistry) and revealed good correlation with the underlying activity. We demonstrated the capacity of fluorescence tomography to noninvasively and longitudinally characterize physiological, cellular, and subcellular processes associated with inflammatory disease burden in the lung. The data presented herein serve to further evince fluorescence molecular imaging as a technology highly appropriate for the biomedical laboratory. C1 [Ntziachristos, Vasilis] Tech Univ Munich, Inst Biol & Med Imaging, D-80333 Munich, Germany. [Ntziachristos, Vasilis] Helmholtz Ctr Munich, D-80333 Munich, Germany. [Haller, Jodi; Hyde, Damon; Deliolanis, Nikolaos; de Kleine, Ruben; Niedre, Mark; Ntziachristos, Vasilis] Massachusetts Gen Hosp, Ctr Mol Imaging Res Lab Bioopt & Mol Imaging, Dept Radiol, Charlestown, MA USA. [Haller, Jodi; Hyde, Damon; Deliolanis, Nikolaos; de Kleine, Ruben; Niedre, Mark; Ntziachristos, Vasilis] Harvard Univ, Sch Med, Charlestown, MA USA. RP Ntziachristos, V (reprint author), Tech Univ Munich, Inst Biol & Med Imaging, Arcisstr 21, D-80333 Munich, Germany. EM v.ntziachristos@tum.de OI Deliolanis, Nikolaos/0000-0002-6392-3035 FU NCI NIH HHS [R33-CA-91807]; NIBIB NIH HHS [R01-EB-00750] NR 50 TC 67 Z9 67 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2008 VL 104 IS 3 BP 795 EP 802 DI 10.1152/japplphysiol.00959.2007 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 271XV UT WOS:000253822900030 PM 18202169 ER PT J AU Kelly, MM Tyrka, AR Anderson, GM Price, LH Carpenter, LL AF Kelly, Megan M. Tyrka, Audrey R. Anderson, George M. Price, Lawrence H. Carpenter, Linda L. TI Sex differences in emotional and physiological responses to the Trier Social Stress Test SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY LA English DT Article DE depression; stress; sex differences; TSST; emotion regulation ID DEPRESSIVE SYMPTOMATOLOGY IDS; GENDER-DIFFERENCES; CORTISOL RESPONSES; PSYCHOSOCIAL STRESS; MAJOR DEPRESSION; NEGATIVE AFFECT; YOUNGER ADULTS; ELDERLY ADULTS; WOMEN; DISORDER AB Women are more likely than men to be diagnosed with depression and anxiety-related disorders, and it has been hypothesized that this difference is related to sex differences in stress reactivity. Women typically report higher levels of negative affect than men in response to psychosocial stressors, but the evidence for sex differences in physiological reactivity to stressful situations is not consistent. The present study sought to expand this work by evaluating sex differences in reactivity to a social stress challenge across neuroendocrine, autonomic and affective response domains. Participants (32 women, 30 men) completed a standardized psychosocial stress challenge (i.e., the Trier Social Stress Test (TSST)), during which several physiological (e.g., cortisol reactivity, heart rate) and psychological (e.g., depression, irritability, anger, fear) measures were assessed. The findings demonstrated that cortisol reactivity and the magnitude of autonomic responding failed to reliably discriminate between women and men. However, women reported more fear, irritability, confusion and less happiness immediately following the TSST compared to men. The broader implications of these results and how they relate to sex differences in the etiology and clinical presentation of anxiety and mood disorders are discussed. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Kelly, Megan M.; Tyrka, Audrey R.; Price, Lawrence H.; Carpenter, Linda L.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Mood Disorders Res Program, Providence, RI 02906 USA. [Anderson, George M.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. RP Kelly, MM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 5, 150 S Huntington Ave, Boston, MA 02130 USA. EM Megan.Kelly@va.gov; Linda_Carpenter_MD@Brown.edu RI Tyrka, Audrey/L-2504-2014 FU NIMH NIH HHS [R01 MH068767] NR 49 TC 93 Z9 98 U1 10 U2 39 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7916 EI 1873-7943 J9 J BEHAV THER EXP PSY JI J. Behav. Ther. Exp. Psychiatry PD MAR PY 2008 VL 39 IS 1 BP 87 EP 98 DI 10.1016/j.jbtep.2007.02.003 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 260GY UT WOS:000253000000008 PM 17466262 ER PT J AU Shin, M Abukawa, H Troulis, MJ Vacanti, JP AF Shin, Michael Abukawa, Harutsugi Troulis, Maria J. Vacanti, Joseph P. TI Development of a biodegradable scaffold with interconnected pores by heat fusion and its application to bone tissue engineering SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE bone tissue engineering; poly(lactide-co-glycolide); interconnected pores; biodegradable scaffold; mesenchymal; stem cells ID MESENCHYMAL STEM-CELLS; IN-VITRO; CULTURE AB Tissue engineering has been proposed as an approach to alleviate the shortage of donor tissue and organs by combining cells and a biodegradable scaffold as a temporary extracellular matrix. While numerous scaffold fabrication methods have been proposed, tissue formation is typically limited to the surface of the scaffolds in bone tissue engineering applications due to early calcification on the surface. To improve tissue formation, a novel scaffold with a hierarchical interconnected pore structure on two distinct length scales has been developed. Here we present the fabrication process and the application of the scaffold to bone tissue engineering. Porous poly(lactide-co-glycolide) (PLGA) scaffolds were made by combining solvent casting/ particulate leaching with heat fusion. Porcine bone marrow-derived mesenchymal stem cells (MSCs) were differentiated into osteoblasts and cultured on these scaffolds in vitro for 2, 4, and 6 weeks. Subsequently, the constructs were assessed using histology and scanning electron microscopy. The bone marrow-derived osteoblasts attached well on these scaffolds. Cells were observed throughout the scaffolds. These initial results show promise for this scaffold to aid in the regeneration of bone. (C) 2007 Wiley Periodicals, Inc. J Biomed Mater Res. C1 [Shin, Michael; Vacanti, Joseph P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Abukawa, Harutsugi; Troulis, Maria J.] Harvard Univ, Sch Dent, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM jvacanti@partners.org NR 19 TC 25 Z9 25 U1 0 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAR 1 PY 2008 VL 84A IS 3 BP 702 EP 709 DI 10.1002/jbm.a.31392 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 260DE UT WOS:000252990200015 PM 17635029 ER PT J AU Sah, AP Estok, DM AF Sah, Alexander P. Estok, Daniel M., II TI Dislocation rate after conversion from hip hemiarthroplasty to total hip arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID REVISION TOTAL HIP; UNITED-STATES; FEMORAL-NECK; BIPOLAR HEMIARTHROPLASTY; INTRACAPSULAR FRACTURES; FAILED HEMIARTHROPLASTY; ACETABULAR COMPONENT; INDEPENDENT PATIENTS; CONTROLLED-TRIAL; SURGICAL VOLUME AB Background: Revision hip arthroplasty is associated with a dislocation rate that is three to five times greater than the rate following primary hip replacement. Conversion of a hip hemiarthroplasty to a total hip replacement is a revision arthroplasty, but it differs from revisions of total hip arthroplasties because a native acetabulum is replaced and the subsequent prosthetic femoral head is smaller. It was our purpose to determine whether the risk of dislocation following conversion surgery is the same as or greater than that following revision total hip replacement. Methods: From 1994 to 2005, eighty-nine hemiarthroplasties were converted to a total hip arthroplasty in seventy-seven patients, and the results were compared with those of 115 first-time revision total hip replacements following a primary total hip replacement in 111 patients. A retrospective chart review was performed, and radiographic measurements were obtained. The patient demographics were similar between the two groups. The percentages of patients who had undergone revision of only the acetabular component as compared with both components as well as the percentages of those who had received a modular femoral stem as compared with a nonmodular stem were also similar between the two groups. Results: Postoperatively, the femoral head size and the positioning of the acetabular component were similar between the two groups. The acetabular components were significantly larger (p < 0.001) in the group in which a total hip arthroplasty had been revised because they required additional acetabular reaming for placement of a new component. There were significantly more dislocations after the conversion procedures (22%) than after the revisions of the total hip arthroplasties (10%) (p < 0.018). Within both groups, the size of the acetabular component, the intraoperative range of motion, and the positioning of the acetabular component were similar between the hips that dislocated and those that did not. However, smaller femoral head components were at greater risk for dislocation after conversion surgery than after revision of a total hip arthroplasty. Conclusions: A substantial reduction of the size of the prosthetic femoral head is unique to conversion arthroplasty and appears to play a role in instability after the revision surgery. While the smallest heads dislocated in the conversion group, a larger femoral head did not ensure stability. The increased dislocation risk with conversion surgery requires emphasis on soft-tissue balance and avoidance of excessive downsizing of the femoral head in an attempt to maximize hip stability. C1 [Sah, Alexander P.; Estok, Daniel M., II] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Sah, AP (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, 55 Fruit St,WHT 535, Boston, MA 02114 USA. EM asah07@gmail.com NR 47 TC 25 Z9 31 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2008 VL 90A IS 3 BP 506 EP 516 DI 10.2106/JBJS.G.00479 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 273QJ UT WOS:000253946500007 PM 18310700 ER PT J AU Okike, K Kocher, MS Mehlman, CT Heckman, JD Bhandari, M AF Okike, Kanu Kocher, Mininder S. Mehlman, Charles T. Heckman, James D. Bhandari, Mohit TI Publication bias in orthopedic research: An analysis of scientific factors associated with publication in the journal of bone and joint surgery (American volume) SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID CLINICAL-TRIALS; ABSTRACTS; PRESENTATIONS; PUBLISH AB Background: Positive outcomes are common in the orthopaedic literature, and there are many who believe it may be due to the preferential publication of studies with positive findings-a phenomenon known as publication bias. The purpose of this investigation was to determine whether positive findings rendered a manuscript submitted to The Journal of Bone and Joint Surgery (American Volume) more likely to be accepted for publication. Methods: A total of 1181 manuscripts submitted to The Journal of Bone and Joint Surgery between January 1, 2004, and June 30, 2005, for publication as scientific articles were analyzed, with 855 meeting the inclusion criteria. The direction of the study findings (positive, neutral, or negative) was independently graded by three blinded reviewers. The final disposition (acceptance or rejection) was recorded, as was information on the scientific characteristics plausibly related to acceptance or rejection. Logistic regression was used to identify factors associated with acceptance for publication. Results: The overall acceptance rate was 21.8% (186 of 855 studies). The study outcome was positive for 72.5% (620) of the manuscripts. The acceptance rate for the 235 manuscripts with nonpositive findings was 23.0% (fifty-four studies) compared with 21.3% (132) of the 620 studies with positive findings (crude odds ratio, 1.10 [95% confidence interval, 0.77 to 1.58]; p = 0.593). After controlling for all covariates, the adjusted odds ratio was 0.92 (95% confidence interval, 0.62 to 1.35; p = 0.652). In the multivariate analysis, the only factor significantly associated with acceptance for publication was level of evidence (p = 0.001). Conclusions: We found no evidence of publication bias in the review of manuscripts for publication by The Journal of Bone and Joint Surgery, as positive and nonpositive studies were accepted at similar rates. The dearth of nonpositive studies in the orthopaedic literature is of concern, and may be due largely to investigator-based factors. Orthopaedic researchers should submit negative and neutral studies for publication, confident that the likelihood of acceptance will not be influenced by the direction of study findings. C1 Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Hamilton Gen Hosp, Hamilton, ON, Canada. RP Okike, K (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM okike@post.harvard.edu OI Okike, Kanu/0000-0001-9310-9969 NR 34 TC 45 Z9 45 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 MAR PY 2008 VL 90A IS 3 BP 595 EP 601 DI 10.2106/JBJS.G.00279 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 273QJ UT WOS:000253946500017 PM 18310710 ER PT J AU Zhang, Q Carter, EA Ma, BY Fischman, AJ Tompkins, RG AF Zhang, Qin Carter, Edward A. Ma, Bangyi Fischman, Alan J. Tompkins, Ronald G. TI Burn-related metabolic and signaling changes in rat brain SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Burn-Association CY MAY 10-13, 2005 CL Chicago, IL SP Amer Burn Assoc ID ACTIVATED PROTEIN-KINASE; INSULIN-RESISTANCE; THERMAL-INJURY; P38; STRESS; EXPRESSION; PATHWAY; TRAUMA; JNK; PHOSPHORYLATION AB Postburn alterations in the morphology and metabolism of brain tissue have been previously reported. It was demonstrated in our previous study that thermal injury decreased glucose usage in rat brain during the ebb phase. The cellular and molecular signaling events that trigger the pathophysiologic alterations, however, have not yet been characterized. In the present report, the authors have examined the effect of burn injury on mitogen-activated protein kinases (MAPKs) activities and insulin signaling in the brain tissue. Rats were subjected to 50% total body surface area full thickness scald injury. Brain samples were collected at 6 hours after injury. Tissue lysates were analyzed for MAPKs activities, insulin receptor substrate (IRS)-1 expression, and Akt activity which were determined by western blot and immunoprecipitation. Burn injury stimulated the stress-responsive components, SAPK/JNK, p38 MAP kinase and p44/42 MAP kinase, and increased IRS-1 expression and Akt activity. There was no change, however, on the phosphorylation of Ser307 of IRS-1 in brain tissue. The present data is consistent with the hypothesis that activation of the three major MAPKs pathways appears to be events involved in the mechanisms of burn injury induced insulin resistance and encephalopathy. Changes in signal transduction pathways in the brain after burn injury provide the underlying molecular mechanism of neurologic abnormalities (burn encephalopathy) that occur in burn patients. C1 [Carter, Edward A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Zhang, Qin; Ma, Bangyi; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Fischman, Alan J.] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Dept Pediat, 51 Blossom St, Boston, MA 02114 USA. FU NIGMS NIH HHS [2 P50 GM 21700-27A1] NR 30 TC 7 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2008 VL 29 IS 2 BP 346 EP 352 DI 10.1097/BCR.0b013e3181667387 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 280EQ UT WOS:000254408500011 PM 18354292 ER PT J AU Zhang, Q Ma, BY Fischman, AJ Tompkins, RG Carter, EA AF Zhang, Qin Ma, Bangyi Fischman, Alan J. Tompkins, Ronald G. Carter, Edward A. TI Increased uncoupling protein 1 mRNA expression in mice brown adipose tissue after burn injury SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Burn-Association CY APR 04-07, 2006 CL Las Vegas, NV SP Amer Burn Assoc ID ENERGY-EXPENDITURE; INSULIN-RESISTANCE; ADIPOCYTES; METABOLISM; MOUSE AB Brown adipose tissue (BAT) contains numerous mitochondria and is characterized by the presence of uncoupling protein 1 (UCP1). UCP1 is the main mediator of thermogenesis that plays an important role in the modulation of energy balance. The authors hypothesize that alterations in the expression of UCP1 might be involved in the major metabolic disorders occurring during burn trauma. The present study is designed to explore the potential role of the UCP1 in metabolic disorders after burn injury. The authors have used the real-time reverse transcription-polymerase chain reaction to quantify UCP1 mRNA expression in the mice BAT and white adipose tissue (WAT). UCP1 mRNA expression was up-regulated in BAT, especially at 24 hours after burn. UCP1 m1RNA expression was detectable and also up-regulated by burn injury in WAT. The authors provide evidence that one of the mechanisms mediating hypermetabolism and increased energy expenditure in burn injury is a pronounced increase in thermogenic capacity, as illustrated by robust gene expression of UCP1 in BAT and WAT. C1 [Zhang, Qin; Ma, Bangyi; Tompkins, Ronald G.; Carter, Edward A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ma, Bangyi] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. [Carter, Edward A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Dept Surg, 51 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [P30 DK040561-12, P30 DK040561]; NIGMS NIH HHS [2 P50 GM 21700-27A1] NR 26 TC 5 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2008 VL 29 IS 2 BP 358 EP 362 DI 10.1097/BCR.0b013c318166739c PG 5 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 280EQ UT WOS:000254408500013 PM 18354294 ER PT J AU Das, S Neuzil, P Albert, CM D'Avila, A Mansour, M Mela, T Ellinor, PT Singh, J Patton, K Ruskin, JN Reddy, VY AF Das, Saumya Neuzil, Petr Albert, Christine M. D'Avila, Andre Mansour, Moussa Mela, Theofanie Ellinor, Patrick T. Singh, Jagmeet Patton, Kristen Ruskin, Jeremy N. Reddy, Vivek Y. TI Catheter ablation of Peri-AV nodal atrial tachycardia from the noncoronary cusp of the aortic valve SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE catheter ablation; electrophysiology; mapping; atrial tachycardia; cryoablation; aortic valve cusp ID LONG-TERM OUTCOMES; ELECTROPHYSIOLOGICAL CHARACTERISTICS; RADIOFREQUENCY ABLATION; VENTRICULAR-TACHYCARDIA; MITRAL ANNULUS; CORONARY-SINUS; JUNCTION AB Catheter Ablation of AT from the Noncoronary AV Cusp. Introduction: Atrial tachycardias (AT) originating from the anteroseptal region of the aortic root, near the atrioventricular node can be challenging to eliminate safely by catheter ablation. In this study, we examine the characteristics of anteroseptal ATs in a cohort of patients at our centers, and demonstrate the long-term efficacy and safety of targeting the arrhythmias from within the base of the noncoronary aortic valve cusp (NCC). Methods & Results: From among a cohort of 54 patients with symptomatic focal AT undergoing invasive electrophysiological evaluation, the point of earliest right atrial (RA) activation was at the peri-AV nodal region in 10 patients, just postero-superior to the His-bundle. Before further mapping, RA lesions placed in two patients were unsuccessful in eliminating the arrhythmia. Because of its proximity to the interatrial septum, the base of the NCC was mapped using a retrograde aortic approach, and revealed a point of early activation without the presence of a His potential. The arrhythmia terminated with <10 seconds of radiofrequency or cryothermal energy delivery and was successfully eliminated in 7 of 10 patients. Transient termination or acceleration of the AT was noted in the other three patients, prompting successful ablation from a left atrial septal position or a reattempt from a para-Hisian RA position. All patients have been arrhythmia free during follow-up (41 +/- 12 months). Conclusions: Catheter ablation from within the base of the NCC represents a safe and effective means to eliminate focal AT arising from the peri-AV nodal region. C1 [Das, Saumya; D'Avila, Andre; Mansour, Moussa; Mela, Theofanie; Ellinor, Patrick T.; Singh, Jagmeet; Ruskin, Jeremy N.; Reddy, Vivek Y.] Harvard Univ, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Das, Saumya; D'Avila, Andre; Mansour, Moussa; Mela, Theofanie; Ellinor, Patrick T.; Singh, Jagmeet; Ruskin, Jeremy N.; Reddy, Vivek Y.] Harvard Univ, Sch Med, Boston, MA USA. [Albert, Christine M.] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [Patton, Kristen] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Neuzil, Petr] Na Homolce Hosp, Div Cardiol, Electrophysiol Sect, Prague, Czech Republic. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009; OI d'Avila, Andre Luiz/0000-0001-8769-1411; Patton, Kristen K./0000-0002-9034-6966 FU NHLBI NIH HHS [K23 HL68064-02] NR 20 TC 32 Z9 33 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAR PY 2008 VL 19 IS 3 BP 231 EP 237 DI 10.1111/j.1540-8167.2007.01024.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 267AC UT WOS:000253479200001 PM 18031512 ER PT J AU Thiagalingam, A Manzke, R D'Avila, A Ho, I Locke, AH Ruskin, JN Chan, RC Reddy, VY AF Thiagalingam, Aravinda Manzke, Robert D'Avila, Andre Ho, Ivan Locke, Andrew H. Ruskin, Jeremy N. Chan, Raymond C. Reddy, Vivek Y. TI Intraprocedural volume imaging of the left atrium and pulmonary veins with rotational x-ray angiography: Implications for catheter ablation of atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE catheter ablation; atrial fibrillation; imaging; electrophysiology; mapping ID CORONARY-ANGIOGRAPHY; COMPLICATIONS; INTEGRATION; ALGORITHM; IMAGES; SYSTEM AB 3-D Anatomy by Rotational X-Ray Angiography. Introduction: The use of preprocedural CT or MR imaging to generate patient-specific cardiac anatomy greatly facilitates catheter ablation of the left atrium and pulmonary veins (LA-PVs) to treat atrial fibrillation (AF). This report details the accuracy and utility of an intraprocedural means to generate 3-D volumetric renderings of the LA-PV anatomy: contrast-enhanced rotational X-ray angiography (3DRA). Methods and Results: Preprocedural CT or MR imaging and intraprocedural rotational angiography was performed in 42 patients undergoing AF ablation procedures. Initially, pulmonary artery (PA) bolus-chase contrast injections were performed (20 mL, 20 mL/s) to establish pulmonary transit time and cardiac isocentering. Depending on cardiac size, either a single PA injection (80-100 mL, 20 mL/s) or two separate dedicated left/right PA branch injections were performed (60 mL each, 20 mL/s). For the latter, the two volumes of the left/right portions of the LA-PVs were registered and fused. LA-PV 3DRA images were assessed qualitatively and quantitatively in comparison with CT/MR images. The majority of the 3DRA acquisitions (71%) were deemed at least "useful" in delineating the LA-PV anatomy. The LA appendage was delineated in 57% of the cases. A blinded quantitative comparison of PV ostial diameters resulted in an absolute difference of only 2.7 +/- 2.3 mm, 2.2 +/- 1.8 mm, 2.4 +/- 2.2 mm, and 2.2 +/- 2.3 mm for the left-superior, left-inferior, right-superior, and right-inferior PVs, respectively. The feasibility for registering the 3DRA image with real-time electroanatomical mapping was also demonstrated. Conclusion: Intraprocedural contrast-enhanced rotational angiography provides volumetric 3-D images of the LA-PVs of comparable diagnostic value to dedicated preprocedural CT/MR imaging. C1 [Thiagalingam, Aravinda; D'Avila, Andre; Ho, Ivan; Locke, Andrew H.; Ruskin, Jeremy N.; Reddy, Vivek Y.] Harvard Univ, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiac Electrophysiol Dept, Boston, MA 02114 USA. [Manzke, Robert; Chan, Raymond C.] Philips Res N Amer, New York, NY USA. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiac Electrophysiol Dept, 55 Fruit St,GRB-109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; FU NHLBI NIH HHS [K23 HL68064] NR 16 TC 55 Z9 55 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAR PY 2008 VL 19 IS 3 BP 293 EP 300 DI 10.1111/j.1540-8167.2007.01013.x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 267AC UT WOS:000253479200012 PM 18005027 ER PT J AU Reddy, VY Neuzil, P D'Avila, A Ruskin, JN AF Reddy, Vivek Y. Neuzil, Petr D'Avila, Andre Ruskin, Jeremy N. TI Isolating the posterior left atrium and pulmonary veins with a "Box" lesion set: Use of epicardial ablation to complete electrical isolation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; epicardial mapping; pulmonary vein; catheter ablation; radiofrequency; pericardium ID FIBRILLATION; ANATOMY; IMPACT AB Epi-Endo Box Lesion for AF. Similar to the surgical mini-maze procedure, the posterior "box" lesion set employs linear ablation lesions along the anterior aspects of both sets of PVs connected by a roof line and an inferior line to electrically isolate the PVs and complete posterior LA wall en masse. However, creating fully transmural linear atrial lesions can be difficult to achieve, even with an irrigated ablation catheter. This report details a case wherein a combined endocardial and epicardial approach was required to create an electrically continuous posterior box lesion in a patient with persistent AF. C1 [Reddy, Vivek Y.; D'Avila, Andre; Ruskin, Jeremy N.] Harvard Univ, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Sch Med, Boston, MA 02114 USA. [Neuzil, Petr] Na Homolce Hosp, Div Cardiol, Electrophysiol Sect, Prague, Czech Republic. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Sch Med, 55 Fruit St,Gray-Bigelow 109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 11 TC 10 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAR PY 2008 VL 19 IS 3 BP 326 EP 329 DI 10.1111/j.1540-8167.2007.00944.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 267AC UT WOS:000253479200018 PM 17887980 ER PT J AU Whalen, MJ Dalkara, T You, ZR Qiu, JH Bermpohl, D Mehta, N Suter, B Bhide, PG Lo, EH Ericsson, M Moskowitz, MA AF Whalen, Michael J. Dalkara, Turgay You, Zerong Qiu, Jianhua Bermpohl, Daniela Mehta, Niyati Suter, Bernhard Bhide, Pradeep G. Lo, Eng H. Ericsson, Maria Moskowitz, Michael A. TI Acute plasmalemma permeability and protracted clearance of injured cells after controlled cortical impact in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; mice; necrosis; plasmalemma; propidium iodide; traumatic brain injury ID TRAUMATIC BRAIN-INJURY; DEATH MECHANISMS; HEAD-INJURY; RATS; INHIBITOR; APOPTOSIS; NECROSIS; CULTURES; NEURONS; MOUSE AB Cell death after traumatic brain injury (TBI) evolves over days to weeks. Despite advances in understanding biochemical mechanisms that contribute to posttraumatic brain cell death, the time course of cell injury, death, and removal remains incompletely characterized in experimental TBI models. In a mouse controlled cortical impact (CCI) model, plasmalemma permeability to propidium iodide (PI) was an early and persistent feature of posttraumatic cellular injury in cortex and hippocampus. In cortical and hippocampal brain regions known to be vulnerable to traumatic cell death, the number of PI + cells peaked early after CCI, and increased with increasing injury severity in hippocampus but not cortex (P < 0.05). Propidium iodide labeling correlated strongly with hematoxylin and eosin staining in injured cells (r = 0.99, P < 0.001), suggesting that plasmalemma damage portends fatal cellular injury. Using PI pulse labeling to identify and follow the fate of a cohort of injured cells, we found that many PI + cells recovered plasmalemma integrity by 24 h and were terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling negative, but nonetheless disappeared from injured brain by 7 days. Propidium iodide-positive cells in dentate gyrus showed significant ultrastructural damage, including plasmalemma and nuclear membrane damage or overt membrane loss, in all cells when examined by laser capture microdissection and transmission electron microscopy 1 to 24 h after CCI. The data suggest that plasmalemma damage is a fundamental marker of cellular injury after CCI; some injured cells might have an extended window for potential rescue by neuroprotective strategies. C1 [Whalen, Michael J.; Dalkara, Turgay; You, Zerong; Qiu, Jianhua; Bermpohl, Daniela; Mehta, Niyati; Suter, Bernhard; Bhide, Pradeep G.; Lo, Eng H.; Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Ctr Neurosci, Charlestown, MA 02129 USA. [Whalen, Michael J.; You, Zerong] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. [Whalen, Michael J.; Qiu, Jianhua; Bermpohl, Daniela; Lo, Eng H.; Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Suter, Bernhard; Bhide, Pradeep G.; Lo, Eng H.; Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Ericsson, Maria] Harvard Univ, Sch Med, Electron Microscopy Facil, Boston, MA USA. RP Whalen, MJ (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Ctr Neurosci, 149 13th St, Charlestown, MA 02129 USA. EM MWhalen@Partners.org RI Moskowitz, Michael/D-9916-2011; OI Bhide, Pradeep/0000-0003-4236-9415 FU NIDA NIH HHS [R01 DA020796-03, R01 DA020796]; NINDS NIH HHS [P30 NS 45776, P30 NS045776, P30 NS045776-06A17807, R01 NS 047447, R01 NS 37074, R01 NS 53560, R01 NS037074, R01 NS043426, R01 NS043426-05, R01 NS047447, R01 NS047447-03, R01 NS053560] NR 34 TC 48 Z9 48 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2008 VL 28 IS 3 BP 490 EP 505 DI 10.1038/sj.jcbfm.9600544 PG 16 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 266DA UT WOS:000253410400007 PM 17713463 ER PT J AU Pitteloud, N Dwyer, AA DeCruz, S Lee, H Boepple, PA Crowley, WF Hayes, FJ AF Pitteloud, Nelly Dwyer, Andrew A. DeCruz, Suzzunne Lee, Hang Boepple, Paul A. Crowley, William F., Jr. Hayes, Frances J. TI Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: Evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SEX STEROID CONTROL; FREE ALPHA-SUBUNIT; NEGATIVE FEEDBACK; CLOMIPHENE CITRATE; ESTRADIOL; ESTROGEN; ANDROGEN; AROMATASE; KETOCONAZOLE; LEVEL AB Context: Studies on the regulation of LH secretion by sex steroids in men are conflicting. Objective: Our aims were to determine the relative contributions of testosterone (T) and estradiol (E-2) to LH regulation and localize their sites of negative feedback. Design: This was a prospective study with three arms. Setting: The study was conducted at a General Clinical Research Center. Patients or Other Participants: Twenty-two normal (NL) men and 11 men with GnRH deficiency due to idiopathic hypogonadotropic hypogonadism (IHH) participated. Intervention: Medical castration and inhibition of aromatase were achieved using high-dose ketoconazole (KC) for 7 d with 1) no sex steroid add-back; 2) T enanthate 125 mg im starting on d 4; or 3) E2 patch 37.5 mu g/d starting on d4. Blood sampling was performed every 10 min for 12 h at baseline, overnight on d 3-4 and d 6-7. Main Outcome Measures: Mean LH levels, LH pulse amplitude, and GnRH pulse frequency were assessed at baseline, d 3-4, and d 6-7. Results: In NL men, KC caused a 3-fold increase in mean LH on d 3-4, which was stable on d 6-7 with no add-back. Addition of T reduced LH levels (34.6 +/- 3.9 to 17.4 +/- 3.6 IU/liter, P < 0.05) by slowing GnRH pulse frequency ( 13.3 +/- 0.4 to 6.7 +/- 1.0 pulses/12 h, P < 0.005). LH amplitude increased (6.9 +/- 1.0 to 12.1 +/- 1.4 IU/liter, P < 0.005). E2 add- back suppressed LH levels (36.4 +/- 5.6 to 19.0 +/- 2.4 IU/liter, P < 0.005), by slowing GnRH pulse frequency (11.4 +/- 0.2 to 8.6 +/- 0.4 pulses/ 12 h, P < 0.05) and had no impact on LH pulse amplitude. In IHH men, restoring normal T levels caused no suppression of mean LH levels or LH amplitude. E-2 add- back normalized mean LH levels and decreased LH amplitude from 14.7 +/- 1.7 to 12 +/- 1.5 IU/liter (P < 0.05). Conclusions: 1) T and E-2 have independent effects on LH. 2) Inhibition of LH by T requires aromatization for its pituitary, but not hypothalamic effects. 3) E-2 negative feedback on LH occurs at the hypothalamus. C1 [Pitteloud, Nelly; Dwyer, Andrew A.; DeCruz, Suzzunne; Boepple, Paul A.; Crowley, William F., Jr.; Hayes, Frances J.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM Hayes.Frances@MGH.Harvard.edu RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NICHD NIH HHS [R01 HD015788, R01 HD15788-15, U54 HD028138]; NIDDK NIH HHS [DK07028-24, T32 DK007028] NR 33 TC 45 Z9 46 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 MAR PY 2008 VL 93 IS 3 BP 784 EP 791 DI 10.1210/jc.2007-2156 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271XT UT WOS:000253822700022 PM 18073301 ER PT J AU Finkelstein, JS Brockwell, SE Mehta, V Greendale, GA Sowers, MR Ettinger, B Lo, JC Johnston, JM Cauley, JA Danielson, ME Neer, RM AF Finkelstein, Joel S. Brockwell, Sarah E. Mehta, Vinay Greendale, Gail A. Sowers, MaryFran R. Ettinger, Bruce Lo, Joan C. Johnston, Janet M. Cauley, Jane A. Danielson, Michelle E. Neer, Robert M. TI Bone mineral density changes during the menopause transition in a multiethnic cohort of women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HIP FRACTURE INCIDENCE; X-RAY ABSORPTIOMETRY; QUANTITATIVE COMPUTED-TOMOGRAPHY; EARLY PERIMENOPAUSAL WOMEN; DIFFERENT SKELETAL SITES; HEALTHY JAPANESE WOMEN; LIFE-STYLE FACTORS; RACIAL-DIFFERENCES; PROXIMAL FEMUR; SEX STEROIDS AB Context: Rates of bone loss across the menopause transition and factors associated with variation in menopausal bone loss are poorly understood. Objective: Our objective was to assess rates of bone loss at each stage of the transition and examine major factors that modify those rates. Design, Setting, and Participants: We conducted a longitudinal cohort study of 1902 African-American, Caucasian, Chinese, or Japanese women participating in The Study of Women's Health Across the Nation. Women were pre- or early perimenopausal at baseline. Outcome Measure: We assessed bone mineral density (BMD) of the lumbar spine and total hip across a maximum of six annual visits. Results: There was little change in BMD during the pre- or early perimenopause. BMD declined substantially in the late perimenopause, with an average loss of 0.018 and 0.010 g/cm(2) center dot yr from the spine and hip, respectively (P < 0.001 for both). In the postmenopause, rates of loss from the spine and hip were 0.022 and 0.013 g/cm(2) center dot yr, respectively (P < 0.001 for both). During the late peri- and postmenopause, bone loss was approximately 35-55% slower in women in the top vs. the bottom tertile of body weight. Apparent ethnic differences in rates of spine bone loss were largely explained by differences in body weight. Conclusions: Bone loss accelerates substantially in the late perimenopause and continues at a similar pace in the first postmenopausal years. Body weight is a major determinant of the rate of menopausal BMD loss, whereas ethnicity, per se, is not. Healthcare providers should consider this information when deciding when to screen women for osteoporosis. C1 [Finkelstein, Joel S.; Neer, Robert M.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Brockwell, Sarah E.; Mehta, Vinay; Johnston, Janet M.; Cauley, Jane A.; Danielson, Michelle E.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Greendale, Gail A.] Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Sowers, MaryFran R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Sowers, MaryFran R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Ettinger, Bruce; Lo, Joan C.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Thier 1051,50 Blosson St, Boston, MA 02114 USA. EM jfinkelstein@partners.org RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [AG012495, AG012505, AG012531, AG012535, AG012539, AG012546, AG012553, AG012554, U01 AG012495, U01 AG012505, U01 AG012531, U01 AG012535, U01 AG012539, U01 AG012546, U01 AG012553, U01 AG012554]; NIDDK NIH HHS [K24 DK002759, K24 DK02759]; NINR NIH HHS [NR004061, U01 NR004061] NR 62 TC 150 Z9 160 U1 3 U2 17 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 MAR PY 2008 VL 93 IS 3 BP 861 EP 868 DI 10.1210/jc.2007-1876 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271XT UT WOS:000253822700032 PM 18160467 ER PT J AU Kratz, M Purnell, JQ Breen, PA Thomas, KK Utzschneider, KM Carr, DB Kahn, SE Hughes, JP Rutledge, EA Van Yserloo, B Yukawa, M Weigle, DS AF Kratz, Mario Purnell, Jonathan Q. Breen, Patricia A. Thomas, Katherine K. Utzschneider, Kristina M. Carr, Darcy B. Kahn, Steven E. Hughes, James P. Rutledge, Elizabeth A. Van Yserloo, Brian Yukawa, Michi Weigle, David S. TI Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV PROTEASE INHIBITORS; INSULIN-RESISTANCE; INFECTED PATIENTS; FAT DISTRIBUTION; LIPODYSTROPHY; DIFFERENTIATION; SENSITIVITY; ADIPOCYTES; RITONAVIR AB Context: The expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy. Objective: The objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy. Design: This was a prospective longitudinal study. Setting: The study was conducted at HIV clinics in Seattle, Washington. Participants: The study population included 31 HIV-infected and 12 control subjects. Interventions: Subjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen. Main Outcome Measures: Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue. Results: Subjects who developed lipoatrophy (n = 10) had elevated fasting triglycerides [3.16 (SD 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (SD 1.27) X 10(-4) min(-1)/mu U center dot ml] after 12 months, whereas those without lipoatrophy (n = 21) did not show any metabolic complications [triglycerides 1.32 (SD 0.58) mmol/liter, P = 0.01 vs. lipoatrophy; insulin sensitivity 3.52 (SD 1.91) X 10(-4) min(-1)/mu U center dot ml, P = 0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident. Conclusions: In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation. C1 [Kratz, Mario; Breen, Patricia A.; Utzschneider, Kristina M.; Kahn, Steven E.; Weigle, David S.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98109 USA. [Thomas, Katherine K.] Univ Washington, Dept Allergy & Infect Dis, Seattle, WA 98109 USA. [Carr, Darcy B.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98109 USA. [Yukawa, Michi] Univ Washington, Dept Gerontol & Geriat Med, Seattle, WA 98109 USA. [Rutledge, Elizabeth A.; Van Yserloo, Brian] Vet Affairs Puget Sound Hlth Care Syst, Dept Biostat, Diabet Endocrinol Res Ctr, Seattle, WA 98108 USA. [Purnell, Jonathan Q.] Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. RP Kratz, M (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Mail Stop M4-B402,1100 Fairview Ave N, Seattle, WA 98109 USA. EM mkratz@fhcrc.org OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [M01-RR-00037, M01 RR000037]; NIDDK NIH HHS [1 K24 DK02860, 1 R01 DK55460, 5-P30-DK17047, K24 DK002860, P30 DK017047, P30 DK035816, P30-DK035816, R01 DK055460] NR 26 TC 12 Z9 12 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 MAR PY 2008 VL 93 IS 3 BP 959 EP 966 DI 10.1210/jc.2007-0197 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271XT UT WOS:000253822700048 PM 18089690 ER PT J AU Marselli, L Thorne, J Ahn, YB Omer, A Sgroi, DC Libermann, T Otu, HH Sharma, A Bonner-Weir, S Weir, GC AF Marselli, Lorella Thorne, Jeffrey Ahn, Yu-Bae Omer, Abdulkadir Sgroi, Dennis C. Libermann, Towia Otu, Hasan H. Sharma, Arun Bonner-Weir, Susan Weir, Gordon C. TI Gene expression of purified beta-cell tissue obtained from human pancreas with laser capture microdissection SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ISLET TRANSPLANTATION; INSULIN-SECRETION; APOPTOSIS; PATHWAY; STRESS; AUTOFLUORESCENCE; HYPERGLYCEMIA; PURIFICATION; ANTIOXIDANT; LANGERHANS AB Context: Human beta-cell gene profiling is a powerful tool for understanding beta-cell biology in normal and pathological conditions. Assessment is complicated when isolated islets are studied because of contamination by non-beta-cells and the trauma of the isolation procedure. Objective: The objective was to use laser capture microdissection (LCM) of human beta-cells from pancreases of cadaver donors and compare their gene expression with that of handpicked isolated islets. Design: Endogenous autofluorescence of beta-cells facilitated procurement of purified beta-cell tissue from frozen pancreatic sections with LCM. Gene expression profiles of three microdissected beta-cell samples and three isolated islet preparations were obtained. The array data were normalized using DNA-Chip Analyzer software (Harvard School of Public Health, Boston, MA), and the lower confidence bound evaluated differentially expressed genes. Real-time PCR was performed on selected acinar genes and on the duct cell markers, carbonic anhydrase II and keratin 19. Results: Endogenous autofluorescence facilitates the microdissection of beta-cell rich tissue in human pancreas. When compared with array profiles of purified beta-cell tissue, with lower confidence bound set at 1.2, there were 4560 genes up-regulated and 1226 genes down-regulated in the isolated islets. Among the genes up-regulated in isolated islets were pancreatic acinar and duct genes, chemokine genes, and genes associated with hypoxia, apoptosis, and stress. Quantitative RT-PCR confirmed the differential expression of acinar gene transcripts and the duct marker carbonic anhydrase II in isolated islets. Conclusion: LCM makes it possible to obtain beta-cell enriched tissue from human pancreas sections without the trauma and ischemia of islet isolation. C1 [Marselli, Lorella; Thorne, Jeffrey; Ahn, Yu-Bae; Omer, Abdulkadir; Sharma, Arun; Bonner-Weir, Susan; Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Marselli, Lorella; Thorne, Jeffrey; Ahn, Yu-Bae; Omer, Abdulkadir; Sharma, Arun; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Sgroi, Dennis C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Pathol Unit, Boston, MA 02114 USA. [Libermann, Towia; Otu, Hasan H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179; Otu, Hasan/0000-0002-9253-8152 FU NCRR NIH HHS [U42 RR016606, U4Z RR 16606]; NIDDK NIH HHS [DK36836, P30 DK036836, U19DK6125] NR 36 TC 55 Z9 55 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 MAR PY 2008 VL 93 IS 3 BP 1046 EP 1053 DI 10.1210/jc.2007-0931 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271XT UT WOS:000253822700059 PM 18073315 ER PT J AU Jain, RK AF Jain, Rakesh K. TI Judah Folkman SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Biographical-Item C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 1 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2008 VL 118 IS 3 BP 823 EP 823 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400002 ER PT J AU Bagby, GC AF Bagby, Grover C. TI Discovering early molecular determinants of leukemogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID SEVERE CONGENITAL NEUTROPENIA; UNFOLDED PROTEIN RESPONSE; FANCONI-ANEMIA; LEUKEMIC CLONES; MUTATIONS; APOPTOSIS; ELASTASE; INDUCE; CELLS; VIVO AB Truncating mutations of the G-CSF receptor are found during disease course in nearly half of all patients with severe congenital neutropenia. In this issue of the JCI, Liu et al. demonstrate that these mutations confer a competitive clonal advantage upon HSCs in mice and that the advantage is conditional because it is observed only in the presence of the ligand G-CSF (see the related article beginning on page 946). Once activated, the mutant receptor requires the function of Stat5 in order to effect clonal expansion of this stem cell population. The results support the notion that early molecular steps in this and other neoplastic processes represent adaptations in which, through somatic mutations, "unfit" stem cells gain a measure of fitness by altering their relationships with their microenvironment. C1 [Bagby, Grover C.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Bagby, Grover C.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Bagby, Grover C.] NW Vet Affairs Canc Res Ctr, Portland, OR USA. RP Bagby, GC (reprint author), Portland VA Med Ctr, Mol Oncol Res Lab, Mailstop R&D2,Bldg 103,Room E221B,3710 SW Vet Hos, Portland, OR 97239 USA. EM grover@ohsu.edu OI Bagby, Grover/0000-0001-6830-2046 FU NHLBI NIH HHS [P01 HL048546, R01 HL072321] NR 20 TC 6 Z9 7 U1 0 U2 0 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 MAR PY 2008 VL 118 IS 3 BP 847 EP 850 DI 10.1172/JCI35109 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400009 PM 18292805 ER PT J AU Kasprowicz, V Ward, SM Turner, A Grammatikos, A Nolan, BE Lewis-Ximenez, L Sharp, C Woodruff, J Fleming, VM Sims, S Walker, BD Sewell, AK Lauer, GM Klenerman, P AF Kasprowicz, Victoria Ward, Scott M. Turner, Alison Grammatikos, Alexandros Nolan, Brian E. Lewis-Ximenez, Lia Sharp, Charles Woodruff, Jenny Fleming, Vicki M. Sims, Stuart Walker, Bruce D. Sewell, Andrew K. Lauer, Georg M. Klenerman, Paul TI Defining the directionality and quality of influenza virus-specific CD8(+) T cell cross-reactivity in individuals infected with hepatitis C virus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID I-PEPTIDE TETRAMERS; ANTAGONIST LIGANDS; IMMUNE-RESPONSES; LYMPHOCYTE; BINDING; MEMORY; CORECEPTOR; CD4(+); CTL; POPULATIONS AB Cross-reactivity of murine and recently human CD8(+) T cells between different viral peptides, i.e., heterologous immunity, has been well characterized. However, the directionality and quality of these cross-reactions is critical in determining their biological importance. Herein we analyzed the response of human CD8(+) T cells that recognize both a hepatitis C virus peptide (HCV-NS3) and a peptide derived from the influenza neuraminidase protein (Flu-NA). To detect the cross-reactive CD8(+) T cells, we used peptide-MHC class I complexes (pMHCs) containing a new mutant form of MHC class I able to bind CD8 more strongly than normal MHC class I complexes. T cell responses against HCV-NS3 and Flu-NA peptide were undetectable in normal donors. In contrast, some responses against the Flu-NA peptide were identified in HCV+ donors who showed strong HCV-NS3-specific reactivity. The Flu-NA peptide was a weak agonist for CD8(+) T cells in HCV+ individuals on the basis of novel pMHCs and functional assays. These data support the idea of cross-reactivity between the 2 peptides, but indicate that reactivity toward the Flu-NA peptide is highly CD8-dependent and occurs predominantly after priming during HCV infection. Our findings indicate the utility of the novel pMHCs in dissecting cross-reactivity and suggest that cross-reactivity between HCV and influenza is relatively weak. Further studies are needed to relate affinity and functionality of cross-reactive T cells. C1 [Ward, Scott M.; Turner, Alison; Grammatikos, Alexandros; Sharp, Charles; Woodruff, Jenny; Fleming, Vicki M.; Sims, Stuart; Klenerman, Paul] Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 1SY, England. [Kasprowicz, Victoria; Nolan, Brian E.; Walker, Bruce D.; Lauer, Georg M.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. [Kasprowicz, Victoria; Nolan, Brian E.; Walker, Bruce D.; Lauer, Georg M.] Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA USA. [Kasprowicz, Victoria; Nolan, Brian E.; Walker, Bruce D.; Lauer, Georg M.] Harvard Univ, Sch Med, Charlestown, MA USA. [Lewis-Ximenez, Lia] Inst Oswaldo Cruz Fiocruz, Dept Virol, Rio De Janeiro, Brazil. [Sewell, Andrew K.] Cardiff Univ, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales. RP Klenerman, P (reprint author), Univ Oxford, Nuffield Dept Clin Med, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 1SY, England. EM paul.klenerman@ndm.ox.ac.uk RI Grammatikos, Alexandros/A-5726-2011; OI Grammatikos, Alexandros/0000-0001-6544-8218; Sharp, Charles/0000-0002-4063-3625; Sewell, Andrew/0000-0003-3194-3135 FU Howard Hughes Medical Institute; NIAID NIH HHS [AI31563, R01 AI031563, U19 AI066345]; Wellcome Trust NR 38 TC 24 Z9 24 U1 0 U2 2 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 MAR PY 2008 VL 118 IS 3 BP 1143 EP 1153 DI 10.1172/JCI33082 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400038 PM 18246203 ER PT J AU Snyder, CF Earle, CC Herbert, RJ Neville, BA Blackford, AL Frick, KD AF Snyder, Claire F. Earle, Craig C. Herbert, Robert J. Neville, Bridget A. Blackford, Amanda L. Frick, Kevin D. TI Preventive care for colorectal cancer survivors: A 5-year longitudinal study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID COMORBIDITY INDEX; BREAST-CANCER; SURVEILLANCE; PHYSICIAN AB Purpose To explore the mix of physician specialties that long-term survivors visit and how the mix relates to preventive care. Patients and Methods Using the Surveillance, Epidemiology, and End Results-Medicare database, we conducted a retrospective, longitudinal study of stage I to III Medicare fee-for-service colorectal cancer patients diagnosed in 1997. We examined physician visits and preventive care each year for 5 years, starting 366 days postdiagnosis, and how preventive service receipt related to the physician mix seen: primary care provider (PCP) only, oncologist only, both, or neither. Results A total of 1,541 patients met the eligibility criteria (mean age, 76; 43% male; 85% white). During 5 years, PCP visits increased from a mean of 4.2 to 4.7 (P<.0001), and oncology visits decreased from 1.3 to 0.5 (P<.0001). Survivor care by PCPs only increased from 44% to 62%, whereas shared care by PCPs and oncologists dropped from 37% to 21% (P<.0001). Survivors who saw both PCPs and oncologists were most likely to receive influenza vaccination, mammograms, and cervical cancer screening; survivors who saw PCPs only were most likely to receive cholesterol screening and bone densitometry. Higher socioeconomic status was associated with increased influenza vaccination, mammograms, and cervical cancer screening (P<.05). Over time, there was a decrease in mammography and cervical cancer screening and an increase in influenza vaccination (P<.05). Conclusion As oncologists become less involved in survivor care, cancer-related screening decreases significantly. These results support the need for survivorship care plans that explicitly outline the roles of PCPs and oncologists in sharing care for cancer survivors, and how these roles may change over time. C1 Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. RP Snyder, CF (reprint author), Johns Hopkins Sch Med, Dept Oncol, 624 N Broadway,Room 657, Baltimore, MD 21205 USA. EM csnyder@jhsph.edu NR 16 TC 78 Z9 80 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2008 VL 26 IS 7 BP 1073 EP 1079 DI 10.1200/JCO.2007.11.9859 PG 7 WC Oncology SC Oncology GA 276XX UT WOS:000254178100010 PM 18309941 ER PT J AU Tepper, J Krasna, MJ Niedzwiecki, D Hollis, D Reed, CE Goldberg, R Kiel, K Willett, C Sugarbaker, D Mayer, R AF Tepper, Joel Krasna, Mark J. Niedzwiecki, Donna Hollis, Donna Reed, Carolyn E. Goldberg, Richard Kiel, Krystyna Willett, Christopher Sugarbaker, David Mayer, Robert TI Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID NEOADJUVANT CHEMORADIOTHERAPY; PREOPERATIVE CHEMORADIATION; RANDOMIZED-TRIAL; CARCINOMA; CHEMOTHERAPY; METAANALYSIS; ADENOCARCINOMA; SURVIVAL AB Purpose The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery, although primary radiation therapy with concurrent chemotherapy produces similar results. As both have curative potential, there has been great interest in the use of trimodality therapy. To this end, we compared survival, response, and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer. Patients and Methods Four hundred seventy-five eligible patients were planned for enrollment. Patients were randomly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m(2) and fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 concurrent with radiation therapy (50.4 Gy total: 1.8 Gy/fraction over 5.6 weeks) followed by esophagectomy with node dissection. Results Fifty-six patients were enrolled between October 1997 and March 2000, when the trial was closed due to poor accrual. Thirty patients were randomly assigned to trimodality therapy and 26 were assigned to surgery alone. Patient and tumor characteristics were similar between groups. Treatment was generally well tolerated. Median follow-up was 6 years. An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy (exact stratified log-rank, P=.002). Five-year survival was 39% (95% CI, 21% to 57%) v 16% (95% CI, 5% to 33%) in favor of trimodality therapy. Conclusion The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer, and support trimodality therapy as a standard of care for patients with this disease. C1 Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Duke Univ, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. St Joseph Canc Inst, Dept Surg, Towson, MD USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. N Cent Canc Treatment Grp, Rochester, MN USA. Northwestern Univ, Dept Med, Chicago, IL 60611 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Tepper, J (reprint author), Univ N Carolina, Sch Med, Dept Radiat Oncol, CB 7512, Chapel Hill, NC 27599 USA. EM tepper@med.unc.edu FU NCI NIH HHS [U10 CA037447] NR 23 TC 534 Z9 559 U1 4 U2 22 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2008 VL 26 IS 7 BP 1086 EP 1092 DI 10.1200/JCO.2007.12.9593 PG 7 WC Oncology SC Oncology GA 276XX UT WOS:000254178100012 PM 18309943 ER PT J AU Barry, EV Vrooman, LM Dahlberg, SE Neuberg, DS Asselin, BL Athale, UH Clavell, LA Larsen, EC Moghrabi, A Samson, Y Schorin, MA Cohen, HJ Lipshultz, SE Sallan, SE Silverman, LB AF Barry, Elly V. Vrooman, Lynda M. Dahlberg, Suzanne E. Neuberg, Donna S. Asselin, Barbara L. Athale, Uma H. Clavell, Luis A. Larsen, Eric C. Moghrabi, Albert Samson, Yvan Schorin, Marshall A. Cohen, Harvey J. Lipshultz, Steven E. Sallan, Stephen E. Silverman, Lewis B. TI Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED BREAST-CANCER; CHILDHOOD HODGKINS-DISEASE; SOUTHWEST-ONCOLOGY-GROUP; SOFT-TISSUE SARCOMAS; COMBINATION CHEMOTHERAPY; 2ND NEOPLASMS; CUMULATIVE INCIDENCE; ADRIAMYCIN; CARDIOTOXICITY; ICRF-187 AB Purpose Dexrazoxane is a drug used to prevent anthracycline-induced cardiotoxicity. A recent report found an association between the use of dexrazoxane and the risk of developing secondary malignant neoplasms (SMNs) in children with Hodgkin's disease. We report the absence of an association of SMNs in children with acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute ALL Consortium Protocol 95-01. Patients and Methods Two hundred five children with high-risk (HR) ALL were randomly assigned to receive doxorubicin alone (n = 100) or doxorubicin with dexrazoxane (n = 105) during the induction and intensification phases of multiagent chemotherapy. We compared incidence of SMNs in these two groups. Results With a median follow-up of 6.2 years, no differences in the incidence of SMNs were noted between the group that received dexrazoxane and the group that did not (P = .66). One SMN (a melanoma located outside of the cranial radiation field) occurred in a patient who was randomly assigned to doxorubicin alone. No SMNs were observed in patients randomly assigned to receive dexrazoxane. Conclusion Dexrazoxane was not associated with an increased risk of SMNs in children treated for HR ALL. Given the potential importance of dexrazoxane as a cardioprotectant, we recommend that dexrazoxane continue to be used and studied in doxorubicin-containing pediatric regimens. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Div Pediat Oncol, Rochester, NY 14642 USA. McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada. Univ Montreal, Div Hematol & Oncol, Hosp St Justine, Montreal, PQ H3C 3J7, Canada. Univ Quebec, Ctr Hosp, Ste Foy, PQ G1V 2M3, Canada. San Jorge Childrens Hosp, Div Pediat Oncol, San Juan, PR USA. Maine Childrens Canc Program, Dept Pediat Hematol Oncol, Scarborough, ME USA. Inova Fairfax Hosp Children, Sect Pediat Hematol Oncol, Falls Church, VA USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. Univ Miami Miller Sch Med, Dept Pediat, Miami, FL USA. RP Barry, EV (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM elly_barry@dfci.harvard.edu FU NCI NIH HHS [CA 68484] NR 38 TC 57 Z9 60 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2008 VL 26 IS 7 BP 1106 EP 1111 DI 10.1200/JCO.2007.12.2481 PG 6 WC Oncology SC Oncology GA 276XX UT WOS:000254178100015 PM 18309945 ER PT J AU Scher, HI Halabi, S Tannock, I Morris, M Sternberg, CN Carducci, MA Eisenberger, MA Higano, C Bubley, GJ Dreicer, R Petrylak, D Kantoff, P Basch, E Kelly, WK Figg, WD Small, EJ Beer, TM Wilding, G Martin, A Hussain, M AF Scher, Howard I. Halabi, Susan Tannock, Ian Morris, Michael Sternberg, Cora N. Carducci, Michael A. Eisenberger, Mario A. Higano, Celestia Bubley, Glenn J. Dreicer, Robert Petrylak, Daniel Kantoff, Philip Basch, Ethan Kelly, William Kevin Figg, William D. Small, Eric J. Beer, Tomasz M. Wilding, George Martin, Alison Hussain, Maha TI Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the prostate cancer clinical trials working group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-II; ANTIGEN EXPRESSION; NATURAL-HISTORY; HORMONE; MEN; DOCETAXEL; THERAPY; MODEL; ESTRAMUSTINE; MITOXANTRONE AB Purpose To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Methods A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Results The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as "new lesions" or " no new lesions," changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. Conclusion PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit. C1 Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urolog Canc, New York, NY 10065 USA. Duke Univ, Med Ctr, Durham, NC USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Sam Camillo Forlanini Hosp, Rome, Italy. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Cleveland Clin, Cleveland, OH 44106 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Yale Canc Ctr, New Haven, CT USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Scher, HI (reprint author), Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urolog Canc, 1275 York Ave, New York, NY 10065 USA. EM byczekb@mskcc.org RI Figg Sr, William/M-2411-2016; OI Martin, Anne/0000-0002-8536-3550; Morris, Michael J./0000-0002-9454-0096 FU NCI NIH HHS [P50 CA092629, P50 CA092629-01, P50 CA92629] NR 40 TC 910 Z9 923 U1 3 U2 24 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2008 VL 26 IS 7 BP 1148 EP 1159 DI 10.1200/JCO.2007.12.4487 PG 12 WC Oncology SC Oncology GA 276XX UT WOS:000254178100021 PM 18309951 ER PT J AU Simon, NM Connor, KM Lang, AJ Rauch, S Krulewicz, S LeBeau, RT Davidson, JRT Stein, MB Otto, MW Foa, EB Pollack, MH AF Simon, Naomi M. Connor, Kathryn M. Lang, Ariel J. Rauch, Sheila Krulewicz, Stan LeBeau, Richard T. Davidson, Jonathan R. T. Stein, Murray B. Otto, Michael W. Foa, Edna B. Pollack, Mark H. TI Paroxetine CR augmentation for posttraumatic stress disorder refractory to prolonged exposure therapy SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; RANDOMIZED CONTROLLED-TRIAL; NATIONAL COMORBIDITY SURVEY; PANIC DISORDER; DSM-IV; ANXIETY DISORDERS; PLACEBO; COMBINATION; PHARMACOTHERAPY AB Objective: Little is known about the efficacy of "next step" strategies for patients with posttraumatic stress disorder (PTSD) who remain symptomatic despite treatment. This study prospectively examines the relative efficacy of augmentation of continued prolonged exposure therapy (PE) with paroxetine CR versus placebo for individuals remaining symptomatic despite a course of PE. Method: Adult outpatients meeting DSM-IV criteria for PTSD were recruited from February 2003 to September 2005 at 4 academic centers. Phase I consisted of 8 sessions of individual PE over a 4- to 6-week period. Participants who remained symptomatic, defined as a score of >= 6 on the Short PTSD Rating Interview (SPRINT) and a Clinical Global Impressions-Severity of Illness scale (CGI-S) score 3, were randomly assigned to the addition of paroxetine CR or matched placebo to an additional 5 sessions of PE (Phase II). Results: Consistent with prior studies, the 44 Phase I completers improved significantly with initial PE (SPRINT: paired t = 7.6, df = 41, p < .0001; CGI-S: paired t = 6.37, df = 41, p < .0001). Counter to our hypothesis, however, we found no additive benefit of augmentation of continued PE with paroxetine CR compared to pill placebo for the 23 randomly assigned patients, with relatively minimal further gains overall in Phase II. Conclusion: Although replication with larger samples is needed before definitive conclusions can be drawn, our data do not support the addition of paroxetine CR compared with placebo to continued PE for individuals with PTSD who remain symptomatic after initial PE, suggesting that the development of novel treatment approaches for PTSD refractory to PE is needed. Clinical Trials Registration: ClinicalTrials.gov identifier NCT00215163. C1 [Simon, Naomi M.; LeBeau, Richard T.; Pollack, Mark H.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Simon, Naomi M.; Pollack, Mark H.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Connor, Kathryn M.; Davidson, Jonathan R. T.] Duke Univ, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC USA. [Connor, Kathryn M.; Davidson, Jonathan R. T.] Duke Univ, Anxiety & Traumat Stress Program, Med Ctr, Durham, NC USA. [Foa, Edna B.] Univ Penn, Ctr Treatment & Study Anxiety, Philadelphia, PA 19104 USA. [Lang, Ariel J.; Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Lang, Ariel J.; Stein, Murray B.] Univ Calif San Diego, Anxiety & Traumat Stress Program, San Diego, CA 92103 USA. [Otto, Michael W.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Krulewicz, Stan] GlaoSmithKline Pharmaceut, Neurosci Med Dev Ctr, King Of Prussia, PA USA. [Rauch, Sheila] Univ Michigan, Dept Psychiat, Sch Med, VA Ann Arbor Hlthcare Syst, Ann Arbor, MI 48109 USA. [Rauch, Sheila] Merck & Co Inc, Merck Res Labs, N Wales, PA USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg 2nd Floor 185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org RI Rauch, Sheila/K-4450-2015 OI Rauch, Sheila/0000-0001-9686-4011 NR 32 TC 36 Z9 37 U1 2 U2 5 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 MAR PY 2008 VL 69 IS 3 BP 400 EP 405 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 283LL UT WOS:000254637600009 PM 18348595 ER PT J AU Loebl, T Angarita, GA Pachas, GN Huang, KL Lee, SH Nino, J Logvinenko, T Culhane, MA Evins, AE AF Loebl, Tsafrir Angarita, Gustavo A. Pachas, Gladys N. Huang, Kai-Lin Lee, Sang H. Nino, Johanna Logvinenko, Tanya Culhane, Melissa A. Evins, A. Eden TI A randomized, double-blind, placebo-controlled trial of long-acting risperidone in cocaine-dependent men SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEEKING BEHAVIOR; AGONISTS; SCALE; ANTAGONISTS; DEPRESSION; SYMPTOMS; ABUSE AB Objective: There is no approved pharmacotherapy for cocaine dependence. Risperidone is an atypical antipsychotic drug with combined dopamine-2/serotonin-2 (D-2/5-HT2) antagonist activity that has been effective in reducing cocaine use in some animal studies. We tested the efficacy of a long-acting, injectable preparation of risperidone on cocaine use in active cocaine users. Method: Thirty-one cocaine-dependent men who met DSM-IV diagnostic criteria for current cocaine dependence entered a 12-week, randomized. double-blind, placebo-controlled trial of intramuscular risperidone, 25 mg every other week. The primary outcome measure was cocaine use as measured by urinary concentration of cocaine metabolites. Secondary outcomes were self-report of cocaine use and craving, depressive symptoms as measured by the Hamilton Rating Scale for Depression (HAM-D), and adverse events. Participants were recruited during a 12-month period from October 2005 to September 2006. Results: Both groups reduced their cocaine use during the study. There were no between-group differences in the primary measure of cocaine use (urinary metabolites [F = 0.7, p = .41]) or on craving measures. Those assigned to risperidone reported significantly worsened depressive symptoms (mean SD HAM-D change scores: +7.4 +/- 8.8 vs. -2.3 +/- 5.8, respectively, F = 7.5, p = .018) and gained significantly more weight (mean weight change: +6.3 +/- 9.4 lb vs. -4.0 +/- 8.9 lb, respectively, F = 4.65, p = .044) than those assigned to placebo. Conclusion: Treatment with long-acting injectable risperidone in active cocaine users was not associated with reduction in cocaine use or craving and was associated with worsening of depressive symptoms and weight gain. Trial Registration: clinicaltrials.gov Identifier: NCT00385801. C1 [Loebl, Tsafrir; Angarita, Gustavo A.; Pachas, Gladys N.; Huang, Kai-Lin; Lee, Sang H.; Nino, Johanna; Logvinenko, Tanya; Culhane, Melissa A.; Evins, A. Eden] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med,Dept Psychiat, Boston, MA 02114 USA. [Loebl, Tsafrir; Angarita, Gustavo A.; Pachas, Gladys N.; Huang, Kai-Lin; Lee, Sang H.; Nino, Johanna; Logvinenko, Tanya; Culhane, Melissa A.; Evins, A. Eden] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Loebl, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med,Dept Psychiat, 60 Staniford St, Boston, MA 02114 USA. EM tloebl@partners.org NR 34 TC 21 Z9 21 U1 1 U2 2 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 MAR PY 2008 VL 69 IS 3 BP 480 EP 486 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 283LL UT WOS:000254637600021 PM 18294021 ER PT J AU Kane, JM Perlis, RH Malhotra, AK AF Kane, John M. Perlis, Roy H. Malhotra, Anil K. TI Clinical insights into pharmacogenetics and schizophrenia, part 1 SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID CATECHOL-O-METHYLTRANSFERASE; SEROTONIN TRANSPORTER GENE; VAL(108/158) MET GENOTYPE; OLANZAPINE TREATMENT; MAJOR DEPRESSION; POLYMORPHISMS; ASSOCIATION; PROMOTER; COMT; METAANALYSIS C1 [Kane, John M.] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA. [Kane, John M.; Malhotra, Anil K.] Yeshiva Univ Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10461 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Malhotra, Anil K.] Zucker Hillside Hosp, Psychiat Res Program, Glen Oaks, NY USA. Bristol Myers Squibb Co, New York, NY 10154 USA. RP Kane, JM (reprint author), Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA. NR 32 TC 1 Z9 1 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2008 VL 69 IS 3 BP 487 EP 494 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 283LL UT WOS:000254637600022 ER PT J AU Hopwood, CJ Talbert, CA Morey, LC Rogers, R AF Hopwood, Christopher J. Talbert, Christy A. Morey, Leslie C. Rogers, Richard TI Testing the incremental utility of the negative impression-positive impression differential in detecting simulated personality assessment inventory profiles SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE Personality Assessment Inventory; faking; dissimulation; validity scales ID FEIGNED MENTAL-DISORDERS AB The usefulness of multiscale inventories depends on their ability to evaluate response styles effectively, such as fake-bad (feigning) and fake-good (defensiveness) profiles. The current investigation combined validity data across clinical, nonclinical, and simulating samples to evaluate the usefulness of the Personality Assessment Inventory (PAI) negative impression (NIM)-positive impression (PIM) difference score to detect simulated profiles. In general, its effect sizes were not appreciably different from those afforded by NIM and PIM alone. Likewise, its incremental contributions in logistic regression were minimal. These results do not support the routine use of a NIM-PIM difference score in detecting response styles with the PAI. (C) 2008 Wiley Periodicals, Inc. C1 [Hopwood, Christopher J.] Texas A&M Univ, Massachusetts Gen Hosp, Dept Psychol, Boston, MA 02114 USA. [Hopwood, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Talbert, Christy A.; Morey, Leslie C.] Texas A&M Univ, College Stn, TX 77843 USA. [Rogers, Richard] Univ N Texas, Denton, TX 76203 USA. RP Hopwood, CJ (reprint author), Texas A&M Univ, Massachusetts Gen Hosp, Dept Psychol, 15 Parkman St WACC 815, Boston, MA 02114 USA. EM chopwood@partners.org RI Morey, Leslie/B-5617-2008 OI Morey, Leslie/0000-0001-7711-5568 NR 13 TC 5 Z9 5 U1 0 U2 1 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 MAR PY 2008 VL 64 IS 3 BP 338 EP 343 DI 10.1002/jclp.20439 PG 6 WC Psychology, Clinical SC Psychology GA 269ZW UT WOS:000253690500009 PM 18302214 ER PT J AU Singh, AK Raman, S Brooks, C Philips, D Desai, R Kandarpa, K AF Singh, Ajay K. Raman, Subha Brooks, Christopher Philips, David Desai, Robert Kandarpa, Krishna TI Giant colonic diverticulum: Percutaneous computed tomography-guided treatment SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE giant sigmoid diverticulum; percutancous drainage; diverticulitis ID SIGMOID DIVERTICULUM AB We present a case of inflamed giant sigmoid diverticulum, which was treated under computed tomographic guidance by dilating the neck and decompressing the inflamed diverticulum. The procedure also involved placement of an internal stent across the neck of the diverticulum, the purpose of which was to decompress the giant diverticulum into the sigmoid colon and prevent acute recurrence. In patients with inflamed giant colonic diverticulum, the percutaneous approach may be useful in treatment of diverticulitis and avoiding a staged Hartmann procedure with end colostomy. C1 [Singh, Ajay K.; Raman, Subha; Brooks, Christopher; Philips, David; Desai, Robert; Kandarpa, Krishna] Univ Massachusetts, Mem Med Ctr, Dept Radiol, Worcester, MA 01655 USA. [Singh, Ajay K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), Univ Massachusetts, Mem Med Ctr, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM asingh1@partners.org NR 10 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2008 VL 32 IS 2 BP 204 EP 206 DI 10.1097/RCT.0b013e3180683bd8 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 284CS UT WOS:000254683500007 PM 18379302 ER PT J AU Dodd, JD Ferencik, M Liberthson, RR Nieman, K Brady, TJ Hoffmann, U Cury, RC Abbara, S AF Dodd, Jonathan D. Ferencik, Maros Liberthson, Richard R. Nieman, Koen Brady, Thomas J. Hoffmann, Udo Cury, Ricardo C. Abbara, Suhny TI Evaluation of efficacy of 64-slice multidetector computed tomography in patients with congenital coronary fistulas SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE coronary vessel anomalies; computed tomography; vascular fistula/diagnosis ID CT; HEART AB Objective: To evaluate the efficacy of 64-slice coronary multi-detector computed tomography (MDCT) in the assessment of congenital coronary artery fistula (CCAF). Methods: Two readers prospectively evaluated the 64-slice coronary MDCT appearances of CCAF in 10 patients (5 men and 5 women; mean age, 58.6 years; range, 19-82 years). Fistula origin, Course, distal entry site, and maximal receiving chamber/vessel dimensions were determined using retrospective multisegment reconstructions at 10% increments of the cardiac cycle. Results: Origin, course, and distal vessel entry. site of CCAF were clearly outlined in all patients. The distal vessel draining site involved multiple small entry vessels in 5 patients and a single entry vessel in 5 patients. The right atrium in 3 patients and right ventricle in all patients were enlarged. Contrast opacification of the receiving chamber (contrast shunt sign) was detected in 4 patients, indicating patency and site of fistula entry. Conclusion: Cardiac 64-slice MDCT provides excellent visualization of the origin, course, and distal vessel entry site of CCAF and the size of the receiving chamber.. C1 [Dodd, Jonathan D.; Ferencik, Maros; Nieman, Koen; Brady, Thomas J.; Hoffmann, Udo; Cury, Ricardo C.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Liberthson, Richard R.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Liberthson, Richard R.] Harvard Univ, Sch Med, Boston, MA USA. RP Dodd, JD (reprint author), St Vincents Univ Hosp, Dept Radiol, Elm Pk, Dublin 4, Ireland. EM jonniedodd@gmail.com NR 11 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2008 VL 32 IS 2 BP 265 EP 270 DI 10.1097/RCT.0b013e318074eb88 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 284CS UT WOS:000254683500019 PM 18379314 ER PT J AU Weissman, JS Koski, G Vogeli, C Thiessen, C Campbell, EG AF Weissman, Joel S. Koski, Greg Vogeli, Christine Thiessen, Carrie Campbell, Eric G. TI Opinions of IRB members and chairs regarding investigators' relationships with industry SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE institutional review boards; conflict of interest; research ethics; human experimentation ID CONFLICTS-OF-INTEREST; CLINICAL-TRIALS AB THE EFFECTS OF CONFLICTS OF INTEREST on the conduct of human research have been roundly debated, but less attention has been paid to the role of Institutional Review Boards (IRBs) in their identification and management. Government and private policy recommendations disagree about IRBs' responsibility in this area. A survey focusing on respondents' attitudes and behaviors regarding consideration of investigator and institutional financial relationships with industry when reviewing research protocols was mailed to a random sample of 893 IRB members and 316 IRB chairs at 115 academic institutions (response rates of 67% and 72%, respectively). More than half of IRB members and chairs felt that industry relationships posed a moderate or big problem for research integrity nationally, and about one-third thought such relationships were a problem at their own institution. Approximately two-thirds felt that investigator-industry relationships should be considered when reviewing protocols regardless of whether they are deemed to be conflicts of interest. While more than 90% of IRB members and chairs believed that investigators' relationships should be disclosed to research participants, 61% of members and chairs reported that these relationships were not always disclosed to participants. While more than 80% believed that institutional relationships should be disclosed to research participants, only 39% of members and chairs said this happened all the time. Some beliefs of IRB members and chairs are at odds with recommendations to limit the role of IRBs in the management of potential investigator conflicts. Lack of unambiguous guidelines has led to inconsistent practices among IRBs. C1 [Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Boston, MA 02114 USA. [Weissman, Joel S.; Koski, Greg; Vogeli, Christine; Campbell, Eric G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Weissman, Joel S.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jweissman@partners.org OI Thiessen, Carrie/0000-0002-1410-0112 NR 33 TC 5 Z9 5 U1 2 U2 3 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS & DIGITAL PUBLISHING DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD MAR PY 2008 VL 3 IS 1 BP 3 EP 13 DI 10.1525/jer.2008.3.1.3 PG 11 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 308KE UT WOS:000256387700002 PM 19385778 ER PT J AU Gorelick, F Pandol, S Thrower, E AF Gorelick, Fred Pandol, Stephen Thrower, Edwin TI Protein kinase C in the pancreatic acinar cell SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis CY OCT 18-19, 2007 CL Kobe, JAPAN SP Japanese Soc Gastroenterol, Japan Soc Hepatol DE alcohol; cholecystokinin; chymotrypsin; ethanol; protease ID KAPPA-B ACTIVATION; INDUCED ZYMOGEN ACTIVATION; PKC-DELTA; CHOLECYSTOKININ; CERULEIN; PHOSPHORYLATION; EXOCYTOSIS; ISOFORMS; CAMP; TRANSLOCATION AB Pathological activation of selective signaling molecules within the pancreatic acinar cell mediates the development of acute pancreatitis. Some of the key early acinar cell events include activation of proteases, inhibition of apical secretion, and elaboration of inflammatory mediators. Previous studies have shown that supraphysiological concentrations of cholecystokinin (CCK) that can cause pancreatitis in vivo, also initiate these pathological responses in dispersed groups of acinar cells (acini). Protein kinase C (PKC) regulates many cellular events and a role for this family of signaling molecules has been described in some of the pathological responses of pancreatitis. Notably, ethanol can activate specific PKC isoforms and sensitize the acinar cells to the pathological effects of CCK. Our preliminary studies in isolated pancreatic acini and a cell-free reconstitution system suggest that PKC can mediate protease activation in the acinar cell. These findings may be relevant to the pathogenesis of pancreatitis from alcohol and other etiologies. C1 [Gorelick, Fred; Thrower, Edwin] Connecticut VA Healthcare, Dept Internal Med, West Haven, CT USA. [Gorelick, Fred; Thrower, Edwin] Yale Univ, West Haven, CT USA. [Pandol, Stephen] VA Greater Los Angeles, Los Angeles, CA USA. RP Thrower, E (reprint author), Yale Univ, Sch Med, VA Healthcare Syst CT, Gl Res Lab, Bldg 4,950 Campbell Ave, West Haven, CT 06516 USA. EM edwin.thrower@yale.edu NR 31 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2008 VL 23 SU 1 BP S37 EP S41 DI 10.1111/j.1440-1746.2007.05282.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284VT UT WOS:000254735700007 PM 18336661 ER PT J AU Odinokova, IV Sung, KF Mareninova, OA Hermann, K Gukovsky, I Gukovskaya, AS AF Odinokova, Irina V. Sung, Kai-Feng Mareninova, Olga A. Hermann, Kip Gukovsky, Ilya Gukovskaya, Anna S. TI Mitochondrial mechanisms of death responses in pancreatitis SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis CY OCT 18-19, 2007 CL Kobe, JAPAN SP Japanese Soc Gastroenterol, Japan Soc Hepatol DE apoptosis; calcium; cytochrome c release; mitochondrial membrane potential; necrosis; pancreatic mitochondria; permeability transition pore; reactive oxygen species ID PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; ACID ETHYL-ESTERS; CELL-DEATH; ACINAR-CELLS; MEMBRANE PERMEABILIZATION; CYCLOPHILIN-D; EARLY EVENTS; APOPTOSIS; NECROSIS AB Pancreatitis is a severe and frequently lethal disorder, a major cause of which is alcohol abuse. Parenchymal cell death is a major complication of pancreatitis. In experimental models of acute pancreatitis, acinar cells have been shown to die through both necrosis and apoptosis, the two principal pathways of cell death. The severity of experimental acute pancreatitis correlates directly with the extent of necrosis and inversely with apoptosis. Thus, understanding the regulation of apoptosis and necrosis is becoming exceedingly important in investigations of the pathogenesis and treatment of pancreatitis. Over the past decade, the mitochondria have emerged as a master regulator of cell death in various physiological and pathological processes. Release of mitochondrial cytochrome c into the cytosol is a central event in apoptosis, whereas mitochondrial depolarization resulting in ATP depletion leads to necrosis. The present review focuses on the mitochondrial mechanisms of death responses in pancreatitis, with emphasis on mitochondrial membrane permeabilization and its role in the balance between apoptosis and necrosis in acute pancreatitis, and alcohol's effects on death responses of pancreatitis. C1 [Odinokova, Irina V.; Sung, Kai-Feng; Mareninova, Olga A.; Hermann, Kip; Gukovsky, Ilya; Gukovskaya, Anna S.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, USC Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90073 USA. RP Gukovskaya, AS (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, USC Res Ctr Alcohol Liver & Pancreat Dis, 11301 Wilshire Blvd,Blg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu NR 48 TC 16 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2008 VL 23 SU 1 BP S25 EP S30 DI 10.1111/j.1440-1746.2007.05271.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284VT UT WOS:000254735700005 PM 18336659 ER PT J AU Castillo, CFD AF Castillo, Carlos Fernandez-del TI Mucinous cystic neoplasms SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2007 CL Washington, DC SP Soc Surg Alimentary Tract DE mucinous cystic neoplasm; ovarian stroma; intraductal papillary mucinous neoplasm ID K-RAS MUTATIONS; SEQUENTIAL ACCUMULATION; P53 OVEREXPRESSION; PANCREAS; MALIGNANCY; TUMORS; CYSTADENOCARCINOMA; PANCREATECTOMY; CYSTADENOMAS; PROGRESSION AB Mucinous cystic neoplasms of the pancreas are uncommon tumors of the pancreas that occur predominantly in middle-aged women and almost exclusively in the body and tail of the pancreas. They are lined by a mucinous epithelium that can exhibit varying grades of dysplasia and are surrounded by a characteristic ovarian-like stroma. Surgery is the treatment of choice, and prognosis is excellent in the absence of invasive carcinoma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pancreas Surg Program, Boston, MA 02114 USA. RP Castillo, CFD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pancreas Surg Program, 15 Parkman St,ACC-460, Boston, MA 02114 USA. EM cfernandez@partners.org NR 19 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR PY 2008 VL 12 IS 3 BP 411 EP 413 DI 10.1007/s11605-007-0347-0 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 259MV UT WOS:000252944300004 PM 17955316 ER PT J AU Bhattacharyya, RP Chiappa, V AF Bhattacharyya, R. P. Chiappa, V. TI A 46 year old woman with dyspnea and mononeuritis multiplex SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Bhattacharyya, R. P.; Chiappa, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 92 EP 92 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100010 ER PT J AU Defonseka, AM Cheng, ET AF Defonseka, A. M. Cheng, E. T. TI A new form of diabetic neuropathy: Metformin-induced vitamin B12 deficiency SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Defonseka, A. M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Cheng, E. T.] Greater Los Angeles Vet Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 102 EP 102 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100037 ER PT J AU Mendenhall, DA Altman, L Bean-Mayberry, B Dumitru, D AF Mendenhall, D. A. Altman, L. Bean-Mayberry, B. Dumitru, D. TI Acute onset virilism - A possibly hairy diagnosis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Mendenhall, D. A.] W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Altman, L.; Dumitru, D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bean-Mayberry, B.] VA Greater Los Angeles Hlth Serv Res & Dev, Ctr Excellence, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 112 EP 112 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100065 ER PT J AU Rhee, CM Cedfeldt, AS AF Rhee, C. M. Cedfeldt, A. S. TI Blinded by the bladder SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Rhee, C. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cedfeldt, A. S.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 125 EP 125 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100100 ER PT J AU Appelle, NA Shunk, RL Kohlwes, JR AF Appelle, N. A. Shunk, R. L. Kohlwes, J. R. TI Accuracy and improvement in ekg interpretation by internal medicine housestaff: A classroom-based approach for teaching EKG interpretation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Appelle, N. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shunk, R. L.] UCSF, VAMC, San Francisco, CA USA. [Kohlwes, J. R.] UCSF, San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 193 EP 194 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100288 ER PT J AU Bray-Hall, ST Abraham, A Aagaard, EM AF Bray-Hall, S. T. Abraham, A. Aagaard, E. M. TI Development of a transitions in care curriculum for medical students SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Bray-Hall, S. T.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Abraham, A.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Aagaard, E. M.] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 198 EP 199 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100301 ER PT J AU Carpenter, LE Chang, A Johnston, B Lee, K Singh, B Chou, CL AF Carpenter, L. E. Chang, A. Johnston, B. Lee, K. Singh, B. Chou, C. L. TI Longitudinal groups across clerkships for third-year medical students enhance reflection about professional development SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Carpenter, L. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chang, A.; Johnston, B.; Lee, K.; Singh, B.; Chou, C. L.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 205 EP 205 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100317 ER PT J AU Halvorson, S Cedfeldt, AS AF Halvorson, S. Cedfeldt, A. S. TI "Rational RX: Mind over marketing" a freely accessible, web-based curriculum for internal medicine residents SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Halvorson, S.] Oregon Hlth & Sci Univ, Portland VA Res Fdn, Portland, OR 97201 USA. [Cedfeldt, A. S.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 216 EP 216 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100347 ER PT J AU Farrell, EA AF Farrell, E. A. TI Bigelow basics: An evidence based approach to the general medical admission SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Farrell, E. A.] Massachusetts Gen Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 217 EP 217 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100350 ER PT J AU Arora, NK Hesse, BW Rimer, BK Viswanath, K Clayman, ML Croyle, RT AF Arora, Neeraj K. Hesse, Bradford W. Rimer, Barbara K. Viswanath, K. Clayman, Marla L. Croyle, Robert T. TI Frustrated and confused: The American public rates its cancer-related information-seeking experiences SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE information seeking; cancer; national survey; health information; information needs ID NATIONAL TRENDS SURVEY; HEALTH INFORMATION; DECISION-MAKING; INTERNET; CARE; QUALITY; PARTICIPATE; PREFERENCES; KNOWLEDGE; NEEDS AB BACKGROUND: Ensuring access to high-quality cancer-related information is important for the success of cancer prevention and control efforts. OBJECTIVE: We conducted a population-based assessment of the barriers faced by people searching for cancer information. DESIGN: Cross-sectional data from the National Cancer Institute's 2003 Health Information National Trends Survey. PARTICIPANTS: A nationally representative sample of individuals in the USA (n=6,369). MEASUREMENTS: We assessed whether respondents had ever sought cancer-related information and examined ratings of their information-seeking experiences and beliefs regarding causes of cancer and its prevention. Linear and logistic regression models were estimated to determine predictors of negative experiences and associations between experiences and cancer beliefs. RESULTS:Nearly one half (44.9%) of Americans had searched for cancer information. Many reported negative experiences, including the search process requiring a lot of effort (47.7%), expressing frustration (41.3%), and concerns about the quality of the information found (57.7%). Respondents lacking health insurance or a high school education experienced the greatest difficulty. Compared to those reporting the most positive experiences, information seekers reporting more negative experiences were more likely to report that almost everything caused cancer [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.5-2.6], that not much can be done to prevent cancer (OR 2.7, 95% CI 1.9-3.8), and that it is hard to know which cancer prevention recommendations to follow (OR 3.2, 95% CI 2.3-4.5). CONCLUSIONS: While a significant proportion of the American public searches for cancer information, suboptimal experiences are common. Facilitation of information seeking will be critical for promoting informed decision making in cancer prevention and control. C1 [Arora, Neeraj K.; Hesse, Bradford W.; Croyle, Robert T.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Rimer, Barbara K.] Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. [Rimer, Barbara K.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Viswanath, K.] Harvard Univ, Dept Soc Human Dev, Boston, MA 02115 USA. [Viswanath, K.] Dana Faber Canc Inst, Boston, MA 02115 USA. [Clayman, Marla L.] Northwestern Univ, Ctr Commun & Med, Chicago, IL USA. Northwestern Univ, Dept Gen Med, Chicago, IL USA. [Clayman, Marla L.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. RP Arora, NK (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. OI Clayman, Marla/0000-0001-8491-3672; Hesse, Bradford/0000-0003-1142-1161 FU NCI NIH HHS [N02-PC-15003] NR 28 TC 67 Z9 68 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 IS 3 BP 223 EP 228 DI 10.1007/s11606-007-0406-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 263JS UT WOS:000253214000001 PM 17922166 ER PT J AU Siegel, LC Sesso, HD Bowman, TS Gaziano, J AF Siegel, L. C. Sesso, H. D. Bowman, T. S. Gaziano, J. TI 9-year changes in physical activity and subsequent risk of type 2 diabetes in men SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Siegel, L. C.; Bowman, T. S.; Gaziano, J.] VA Boston Healthcare Syst, Boston, MA USA. [Sesso, H. D.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 232 EP 233 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100392 ER PT J AU Percac-Lima, S Grant, RW Green, A Ashburner, J Gamba, G Oo, S Richter, JM Atlas, SJ AF Percac-Lima, S. Grant, R. W. Green, A. Ashburner, J. Gamba, G. Oo, S. Richter, J. M. Atlas, S. J. TI A patient-tailored navigator program for colorectal cancer screening in a community health center: A randomized controlled trial SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Percac-Lima, S.; Gamba, G.; Oo, S.] Massachusetts Gen Hosp, Chelsea, MA USA. [Grant, R. W.; Green, A.; Ashburner, J.; Richter, J. M.; Atlas, S. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 237 EP 238 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100406 ER PT J AU Atlas, SJ Lester, WT Grant, RW Ashburner, JM Chang, Y Barry, MJ AF Atlas, S. J. Lester, W. T. Grant, R. W. Ashburner, J. M. Chang, Y. Barry, M. J. TI A randomized trial of an informatics-based intervention to increase breast cancer screening in a primary care network SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Atlas, S. J.; Lester, W. T.; Grant, R. W.; Ashburner, J. M.; Chang, Y.; Barry, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 239 EP 240 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100412 ER PT J AU Volpp, KG John, L Norton, L Fassbender, J Troxel, A Loewenstein, GF AF Volpp, K. G. John, L. Norton, L. Fassbender, J. Troxel, A. Loewenstein, G. F. TI A randomized controlled trial of strategies for weight loss SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Volpp, K. G.; Norton, L.] Univ Penn, Sch Med, CHERP, Philadelphia VAMC, Philadelphia, PA 19104 USA. [Volpp, K. G.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [John, L.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 239 EP 239 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100411 ER PT J AU Linder, JA Rigotti, NA Schneider, LI Kelley, JK Brawarsky, P Haas, JS AF Linder, J. A. Rigotti, N. A. Schneider, L. I. Kelley, J. K. Brawarsky, P. Haas, J. S. TI An electronic health record-based intervention to improve tobacco treatment in primary care: A randomized controlled trial SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Linder, J. A.; Schneider, L. I.; Kelley, J. K.; Brawarsky, P.; Haas, J. S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rigotti, N. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 246 EP 247 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100431 ER PT J AU Singh, H Petersen, LA Daci, K Collins, C Petersen, NJ Shethia, A El-Serag, H AF Singh, H. Petersen, L. A. Daci, K. Collins, C. Petersen, N. J. Shethia, A. El-Serag, H. TI An evaluation of missed opportunities in colorectal cancer diagnosis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Singh, H.; Petersen, L. A.; Petersen, N. J.; Shethia, A.; El-Serag, H.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Daci, K.; Collins, C.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 247 EP 247 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100432 ER PT J AU Steinman, M Yang, K Byron, SC Maselli, J Gonzales, R AF Steinman, M. Yang, K. Byron, S. C. Maselli, J. Gonzales, R. TI Antibiotic utilization among health plans in the united states: Implications for quality, cost, and public health SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Steinman, M.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Byron, S. C.] Natl Comm Qual Assurance, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 247 EP 247 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100433 ER PT J AU Lorenz, KA Sherbourne, CD Shugarman, LR Meredith, LS Rubenstein, LV Wen, L Cohen, A Goebel, J Lanto, A Asch, SM AF Lorenz, K. A. Sherbourne, C. D. Shugarman, L. R. Meredith, L. S. Rubenstein, L. V. Wen, L. Cohen, A. Goebel, J. Lanto, A. Asch, S. M. TI Are primary care physicians more likely to address painful symptoms in seriously ill patients? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Lorenz, K. A.; Rubenstein, L. V.; Asch, S. M.] Univ Calif Los Angeles, RAND Corp, VA Greater Los Angeles, Los Angeles, CA USA. [Sherbourne, C. D.; Shugarman, L. R.; Meredith, L. S.] RAND Corp, Santa Monica, CA USA. [Wen, L.] VA Long Beach, Long Beach, CA USA. [Goebel, J.] CSULB, Sch Nursing, Long Beach, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 249 EP 249 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100439 ER PT J AU Pollack, C Mallya, G Polsky, D AF Pollack, C. Mallya, G. Polsky, D. TI Are physicians ready to practice in a consumer-driven environment? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Pollack, C.] Univ Penn, Philadelphia VA Med Ctr, RWJ Clin Scholar, Philadelphia, PA 19104 USA. [Polsky, D.] Philadelphia VAMC CHERP, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 249 EP 249 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100438 ER PT J AU Snyder, CF Earle, CC Herbert, RJ Neville, BA Blackford, AL Frick, KD AF Snyder, Claire F. Earle, Craig C. Herbert, Robert J. Neville, Bridget A. Blackford, Amanda L. Frick, Kevin D. TI Trends in follow-up and preventive care for colorectal cancer survivors SO JOURNAL OF GENERAL 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 DE preventive care; cancer survivors; coordination of care ID CLINICAL-ONCOLOGY; COMORBIDITY INDEX; AMERICAN-SOCIETY; SURVEILLANCE; PHYSICIAN AB BACKGROUND: As cancer patients transition from treatment to survivorship, the responsibility of primary care providers (PCPs) versus oncology specialists is unclear. OBJECTIVES: To explore (1) physician types (PCPs versus oncology specialists) survivors visit during survivorship year 1, (2) preventive care received, (3) how preventive care receipt relates to physician types visited, and (4) trends in physician types visited and preventive care received over time. DESIGN: Retrospective cross-sectional study of 5 cohorts of cancer survivors in survivorship year 1. SUBJECTS: Twenty thousand sixty-eight survivors diagnosed with stage 1-3 colorectal cancer between 1997 and 2001. MEASUREMENTS: Using the SEER-Medicare database, we assessed the mean number of visits to different physician types, the percentage of survivors receiving preventive services, how receipt of preventive services related to physician types visited, and trends over time in physician visits and preventive care. RESULTS: There was a trend over time of increased visits to all physician types, which was statistically significant for oncology specialists and other physicians (p <.001) but not PCPs. The percentage of survivors receiving preventive services remained relatively stable across the 5 cohorts, except for an increase in bone densitometry (p <.05). Survivors who visited both a PCP and oncology specialist were most likely to receive each preventive care service (p <.05). CONCLUSIONS: Oncology specialist follow-up in survivorship year 1 is intensifying over time. Survivors not being followed-up by both PCPs and oncology specialists were less likely to receive preventive care. Clarifying the roles of PCPs and oncology specialists during follow-up can improve the quality of care for survivors. C1 [Snyder, Claire F.] Johns Hopkins Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD USA. [Snyder, Claire F.; Herbert, Robert J.; Frick, Kevin D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Snyder, Claire F.; Blackford, Amanda L.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. [Earle, Craig C.; Neville, Bridget A.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. RP Snyder, CF (reprint author), 624 N Broadway Rm 657, Baltimore, MD 21205 USA. EM csnyder@jhsph.edu NR 15 TC 66 Z9 69 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 IS 3 BP 254 EP 259 DI 10.1007/s11606-007-0497-5 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 263JS UT WOS:000253214000006 PM 18197456 ER PT J AU Bokhour, BG Solomon, JL Knapp, H Asch, SM Gifford, AL AF Bokhour, B. G. Solomon, J. L. Knapp, H. Asch, S. M. Gifford, A. L. TI Barriers and facilitators to routine HIV testing in VA primary care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Bokhour, B. G.; Solomon, J. L.; Gifford, A. L.] ENRM VA Med Ctr, Bedford, MA USA. [Knapp, H.; Asch, S. M.] Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 256 EP 256 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100457 ER PT J AU Thorndike, AN Healey, E Sonnenberg, L Brill-Daley, K Regan, S AF Thorndike, A. N. Healey, E. Sonnenberg, L. Brill-Daley, K. Regan, S. TI Be fit worksite wellness program to promote weight loss and physical activity SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Thorndike, A. N.; Healey, E.; Sonnenberg, L.; Brill-Daley, K.; Regan, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thorndike, A. N.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 257 EP 257 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100461 ER PT J AU Keating, NL Landrum, M Arora, NK Malin, JL Ganz, PA Van Ryn, M Weeks, JC AF Keating, N. L. Landrum, M. Arora, N. K. Malin, J. L. Ganz, P. A. Van Ryn, M. Weeks, J. C. 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TI Combined medication adherence to cardiovascular risk reduction therapy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Bryson, C. L.; Sharp, N. D.; Perkins, M.; Liu, F.] Univ Washington, Hlth Serv Res & Dev Ctr Excellence, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Maciejewski, M. L.] Durham VAMC, Hlth Serv Res & Dev, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 268 EP 268 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100490 ER PT J AU Singh, H Mani, S Espadas, D Franklin, V Petersen, LA AF Singh, H. Mani, S. Espadas, D. Franklin, V. Petersen, L. A. TI Communication ambiguity in an advanced computerized order-entry system SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Singh, H.; Mani, S.; Espadas, D.; Petersen, L. A.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Singh, H.; Mani, S.; Espadas, D.; Petersen, L. A.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. 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NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 272 EP 272 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100501 ER PT J AU Volpp, KG Rosenbaum, P Rosen, A Romano, PS Bellini, LM Itani, KM Cen, L Shoshan, O Halenar, M Silber, JH AF Volpp, K. G. Rosenbaum, P. Rosen, A. Romano, P. S. Bellini, L. M. Itani, K. M. Cen, L. Shoshan, O. Halenar, M. Silber, J. H. TI Did high-risk patients experience worse outcomes under ACGME duty hour rules? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Volpp, K. G.] Univ Penn, Sch Med, CHERP, VAMC, Philadelphia, PA 19104 USA. [Rosenbaum, P.] Univ Penn Wharton Sch, Philadelphia, PA USA. [Rosen, A.] Boston Univ, Boston, MA 02215 USA. [Rosen, A.] Bedford VA, Boston, MA 02215 USA. [Romano, P. S.] Univ Calif Davis, Sacramento, CA 95817 USA. [Bellini, L. M.] Univ Penn, Philadelphia, PA 19104 USA. [Cen, L.] VAMC, CHERP, Philadelphia, PA USA. [Shoshan, O.; Halenar, M.; Silber, J. H.] Childrens Hosp Philadelphia, COR, Philadelphia, PA 19104 USA. [Silber, J. H.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Silber, J. H.] Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. RI Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. 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A.] Yale Univ, New Haven, CT USA. [Goulet, J. L.; Mattocks, K.; Braithwaite, S.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Samet, J.] Boston Univ, Boston, MA 02215 USA. [Crystal, S.] Rutgers State Univ, New Brunswick, NJ 08903 USA. [Rodriquez-Barradas, M.] Debakey VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 298 EP 299 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100569 ER PT J AU Frank, D Rees, C Young, B AF Frank, D. Rees, C. Young, B. TI Experiences of discrimination and self-reported health in a diverse population of diabetic veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Frank, D.] VA Puget Sound, Seattle, WA USA. [Young, B.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 301 EP 301 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100575 ER PT J AU Volpp, KG Pauly, MV Troxel, A Glick, H Weiner, J Asch, DA Deguzman, J Wan, F Audrain, J AF Volpp, K. G. Pauly, M. V. Troxel, A. Glick, H. Weiner, J. Asch, D. A. Deguzman, J. Wan, F. Audrain, J. TI Financial incentives for smoking cessation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Volpp, K. G.; Asch, D. A.] Univ Penn, Sch Med, CHERP, Philadelphia VAMC, Philadelphia, PA 19104 USA. [Volpp, K. G.; Pauly, M. V.; Troxel, A.; Glick, H.; Weiner, J.; Asch, D. A.; Deguzman, J.; Wan, F.; Audrain, J.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 304 EP 304 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100585 ER PT J AU Majesko, AA Mcginnis, K Ibrahim, S Butt, AA AF Majesko, A. A. Mcginnis, K. Ibrahim, S. Butt, A. A. TI Gender and prevalence of major comorbidities among patients with hepatitis C. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Majesko, A. A.; Butt, A. A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Mcginnis, K.; Ibrahim, S.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 306 EP 306 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100590 ER PT J AU Rahilly-Tierney, CR Bowman, TS Djousse, L Sesso, H Gaziano, J AF Rahilly-Tierney, C. R. Bowman, T. S. Djousse, L. Sesso, H. Gaziano, J. TI Fourteen year change in high-density lipoprotein cholesterol and risk of incident coronary heart disease among U.S. male physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Rahilly-Tierney, C. R.] Boston VA Healthcare, Jamaica Plain, MA USA. [Bowman, T. S.] VA Boston Healthcare Syst, Boston, MA USA. [Djousse, L.] Boston Univ, Boston, MA 02215 USA. [Sesso, H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gaziano, J.] Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 306 EP 306 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100589 ER PT J AU Korthuis, PT Zephyrin, LC Fleishman, JA Saha, S Josephs, JS Mcgrath, MM Hellinger, J Gebo, KA AF Korthuis, P. T. Zephyrin, L. C. Fleishman, J. A. Saha, S. Josephs, J. S. Mcgrath, M. M. Hellinger, J. Gebo, K. A. CA Hiv Res Network TI Health related quality of life in HIV-infected patients: The role of substance use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Korthuis, P. T.; Saha, S.; Mcgrath, M. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Zephyrin, L. C.] Columbia Univ, Dept Gynecol & Obstet, New York, NY USA. [Fleishman, J. A.] Agcy Healthcare Res & Qual, Rockville, MD USA. [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Josephs, J. S.; Gebo, K. A.; Hiv Res Network] Johns Hopkins Univ, Baltimore, MD USA. [Hellinger, J.] Community Med Alliance, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 312 EP 312 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100606 ER PT J AU Lorenz, KA Sherbourne, CD Shugarman, LR Rubenstein, LV Wen, L Cohen, A Goebel, J Lanto, A Asch, S AF Lorenz, K. A. Sherbourne, C. D. Shugarman, L. R. Rubenstein, L. V. Wen, L. Cohen, A. Goebel, J. Lanto, A. Asch, S. TI How can we improve the accuracy of routine pain screening? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Lorenz, K. A.; Rubenstein, L. V.; Asch, S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Lorenz, K. A.; Rubenstein, L. V.; Asch, S.] RAND Corp, Los Angeles, CA USA. [Lorenz, K. A.; Rubenstein, L. V.; Cohen, A.; Lanto, A.; Asch, S.] VA Greater Los Angeles, Los Angeles, CA USA. [Sherbourne, C. D.; Shugarman, L. R.] RAND Corp, Santa Monica, CA USA. [Wen, L.] VA Long Beach, Long Beach, CA USA. [Goebel, J.] CSULB, Sch Nursing, Long Beach, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 317 EP 317 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100620 ER PT J AU Leykum, L Piwinski, S Pao, W Huerta, V Ray, N Arevalo, T AF Leykum, L. Piwinski, S. Pao, W. Huerta, V. Ray, N. Arevalo, T. TI Impact of a hospalist-run observation unit on length of stay SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Leykum, L.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Pao, W.; Huerta, V.; Ray, N.] Univ Hlth Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 320 EP 320 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100628 ER PT J AU Volpp, K Rosen, A Romano, PS Itani, KM Mi, L Even-Shoshan, O Halenar, M Silber, JH AF Volpp, K. Rosen, A. Romano, P. S. Itani, K. M. Mi, L. Even-Shoshan, O. Halenar, M. Silber, J. H. TI Impact of ACGME duty hour rules on prolonged length of stay among medicare patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Volpp, K.] Philadelphia VAMC, CHERP, Philadelphia, PA USA. [Volpp, K.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Rosen, A.] Bedford VA, Boston, MA USA. [Rosen, A.] Boston Univ, Boston, MA 02215 USA. [Romano, P. S.] Univ Calif Davis, Sacramento, CA 95817 USA. [Itani, K. M.] Boston VA, Boston, MA USA. [Mi, L.; Even-Shoshan, O.; Halenar, M.] Childrens Hosp Philadelphia, COR, Philadelphia, PA 19104 USA. [Silber, J. H.] Univ Penn, Wharton Sch, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RI Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 320 EP 320 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100629 ER PT J AU Lopez, L Cohen, A Hicks, LS Mckean, S Weissman, J AF Lopez, L. Cohen, A. Hicks, L. S. Mckean, S. Weissman, J. TI Impact of hospitalists on the quality of care of acute medical conditions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Cohen, A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mckean, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Weissman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 321 EP 321 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100631 ER PT J AU Mortensen, E Restrepo, M Pugh, J Anzueto, A AF Mortensen, E. Restrepo, M. Pugh, J. Anzueto, A. TI Impact of prior outpatient antibiotic use on mortality for patients hospitalized with community acquired pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Mortensen, E.] UTHSCSA, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Restrepo, M.; Pugh, J.; Anzueto, A.] Audie L Murphy VA Hosp, San Antonio, TX USA. [Restrepo, M.; Pugh, J.; Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 322 EP 322 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100633 ER PT J AU Federman, A Halm, EA Sano, M Safran, DG Siu, AL AF Federman, A. Halm, E. A. Sano, M. Safran, D. G. Siu, A. L. TI Impaired cognitive performance is associated with limited health literacy in older adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Federman, A.; Halm, E. A.] Mt Sinai Sch Med, New York, NY USA. [Sano, M.; Siu, A. L.] James J Peters Vet Adm Med Ctr, New York, NY USA. [Safran, D. G.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 324 EP 324 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100639 ER PT J AU Murkofsky, RL Marcantonio, ER O'Malley, AJ Caudry, DJ Buchanan, JL AF Murkofsky, R. L. Marcantonio, E. R. O'Malley, A. J. Caudry, D. J. Buchanan, J. L. TI Influence of resident and facility factors on the hospitalization of nursing home residents: Findings from an expert panel SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Murkofsky, R. L.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Marcantonio, E. R.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [O'Malley, A. J.; Caudry, D. J.; Buchanan, J. L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 329 EP 329 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100653 ER PT J AU Farwell, WR Sesso, HD Gaziano, JM AF Farwell, W. R. Sesso, H. D. Gaziano, J. M. TI Is high-density-lipoprotein cholesterol associated with the risk of developing prostate cancer? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Farwell, W. R.; Sesso, H. D.; Gaziano, J. M.] Harvard Univ, Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 334 EP 334 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100667 ER PT J AU Salanitro, AH Safford, MM Houston, TK Williams, J Kiefe, CI Ovalle, F Allison, JJ Estrada, CA AF Salanitro, A. H. Safford, M. M. Houston, T. K. Williams, J. Kiefe, C. I. Ovalle, F. Allison, J. J. Estrada, C. A. TI Is patient complexity associated with physician performance on diabetes measures? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Salanitro, A. H.; Estrada, C. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Safford, M. M.; Houston, T. K.; Williams, J.; Kiefe, C. I.; Ovalle, F.; Allison, J. J.] Univ Birmingham, Birmingham, AL USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 335 EP 336 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100671 ER PT J AU Gopal, RK Miyoshi, TJ Glasheen, JJ Prochazka, AV AF Gopal, R. K. Miyoshi, T. J. Glasheen, J. J. Prochazka, A. V. TI Long-term impact of resident work-hour restrictions on burnout SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Gopal, R. K.; Prochazka, A. V.] Denver VAMC, Denver, CO USA. [Miyoshi, T. J.] Univ Rochester, Rochester, NY USA. [Glasheen, J. J.] UCHSC, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 340 EP 340 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100683 ER PT J AU Saha, S Wimmers, PF Guiton, G Wilkerson, L AF Saha, S. Wimmers, P. F. Guiton, G. Wilkerson, L. TI Medical school diversity and educational outcomes in the United States SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Wimmers, P. F.; Wilkerson, L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Guiton, G.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 344 EP 344 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100695 ER PT J AU Bryson, CL Au, DH Sun, H Williams, EC Kivlahan, DR Bradley, KA AF Bryson, C. L. Au, D. H. Sun, H. Williams, E. C. Kivlahan, D. R. Bradley, K. A. TI Medication adherence decreases with increasing AUDIT-C alcohol screening scores SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Bryson, C. L.; Au, D. H.; Sun, H.; Williams, E. C.; Kivlahan, D. R.; Bradley, K. A.] Univ Washington, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 346 EP 346 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100700 ER PT J AU Isaac, T Weissman, J Davis, R Massagli, M Cyrulik, A Sands, DZ Weingart, SN AF Isaac, T. Weissman, J. Davis, R. Massagli, M. Cyrulik, A. Sands, D. Z. Weingart, S. N. TI Medication alerts in ambulatory care: More noise than news for prescribers? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Isaac, T.] VA Boston Healthcare, MAVERIC, Boston, MA USA. [Weissman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Davis, R.; Sands, D. Z.] Harvard Univ, Boston, MA 02115 USA. [Massagli, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cyrulik, A.] Blue Cross & Blue Shield Massachusetts, Boston, MA USA. [Weingart, S. N.] Harvard Univ, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 346 EP 347 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100701 ER PT J AU Cohen, BE Kim, SE Gima, KS Bertenthal, D Marmar, CR Seal, KH AF Cohen, B. E. Kim, S. E. Gima, K. S. Bertenthal, D. Marmar, C. R. Seal, K. H. TI Mental health disorders and PTSD increase non-mental health services utilization: A study of 180,324 veterans returning from Iraq and Afghanistan seen at department of veterans affairs facilities SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Cohen, B. E.; Kim, S. E.; Bertenthal, D.; Marmar, C. R.; Seal, K. H.] Univ Calif San Francisco, San Francisco SF VA Med Ctr, San Francisco, CA 94143 USA. [Gima, K. S.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 347 EP 348 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100704 ER PT J AU Yee, EF White, RE Lee, SJ Yano, E Washington, D Murata, GH Handanos, C Hoffman, RM AF Yee, E. F. White, R. E. Lee, S. J. Yano, E. Washington, D. Murata, G. H. Handanos, C. Hoffman, R. M. TI Mental illness and pain as barriers to cancer screening in women SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Yee, E. F.; Murata, G. H.; Handanos, C.; Hoffman, R. M.] New Mexico VA Hlth Care Syst, Albuquerque, NM USA. [White, R. E.] Lovelace Clin Fdn, Albuquerque, NM USA. [Lee, S. J.] Univ New Mexico, Albuquerque, NM 87131 USA. [Yano, E.] VA Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. [Washington, D.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 348 EP 348 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100705 ER PT J AU Steinman, M Goldstein, MK AF Steinman, M. Goldstein, M. K. TI New methods for performance measurement in hypertension: Results from an expert panel SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Steinman, M.] UCSF, San Francisco VAMC, San Francisco, CA USA. [Goldstein, M. K.] Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 351 EP 351 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100713 ER PT J AU Long, JA Kimmel, SE Yang, W Troxel, A Volpp, K AF Long, J. A. Kimmel, S. E. Yang, W. Troxel, A. Volpp, K. TI Novel predictors of medication adherence among veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Long, J. A.; Volpp, K.] VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Kimmel, S. E.; Yang, W.; Troxel, A.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 352 EP 352 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100717 ER PT J AU Hausmann, L Kresevic, D Cohen, PZ Grant, R Zickmund, S Mor, M Geng, M Gordon, HS Ibrahim, SA AF Hausmann, L. Kresevic, D. Cohen, P. Z. Grant, R. Zickmund, S. Mor, M. Geng, M. Gordon, H. S. Ibrahim, S. A. TI Patient race and doctor-patient communication in the orthopedic setting SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Hausmann, L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kresevic, D.; Grant, R.] Univ Hosp Case Med Ctr, Louis Stokes DVA Med Ctr, Cleveland, OH USA. [Cohen, P. Z.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Mor, M.; Geng, M.; Ibrahim, S. A.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gordon, H. S.] Univ Illinois, Jesse Brown VAMC, Chicago, IL USA. RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 358 EP 358 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100733 ER PT J AU Saha, S Korthuis, PT Sharp, V Cohn, JA Haidet, PM Moore, RD Beach, MC AF Saha, S. Korthuis, P. T. Sharp, V. Cohn, J. A. Haidet, P. M. Moore, R. D. Beach, M. C. TI Patient-provider cultural dissimilarity and racial disparities in HIV care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Korthuis, P. T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cohn, J. A.] Wayne State Univ, Detroit, MI USA. [Sharp, V.] Columbia Univ, St Lukes Roosevelt Hosp, New York, NY USA. [Haidet, P. M.] Baylor Coll Med, Houston, TX 77030 USA. [Moore, R. D.; Beach, M. C.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 359 EP 360 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100737 ER PT J AU Starrels, JL Barg, FK Metlay, JP AF Starrels, J. L. Barg, F. K. Metlay, J. P. TI Patterns and determinants of inappropriate antibiotic use among injection drug users SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Starrels, J. L.; Metlay, J. P.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Barg, F. K.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 361 EP 361 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100740 ER PT J AU Obara, H Tokuda, Y Miyagi, S Tamaki, K Sadohara, M Orlander, JD AF Obara, H. Tokuda, Y. Miyagi, S. Tamaki, K. Sadohara, M. Orlander, J. D. TI Perceived preparedness of Japanese medical graduates for postgraduate training: A comparison to us graduates SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Obara, H.] Boston Univ, Boston, MA 02215 USA. [Tokuda, Y.] St Lukes Life Sci Inst, Chuo City, Tokyo, Japan. [Miyagi, S.] Muribushi Project For Okinawa Residency Programs, Okinawa, Japan. [Tamaki, K.] Okinawa Chubu Hosp, Okinawa, Japan. [Sadohara, M.] Fukuoka Tokushukai Hosp, Fukuoka, Japan. [Orlander, J. D.] VA Boston Hlth Care Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 362 EP 362 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100743 ER PT J AU Barrett, TW Mori, M Malley, JPO AF Barrett, T. W. Mori, M. Malley, J. P. O' TI Perioperative beta-blockers and statins and effects of withdrawal or initiation on short term mortality after vascular surgery SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Barrett, T. W.] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Barrett, T. W.] Portland VA Med Ctr, Sect Gen Med, Portland, OR USA. [Mori, M.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA. [Malley, J. P. O'] Oregon Hlth & Sci Univ, Ctr Biostat Comp & Informat Biol & Med, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 363 EP 363 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100747 ER PT J AU Lawrence, VA Hazuda, HP Cornell, JE AF Lawrence, V. A. Hazuda, H. P. Cornell, J. E. TI Perioperative depression and elders' recovery after major open abdominal surgery SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Lawrence, V. A.; Hazuda, H. P.; Cornell, J. E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lawrence, V. A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 363 EP 364 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100748 ER PT J AU Weiner, MG Field, S Garvin, JH Holmes, JH Synnestvedt, M Long, JA AF Weiner, M. G. Field, S. Garvin, J. H. Holmes, J. H. Synnestvedt, M. Long, J. A. TI Persistently elevated HBA1C: Poor quality doctors or challenging patients? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Weiner, M. G.; Field, S.; Holmes, J. H.; Synnestvedt, M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Garvin, J. H.; Long, J. A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 364 EP 365 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100750 ER PT J AU Gordon, AJ Hilton, M Haas, GL Andree, T Goldstein, G AF Gordon, A. J. Hilton, M. Haas, G. L. Andree, T. Goldstein, G. TI Personal, medical, and healthcare utilization differences between metropolitan and non-metropolitan homeless veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Gordon, A. J.; Haas, G. L.; Goldstein, G.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 365 EP 365 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100751 ER PT J AU Grosheider, T Luther, J Ramgopal, R Gordon, AJ AF Grosheider, T. Luther, J. Ramgopal, R. Gordon, A. J. TI Physician attitudes towards harm reduction in office-based opioid agonist therapy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Grosheider, T.; Luther, J.; Ramgopal, R.; Gordon, A. J.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 366 EP 367 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100755 ER PT J AU Aagaard, EM Gonzales, R Camargo, CA Auten, R Levin, SK Maselli, J Metlay, JP AF Aagaard, E. M. Gonzales, R. Camargo, C. A., Jr. Auten, R. Levin, S. K. Maselli, J. Metlay, J. P. TI Physician champions influence the effectiveness of interventions to improve antibiotic prescribing quality SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Aagaard, E. M.] Univ Colorado, Aurora, CO USA. [Gonzales, R.; Levin, S. K.; Maselli, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Metlay, J. P.] Univ Penn, VA Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 367 EP 367 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100757 ER PT J AU Saha, S Korthuis, PT Cohn, JA Sharp, V Moore, RD Beach, MC AF Saha, S. Korthuis, P. T. Cohn, J. A. Sharp, V. Moore, R. D. Beach, M. C. TI Physician cultural competence, patient self-management, and clinical outcomes among persons living with HIV/AIDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Korthuis, P. T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cohn, J. A.] Wayne State Univ, Detroit, MI USA. [Sharp, V.] St Lukes & Roosevelt Hosp, New York, NY USA. [Moore, R. D.; Beach, M. C.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 367 EP 368 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100758 ER PT J AU Barry, MJ Wescott, PH Reifler, EJ Chang, Y Moulton, BW AF Barry, M. J. Wescott, P. H. Reifler, E. J. Chang, Y. Moulton, B. W. TI Potential jurors' reactions to a PSA malpractice case SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Barry, M. J.; Chang, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wescott, P. H.; Reifler, E. J.] Fdn Informed Med Decis Making, Boston, MA 02114 USA. [Moulton, B. W.] Amer Soc Law Med & Eth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 372 EP 372 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100769 ER PT J AU Kressin, NR Glickman, M Orner, MB Manze, M Berlowitz, DR AF Kressin, N. R. Glickman, M. Orner, M. B. Manze, M. Berlowitz, D. R. TI Predicting blood pressure control: Is race, or factors associated with race, more important? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Kressin, N. R.; Berlowitz, D. R.] Boston Univ, Bedford, MA USA. [Manze, M.] Boston Univ, Med Ctr, Boston, MA 02215 USA. [Orner, M. B.] US Dept Vet Affairs, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 372 EP 373 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100771 ER PT J AU Lopez, L Cohen, AP Schneider, EC Weingart, SN Epstein, AM Weissman, J AF Lopez, L. Cohen, A. P. Schneider, E. C. Weingart, S. N. Epstein, A. M. Weissman, J. TI Predictors of disclosure of hospital adverse events and its impact on patient's quality ratings SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Lopez, L.; Weissman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cohen, A. P.; Schneider, E. C.; Epstein, A. M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Weingart, S. N.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 374 EP 375 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100776 ER PT J AU Aujesky, D Mor, MK Geng, M Fine, MJ Ibrahim, SA AF Aujesky, D. Mor, M. K. Geng, M. Fine, M. J. Ibrahim, S. A. TI Predictors of hospital readmission after acute pulmonary embolism SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Aujesky, D.] Univ Lausanne, Lausanne, Switzerland. [Mor, M. K.; Geng, M.; Fine, M. J.; Ibrahim, S. A.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Mor, M. K.; Geng, M.; Fine, M. J.; Ibrahim, S. A.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 375 EP 375 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100778 ER PT J AU Sherman, SE Cummins, S Finney, J Kalra, P Kuschner, W York, L Zhu, S AF Sherman, S. E. Cummins, S. Finney, J. Kalra, P. Kuschner, W. York, L. Zhu, S. TI Preliminary results from a study of telephone care coordination for smoking cessation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Sherman, S. E.] New York Harbor Healthcare Syst, New York, NY USA. [Finney, J.] Stanford Univ, Menlo Pk, CA USA. [Kalra, P.] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Kuschner, W.] Stanford Univ, Stanford, CA 94305 USA. [York, L.] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 376 EP 377 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100782 ER PT J AU Beste, LA Sun, H Maynard, C Bishop, MJ Henderson, W Schifftner, T Hughes, G Todd-Sternberg, J Kivlahan, DR Hawkins, E Harris, A Debenedetti, A Bradley, K AF Beste, L. A. Sun, H. Maynard, C. Bishop, M. J. Henderson, W. Schifftner, T. Hughes, G. Todd-Sternberg, J. Kivlahan, D. R. Hawkins, E. Harris, A. Debenedetti, A. Bradley, K. TI Prevalence of alcohol misuse in patients undergoing common surgeries in VA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Beste, L. A.; Sun, H.; Maynard, C.; Todd-Sternberg, J.; Hawkins, E.; Debenedetti, A.; Bradley, K.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Bishop, M. J.; Hughes, G.; Kivlahan, D. R.] Univ Washington, Seattle, WA 98195 USA. [Henderson, W.; Schifftner, T.] VA Fitzimmons, Natl Surgical Qual Improvement Program, Aurora, CO USA. [Harris, A.] VA Palo Alto, Palo Alto, CA USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 377 EP 377 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100784 ER PT J AU Kertesz, SG Hwang, SW Ritchey, FJ Lagory, M AF Kertesz, S. G. Hwang, S. W. Ritchey, F. J. Lagory, M. TI Priced out of the safety net? Declining access to health care among birmingham's homeless, 1995-2005 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Kertesz, S. G.] U Alabama, Birmingham VAMC, Birmingham, AL USA. [Hwang, S. W.] Univ Toronto, Toronto, ON, Canada. [Ritchey, F. J.; Lagory, M.] Univ Alabama, Birmingham, AL USA. RI Hwang, Stephen/D-2297-2011 OI Hwang, Stephen/0000-0002-1276-1101 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 379 EP 380 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100790 ER PT J AU Fischer, MA Stedman, M Lii, J Vogeli, C Weissman, J AF Fischer, M. A. Stedman, M. Lii, J. Vogeli, C. Weissman, J. TI Primary medication adherence in patients receiving electronic prescriptions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Fischer, M. A.; Stedman, M.; Lii, J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Weissman, J.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Weissman, J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 381 EP 381 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100794 ER PT J AU Mccolgan, K Dykes, P Carroll, D Hurley, AC Lipsitz, SR Benoit, A Tsurikova, R Middleton, B AF Mccolgan, K. Dykes, P. Carroll, D. Hurley, A. C. Lipsitz, S. R. Benoit, A. Tsurikova, R. Middleton, B. TI Professional caregivers perceptions of fall risk communication and interventions to prevent falls in acute care hospitals SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Mccolgan, K.; Hurley, A. C.; Lipsitz, S. R.; Tsurikova, R.; Middleton, B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dykes, P.; Benoit, A.] Partners HealthCare Syst Inc, Wellesley, MA USA. [Carroll, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 381 EP 382 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100795 ER PT J AU Kansagara, DL Ramsay, RS Labby, D Bricker, S Saha, S AF Kansagara, D. L. Ramsay, R. S. Labby, D. Bricker, S. Saha, S. TI Prospective cohort study of a post-hospital discharge intervention in chronically ill medicaid patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Kansagara, D. L.; Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Ramsay, R. S.; Labby, D.] CareOregon, Portland, OR USA. [Bricker, S.] Texas Hlth & Human Serv Commissi, Austin, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 382 EP 383 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100798 ER PT J AU Zickmund, S Tirado, C Campbell, S Weinrieb, R AF Zickmund, S. Tirado, C. Campbell, S. Weinrieb, R. TI Provider communication cited as barrier to antiviral therapy for hepatitis C-infected methadone using patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Zickmund, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Tirado, C.] Univ Texas Southwestern, Dallas, TX USA. [Campbell, S.] Univ Penn, Philadelphia, PA 19104 USA. [Weinrieb, R.] VA Philadelphia Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 383 EP 383 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100799 ER PT J AU Gavin, CEM Lawler, E Scranton, R Gagnon, D Gaziano, J AF Gavin, C. E. Mclaughlin Lawler, E. Scranton, R. Gagnon, D. Gaziano, J. TI Reduction in glycosylated hemoglobin and the risk of cardiac events among veterans starting treatment for type 2 diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Gavin, C. E. Mclaughlin; Lawler, E.; Scranton, R.; Gagnon, D.; Gaziano, J.] Boston VA Healthcare Syst, MAVERIC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 392 EP 392 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100823 ER PT J AU Mourad, M Kohlwes, J AF Mourad, M. Kohlwes, J. TI See one, do one, teach one - An evaluation of procedural skills education during internal medicine residency SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Kohlwes, J.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 398 EP 398 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100841 ER PT J AU Eckman, MH Greenberg, SM Rosand, J AF Eckman, M. H. Greenberg, S. M. Rosand, J. TI Should we test for CYP2C9 before initiating anticoagulant therapy in patients with atrial fibrillation? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Eckman, M. H.] Univ Cincinnati, Cincinnati, OH USA. [Greenberg, S. M.; Rosand, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 401 EP 401 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100849 ER PT J AU Schnipper, JL Hamann, C Ndumele, C Liang, C Carty, M Karson, AS Bhan, I Coley, M Poon, EG Turchin, A Labonville, S Diedrichsen, E Lipsitz, S Broverman, C Mccarthy, P Gandhi, T AF Schnipper, J. L. Hamann, C. Ndumele, C. Liang, C. Carty, M. Karson, A. S. Bhan, I. Coley, M. Poon, E. G. Turchin, A. Labonville, S. Diedrichsen, E. Lipsitz, S. Broverman, C. Mccarthy, P. Gandhi, T. TI The effects of a medication reconciliation application and process redesign on potential adverse drug events: Results of a controlled trial SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Schnipper, J. L.] Soc Gen Internal Med, Boston, MA USA. [Hamann, C.; Bhan, I.; Diedrichsen, E.; Mccarthy, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ndumele, C.; Liang, C.; Carty, M.; Poon, E. G.; Labonville, S.; Gandhi, T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Karson, A. S.] Massachusetts Gen Hosp, Lexington, MA USA. [Coley, M.] Harvard Univ, Chestnut Hill, MA USA. [Turchin, A.] Harvard Univ, Sch Med, Wellesley, MA USA. [Lipsitz, S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Broverman, C.] Partners Informat Syst Clin Informat Res & Dev, Wellesley, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 413 EP 413 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100882 ER PT J AU Pollack, C Mallya, G Polsky, D AF Pollack, C. Mallya, G. Polsky, D. TI The impact of consumer-directed healthplans and patient socioeconomic status on physician recommendations for colorectal cancer screening SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Pollack, C.; Mallya, G.] Univ Penn, Philadelphia VA Med Ctr, RWJ Clin Scholars Program, Philadelphia, PA 19104 USA. [Polsky, D.] Philadelphia VAMC, CHERP, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 414 EP 414 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100886 ER PT J AU Korthuis, PT Saha, S Moore, RD Cohn, JA Sharp, V Beach, MC AF Korthuis, P. T. Saha, S. Moore, R. D. Cohn, J. A. Sharp, V. Beach, M. C. TI The impact of substance use on communication quality SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Korthuis, P. T.; Saha, S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Moore, R. D.; Beach, M. C.] Johns Hopkins Univ, Baltimore, MD USA. [Cohn, J. A.] Wayne State Univ, Detroit, MI USA. [Sharp, V.] St Lukes & Roosevelt Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 417 EP 417 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100893 ER PT J AU Haskell, SG Bean-Mayberry, B AF Haskell, S. G. Bean-Mayberry, B. TI The National Women Veterans hormone replacement therapy survey: Factors associated with continuing hormone therapy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Haskell, S. G.] VA CT Healthcare Syst, West Haven, CT USA. [Bean-Mayberry, B.] VA Greater Los Angeles Hlth Serv Res & Dev, Ctr Excellence, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 418 EP 419 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100897 ER PT J AU Garner, C Evans-Molina, C Shea, C Henault, L Hylek, E AF Garner, C. Evans-Molina, C. Shea, C. Henault, L. Hylek, E. TI The psychological impact of a black box warning drug-warfarin SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Garner, C.; Henault, L.; Hylek, E.] Boston Med Ctr, Boston, MA USA. [Evans-Molina, C.] Univ Virginia, Charlottesville, VA USA. [Shea, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 420 EP 420 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100901 ER PT J AU Korthuis, PT Saha, S Moore, RD Cohn, JA Sharp, V Beach, MC AF Korthuis, P. T. Saha, S. Moore, R. D. Cohn, J. A. Sharp, V. Beach, M. C. TI The role of communication self-efficacy in patient comfort discussing substance use issues SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Korthuis, P. T.; Saha, S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Cohn, J. A.] Wayne State Univ, Detroit, MI USA. [Sharp, V.] St Lukes Roosevelt Hosp, New York, NY 10025 USA. [Moore, R. D.; Beach, M. C.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 423 EP 424 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100911 ER PT J AU Nadkarni, M Bates, C Fosburgh, B Holmboe, E AF Nadkarni, M. Bates, C. Fosburgh, B. Holmboe, E. TI The resident continuity clinic experience: A national survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Nadkarni, M.] Univ Virginia, Charlottesville, VA USA. [Bates, C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Fosburgh, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Holmboe, E.] Yale Univ, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 423 EP 423 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100909 ER PT J AU Aujesky, D Stone, RA Geng, M Obrosky, DS Fine, MJ Ibrahim, SA AF Aujesky, D. Stone, R. A. Geng, M. Obrosky, D. S. Fine, M. J. Ibrahim, S. A. TI Thrombolytic therapy and mortality in patients with acute pulmonary embolism SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Aujesky, D.] Univ Lausanne, Lausanne, Switzerland. [Stone, R. A.; Geng, M.; Obrosky, D. S.; Fine, M. J.; Ibrahim, S. A.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Stone, R. A.; Geng, M.; Obrosky, D. S.; Fine, M. J.; Ibrahim, S. A.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 425 EP 425 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100915 ER PT J AU Gordon, AJ Kavanaugh, G Paidisetty, S Ramgopal, R Liberto, JG AF Gordon, A. J. Kavanaugh, G. Paidisetty, S. Ramgopal, R. Liberto, J. G. TI Translating research into practice: Facilitators and barriers of implementing buprenorphine in the Veteran Health Administration SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Gordon, A. J.; Paidisetty, S.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kavanaugh, G.; Liberto, J. G.] Univ Maryland, VA Maryland Healthcare Syst, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 426 EP 426 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100917 ER PT J AU Mccall-Hosenfeld, JS Liebschutz, J Freund, KM AF Mccall-Hosenfeld, J. S. Liebschutz, J. Freund, K. M. TI Victimization by a known assailant is associated with delay to presentation for care after sexual assault SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Mccall-Hosenfeld, J. S.; Liebschutz, J.; Freund, K. M.] Boston Univ, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 437 EP 438 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100948 ER PT J AU Spira, AP Friedman, L Aulakh, JS Lee, T Sheikh, JI Yesavage, JA AF Spira, Adam P. Friedman, Leah Aulakh, Jasdeep S. Lee, Tina Sheikh, Javaid I. Yesavage, Jerome A. TI Subclinical anxiety symptoms, sleep, and daytime dysfunction in older adults with primary insomnia SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Profess Sleep Soc DE anxiety; depression; insomnia actigraphy ID DSM-IV; PREVALENCE; DISORDERS AB "Both Insomnia complaints and anxiety-related distress are common in older adults, and are associated with poor daytime functioning. We investigated whether subclinical levels of anxiety were associated with sleep disturbance and daytime functioning in older adults who met diagnostic criteria for primary insomnia, and therefore but did not meet criteria for depression or an anxiety disorder. After adjustment for depressive symptoms, elevated state anxiety was associated with higher levels of wake after sleep onset (measured by both actigraphy and sleep log) and and shorter sleep sleep onset latency (measured by sleep log). Higher levels of trait anxiety were associated with greater wake after sleep onset (measured by sleep log). Elevated state and trait anxiety were associated with worse and social functioning, and higher levels of trait anxiety were associated with worse role functioning. Thus, subclinical anxiety symptoms may be an important target for clinical intervention to improve sleep and functioning in older adults with primary insomnia.". C1 [Spira, Adam P.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Spira, Adam P.] San Francisco VA Med Ctr, San Francisco, CA USA. [Friedman, Leah; Aulakh, Jasdeep S.; Sheikh, Javaid I.; Yesavage, Jerome A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Aulakh, Jasdeep S.; Lee, Tina; Sheikh, Javaid I.; Yesavage, Jerome A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Spira, AP (reprint author), 4150 Clement St,181-G, San Francisco, CA USA. EM adam.spira@ucsf.edu FU NIA NIH HHS [AG 12914] NR 19 TC 7 Z9 8 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD MAR PY 2008 VL 21 IS 1 BP 56 EP 60 DI 10.1177/0891988707311043 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 266SQ UT WOS:000253457700008 PM 18287171 ER PT J AU Ramirez, AM Chaya, CJ Gordon, LK Giaconi, JA AF Ramirez, Adilana M. Chaya, Craig J. Gordon, Lynn K. Giaconi, JoAnn A. TI A comparison of semiautomated versus manual goldmann kinetic perimetry in patients with visually significant glaucoma SO JOURNAL OF GLAUCOMA LA English DT Article DE perimetry; Goldmann; octopus; glaucoma ID LONG-TERM FLUCTUATION; FIELD; VARIABILITY; THRESHOLD AB Purpose: To determine if semiautomated kinetic perimetry (SKP) is reproducible and comparable to Goldmann manual kinetic perimetry (GVF). Methods: Glaucoma patients were recruited to perform visual field testing using GVF and SKP. Specific isopters were tested, quantified, and compared. Visual field patterns were analyzed for shape and defect. Results: Ten patients (16 eyes) underwent visual field studies using SKP and GVF, and 8 patients completed a second SKP on a different day. Individual isopter areas were similar between GVF and SKP, although 60% of isopters were larger oil SKP by ail average of 15%. This was statistically significant for the smaller isopters, I4e (P = 0.02) and I2e (P = 0.05). Retesting with SKP on a separate day, showed similar isopter areas (P values = 0.3 to 1.0), however, the exact location of isopters in degrees from central fixation tended to vary with the smaller test object sizes. Isopler position in degrees from the central axis agreed in at least 3 quadrants in approximately 65% of fields compared. SKP visual field defects and patterns were similar between test strategies. Conclusions: SKP and GVF testing produce similar visual field results in glaucoma patients, and SKP testing seems to be reliable and reproducible in this population. However, overlapping isopters, typically associated with nonorgamic vision loss, and jagged isopters were sometimes observed in SK P visual fields. Further study of SKP is needed to explore these findings. C1 [Ramirez, Adilana M.; Gordon, Lynn K.; Giaconi, JoAnn A.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Chaya, Craig J.] Greater Los Angeles VA Healthcare Syst, Dept Med, Los Angeles, CA USA. [Gordon, Lynn K.; Giaconi, JoAnn A.] Greater Los Angeles VA Healthcare Syst, Ophthalmol Sect, Los Angeles, CA USA. RP Giaconi, JA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, 100 Stein Pl, Los Angeles, CA 90095 USA. EM giaconi@jsei.ucla.edu NR 16 TC 8 Z9 9 U1 0 U2 3 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 MAR PY 2008 VL 17 IS 2 BP 111 EP 117 PG 7 WC Ophthalmology SC Ophthalmology GA 280FZ UT WOS:000254412400005 PM 18344756 ER PT J AU Calderon, SAL Paiva, A Ring, D AF Calderon, Santiago A. Lozano Paiva, Alex Ring, David TI Patient satisfaction after open carpal tunnel release correlates with depression SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE carpal tunnel syndrome; depression; nerve dysfunction; open carpal tunnel release; patient satisfaction ID ADVANCED DISEASE; SURGERY; SYMPTOMS; VALIDATION; SCALE; OLDER; AGE; SHOULDER; PAIN; ARM AB Purpose To test the null hypothesis that depression does not correlate with patient satisfaction after open release of electrodiagnostically confirmed carpal tunnel syndrome when controlling for other demographic, disease-related, and psychosocial factors. Methods Eighty-two survey respondents who had recovered (minimum 2 years after surgery) from a limited incision open carpal tunnel release completed measures of satisfaction, perceived disability, depression, pain catastrophizing, and pain anxiety. Univariate and multivariate analyses sought predictors of satisfaction and perceived disability from among demographic, disease related, and psychological factors. Results The average satisfaction score was 8 points (range, 0-10) and the average Disabilities of the Arm, Shoulder, and Hand score was 13 points (range, 0-76). Predictors of greater dissatisfaction included greater depression and the categorical electrophysiologic test rating. Predictors of perceived disability included depression, pain catastrophizing, and static numbness. Depression was the dominant predictor of both satisfaction and perceived disability. Conclusions Dissatisfaction and perceived disability after limited open carpal tunnel release for electrodiagnostically confirmed idiopathic carpal tunnel syndrome is predicted primarily by depression and ineffective coping skills and to a lesser degree by clinical or electrophysiologic evidence of advanced nerve damage. C1 [Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100, Boston, MA 02114 USA. EM dring@partners.org NR 24 TC 21 Z9 21 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2008 VL 33A IS 3 BP 303 EP 307 DI 10.1016/j.jhsa.2007.11.025 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 284RQ UT WOS:000254723900001 ER PT J AU Horner, MD Selassie, AW Lineberry, L Ferguson, PL Labbate, LA AF Horner, Michael D. Selassie, Anbesaw W. Lineberry, Lee Ferguson, Pamela L. Labbate, Lawrence A. TI Predictors of psychological symptoms 1 year after traumatic brain injury: A population-based, epidemiological study SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE anxiety; brain damage; chronic; depression; epidemiologic studies,follow-up studies; mood disorders ID NATIONAL PROBABILITY SAMPLE; AMERICAN DRINKING PRACTICES; PSYCHIATRIC-DISORDERS; HEAD-INJURY; AXIS-I; DEPRESSION; REHABILITATION; QUESTIONNAIRE; INDIVIDUALS; OUTPATIENTS AB Objective: To examine self-reported psychological symptoms 1 year after traumatic brain injury (TBI) in a populationbased sample. Participants: There were 1560 adults who had sustained TBI. Design: A telephone survey with questions about recent mood and anxiety symptoms, and diagnoses since TBI. Polychotomous logistic regression with 3 response levels (probable, possible, and no mood or anxiety symptoms) identified predictors of psychological symptoms. Results: Overall, 40% of participants had clinically significant mood or anxiety symptoms-12.6% with probable symptoms and 27.5% with possible symptoms. Main risk factors for probable symptoms included younger age, poor physical functioning, inadequate social support, and being a white woman. Other risk factors included being retired or unemployed, and pre-TBI psychiatric disorder or multiple concussions. Conclusions: These findings suggest the need for careful screening of persons with TBI who are at particular risk of developing psychological symptoms, and persons who have recently sustained TBI and their families to be educated about the possibility of developing such symptoms. C1 [Horner, Michael D.; Labbate, Lawrence A.] Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. [Horner, Michael D.; Labbate, Lawrence A.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Selassie, Anbesaw W.; Lineberry, Lee; Ferguson, Pamela L.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. RP Horner, MD (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM hornermd@musc.edu NR 49 TC 14 Z9 15 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD MAR-APR PY 2008 VL 23 IS 2 BP 74 EP 83 DI 10.1097/01.HTR.0000314526.01006.c8 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 280KW UT WOS:000254426700002 PM 18362761 ER PT J AU Ison, MG Sharma, A Shepard, JAO Wain, JC Ginns, LC AF Ison, Michael G. Sharma, Amita Shepard, Jo-Anne O. Wain, John C. Ginns, Leo C. TI Outcome of influenza infection managed with oseltamivir in lung transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID BRONCHIOLITIS OBLITERANS SYNDROME; RESPIRATORY VIRAL-INFECTIONS; UNITED-STATES; IMMUNE-RESPONSE; VIRUS-INFECTION; VACCINATION AB Background: influenza causes significant morbidity and mortality in lung transplant recipients and likely predisposes to obliterative bronchiolitis. Neuraminidase inhibitors shorten the duration of symptoms and virus shedding and the number of antibiotic-requiring complications in ambulatory immunocompetent patients, although the efficacy of these agents in lung transplant recipients has not been assessed previously. Methods: In this study, 9 lung transplant patients who were treated with oseltamivir for influenza infections were identified and analyzed retrospectively. Results: Oseltamivir was well tolerated. Infection resolved in all patients and there were no deaths. Two patients developed pneumonia shortly after their influenza infection and both responded to antibiotic therapy. None of the patients had persistent abnormalities noted on chest imaging and most did,not show significant changes on pulmonary function testing. Two patients with the lowest pulmonary function test (PFT) values pre-infection had persistent defects after infection. Conclusions: Oseltamivir is well tolerated in lung transplant recipients and may reduce the risk of complications, although further studies are warranted. C1 [Ison, Michael G.; Sharma, Amita] Northwestern Univ, Div Infect Dis & Organ Transplantat, Feinberg Sch Med, Transplant & Immunocompromised Host Infect Dis Se, Chicago, IL 60611 USA. [Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Thorac Radiol, Boston, MA 02114 USA. [Wain, John C.] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. [Ginns, Leo C.] Massachusetts Gen Hosp, Lung Transplant Program, Pulm & Crit Care Unit, Gen Med Serv, Boston, MA 02114 USA. [Sharma, Amita; Shepard, Jo-Anne O.; Wain, John C.; Ginns, Leo C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ison, MG (reprint author), Northwestern Univ, Div Infect Dis & Organ Transplantat, Feinberg Sch Med, Transplant & Immunocompromised Host Infect Dis Se, 645 N Michigan Ave,Suite 900, Chicago, IL 60611 USA. EM mgison@northwestern.edu NR 24 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAR PY 2008 VL 27 IS 3 BP 282 EP 288 DI 10.1016/j.healun.2007.11.575 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 278ZP UT WOS:000254325100007 PM 18342750 ER PT J AU Konig, A Kilian, E Sohn, HY Rieber, J Schiele, TM Siebert, U Gothe, RM Reichart, B Klauss, V AF Koenig, Andreas Kilian, Eckehard Sohn, Hae-Young Rieber, Johannes Schiele, Thomas Michael Siebert, Uwe Gothe, Raffaella M. Reichart, Bruno Klauss, Volker TI Assessment and characterization of time-related differences in plaque composition by intravascular ultrasound-derived radiofrequency analysis in heart transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID CARDIAC ALLOGRAFT VASCULOPATHY; ATHEROSCLEROSIS; CLASSIFICATION; PROGRESSION; VALIDATION; OUTCOMES AB Background: The survival of heart transplant patients is limited by cardiac allograft vasculopathy (CAV). Intravascular ultrasound (IVUS) and IVUS-derived radiofrequency plaque composition analysis (IVUS-RF) provide further information about the process of coronary atherosclerosis. Methods: In this study we aimed to assess the time-dependent differences in disease progression in patients with CAV. Fifty-six patients were divided into three groups according to time interval after transplantation (Group I: 1 to 3 months, 18 patients; Group II, 1 to 5 years, 20 patients; Group III: 5 to 15 years, 18 patients). Results: IVUS-RF revealed time-dependent increase s in all plaque components. The largest increase was shown for fibrotic, fibrofatty and necrotic tissue between Groups I and II. Dense calcium area increased uniformly in all groups. IVUS-RF-derived plaque type analysis revealed predominantly fibrotic plaques in all groups with a decrease of frequency over time. Fibrolipidic and fibrotic-calcific plaques increased uniformly. High-risk lesions, such as thick-cap fibroatheromas (FAs), increased in Groups I and II and decreased in Group III. Thin-cap FAs were detected only in Group III. Conclusions: IVUS-RF, as compared with gray-scale IVUS, provides better detailed information about the development of CAV by plaque morphology and composition analysis in different stages after heart transplantation. Serial IVUS-RF analysis in these patients may improve the stratification of heart transplant recipients. C1 [Koenig, Andreas; Sohn, Hae-Young; Rieber, Johannes; Schiele, Thomas Michael; Klauss, Volker] Univ Munich, Dept Med, Div Cardiol, Med Klin & Poliklin Innestadt, D-80336 Munich, Germany. [Kilian, Eckehard; Reichart, Bruno] Univ Munich, Klinikum Grosshadern, Dept Cardiac Surg, D-8000 Munich, Germany. [Siebert, Uwe; Gothe, Raffaella M.] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & Hlth Technol As, Hall In Tirol, Austria. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assesment, Boston, MA 02115 USA. RP Konig, A (reprint author), Univ Munich, Dept Med, Div Cardiol, Med Klin & Poliklin Innestadt, Ziemssenstr 1, D-80336 Munich, Germany. EM andreas.koenig@med.uni-muenchen.de 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAR PY 2008 VL 27 IS 3 BP 302 EP 309 DI 10.1016/j.healun.2007.12.003 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 278ZP UT WOS:000254325100010 PM 18342753 ER PT J AU Boyko, EJ Barr, ELM Zimmet, PZ Shaw, JE AF Boyko, E. J. Barr, E. L. M. Zimmet, P. Z. Shaw, J. E. TI Two-hour glucose predicts the development of hypertension over 5 years: the AusDiab study SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE glucose; epidemiology; insulin; risk factors ID ENDOTHELIUM-DEPENDENT VASODILATION; IMPAIRED FASTING GLUCOSE; DISEASE RISK-FACTORS; LIFE-STYLE; CARDIOVASCULAR-DISEASE; AUSTRALIAN ADULTS; FOLLOW-UP; TOLERANCE; HYPERGLYCEMIA; OBESITY AB Elevated 2-h plasma glucose concentration (2hPG) from an oral glucose tolerance (OGTT) test more strongly predicts risk of subsequent cardiovascular disease than fasting plasma glucose (FPG), but the association between these glucose measurements and hypertension risk is less clear. We examined the association between 2hPG, FPG and risk of hypertension. We conducted a prospective observational study (The Australian Diabetes, Obesity and Lifestyle Study-AusDiab) among 4413 Australian residents who attended a baseline (1999 2000) and follow-up (2004-2005) examinations. Measurements included blood pressure (mean of two readings), 75 g OGTT, fasting insulin, anthropometrics, dietary and alcohol intake, medical history and physical activity. Hypertension was defined as a systolic blood pressure (SBP)>= 140 or a diastolic blood pressure (DBP)>= 90mm Hg or treatment with medication for hypertension. HOMA-S was calculated as a measure of insulin sensitivity using the HOMA2 calculator. Hypertension developed in 14% of the 4306 subjects available for this analysis. Higher 2hPG was significantly related to greater risk of hypertension after adjustment for age, gender, FPG, BMI (baseline and difference), waist circumference (baseline and difference), education, exercise, alcohol intake, baseline SBP and smoking (OR (95% CI) 1.12 (1.01 to 1.23)), but no significant association was seen between FPG and hypertension in this model (1.02 (0.88-1.19)). Further adjustment for HOMA-S did not change these findings. Higher baseline 2hPG was more strongly associated with an increase in SBP than in DBP over 5 years. We conclude that higher 2hPG predicted future hypertension occurrence in this population. C1 [Boyko, E. J.] Univ Washington, Dept Med, Seattle ERIC, Seattle, WA 98101 USA. [Boyko, E. J.; Barr, E. L. M.; Zimmet, P. Z.; Shaw, J. E.] Int Diabet Inst, Caulfield, Vic, Australia. [Boyko, E. J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Boyko, EJ (reprint author), Univ Washington, Dept Med, Seattle ERIC, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM eboyko@u.washington.edu RI Shaw, Jonathan/E-7388-2010 OI Shaw, Jonathan/0000-0002-6187-2203 NR 43 TC 11 Z9 15 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD MAR PY 2008 VL 22 IS 3 BP 168 EP 176 DI 10.1038/sj.jhh.1002316 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 262HA UT WOS:000253138400003 PM 18046430 ER PT J AU Cook, CH Bickerstaff, AA Wang, JJ Nadasdy, T Della Pelle, P Colvin, RB Orosz, CG AF Cook, Charles H. Bickerstaff, Alice A. Wang, Jiao-Jing Nadasdy, Tibor Della Pelle, Patricia Colvin, Robert B. Orosz, Charles G. TI Spontaneous renal allograft acceptance associated with "Regulatory" dendritic cells and IDO SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION; DELAYED-TYPE HYPERSENSITIVITY; TRANSCRIPTION FACTOR FOXP3; T-CELLS; TRYPTOPHAN CATABOLISM; TGF-BETA; CUTTING EDGE; LONG-TERM; TRANSPLANTATION TOLERANCE; KIDNEY-TRANSPLANTS AB MHC-mismatched DBA/2 renal allografts are spontaneously accepted by C57BL/6 mice by poorly understood mechanisms, but both immune regulation and graft acceptance develop without exogenous immune modulation. Previous studies have shown that this model of spontaneous renal allograft acceptance is associated with TGF-beta-dependent immune regulation, suggesting a role for T regulatory cells. The current study shows that TGF-beta immune regulation develops 30 days posttransplant, but is lost by 150 days posttransplant. Despite loss of detectable TGF-beta immune regulation, renal allografts continue to function normally for >200 days posttransplantation. Because of its recently described immunoregulatory capabilities, we studied IDO expression in this model, and found that intragraft IDO gene expression progressively increases over time, and that IDO in "regulatory" dendritic cells (RDC) may contribute to regulation associated with long-term maintenance of renal allografts. Immunohistochemistry evaluation confirms the presence of both Foxp3(+) T cells and IDO(+) DCs in accepted renal allografts, and localization of both cell types within accepted allografts suggests the possibility of synergistic involvement in allograft acceptance. Interestingly, at the time when RDCs become detectable in spleens of allograft acceptors, similar to 30% of these mice challenged with donor-matched skin allografts accept these skin grafts, demonstrating progression to "true" tolerance. Together, these data suggest that spontaneous renal allograft acceptance evolves through a series of transient mechanisms, beginning with TGF-beta and T regulatory cells, which together may stimulate development of more robust regulation associated with RDC and IDO. C1 [Cook, Charles H.; Bickerstaff, Alice A.; Wang, Jiao-Jing; Orosz, Charles G.] Ohio State Univ, Dept Surg, Columbus, OH 43210 USA. [Cook, Charles H.] Ohio State Univ, Dept Anesthesiol, Columbus, OH 43210 USA. [Nadasdy, Tibor] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Della Pelle, Patricia; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Cook, CH (reprint author), Ohio State Univ, Dept Surg, 410 W 10th Ave,N747 Doan Hall, Columbus, OH 43210 USA. EM charles.cook@osumc.edu RI Cook, Charles/D-5574-2009 OI Cook, Charles/0000-0003-4446-3616 FU NIAID NIH HHS [R01 AI053094-03, R01 AI053094-05, R01 AI053094, R01 AI053094-04] NR 57 TC 50 Z9 52 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2008 VL 180 IS 5 BP 3103 EP 3112 PG 10 WC Immunology SC Immunology GA 313GV UT WOS:000256730000048 PM 18292533 ER PT J AU Schmader, K Gnann, JW Watson, CP AF Schmader, Kenneth Gnann, John W., Jr. Watson, C. Peter TI The epidemiological, clinical, and pathological rationale for the herpes zoster vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; NOTTINGHAM HEALTH PROFILE; POSTHERPETIC NEURALGIA; RISK-FACTORS; DOUBLE-BLIND; NEUROPATHIC PAIN; ANTIRETROVIRAL THERAPY; OLDER-ADULTS AB Worldwide, herpes zoster (HZ) affects millions of patients (particularly older adults) annually and causes significant suffering due to acute and chronic pain, or postherpetic neuralgia (PHN). The objective of this article is to explain the rationale for the HZ vaccine by summarizing data on the epidemiology of HZ in the immunocompetent host, with a focus on recent incidence and risk factor studies; to review information on the burden of HZ; and to discuss the challenges of lessening the morbidity of the disease. The incidence and severity of HZ and PHN are highest in older adults. Given the central nervous system damage caused by HZ, the difficulty of adequately treating HZ to prevent PHN, and the intractability of PHN, the advent of the HZ vaccine appears to be a crucial innovation for preventing HZ and PHN. C1 [Schmader, Kenneth] Durham Vet Affairs Med Ctr, GRECC, Durham, NC USA. [Schmader, Kenneth] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27706 USA. [Schmader, Kenneth] Duke Univ, Med Ctr, Div Geriatr, Dept Med, Durham, NC 27706 USA. [Gnann, John W., Jr.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Gnann, John W., Jr.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Watson, C. Peter] Univ Toronto, Dept Med, Toronto, ON, Canada. RP Schmader, K (reprint author), Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr 182, Durham, NC 27705 USA. EM schma001@mc.duke.edu FU NIAID NIH HHS [K24-AI-51324-03] NR 59 TC 59 Z9 62 U1 0 U2 1 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 MAR 1 PY 2008 VL 197 SU 2 BP S207 EP S215 DI 10.1086/522152 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 271FF UT WOS:000253773600032 PM 18419399 ER PT J AU Winn, RA Tennis, M Sergew, A Williams, L Randall, J Van Scoyk, M AF Winn, R. A. Tennis, M. Sergew, A. Williams, L. Randall, J. Van Scoyk, M. TI Prostacyclin and its synthetic analogues are small molecule agonists of frizzled 9 mediating growth inhibition of non small cell lung cancer cells SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Annual Combined Meeting of the Central-Society-for-Clinical-Reseach/Midwestern Section of the American-Federation-for-Medical-Research CY APR 24-25, 2008 CL Chicago, IL SP Cent Soc Clin Res, Amer Federat Med Res, Midwestern Sect C1 [Winn, R. A.; Tennis, M.; Sergew, A.; Williams, L.; Randall, J.; Van Scoyk, M.] Denver VAMC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2008 VL 56 IS 3 MA 109 BP 648 EP 648 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 273FY UT WOS:000253917000124 ER PT J AU Crawford, DC Nord, AS Badzioch, MD Ranchalis, J McKinstry, LA Ahearn, M Bertucci, C Shephard, C Wong, M Rieder, MJ Schellenberg, GD Nickerson, DA Heagerty, PJ Wijsman, EM Jarvik, GP AF Crawford, Dana C. Nord, Alex S. Badzioch, Michael D. Ranchalis, Jane McKinstry, Laura A. Ahearn, Magdalena Bertucci, Caterina Shephard, Cynthia Wong, Michelle Rieder, Mark J. Schellenberg, Gerard D. Nickerson, Deborah A. Heagerty, Patrick J. Wijsman, Ellen M. Jarvik, Gail P. TI A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk SO JOURNAL OF LIPID RESEARCH LA English DT Article DE very low density lipoprotein receptor; apolipoprotein E; body mass index; triglycerides ID APOLIPOPROTEIN-E POLYMORPHISM; DENSITY-LIPOPROTEIN RECEPTOR; INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; WALL THICKNESS; HEMODIALYSIS-PATIENTS; GENETIC ASSOCIATION; CARDIOVASCULAR-DISEASE; ASYMPTOMATIC ADULTS; CHOLESTEROL LEVELS AB The genetic factors associated with carotid artery disease (CAAD) are not fully known. Because of its role in lipid metabolism, we hypothesized that common genetic variation in the very low density lipoprotein receptor (VLDLR) gene is associated with severe CAAD (> 80% stenosis), body mass index (BMI), and lipid traits in humans. VLDLR was resequenced for variation discovery in 92 subjects, and single nucleotide polymorphisms (tagSNPs) were chosen for genotyping in a larger cohort (n = 1,027). Of the 17 tagSNPs genotyped, one tagSNP (SNP 1226; rs1454626) located in the 5' flanking region of VLDLR was associated with CAAD, BMI, and LDL-associated apolipoprotein B (apoB). We also identified receptor-ligand genetic interactions between VLDLR 1226 and APOE genotype for predicting CAAD case status.jr These findings may further our understanding of VLDLR function, its ligand APOE, and ultimately the pathogenesis of CAAD in the general population. C1 [Nord, Alex S.; Badzioch, Michael D.; Ranchalis, Jane; McKinstry, Laura A.; Schellenberg, Gerard D.; Wijsman, Ellen M.; Jarvik, Gail P.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA. [Ahearn, Magdalena; Bertucci, Caterina; Shephard, Cynthia; Wong, Michelle; Rieder, Mark J.; Nickerson, Deborah A.] Univ Washington, Div Med Genet, Dept Genome Sci, Seattle, WA 98195 USA. [Heagerty, Patrick J.; Wijsman, Ellen M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Schellenberg, Gerard D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Schellenberg, Gerard D.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Jarvik, GP (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM pair@u.wasliington.edu RI Crawford, Dana/C-1054-2012; Jarvik, Gail/N-6476-2014; OI Jarvik, Gail/0000-0002-6710-8708; Wijsman, Ellen/0000-0002-2725-6669 FU NHLBI NIH HHS [U01 HL-66682, R01 HL-074366, U01 HL-66728, P01 HL-30086, R01 HL-67406]; NIEHS NIH HHS [N01 ES-15478] NR 74 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2008 VL 49 IS 3 BP 588 EP 596 DI 10.1194/jlr.M700409-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266EY UT WOS:000253418500012 PM 18056683 ER PT J AU Walsh, CJ Hanumara, NC Slocum, AH Shepard, JA Gupta, R AF Walsh, Conor J. Hanumara, Nevan C. Slocum, Alexander H. Shepard, Jo-Anne Gupta, Rajiv TI A Patient-Mounted, Telerobotic Tool for CT-Guided Percutaneous Interventions SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article DE medical; patient-mounted; robotics; disposable; spherical mechanism; image-guided; computed tomography; percutaneous interventions; biopsy ID BRACHYTHERAPY SEED PLACEMENT; GUIDANCE; BIOPSY; SYSTEM; ROBOT AB This paper describes Robopsy, an economical, patient-mounted, telerobotic, needle guidance and insertion system, that enables faster, more accurate targeting during CT-guided biopsies and other percutaneous interventions. The current state of the art imaging technology facilitates precise location of sites within the body; however, there is no mechanical equivalent to then facilitate precise targeting. The lightweight, disposable actuator unit, which affixes directly to the patient, is composed primarily of inexpensive, injection molded, radiolucent, plastic parts that snap together, whereas the four micromotors and control electronics are retained and reused. By attaching to a patient, via an adhesive pad and optional strap points, the device moves passively with patient motion and is thus inherently safe. The device's mechanism tilts the needle to a two degree-of-freedom compound angle, toward the patient's head or feet (in and out of the scanner bore) and left or right with respect to the CT slice, via two motor-actuated concentric, crossed, and partially nested hoops. A carriage rides in the hoops and interfaces with the needle via a two degree-of-freedom friction drive that both grips the needle and inserts it. This is accomplished by two rubber rollers, one passive and one driven, that grip the needle via a rack and pinion drive. Gripping is doctor controlled; thus when not actively being manipulated, the needle is released and allowed to oscillate within a defined region so as to minimize tissue laceration due to the patient breathing. Compared to many other small robots intended for medical applications, Robopsy is an order of magnitude less costly and lighter while offering appropriate functionality to improve patient care and procedural efficiency. This demonstrates the feasibility of developing cost-effective disposable medical robots, which could enable their more widespread application. [DOI: 10.1115/1.2902854] C1 [Walsh, Conor J.; Hanumara, Nevan C.; Slocum, Alexander H.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Shepard, Jo-Anne; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Walsh, CJ (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. FU Center for Integration of Medicine and Innovative Technology (CIMIT); U. S. Army Medical Acquisition Activity (USAMRAA) [DAMD 17-02-2-0006] FX The authors would like to thank the Center for Integration of Medicine and Innovative Technology (CIMIT) for providing funding for this work from U. S. Army Medical Acquisition Activity (USAMRAA) under cooperative Agreement No. DAMD 17-02-2-0006 and for MGH for providing the use of the CT facilities. In addition, the MIT IDEAS Competition, MIT $100K Competition and the NCIIA BMEidea competition have provided strategic and financial assistance to the project. The project began in MIT course 2.75 Precision Machine Design taught by Professor Alexander Slocum and the authors wish to acknowledge student design team member Steven Barrett for his contribution to the initial research, concept generation, analysis, and testing. Special thanks also to Professor Bernie Roth for his input on the background of spherical mechanisms. NR 19 TC 18 Z9 18 U1 2 U2 12 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 EI 1932-619X J9 J MED DEVICES JI J. Med. Devices PD MAR PY 2008 VL 2 IS 1 AR 011007 DI 10.1115/1.2902854 PG 10 WC Engineering, Biomedical SC Engineering GA V18TF UT WOS:000208026400007 ER PT J AU Xu, C Houck, JR Fan, WH Wang, P Chen, Y Upton, M Futran, ND Schwartz, SM Zhao, LP Chen, C Mendez, E AF Xu, Chang Houck, John R. Fan, Wenhong Wang, Pei Chen, Yu Upton, Melissa Futran, Neal D. Schwartz, Stephen M. Zhao, Lue P. Chen, Chu Mendez, Eduardo TI Simultaneous isolation of DNA and RNA from the same cell population obtained by laser capture microdissection for genome and transcriptome profiling SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID PROSTATE-CANCER; TUMOR SAMPLES; TISSUE; HETEROGENEITY; AMPLIFICATION; CARCINOMA AB Laser capture microdissection (LCM) is used extensively for genome and transcriptome profiling. Traditionally, however, DNA and RNA are purified from separate populations of LCM-harvested cells, limiting the strength of inferences about the relationship between gene expression and gene sequence variation. There have been no published protocols for the simultaneous isolation of DNA and RNA from the same cells that are obtained by LCM of patient tissue specimens. Here we report an adaptation of the Qiagen AllPrep method that allows the purification of DNA and RNA from the same LCM-harvested cells. We compared DNA and RNA purified by the QIAamp DNA Micro kit and the PicoPure RNA Isolation kit, respectively, from LCM-collected cells from adjacent tissue sections of the same specimen. The adapted method yields 90% of DNA and 38% of RNA compared with the individual methods. When tested with the GeneChip 250K Nsp Array, the concordance rate of the single nucleotide polymorphism heterozygosity calls was 98%. when tested with the GeneChip U133 Plus 2.0 Array, the correlation coefficient of the raw gene expression was 97%. Thus, we developed a method to obtain both DNA and RNA material from a single population of LCM-harvested cells and herein discuss the strengths and limitations of this methodology. C1 [Xu, Chang; Futran, Neal D.; Chen, Chu; Mendez, Eduardo] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Upton, Melissa] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Zhao, Lue P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Houck, John R.; Chen, Yu; Futran, Neal D.; Schwartz, Stephen M.; Zhao, Lue P.; Chen, Chu; Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Fan, Wenhong; Zhao, Lue P.] Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Seattle, WA 98104 USA. [Wang, Pei] Fred Hutchinson Canc Res Ctr, Program Canc Prevent, Seattle, WA 98104 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. RP Mendez, E (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, 1959 NE Pacific St,Box 356515, Seattle, WA 98195 USA. EM edmendez@u.washington.edu FU NCI NIH HHS [R01 CA 095419, R01 CA095419]; NCRR NIH HHS [5 K12 RR023265-04, K12 RR023265] NR 20 TC 14 Z9 15 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAR PY 2008 VL 10 IS 2 BP 129 EP 134 DI 10.2353/jmoldx.2008.070131 PG 6 WC Pathology SC Pathology GA 272QM UT WOS:000253874500003 PM 18258925 ER PT J AU Shimazaki, K Jirawuthiworavong, GV Heckenlively, JR Gordon, LK AF Shimazaki, Kaori Jirawuthiworavong, Guy V. Heckenlively, John R. Gordon, Lynn K. TI Frequency of anti-retinal antibodies in normal human serum SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID CANCER-ASSOCIATED RETINOPATHY; CELL LUNG-CANCER; ANTIRECOVERIN AUTOANTIBODIES; AUTOIMMUNE RETINOPATHY; RECOVERIN ANTIBODIES; APOPTOTIC DEATH; BIPOLAR CELLS; CAR SYNDROME; OPTIC-NERVE; IN-VIVO AB Background: Anti-retinal antibodies have been described in the context of autoimmune retinopathies and are often presumed to be pathogenic or disease associated. However, full characterization of patterns of anti-retinal antibody reactivity in normal human serum has been limited. The purpose of this work was to identify the profile of anti-retinal IgG antibodies in serum used as controls in laboratory testing. Methods: Normal human sera used in commercial diagnostic laboratories were tested for the presence of immunoreactivity against soluble human retinal proteins using Western blot analysis of fractionated soluble human retinal proteins. Reactivity was quantified using computerized densitometry, and the level of reactivity was standardized relative to a control positive serum with known reactivity against recoverin, Results: Some anti-retinal reactivity was observed in the majority of all tested normal sera. Reactivity against one to two protein bands was observed in 33%. Reactivity against five or more distinct bands was observed in 22%. There was a tendency for serum from women to react with three or more protein bands compared with serum from men. Conclusions: The presence of anti-retinal antibodies is observed in a majority of normal control human sera, suggesting that identification of new candidate retinal autoantigens should be cautiously interpreted and subject to rigorous testing for disease association. Additional studies will aid development of a standardized protocol for validation of potential pathogenic seroreactivity. C1 [Shimazaki, Kaori] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA. [Jirawuthiworavong, Guy V.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Heckenlively, John R.] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Gordon, LK (reprint author), 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu FU NEI NIH HHS [T32 EY07026-28] NR 35 TC 29 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD MAR PY 2008 VL 28 IS 1 BP 5 EP 11 DI 10.1097/WNO.0b013e318167549f PG 7 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 271ZW UT WOS:000253828200002 PM 18347451 ER PT J AU Herbert, MR AF Herbert, M. R. TI Autism - Brain and body: From metabolism to function to structure SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Herbert, M. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 16 EP 16 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800035 ER PT J AU Yao, JK Messamore, E AF Yao, J. K. Messamore, E. TI Arachidonic acid and niacin sensitivity in schizophrenia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Messamore, E.] Portland VA Med Ctr, Portland, OR USA. [Yao, J. K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Yao, J. K.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 35 EP 36 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800087 ER PT J AU Macklis, JD AF Macklis, J. D. TI Molecular development and cellular repair of corticospinal motor neuron (and other forebrain projection neuron) circuitry SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Macklis, J. D.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 79 EP 79 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800188 ER PT J AU Moser, AB Hubbard, WC Blackwell, ML Eichler, FS AF Moser, A. B. Hubbard, W. C. Blackwell, M. L. Eichler, F. S. TI LC-MSMS lipid analysis of luxol fast blue highlighted regions in X-linked adrenoleukodystrophy brain tissue samples SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Moser, A. B.] Kennedy Krieger Inst, Baltimore, MD USA. [Hubbard, W. C.] Johns Hopkins Univ, Baltimore, MD USA. [Blackwell, M. L.] Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Eichler, F. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 124 EP 124 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800299 ER PT J AU Kaminska, A Yamada, K Liu, K Bosco, D Brown, H Brown, R Brady, S Morfini, G AF Kaminska, A. Yamada, K. Liu, K. Bosco, D. Brown, H. Brown, R. Brady, S. Morfini, G. TI Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving selective degeneration of motor neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Kaminska, A.; Yamada, K.; Liu, K.; Bosco, D.; Brady, S.; Morfini, G.] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60680 USA. [Brown, H.; Brown, R.; Brady, S.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 127 EP 127 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800308 ER PT J AU Valencia, A Sapp, E Reeves, PB Li, X Kegel, KB Chase, K Aronin, N DiFiglia, M AF Valencia, A. Sapp, E. Reeves, P. B. Li, X. Kegel, K. B. Chase, K. Aronin, N. DiFiglia, M. TI Early deficits in AKT/PKB signaling through lipid rafts in Huntington's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Valencia, A.; Sapp, E.; Reeves, P. B.; Li, X.; Kegel, K. B.; DiFiglia, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Charlestown, MA USA. [Chase, K.; Aronin, N.] Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 128 EP 129 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800313 ER PT J AU Burns, MR Solowska, JM Falnikar, A Himes, TB Morfini, GA Brady, ST Baas, PW AF Burns, M. R. Solowska, J. M. Falnikar, A. Himes, T. B. Morfini, G. A. Brady, S. T. Baas, P. W. TI Pathogenic spastin alters neurite morphology and inhibits fast axonal transport SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Burns, M. R.; Morfini, G. A.; Brady, S. T.] Univ Illinois Chicago, Coll Med, Chicago, IL USA. [Solowska, J. M.; Falnikar, A.; Baas, P. W.] Drexel Univ, Coll Med, Philadelphia, PA USA. [Himes, T. B.] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 130 EP 130 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800318 ER PT J AU Goody, RJ Schittone, SA Tyler, KL AF Goody, Robin J. Schittone, Stephanie A. Tyler, Kenneth L. TI Experimental reovirus-induced acute flaccid paralysis and spinal motor neuron cell death SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE acute flaccid paralysis; apoptosis; motor neurons; reovirus; viral myelitis ID CENTRAL-NERVOUS-SYSTEM; SINDBIS VIRUS-INFECTION; WEST-NILE ENCEPHALITIS; CORD-INJURY; INDUCED APOPTOSIS; CALPAIN; MICE; PATHOGENESIS; ISCHEMIA; MOUSE AB Acute flaccid paralysis (AFP) describes the loss of motor function in 1 or more limbs commonly associated with viral infection and destruction of motor neurons in the anterior horns of the spinal cord. Therapy is limited, and the development of effective treatments is hampered by a lack of experimental models. Reovirus infection of neonatal mice provides a model for the study of CNS viral infection pathogenesis. Injection of the Reovirus serot Type 3 strains Abney T3A) or Dearing (T3D) into the hindlimb of 1-day-old mice resulted in the development of AFP in more than 90% of infected mice. Acute flaccid paralysis began in the ipsilateral hindlimb at 8 to 0 days postinfection and progressed to paraplegia 24 hours later. Paralysis correlated with injury, neuron loss, and spread of viral ntigen first to the ipsilateral and then to the contralateral anterior horns. As demonstrated by the activation of caspase 3 and its olocalization with viral antigen in the anterior horn and concompitant cleavage of poly-(adenosine diphosphate-ribose) polymerase, AFP was associated with apoptosis. Calpain activity and inducible nitric oxide synthase expression were both elevated in the spinal,chords of paralyzed animals. This study represents the first detailed characterization of a novel and highly efficient experimental model,of virus-induced AFP that will facilitate evaluation of therapeutic strategies targeting virus-induced paralysis. C1 [Goody, Robin J.; Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, Denver, CO 80262 USA. [Schittone, Stephanie A.; Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, 4200 E 9th Ave, Denver, CO 80262 USA. EM Ken.Tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS NIH HHS [R01 NS050138, R01 NS051403, R01 NS051403-03, R01 NS050138-04, 5R01NS050138, 1R01NS051403] NR 41 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAR PY 2008 VL 67 IS 3 BP 231 EP 239 DI 10.1097/NEN.0b013e31816564f0 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 268DC UT WOS:000253557500006 PM 18344914 ER PT J AU Stasheff, SF AF Stasheff, Steven F. TI Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VISUAL-SYSTEM DEVELOPMENT; EYE-SPECIFIC SEGREGATION; ROD-BIPOLAR CELL; MAMMALIAN RETINA; PHOTORECEPTOR DEGENERATION; ROYAL-COLLEGE; MULTIFOCAL ERG; SURGEONS RAT; INNER RETINA; IN-VIVO AB Complex alterations in the anatomy of outer retinal pathways accompany photoreceptor degeneration in the rd1 mouse model of retinitis pigmentosa, whereas inner retinal neurons appear relatively preserved. However, the progressive loss of photoreceptor input likely alters the neural circuitry of the inner retina. This study investigated resulting changes in the activity of surviving ganglion cells. Multi-electrode recording monitored spontaneous and light-evoked extracellular action potentials simultaneously from 30 to 90 retinal ganglion cells of wild-type (wt) or rd1 mice. In rd1 mice, this activity evolves through three phases. First, normal spontaneous "waves" of correlated firing are seen at postnatal day 7 (P7) and last until shortly after eye opening. Second, at P14, full-field light flashes evoke reliable responses in many cells, with preferential preservation of OFF responses. These diminish as photoreceptor degeneration progresses. Third, once light-evoked responses have disappeared in early adulthood, surviving rd1 ganglion cells fire at a much higher spontaneous frequency than normal, sometimes in rhythmic bursts that are distinct from the developmental "waves." This hyperactivity is sustained well into adulthood, for weeks after photoreceptors have disappeared. Thus striking alterations occur in inner retinal physiology as retinal degeneration progresses in the rd1 mouse. Blindness occurs in the face of sustained hyperactivity among ganglion cells, which remain viable for months despite this activity. ON and OFF responses are differentially affected in early stages of degeneration. While the source of these changes remains to be learned, such features should be considered in designing more effective treatments for these disorders. C1 [Stasheff, Steven F.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Stasheff, Steven F.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Stasheff, Steven F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stasheff, SF (reprint author), Univ Iowa, Dept Pediat Neurol, 4184 MERF,375 Newton Rd, Iowa City, IA 52242 USA. EM steven-stasheff@uiowa.edu FU NINDS NIH HHS [NS 01701-09] NR 63 TC 118 Z9 121 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2008 VL 99 IS 3 BP 1408 EP 1421 DI 10.1152/jn.00144.2007 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 273YW UT WOS:000253969300032 PM 18216234 ER PT J AU Mendez, MF Lauterbach, EC Sampson, SM AF Mendez, Mario F. Lauterbach, Edward C. Sampson, Shirlene M. CA ANPA Comm Res TI An evidence-based review of the psychopathology of frontotemporal dementia: A report of the ANPA Committee on Research SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Review ID FRONTAL-LOBE DEMENTIA; NON-ALZHEIMER TYPE; CLINICAL DIAGNOSTIC-CRITERIA; PROGRESSIVE SUPRANUCLEAR PALSY; RANDOMIZED CONTROLLED-TRIAL; KLUVER-BUCY-SYNDROME; PICKS-DISEASE; VASCULAR DEMENTIA; TEMPORAL VARIANT; CORTICOBASAL DEGENERATION AB The Committee on Research of the American Neuropsychiatric Association conducted a review of the noncognitive neuropsychiatric manifestations of frontotemporal dementia. The Committee on Research searched reviews and several online databases for all pertinent publications. Single case reports without pathology were excluded, except for psychosis, where single cases made up much of the literature. The strongest evidence supports an association of frontotemporal dementia with the following behaviors: apathy-abulia; disinhibition-impulsivity; loss of insight and self-referential behavior; decreased emotion and empathy; violation of social and moral norms; changes in dietary or eating behavior; and repetitive behaviors. Frontotemporal dementia is less frequently associated with anxiety and mood disorders, which may be a prodrome or risk factor, and rarely presents with delusions or hallucinations. The results of this review highlight the distinct neuropsychiatric manifestations of frontotemporal dementia and the need to reconsider the current diagnostic criteria for this disorder. C1 [Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, Los Angeles, CA 90073 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90024 USA. [Lauterbach, Edward C.] Mercer Univ, Dept Psychiat & Behav Sci, Macon, GA 31207 USA. [Sampson, Shirlene M.] Mayo Clin, Dept Psychiat, Rochester, MN USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu NR 191 TC 55 Z9 56 U1 4 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2008 VL 20 IS 2 BP 130 EP 149 DI 10.1176/appi.neuropsych.20.2.130 PG 20 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 331DC UT WOS:000257991900002 PM 18451185 ER PT J AU Mendez, MF Shapira, JS Licht, EA AF Mendez, Mario F. Shapira, Jill S. Licht, Eliot A. TI "Denkfaulheit" in frontotemporal dementia: A preliminary analysis SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CLINICAL-FEATURES; PICKS-DISEASE; WORK GROUP; CONSENSUS; DIAGNOSIS; CRITERIA AB The initial recognition of frontotemporal dementia is often difficult. Frontotemporal dementia presents with subtle personality changes in the absence of a definitive biomarker. The authors report an analysis of cognitive shallowness, or "Denkfaulheit," in patients with frontotemporal dementia early in its course. C1 [Mendez, Mario F.; Shapira, Jill S.; Licht, Eliot A.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. [Mendez, Mario F.; Shapira, Jill S.; Licht, Eliot A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Mendez, Mario F.; Shapira, Jill S.; Licht, Eliot A.] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Mmendez@UCLA.edu NR 15 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2008 VL 20 IS 2 BP 219 EP 222 DI 10.1176/appi.neuropsych.20.2.219 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 331DC UT WOS:000257991900010 PM 18451193 ER PT J AU Lauriat, TL Shiue, L Haroutunian, V Verbitsky, M Ares, M Ospina, L McInnes, LA AF Lauriat, Tara L. Shiue, Lily Haroutunian, Vahram Verbitsky, Miguel Ares, Manuel, Jr. Ospina, Luz McInnes, L. Alison TI Developmental expression profile of quaking, a candidate gene for schizophrenia, and its target genes in human prefrontal cortex and hippocampus shows regional specificity SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE myelin; human development; splicing; schizophrenia ID CENTRAL-NERVOUS-SYSTEM; ANTERIOR CINGULATE CORTEX; MULTIPLE BRAIN-REGIONS; MYELINATION-RELATED GENES; RNA-BINDING PROTEINS; MESSENGER-RNA; BASIC-PROTEIN; PROTEOLIPID PROTEIN; BIPOLAR DISORDER; QKI AB Decreased expression of oligodendrocyte/myelin-related (OMR) genes, including quaking (QKI), is a consistent finding in gene expression studies of post-mortem brain from subjects with schizophrenia, and these changes are most prominent in the hippocampus vs. the prefrontal cortex (PFC). Although expression of QKI and other OMR genes has been examined in rodents, little is known about their developmental trajectory in the human brain. Therefore, we examined expression of QKI and several putative mRNA targets of QKI in human PFC and hippocampus at different ages. The pattern of QKI expression in the PFC resembled that reported in rodents, with high QKI-5 in the fetal brain and an increase in QKI-6 and QKI-7 during the period of active myelination, although QKI-5 expression did not decrease substantially during postnatal development in the PFC in humans as it does in rodent brain. Most of the putative QKI target genes also showed linear increases in expression with increasing age in the PFC. In contrast, expression of these genes showed little evidence of developmental regulation in the hippocampus. Correlations between expression levels of the nuclear vs. cytoplasmic QKI isoforms, and putative splicing targets of the former, also differed between tissues. Thus, we speculate that a robust increase in OMR gene expression normally occurs with age in the PFC, but not in the hippocampus, which may explain why decreases in OMR gene expression in schizophrenia are more pronounced in the latter tissue. We also suggest that OMR transcripts might be processed by different splicing proteins in different tissues. (c) 2007 Wiley-Liss, Inc. C1 [Lauriat, Tara L.; Haroutunian, Vahram; Verbitsky, Miguel; Ospina, Luz; McInnes, L. Alison] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Shiue, Lily; Ares, Manuel, Jr.] Univ Calif Santa Cruz, Sinsheimer Labs, Ctr Mol Biol RNA, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA. [Haroutunian, Vahram] Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. [McInnes, L. Alison] Mt Sinai Sch Med, Dept Genet & Gen Sci, New York, NY USA. RP McInnes, LA (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1229, New York, NY 10029 USA. EM alison.mcinnes@mssm.edu OI Lauriat, Tara/0000-0003-0729-9386; Ares, Manny/0000-0002-2552-9168 FU NIMH NIH HHS [MH0066392, MH064673, MH074026] NR 49 TC 17 Z9 17 U1 0 U2 0 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 MAR PY 2008 VL 86 IS 4 BP 785 EP 796 DI 10.1002/jnr.21534 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 273WC UT WOS:000253961700006 PM 17918747 ER PT J AU van Leyen, K Arai, K Jin, G Kenyon, V Gerstner, B Rosenberg, PA Holman, TR Lo, EH AF van Leyen, Klaus Arai, Ken Jin, Guang Kenyon, Victor Gerstner, Bettina Rosenberg, Paul A. Holman, Theodore R. Lo, Eng H. TI Novel lipoxygenase inhibitors as neuroprotective reagents SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neurodegeneration; stroke; Alzheimer's disease; Parkinson's disease; lipoxygenase; neuron; oligodendrocyte; HT22; oxidative stress; drug screening; neuroprotection ID OXIDATIVE STRESS; GLUTATHIONE DEPLETION; CORTICAL-NEURONS; 12-LIPOXYGENASE; APOPTOSIS; 12/15-LIPOXYGENASE; BRAIN; ACID AB The lipid-metabolizing enzyme 12/15-lipoxygenase (12/15-LOX) mediates cell death resulting from oxidative stress in both neurons and oligodendrocytes. Specifically, it may contribute to the pathophysiology of stroke and Alzheimer's and Parkinson's diseases. We report here that two of three specific 12/15-LOX inhibitors, derived from a virtual screen by computer modeling and validated by inhibition of recombinant human 15-LOX in vitro, are able to rescue both neuronal as well as oligodendroglial cells from cell death induced by oxidative stress. Thus, in a fairly streamlined process, an initial virtual screen of 50,000 compounds in a library of drug-like molecules has led to the identification of two novel drug candidates for targeting LOX. Future studies of these novel neuroprotective inhibitors of 12/15-LOX may provide new therapeutic opportunities to combat stroke and other neurodegenerative diseases. (c) 2007 Wiley-Liss, Inc. C1 [van Leyen, Klaus; Arai, Ken; Jin, Guang; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Kenyon, Victor; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. [Gerstner, Bettina; Rosenberg, Paul A.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Gerstner, Bettina; Rosenberg, Paul A.] Harvard Med Sch, Boston, MA USA. [Gerstner, Bettina] Charite Univ Med Berlin, Dept Neonatol, D-13353 Berlin, Germany. RP van Leyen, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, 149 13th St,R 2401, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu RI van Leyen, Klaus/C-9126-2013; OI Rosenberg, Paul/0000-0002-5185-1118 FU NIGMS NIH HHS [GM56062, R01 GM056062, R29 GM056062]; NINDS NIH HHS [NS38475, NS049430, P01 NS038475, R01 NS049430, R01 NS049430-04, R01 NS049430-05] NR 20 TC 52 Z9 52 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR PY 2008 VL 86 IS 4 BP 904 EP 909 DI 10.1002/jnr.21543 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 273WC UT WOS:000253961700016 PM 17960827 ER PT J AU Huaman, ET Juvet, LM Nastri, A Denman, WT Kaban, LB Dodson, TB AF Huaman, Evelyn T. Juvet, Lawrence M. Nastri, Alf Denman, William T. Kaban, Leonard B. Dodson, Thomas B. TI Changing patterns of hospital length of stay after orthognathic surgery SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB Purpose: The purpose of this study was to estimate the hospital length of stay (LOS) and identify factors associated with LOS in orthognathic surgery patients. Materials and Methods: Using a retrospective cohort study design, we enrolled a sample composed of patients who underwent orthognathic surgery at Massachusetts General Hospital between January 1994 and July 2006. The primary predictor variables were fixation type (rigid/nonrigid), anesthesia technique (hypotensive/normotensive), and perioperative steroid use (yes/no). The outcome variable was LOS. Descriptive statistics were computed for all variables. Bivariate analyses were used to identify factors associated with duration of LOS with P values less than .15. Multiple regression modeling was used to assess the relationship between the primary predictor variables and LOS. The level of statistical significance was set at P less than .05. Results: The study sample was comprised of 627 subjects (58.5% female) with a mean age of 26.1 +/- 10.2 years. The overall mean LOS was 1.7 +/- 1.2 days. During the study period, LOS decreased from 2.3 to 1.3 days (P <.001). In the adjusted multiple regression model, rigid fixation, procedure type, and length of operation were statistically significantly associated with LOS (P <.05). Conclusion: The results of this study indicate that individual variables associated with duration of LOS are complexity of the orthognathic procedure and type of fixation used. In the multiple logistic regression model, LOS decreases significantly when rigid fixation, hypotensive anesthesia, and perioperative steroids are used in combination. (c) 2008 American Association of Oral and Maxillofacial Surgeons. C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. EM tbdodson@partners.org NR 10 TC 13 Z9 14 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2008 VL 66 IS 3 BP 492 EP 497 DI 10.1016/j.joms.2007.08.025 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 269KR UT WOS:000253648400011 PM 18280382 ER PT J AU Gray, ML Burstein, D Kim, YJ Maroudas, A AF Gray, Martha L. Burstein, Deborah Kim, Young-Jo Maroudas, Alice TI Magnetic resonance imaging of cartilage glycosaminoglycan: Basic principles, imaging technique, and clinical applications SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE arthritis; glycosaminoglycan; MRI; sodium; dGEMRIC ID GADOLINIUM-ENHANCED MRI; FEMORAL-HEAD CARTILAGE; ARTICULAR-CARTILAGE; KNEE CARTILAGE; EARLY OSTEOARTHRITIS; HIP-DYSPLASIA; GD-DTPA; DEGRADATION; GD-DTPA(2-); OSTEOTOMY AB Many new therapeutic strategies have been and are being developed to prevent, correct, or slow the progression of osteoarthritis. Our ability to evaluate the efficacy of these techniques, or to determine the situations for which they might provide the most benefit, critically depends on diagnostic measures that can serve as proxies for the present or predicted state of the cartilage. We focus here on a body of work surrounding the development of magnetic resonance imaging (MRI) techniques to noninvasively image the glycosaminoglycan (GAG) concentration of articular cartilage. These techniques are based on the concept of fixed charge in cartilage resulting from the glycosaminoglycans. Starting with sodium MRI, and the subsequent development of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) based on proton MRI, these techniques permit "visualization" of the charged GAG distribution in cartilage in vitro or in vivo. The dGEMRIC technique has been used in preliminary clinical studies to understand treatment strategies and to monitor disease, and as such is allowing studies that a decade ago would have been impossible. This new technical capability offers the promises of speeding development of effective therapies and focusing their use in areas where they can be most successful. (C) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 [Gray, Martha L.; Burstein, Deborah] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gray, Martha L.] BIDMC, New England Baptist Bone & Joint Ctr, Boston, MA USA. [Gray, Martha L.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Burstein, Deborah] BIDMC, Dept Radiol, Boston, MA USA. [Kim, Young-Jo] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Kim, Young-Jo] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Maroudas, Alice] Technion Israel Inst Technol, Haifa, Israel. RP Gray, ML (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM mgray@umit.edu NR 38 TC 79 Z9 80 U1 2 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAR PY 2008 VL 26 IS 3 BP 281 EP 291 DI 10.1002/jor.20482 PG 11 WC Orthopedics SC Orthopedics GA 264XW UT WOS:000253324700003 PM 17876836 ER PT J AU Skittone, LK Liu, XH Tseng, A Kim, HT AF Skittone, Laura K. Liu, Xuhui Tseng, Alice Kim, Hubert T. TI Matrix metalloproteinase-2 expression and promoter/enhancer activity in skeletal muscle atrophy SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE transgenic mice; matrix metalloproteinase-2; muscular atrophy; disuse; Achilles tendon ID REPERFUSION INJURY; ACID-PHOSPHATASE; RATS; MATRIX-METALLOPROTEINASE-2; INHIBITOR; PATHWAYS; ISCHEMIA; MMP-2 AB Matrix metalloproteinase-2 (MMP-2) appears to be the dominant MMP activated during skeletal muscle atrophy. However, little is known about cell-specific regulatory mechanisms of MMP-2 transcription in vivo. In this study, we used a mouse model of muscle atrophy induced by complete Achilles tendon transection. Time-dependent muscle weight loss, nuclei density reduction, and extracellular matrix degeneration were observed consistently after Achilles tendon transection. Increased MMP-2 expression was confirmed at the mRNA and protein level. Experiments using transgenic mice with a MMP-2 promoter/enhancer reporter construct demonstrated markedly increased MMP-2 promoter/enhancer activity in atrophic skeletal muscle. Tissue-specific upregulation of MMP-2 promoter activity was observed not only in myocytes, but also in blood vessels, nerve, and fascia. The transcription factors c-Jun and FosB were expressed at high levels in atrophic muscle, suggesting a role in MMP-2 upregulation. These findings show that increased MMP-2 activity in disused atrophic muscle and supporting tissues is regulated, at least in part, by increased MMP-2 promoter/enhancer activity. (C) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 [Skittone, Laura K.; Tseng, Alice; Kim, Hubert T.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Liu, Xuhui; Kim, Hubert T.] Univ Calif San Francisco, Dept Orthoped Surg, San Francisco, CA 94143 USA. RP Kim, HT (reprint author), San Francisco VA Med Ctr, 4150 Clement St,112, San Francisco, CA 94121 USA. EM kimh@orthosurg.ucsf.edu NR 20 TC 18 Z9 19 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAR PY 2008 VL 26 IS 3 BP 357 EP 363 DI 10.1002/jor.20513 PG 7 WC Orthopedics SC Orthopedics GA 264XW UT WOS:000253324700011 PM 17960656 ER PT J AU Billings, JA AF Billings, J. Andrew TI Dignity SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID CARE; LIFE; PERSPECTIVES; END C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, FND 600,55 Fruit St, Boston, MA 02114 USA. EM jbillings@partners.org NR 13 TC 11 Z9 11 U1 0 U2 0 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 MAR PY 2008 VL 11 IS 2 BP 138 EP 139 DI 10.1089/jpm.2008.9963 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 283QM UT WOS:000254651600001 PM 18333720 ER PT J AU Wu, P Lorenz, KA Chodosh, J AF Wu, Pauline Lorenz, Karl A. Chodosh, Joshua TI Advance care planning among the oldest old SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriat Soc ID OF-LIFE CARE; DECISION-MAKING; END; QUALITY; DIRECTIVES; TRIAL AB Objectives: To describe end-of-life advance care planning among the oldest-old (those >= 85 years) and to identify patient characteristics and healthcare utilization patterns associated with likelihood of care planning documentation. Design: Medical charts were abstracted for evidence of advance care planning documentation (including surrogate for health care decisions) and linked to patient demographic, clinical, and health utilization characteristics. Setting: Veterans Affairs Greater Los Angeles Healthcare System (VA GLAHS). Participants: All Veterans (n = 175) aged >= 85 who died between September 1999 and October 2000 and used services at the VA GLAHS in the last year of life. Measurements: The association of patient demographic, clinical, and health care utilization characteristics with documentation of advance care planning and surrogates was modeled using multivariate logistic regression. Results: Among veterans (mean age at death, 89.4 +/- 3.8 years), 50 of 149 (34%) electronic available records had documented care preferences whereas 68 (46%) had documentation of surrogates. Considering demographic, clinical, and service use characteristics, only age (adjusted odds ratio [AOR]: 1.1 per year; 95% confidence interval [CI]: 1.0-1.2) and outpatient visits (AOR: 1.6 per quartile of general and geriatric medicine visit frequency; 95% CI: 1.1-2.3) were associated with advance directive completion. A multivariable regression model using the same predictors to predict documentation of surrogates found similar associations with total outpatient visits (AOR: 1.5; 95% CI: 1.0-2.0) and general and geriatric medicine utilization. (AOR: 1.4; 95% CI: 1.0-2.0). Conclusion: Even in a health care system known for high-quality chronic illness care, documentation of advance care planning and selected proxies for health care decisions at the end of life was infrequent. Outpatient primary care and geriatric providers' visits were more frequent among those who had documented advance care planning, suggesting that involvement of these practitioners may improve end-of-life care. C1 [Wu, Pauline] Univ Med & Dent New Jersey, Sch Osteopath Med, Stratford, NJ 08084 USA. [Wu, Pauline] UCLA San Fernando Valley, Dept Psychiat, North Hills, CA USA. [Lorenz, Karl A.; Chodosh, Joshua] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. [Chodosh, Joshua] VA Greater Los Angeles Geriatr Res Educ & Clin Ct, Sepulveda, CA USA. [Chodosh, Joshua] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. RP Chodosh, J (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC, 11301 Wilshire Blvd,Mail Code 11G, Los Angeles, CA 90073 USA. EM jchodosh@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 NR 26 TC 12 Z9 12 U1 0 U2 5 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 MAR PY 2008 VL 11 IS 2 BP 152 EP 157 DI 10.1089/jpm.2007.0134 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 283QM UT WOS:000254651600008 PM 18333727 ER PT J AU Robinson, LA Emmons, KM Moolchan, ET Ostroff, JS AF Robinson, Leslie A. Emmons, Karen M. Moolchan, Eric T. Ostroff, Jamie S. TI Developing smoking cessation programs for chronically ill teens: Lessons learned from research with healthy adolescent smokers SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article; Proceedings Paper CT Conference on Tobacco Control Strategies for Medically At-Risk Youth CY OCT 06-08, 2005 CL St Jude Childrens Res Hosp, Memphis, TN HO St Jude Childrens Res Hosp DE adolescents; chronic illness; pediatric; smoking cessation; tobacco use ID RANDOMIZED CLINICAL-TRIAL; NICOTINE PATCH; CANCER SURVIVORS; CHILDHOOD-CANCER; USE TOBACCO; PREDICTORS; PREVENTION; BEHAVIOR; RISK; INTERVENTION AB Objective Medically fragile teens who smoke need access to smoking cessation programs, because they are at even higher risk than their healthy peers for smoking-related complications. Methods To date, no studies on the outcome of smoking cessation programs for medically ill teens have been conducted. To suggest directions for future research, we turn to the literature on smoking cessation in the general population of teens and occasionally to the literature on adult smokers. Results Four areas are explored: (a) the prevalence of unaided cessation in healthy teens; (b) the outcomes of various treatments for smoking cessation in healthy adolescents; (c) special issues that should be considered when designing programs for medically ill teens; and (d) lessons learned from previous research. Conclusions Medically ill teens face a number of medical, emotional, social, and developmental challenges that can affect the quitting process. Research is sorely needed to address the unique needs of this population. C1 Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Moolchan, Eric T.] Natl Inst Hlth, Natl Inst Drug Abuse, Intramural Res Program, Bethesda, MD 20892 USA. [Ostroff, Jamie S.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. RP Robinson, LA (reprint author), Univ Memphis, Dept Psychol, 202 Psychol, Memphis, TN 38152 USA. EM Robinson@mail.psyc.memphis.edu OI Ostroff, Jamie/0000-0003-2671-5680 FU NCI NIH HHS [CA117417] NR 68 TC 5 Z9 5 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD MAR PY 2008 VL 33 IS 2 BP 133 EP 144 DI 10.1093/jpepsy/jsm112 PG 12 WC Psychology, Developmental SC Psychology GA 258XG UT WOS:000252903100004 PM 18056143 ER PT J AU Biederman, J Pliszka, SR AF Biederman, Joseph Pliszka, Steven R. TI Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents SO JOURNAL OF PEDIATRICS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; FILM-COATED TABLETS; DSM-IV ADHD; DOUBLE-BLIND; DIAGNOSTIC-CRITERIA; INDUCED WAKEFULNESS; SAMPLE; EFFICACY; SAFETY; METHYLPHENIDATE AB Objective This secondary analysis evaluated the efficacy of modafinil in children and adolescents by subtype of attention-deficit/hyperactivity disorder (ADHD) using pooled data from 3 double-blind, placebo-controlled studies. Study design The patients were boys and girls age 6 to 17 years. ADHD subtype diagnoses (ie, inattentive, by impulsive, combined) were based on criteria published in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Patients received modafinil (170 to 425 mg) or placebo once daily for 7 to 9 weeks. Efficacy assessment used the Attention-Deficity/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) School and Home Versions, Clinical Global Impression of Improvement scale (CGI-I), and Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S). Results A total of 638 patients received modafinil (n = 423) or placebo (n = 215). The inattentive, hyperactive-impulsive, and combined subtypes included 187 (30%), 27 (4%), and 403 (65%) patients, respectively. Modafinil (vs placebo) significantly improved mean total scores for the ADHD-RS-IV School and Home Versions for the inattentive (change from baseline: School, modafinil, -15.7, placebo, -7.1; Home, modafinil, -13.8, placebo, -5.9) and combined subtypes (School, -16.5 vs -8.8; Home, -15.7 vs -7.6). Modafinil was associated with greater improvements on the CGI-I and improved CPRS-R:S subscale scores in inattentive and combined subtypes. Conclusions Modafinil improved ADHD symptoms and behaviors inpatients with the inattentive and combined subtypes as determined by teachers, investigators, and parents. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Pliszka, Steven R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. EM jbiederman@partners.org NR 31 TC 26 Z9 26 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD MAR PY 2008 VL 152 IS 3 BP 394 EP 399 DI 10.1016/j.jpeds.2007.07.052 PG 6 WC Pediatrics SC Pediatrics GA 268SN UT WOS:000253599800021 PM 18280848 ER PT J AU Santulli, RJ Kinney, WA Ghosh, S DeCorte, BL Liu, L Tuman, RWA Zhou, Z Huebert, N Bursell, SE Clermont, AC Grant, MB Shaw, LC Mousa, SA Galemmo, RA Johnson, DL Maryanoff, BE Damiano, BP AF Santulli, Rosemary J. Kinney, William A. Ghosh, Shyamali DeCorte, Bart L. Liu, Li Tuman, Robert W. A. Zhou, Zhao Huebert, Norman Bursell, Sven E. Clermont, Alan C. Grant, Maria B. Shaw, Lynn C. Mousa, Shaker A. Galemmo, Robert A., Jr. Johnson, Dana L. Maryanoff, Bruce E. Damiano, Bruce P. TI Studies with an orally bioavailable alpha(v) integrin antagonist in animal models of ocular vasculopathy: Retinal neovascularization in mice and retinal vascular permeability in diabetic rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ALPHA-V-INTEGRINS; IN-VIVO; CHOROIDAL NEOVASCULARIZATION; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; PROLIFERATIVE RETINOPATHY; MACULAR DEGENERATION; VITRONECTIN RECEPTOR; ALPHA(V)BETA(3); ANGIOGENESIS AB The alpha(v) integrins are key receptors involved in mediating cell migration and angiogenesis. In age-related macular degeneration (AMD) and diabetic retinopathy, angiogenesis plays a critical role in the loss of vision. These ocular vasculopathies might be treatable with a suitable alpha(v) antagonist, and an oral drug would offer a distinct advantage over current therapies. (3,S,beta,S)-1,2,3,4-Tetrahydro-beta-[[1-[1-oxo-3-(1,5,6,7-tetrahydro-1,8-naphthyridin-2-yl) propyl]-4-piperidinyl]methyl]-3-quinolinepropanoic acid (JNJ-26076713) is a potent, orally bioavailable, nonpeptide alpha(v) antagonist derived from the arginine-glycine-asparagine binding motif in the matrix protein ligands (e.g., vitronectin). This compound inhibits alpha(v)beta(3) and alpha(v)beta(5) binding to vitronectin in the low nanomolar range, it has excellent selectivity over integrins alpha(11b)beta(3) and alpha(5)beta(1), and it prevents adhesion to human, rat, and mouse endothelial cells. JNJ-26076713 blocks cell migration induced by vascular endothelial growth factor, fibroblast growth factor (FGF), and serum, and angiogenesis induced by FGF in the chick chorioallantoic membrane model. JNJ-26076713 is the first alpha(V) antagonist reported to inhibit retinal neovascularization in an oxygen-induced model of retinopathy of prematurity after oral administration. In diabetic rats, orally administered JNJ-26076713 markedly inhibits retinal vascular permeability, a key early event in diabetic macular edema and AMD. Given this profile, JNJ-26076713 represents a potential therapeutic candidate for the treatment of age-related macular degeneration, macular edema, and proliferative diabetic retinopathy. C1 [Santulli, Rosemary J.; Kinney, William A.; Ghosh, Shyamali; DeCorte, Bart L.; Liu, Li; Tuman, Robert W. A.; Zhou, Zhao; Huebert, Norman; Galemmo, Robert A., Jr.; Johnson, Dana L.; Maryanoff, Bruce E.; Damiano, Bruce P.] Johnson & Johnson Pharmaceut Res & Dev, Spring House, PA 19477 USA. [Galemmo, Robert A., Jr.] Neuromed Pharmaceut, Vancouver, BC, Canada. [Grant, Maria B.; Shaw, Lynn C.] Univ Florida, Gainesville, FL USA. [Mousa, Shaker A.] Albany Coll Pharm, Pharmaceut Res Inst, Albany, NY USA. [Bursell, Sven E.; Clermont, Alan C.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Santulli, RJ (reprint author), Johnson & Johnson Pharmaceut Res & Dev, Welsh & McKean Rds, Spring House, PA 19477 USA. EM rsantull@prdus.jnj.com NR 44 TC 20 Z9 22 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 2008 VL 324 IS 3 BP 894 EP 901 DI 10.1124/jpet.107.131656 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266OH UT WOS:000253445200002 PM 18083913 ER PT J AU Wolin, KY Bennett, GG AF Wolin, Kathleen Y. Bennett, Gary G. TI Interrelations of Socioeconomic Position and Occupational and Leisure-Time Physical Activity in the National Health and Nutrition Examination Survey SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE NHANES; socioeconomic status; exercise AB Background: The interrelations between various physical activity domains have received little empirical attention in the United States. Of particular interest, given the potential applicability to traditionally underserved communities, is the nature of the association between occupational physical activity (OPA) and leisure-time physical activity (LTPA). Methods: 5448 adult men and women who participated in NHANES 1999-2000 were included in analyses. Linear regression was used to examine the bivariate and multivariable associations of OPA and education with LTPA. Generalized logit models were used to examine the association of education with OPA. Results: We found no association between education and LTPA. OPA was significantly positively associated with LTPA (P < .001). The association between OPA and LTPA was not strongest among those with low education and held only for men in gender-stratified analysis. Education was inversely associated with OPA (P < .001) in multivariable analysis. Conclusions: Our findings lend preliminary support to the hypothesis that OPA is an important determinant of LTPA, particularly in men. This provides additional support to calls for assessment of OPA, particularly among individuals of low social class. C1 [Wolin, Kathleen Y.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Wolin, KY (reprint author), Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. FU NCI NIH HHS [R25 CA100600-02, R25 CA100600] NR 23 TC 18 Z9 18 U1 1 U2 3 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAR PY 2008 VL 5 IS 2 BP 229 EP 241 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V18OX UT WOS:000208015200003 PM 18382032 ER PT J AU Friedman, SL Choueiri, R Gilmore, D AF Friedman, Sandra L. Choueiri, Roula Gilmore, Dana TI Staff Carers' Understanding of End of Life Care SO JOURNAL OF POLICY AND PRACTICE IN INTELLECTUAL DISABILITIES LA English DT Article DE end of life care; intellectual disabilities; palliative care; special health care needs; staff carers AB Staff carers in pediatric skilled nursing facilities (PSNF) deal directly with dying residents, and are on the forefront of communication with families. These providers have expressed misunderstandings regarding the meaning of resuscitation status and redirection of care. This descriptive study evaluated perceptions and understanding of end of life issues by the staff in a PSNF who provide care for individuals with severe developmental disabilities and complex medical problems. A 16-item pre-intervention survey was administered to the staff prior to an informational presentation explaining issues related to end of life care. An 8-item post-intervention survey assessed any change in understanding of these issues. A total of 55 persons completed either a pre- or post-intervention survey; 47 staff completed both surveys. While most staff carers were comfortable with providing care for patients with serious illnesses or needing comfort measures (narcotics, oxygen) when they are dying, they are significantly less comfortable with discontinuation of feeds or routine medications at the end of life. Observed was a significant increase in those who indicated it is acceptable to stop feedings for a dying patient in the post-intervention survey, but there no significant difference in understanding of definition of DNR before or after the intervention. Authors note the need to provide more comprehensive information and support to assist staff carers to understand aspects of end of life care in a PSNF setting. C1 [Friedman, Sandra L.] Childrens Hosp, Inst Community Inclus, Div Gen Pediat, Boston, MA 02115 USA. [Friedman, Sandra L.; Choueiri, Roula] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gilmore, Dana] Univ Massachusetts, Boston, MA USA. [Friedman, Sandra L.; Choueiri, Roula] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Friedman, SL (reprint author), Childrens Hosp, Inst Community Inclus, Div Gen Pediat, 300 Longwood Ave, Boston, MA 02115 USA. EM Sandra.friedman@childrens.harvard.edu NR 43 TC 2 Z9 2 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1741-1122 J9 J POLICY PRACT INTEL JI J. Policy Pract. Intellect. Disabil. PD MAR PY 2008 VL 5 IS 1 BP 56 EP 64 DI 10.1111/j.1741-1130.2007.00142.x PG 9 WC Health Policy & Services; Rehabilitation SC Health Care Sciences & Services; Rehabilitation GA V13QE UT WOS:000207680500036 ER PT J AU Biederman, J Petty, CR Fried, R Doyle, AE Mick, E Aleardi, M Monuteaux, MC Seidman, LJ Spencer, T Faneuil, AR Holmes, L Faraone, SV AF Biederman, Joseph Petty, Carter R. Fried, Ronna Doyle, Alysa E. Mick, Eric Aleardi, Megan Monuteaux, Michael C. Seidman, Larry J. Spencer, Thomas Faneuil, Alicia R. Holmes, Lauren Faraone, Stephen V. TI Utility of an abbreviated questionnaire to identify individuals with ADHD at risk for functional impairments SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE executive function deficits; functional impairment; ADHD; adults ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SUBTHRESHOLD DIAGNOSES; EXECUTIVE FUNCTIONS; LATE-ONSET AB Objective: To discern whether a subset of items from the 99-item Current Behavior Scale (CBS) of behaviorally defined Executive Function Deficits (EFDs) in adults with Attention-Deficit/Hyperactivity Disorder (ADHD) can identify a group at risk for poor outcome. Methods: Subjects were 200 adults with ADHD participating in a family study of ADHD in adults. Factor analysis was used to reduce the number of items in the 99-item CBS. Results: The one factor solution provided eight items with factor loadings above 0.70. This abbreviated set of items was highly correlated with the 99-item CBS (0.91) and was similarly related to functional outcomes compared to the 99-item CBS (average correlation of 0.30 versus 0.32). Conclusion: For adults with ADHD, a set of eight empirically-derived from the CBS similarly correlated with negative outcomes compared to the 99-item CBS, raising the possibility of utilization as a mechanism for identification of EFDs in adults with ADHD. (C) 2006 Elsevier Ltd. All rights reserved. C1 [Biederman, Joseph; Petty, Carter R.; Fried, Ronna; Doyle, Alysa E.; Mick, Eric; Aleardi, Megan; Monuteaux, Michael C.; Seidman, Larry J.; Spencer, Thomas; Faneuil, Alicia R.; Holmes, Lauren; Faraone, Stephen V.] Massachusetts Gen Hosp, Pediat Psychopharmacol & Adult ADHD, Clin & Res Programs, Boston, MA 02114 USA. [Biederman, Joseph; Petty, Carter R.; Fried, Ronna; Doyle, Alysa E.; Mick, Eric; Aleardi, Megan; Monuteaux, Michael C.; Seidman, Larry J.; Spencer, Thomas; Faneuil, Alicia R.; Holmes, Lauren; Faraone, Stephen V.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol & Adult ADHD, Clin & Res Programs, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH054509, R01 MH057934, R01 MH057934-05] NR 18 TC 6 Z9 6 U1 0 U2 3 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 MAR PY 2008 VL 42 IS 4 BP 304 EP 310 DI 10.1016/j.jpsychires.2006.12.004 PG 7 WC Psychiatry SC Psychiatry GA 276JO UT WOS:000254137300007 PM 17335849 ER PT J AU Flessner, CA Woods, DW Franklin, ME Cashin, SE Keuthen, NJ AF Flessner, Christopher A. Woods, Douglas W. Franklin, Martin E. Cashin, Susan E. Keuthen, Nancy J. CA TLC-SAB TI The Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A): Development of an instrument for the assessment of "Focused" and "Automatic" hair pulling SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE focused; automatic; pulling; trichotillomania ID ANXIETY STRESS SCALES; PSYCHOMETRIC PROPERTIES; ECONOMIC-IMPACT; SKIN-PICKING; PHENOMENOLOGY; COMORBIDITY; IMPAIRMENT; PULLERS; SAMPLES AB This article describes the development of the Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A), which was designed to assess "automatic" and "focused" pulling subtypes of trichotillomania (TTM). Participants reporting symptoms of TTM (n=1,697) completed an internet survey; participants were later randomly assigned to either Exploratory (n=848) or Confirmatory (n=849) Analyses. Exploratory Analyses examined the development and psychometric properties of the MIST-A. Results of an exploratory factor analysis revealed a two-factor solution. Factor 1 ("focused" pulling scale) and 2 ("automatic" pulling scale) consisted of ten and five items respectively, with both scales demonstrating adequate internal consistency and good construct and discriminant validity. Subsequent confirmatory factor analysis demonstrated support for the scale's underlying factor structure. The MIST-A provides researchers with a reliable and valid assessment of "automatic" and "focused" pulling, although replication using a clinically ascertained sample is necessary. C1 [Woods, Douglas W.] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53211 USA. [Franklin, Martin E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Woods, DW (reprint author), Univ Wisconsin, Dept Psychol, POB 413, Milwaukee, WI 53211 USA. EM dwoods@uwm.edu RI Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015; OI Stein, Dan/0000-0001-7218-7810 NR 33 TC 45 Z9 45 U1 4 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD MAR PY 2008 VL 30 IS 1 BP 20 EP 30 DI 10.1007/s10862-007-9073-x PG 11 WC Psychology, Clinical SC Psychology GA 272YI UT WOS:000253897200003 ER PT J AU Colditz, GA Emmons, KM Vishwanath, K Kerner, JF AF Colditz, Graham A. Emmons, Karen M. Vishwanath, K. Kerner, Jon F. TI Translating science to practice: Community and academic perspectives SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Article DE barriers to change; behavior change; dissemination ID WORKPLACE SMOKING; HEALTH-PROMOTION; PARTICIPATORY RESEARCH; PHYSICAL-ACTIVITY; SOCIAL ECOLOGY; PUBLIC-HEALTH; CARE; RESTRICTIONS; METAANALYSIS; HOUSEHOLD AB While evidence reviews inform practice and policy guidelines, the gap between guidelines and implementation may be growing. We place dissemination and implementation research in the context of other changes needed to drive research into practice. Multilevel approaches to research and dissemination are needed as are metrics to inform academic appointment and promotions. Moving beyond funding that stops and starts with grant cycles is a key issue from the community perspective to ensure continuity and improved health. Transdisciplinary approaches that cut across disciplinary boundaries to develop shared conceptual frameworks may help speed the integration of research with practice. Identifying and implementing structural changes to develop and support transdisciplinary teams may further facilitate this process. Changes in the approaches used to structure and implement scientific advances into practice will help achieve the enormous potential to advance the health of the population. C1 Washington Univ, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, Dept Prevent & Control, St Louis, MO USA. [Emmons, Karen M.; Vishwanath, K.] Dana Faber Cancer Inst, Soc Human Dev & Hlth, Boston, MA USA. [Emmons, Karen M.; Vishwanath, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Emmons, Karen M.] Dana Faber Harvard Cnc Ctr, Initiat Eliminate Canc Ctr, Boston, MA 02115 USA. [Kerner, Jon F.] Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Colditz, GA (reprint author), Washington Univ, Dept Surg, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM colditzg@wustl.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 35 TC 30 Z9 30 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD MAR-APR PY 2008 VL 14 IS 2 BP 144 EP 149 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265DY UT WOS:000253340500011 PM 18287920 ER PT J AU Chiao, JC Goldman, JM David, H Kazanzides, P Peine, WJ Stiehl, JB Yen, D Dagalakis, NG AF Chiao, J. C. Goldman, Julian M. David, Heck Kazanzides, Peter Peine, William J. Stiehl, James B. Yen, Dwight Dagalakis, Nicholas G. TI Metrology and standards needs for some categories of medical devices SO JOURNAL OF RESEARCH OF THE NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY LA English DT Article DE computer assisted surgical navigation; medical devices; networked medical device interoperability; neurostimulation implants; surgical robots; surgical simulation systems ID SPINAL-CORD STIMULATION; TOTAL KNEE ARTHROPLASTY; ROBOTIC SYSTEM; PAIN; SURGERY AB With rapid advances in meso, micro- and nano-scale technology devices and electronics, a new generation of advanced medical devices is emerging, which promises medical treatment that is less invasive and more accurate, automated, and effective. We examined the technological and economic status of five categories of medical devices. A set of metrology needs is identified for each of these categories and suggestions are made to address them. C1 [Chiao, J. C.] Univ Texas Arlington, Dept Elect Engn, Arlington, TX 76019 USA. [Goldman, Julian M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [David, Heck] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX 75206 USA. [Kazanzides, Peter] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Peine, William J.] Purdue Univ, Sch Mech Engn, W Lafayette, IN 47907 USA. [Peine, William J.] Purdue Univ, Regenstrief Ctr Healthcare Engn, W Lafayette, IN 47907 USA. [Stiehl, James B.] Columbia St Marys Hosp, Dept Orthopaed Surg, Milwaukee, WI 53211 USA. [Yen, Dwight] US FDA, Gen Surg Devices Branch, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. [Dagalakis, Nicholas G.] Natl Inst Stand & Technol, Intelligent Syst Div, Gaithersburg, MD 20899 USA. RP Chiao, JC (reprint author), Univ Texas Arlington, Dept Elect Engn, Arlington, TX 76019 USA. EM jcchiao@uta.edu; jmgoldman@partners.org; davidhec@baylorhealth.edu; pkaz@jhu.edu; peine@purdue.edu; jbstiehl@aol.com; dwight.yen@fda.hhs.gov; nicholas.dagalakis@nist.gov RI Kazanzides, Peter/A-3358-2010; OI Kazanzides, Peter/0000-0002-6117-5467 NR 31 TC 4 Z9 4 U1 0 U2 9 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 1044-677X J9 J RES NATL INST STAN JI J. Res. Natl. Inst. Stand. Technol. PD MAR-APR PY 2008 VL 113 IS 2 BP 121 EP 129 DI 10.6028/jres.113.009 PG 9 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 321UD UT WOS:000257331100004 PM 27096115 ER PT J AU Duckworth, AD Kulijdian, A Mckee, MD Ring, D AF Duckworth, Andrew D. Kulijdian, Anna McKee, Michael D. Ring, David TI Residual subluxation of the elbow after dislocation or fracture-dislocation: Treatment with active elbow exercises and avoidance of varus stress SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID RADIAL HEAD; INSTABILITY AB During a 6-year period, 2 surgeons prescribed active elbow exercises and avoidance of shoulder abduction (varus stress) for 23 patients (15 men, 8 women) with a mean age of 43 years (range, 19-74 years) who had slight residual subluxation of a dislocated elbow after either nonoperative (3 simple dislocations and 2 fracture-dislocations) or operative treatment (18 fracture-dislocations). A stable elbow was achieved in all 23 patients, although 1 patient, treated late, had a very slight residual posterior subluxation of the radial head on radiographs. After a mean of 24 months (range, 12-45 months), the average flexion arc was 113 degrees, with mean flexion of 132 degrees and mean flexion contracture of 20 degrees. The mean Broberg-Morrey score was 90 points (range, 6 1100 points). Ratings were excellent in 9 patients, good in 10, and fair in 4. Mild radiographic signs of arthrosis (type I Broberg-Morrey) were present in 2 patients. Slight postreduction subluxation of the elbow, without detrimental contact of the articular surfaces, a type of pseudosubluxation of the elbow sometimes referred to as the "drop sign," can be treated with active exercises and avoidance of varus stress. C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Dept Orthopaed Surg, Boston, MA 02114 USA. [Duckworth, Andrew D.] Royal Infirm Edinburgh NHS Trust, Dept Gen Surg, Edinburgh, Midlothian, Scotland. [Kulijdian, Anna; McKee, Michael D.] Univ Toronto, Toronto, ON, Canada. [Ring, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Dept Orthopaed Surg, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 11 TC 12 Z9 14 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR-APR PY 2008 VL 17 IS 2 BP 276 EP 280 DI 10.1016/j.jse.2007.06.006 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 279OD UT WOS:000254363600016 PM 18162410 ER PT J AU Duckworth, AD Ring, D Kulijdian, A Mckee, MD AF Duckworth, Andrew D. Ring, David Kulijdian, Anna McKee, Michael D. TI Unstable elbow dislocations SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID RADIAL HEAD; INSTABILITY; COMPLEX; ADULT; JOINT AB Seventeen patients with a posterior dislocation of the elbow and either no fracture or a minimal capsuloligamentous avulsion fracture were treated operatively for persistent redislocation after manipulative reduction. Fifteen had open reduction and ligament repair (3 with ancillary hinged external fixatin), and 2 infirm patients had closed reduction and cross pinning of the elbow joint. Among the 12 patients treated with ligament repair alone, 1 redislocated (treated with a second surgery for hinged external fixation) and 4 had residual subluxation (treated with temporary casting of protected active exercises) after ligament repair alone (42% residual instability). A concentric, stable elbow was eventually achieved in all 17 patients. The average flexion arc was 113 degrees. The average Broberg and Morrey score was 88, with 3 excellent, 10 good, and 2 fair results. A small percentage of elbow dislocations require operative treatment. Ligament repair alone may not be sufficient, and protection with a hinged external fixator is recommended. C1 [Duckworth, Andrew D.] Univ Edinburgh, Sch Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Ring, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Dept Orthopaed Surg, Boston, MA 02114 USA. [McKee, Michael D.] Univ Toronto, Toronto, ON, Canada. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Dept Orthopaed Surg, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 16 TC 17 Z9 21 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR-APR PY 2008 VL 17 IS 2 BP 281 EP 286 DI 10.1016/j.jse.2007.06.007 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 279OD UT WOS:000254363600017 PM 18069007 ER PT J AU Sekerak, RJ Zimmermann, KP AF Sekerak, R. J. Zimmermann, K. P. TI Chin-up strength tests: does stature matter? SO JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS LA English DT Article DE physical fitness; muscle strength; exercise physiology ID BODY-SIZE; MOVEMENT PERFORMANCE; MUSCLE STRENGTH AB Aim. Many organizations place high value on employee physical fitness and use standardized physical fitness tests (PFT) to quantify it. The chin-up strength test is an example of such a test. Participants' anecdotal reports raise some concern that the latter is inherently biased against tall individuals. A demonstration that tall individuals are less likely than short individuals to achieve maximum score on a chin-up strength test, and modified scoring tables that equalize this likelihood across the stature range are sought. Methods. A statistical summary of 85 chin-up test outcomes is analyzed for likelihood of maximum scores as a function of stature. Scoring tables modified by reducing the number of chin-ups required for maximum score in a ratio inverse to a fixed power of the stature ratios are introduced. Results. Statistical analysis shows that short individuals are more likely to achieve maximum chin-up test scores (P<0.05). Stature adjusted scoring tables are shown to neutralize this trend. Conclusion. Current scoring standards for chin-up strength tests favor short statures. Bias-free chin-up strength tests can be achieved by using stature-adjusted scoring tables. Similar bias problems may exist for other strength tests. C1 [Sekerak, R. J.] Waikato Hosp, Rehabil Serv, Hamilton, New Zealand. [Zimmermann, K. P.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Zimmermann, K. P.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. RP Zimmermann, KP (reprint author), MEDVAMC, RCL 117,2002 Holcombe, Houston, TX 77030 USA. EM zimmermann.kunop@med.va.gov NR 16 TC 0 Z9 0 U1 1 U2 5 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0022-4707 J9 J SPORT MED PHYS FIT JI J. Sports Med. Phys. Fit. PD MAR PY 2008 VL 48 IS 1 BP 37 EP 42 PG 6 WC Sport Sciences SC Sport Sciences GA 333IT UT WOS:000258146900006 PM 18212708 ER PT J AU Jellinek, MS Beresin, E AF Jellinek, Michael S. Beresin, Eugene TI Money talks: Becoming more comfortable with understanding a family's finances SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID PSYCHOTHERAPY C1 [Jellinek, Michael S.] Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. [Beresin, Eugene] Massachusetts Gen Hosp, Child & Adolescent Psychiat Residency Program, Boston, MA 02114 USA. RP Jellinek, MS (reprint author), Newton Wellesley Hosp, 2014 Washington St, Newton, MA 02462 USA. EM mjellinek@partners.org NR 6 TC 2 Z9 2 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 MAR PY 2008 VL 47 IS 3 BP 249 EP 253 DI 10.1097/chi.0b013e3181619858 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 265EV UT WOS:000253342800007 PM 18512293 ER PT J AU Schlozman, SC AF Schlozman, Steven C. TI Shunned: Discrimination against people with mental illness SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review ID STIGMA; HEALTH C1 [Schlozman, Steven C.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM sschlozman@partners.org NR 6 TC 0 Z9 0 U1 0 U2 4 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 MAR PY 2008 VL 47 IS 3 BP 352 EP 353 DI 10.1097/chi0000270805.43067.0d PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 265EV UT WOS:000253342800020 ER PT J AU Whitman, C Bender, S AF Whitman, Christine Bender, Suzanne TI Yes, your teen is crazy! Loving your kids without losing your mind SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Whitman, Christine; Bender, Suzanne] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Whitman, C (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM cawhitman@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 MAR PY 2008 VL 47 IS 3 BP 355 EP 356 DI 10.1097/01.chi0000270807.81185.09a PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 265EV UT WOS:000253342800022 ER PT J AU Heath, M Jaimes, N Lemos, B Mostaghimi, A Wang, LC Penas, PE Nghiem, P AF Heath, Michelle Jaimes, Natalia Lemos, Bianca Mostaghimi, Arash Wang, Linda C. Penas, Pablo E. Nghiem, Paul TI Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; RADIATION; THERAPY; CANCER; BIOPSY; TUMOR; SKIN AB Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a mortality of 33%. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. No systematic analysis has been published to define the clinical features that are characteristic of MCC. Objective. We sought to define the clinical characteristics present at diagnosis to identify features that may aid clinicians in recognizing MCC. Methods: We conducted a cohort study of 195 patients given the diagnosis of MCC between 1980 and 2007. Data were collected prospectively in the majority of cases, and medical records were reviewed. Results. An important finding was that 88% of MCCs were asymptomatic (nontender) despite rapid growth in the prior 3 months (63% of lesions) and being red or pink (56%). A majority of MCC lesions (56%) were presumed at biopsy to be benign, with a cyst/acneiform lesion being the single most common diagnosis (32%) given. The median delay from lesion appearance to biopsy was 3 months (range 1-54 months), and median tumor diameter was 1.8 cm. Similar to earlier studies, 81% of primary MCCs occurred on ultraviolet-exposed sites, and our cohort was elderly (90% > 50 years), predominantly white (98%), and often profoundly immune suppressed (7.8%). An additional novel finding was that chronic lymphocytic leukemia was more than 30-fold overrepresented among patients with MCC. Limitations. The study was limited to patients seen at a tertiary care center. Complete clinical data could not be obtained on all patients. This study could not assess the specificity of the clinical characteristics of MCC. Conclusions: To our knowledge, this study is the first to define clinical features that may serve as clues in the diagnosis of MCC. The most significant features can be summarized in an acronym: AEIOU (asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than 50 years, and ultraviolet-exposed site on a person with fair skin). In our series, 89% of primary MCCs had 3 or more of these findings. Although MCC is uncommon, when present in combination, these features may indicate a concerning process that would warrant biopsy. In particular, a lesion that is red and expanding rapidly yet asymptomatic should be of concern. C1 [Heath, Michelle; Jaimes, Natalia; Lemos, Bianca; Nghiem, Paul] Univ Washington, Div Dermatol, Seattle, WA 98109 USA. [Nghiem, Paul] Seattle Canc Care Alliance, Seattle, WA USA. [Nghiem, Paul] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Mostaghimi, Arash; Wang, Linda C.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Penas, Pablo E.] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. RP Nghiem, P (reprint author), Univ Washington, Div Dermatol, 815 Mercer St, Seattle, WA 98109 USA. EM pnghiem@u.washington.edu RI Nghiem, Paul/A-9210-2011; OI Nghiem, Paul/0000-0003-2784-963X; Lemos, Bianca/0000-0002-2222-0499; Fernandez Penas, Pablo/0000-0003-4882-1564 FU NCI NIH HHS [P50 CA093683, P50 CA093683-04]; NIAMS NIH HHS [K02 AR050993, K02 AR050993-02, K02 AR050993-03, K02 AR050993-04, K02-AR050993] NR 25 TC 248 Z9 257 U1 2 U2 14 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 MAR PY 2008 VL 58 IS 3 BP 375 EP 381 DI 10.1016/j.jaad.2007.11.020 PG 7 WC Dermatology SC Dermatology GA 266TO UT WOS:000253460100002 PM 18280333 ER PT J AU Laber, K Veatch, LM Lopez, MF Mulligan, JK Lathers, DMR AF Laber, Kathy Veatch, Lynn M. Lopez, Marcelo F. Mulligan, Jennifer K. Lathers, Deanne M. R. TI Effects of housing density on weight gain, immune function, behavior, and plasma corticosterone concentrations in BALB/c and C57BL/6 mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID INBRED MOUSE STRAINS; CAGE FLOOR SPACE; DENDRITIC CELLS; ADULT MICE; STRESSOR; ANXIETY; INFECTION; EXPOSURE; NOVELTY AB The Guide for the Care and Use of Laboratory Animals contains recommended housing densities for rodent species that are commonly used by the scientific community. However, at the time of the Guide's publication, housing density recommendations were based heavily on the professional judgment of qualified scientists. Some scientists therefore question whether rodents can be housed at greater densities, whereas others wonder whether the space currently provided for rodents is sufficient. The present study was designed to determine the effect of housing adult female BALB/c- and C57BL/6-mice in standard 75-in(2) (484-cm(2)) ventilated cages at various housing densities (n = 2, 5, and 10 mice/cage). Measures of weight gain, plasma corticosterone, behavior, and immune parameters were evaluated at 7,28, and 70 d after housing allocation. Housing BALB/c mice at 10/cage had negative effects on weight gain, corticosterone, behavior, and immune parameters. Housing C57BL/6 mice at 10/cage did not affect immune function or weight gain, although behavior and corticosterone showed statistical trends implying a negative effect Differences associated with housing densities of 2 and 5 mice/cage were less robust for all variables measured. We conclude that housing female BALB/c mice at 10 mice/cage (that is, at twice the Guide-recommended density) affects their physiology. We also conclude that mice vary in their responses in the parameters measured. These observations support the conclusion that it will be extremely challenging to scientifically determine an optimal cage density standard that can be uniformly applied across all mouse strains. C1 [Laber, Kathy; Veatch, Lynn M.; Lopez, Marcelo F.; Mulligan, Jennifer K.; Lathers, Deanne M. R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Laber, Kathy; Veatch, Lynn M.; Lathers, Deanne M. R.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Laber, K (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. EM laberlk@musc.edu NR 36 TC 26 Z9 26 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD MAR PY 2008 VL 47 IS 2 BP 16 EP 23 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 279OJ UT WOS:000254364200003 PM 18351717 ER PT J AU White, HK Levy, C AF White, Heidi K. Levy, Cari TI AMDA foundation futures: Inspiring the next generation of long-term care physicians SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material C1 [White, Heidi K.] Duke Univ, Sch Med, Div Geriatr, Durham, NC 27710 USA. [White, Heidi K.] VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Levy, Cari] Denver Vet Affairs Med Ctr, Denver, CO USA. [Levy, Cari] Univ Colorado, Denver, CO 80202 USA. [Levy, Cari] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP White, HK (reprint author), Duke Univ, Sch Med, Div Geriatr, Box 3003, Durham, NC 27710 USA. EM White031@mc.duke.edu NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAR PY 2008 VL 9 IS 3 BP 147 EP 148 DI 10.1016/j.jamda.2007.12.094 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 272AA UT WOS:000253828600003 PM 18294595 ER PT J AU Ix, JH Katz, R Kestenbaum, B Fried, LF Kramer, H Stehman-Breen, C Shlipak, MG AF Ix, Joachim H. Katz, Ronit Kestenbaum, Bryan Fried, Linda F. Kramer, Holly Stehman-Breen, Catherine Shlipak, Michael G. TI Association of mild to moderate kidney dysfunction and coronary calcification SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CYSTATIN-C CONCENTRATION; GLOMERULAR-FILTRATION-RATE; BEAM COMPUTED-TOMOGRAPHY; ARTERY CALCIFICATION; HEART-FAILURE; CARDIOVASCULAR EVENTS; SERUM CREATININE; RENAL-DISEASE; ATHEROSCLEROSIS MESA; ELDERLY PERSONS AB Coronary artery calcification (CAC) is prevalent and predicts mortality among patients with ESRD, but whether less severe kidney dysfunction is associated with CAC is uncertain. To address this question, 6749 participants of the Multi-Ethnic Study of Atherosclerosis, who were middle-aged and without known cardiovascular disease, were evaluated. Renal function was categorized by cystatin C quartiles and estimated GFR (eGFR; < to > 60 ml/min per 1.73 m(2)), and CAC was evaluated by computed tomography (CT). Fifty percent of participants had CAC, mean cystatin C was 0.90 mg/L and 10% had eGFR < 60 ml/min per 1.73 m(2). In unadjusted analysis, kidney dysfunction by either measure was strongly associated with CAC; however, the associations were lost after adjustment for age, gender, race, hypertension, and IL-6 (relative risk 1.04 [95% confidence interval 0.97 to 1.11] for the highest cystatin C quartile compared with the lowest, and relative risk 1.03 [95% confidence interval 0.98 to 1.08) for eGFR below compared with above 60 m/min per 1.73 m(2)). Similarly, neither higher cystatin C nor eGFR < 60 was associated with severity of CAC. These results suggest that a higher burden of CAC is unlikely to explain the association between mild to moderate kidney dysfunction and cardiovascular mortality. C1 [Ix, Joachim H.; Shlipak, Michael G.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Kestenbaum, Bryan] Univ Washington, Dept Med, Seattle, WA USA. [Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Stehman-Breen, Catherine] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv, Pittsburgh, PA USA. [Kramer, Holly] Loyola Univ, Dept Med, Maywood, IL 60153 USA. [Kramer, Holly] Loyola Univ, Div Nephrol, Maywood, IL 60153 USA. [Stehman-Breen, Catherine] Amgen Thousand Oaks, Oakland, CA USA. [Shlipak, Michael G.] Univ Calif San Diego, Dept Epidemiol & Biostat, San Diego, CA 92103 USA. [Shlipak, Michael G.] Vet Affairs Med Ctr, San Diego, CA 92161 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu OI Kramer, Holly/0000-0002-6374-837X FU NHLBI NIH HHS [N01HC95159, N01-HC-95165, N01-HC-95169, N01HC95165, N01HC95169, N01-HC-95159] NR 48 TC 42 Z9 44 U1 1 U2 2 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 MAR PY 2008 VL 19 IS 3 BP 579 EP 585 DI 10.1681/ASN.2007070765 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 270AD UT WOS:000253691200024 PM 18235089 ER PT J AU Isakova, T Gutierrez, O Shah, A Castaldo, L Holmes, J Lee, H Wolf, M AF Isakova, Tamara Gutierrez, Orlando Shah, Anand Castaldo, Lorraine Holmes, Julie Lee, Hang Wolf, Myles TI Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; FIBROBLAST GROWTH FACTOR-23; VITAMIN-D METABOLISM; VASCULAR CALCIFICATION; PHOSPHATE HOMEOSTASIS; RENAL-INSUFFICIENCY; DIETARY PHOSPHORUS; HEALTHY-MEN; FIBROBLAST-GROWTH-FACTOR-23; DEFICIENCY AB Normophosphatemia and normocalcemia are maintained in chronic kidney disease (CKD) by increased levels of fibroblast growth factor-23 (FGF-23) and parathyroid hormone (PTH), but the stimuli for secretion of these hormones in early CKD are incompletely understood. Most human physiologic studies have focused on random or fasting measurements of phosphorus, calcium, FGF-23, and PTH, but in this study, the hypothesis was that measurements in the postprandial state may reveal intermittent stimuli that lead to increased FGF-23 and PTH levels. The 4-h postprandial response in 13 patients with CKD and fasting normophosphatemia and normocalcemia (mean GFR 41 +/- 8 ml/min per m(2)) was compared with 21 healthy volunteers. Compared with healthy subjects, fasting patients with CKD had significantly higher levels of FGF-23 and fractional excretion of phosphorus; lower fractional excretion of calcium; and no difference in serum calcium, phosphorus, and PTH levels. After standardized meals, urinary phosphorus excretion in both groups increased despite unchanged serum phosphorus and FGF-23 levels. Postprandial urinary calcium excretion also increased in both groups, and this was accompanied by significantly reduced serum calcium and increased PTH levels in patients with CKD only; therefore, FGF-23 does not seem to be an acute postprandial regulator of phosphaturia in CKD or in health, but inappropriate postprandial calciuria with episodic, relative hypocalcemia may represent a previously unreported mechanism of secondary hyperparathyroidism in CKD. C1 [Isakova, Tamara; Gutierrez, Orlando; Shah, Anand; Castaldo, Lorraine; Holmes, Julie; Lee, Hang; Wolf, Myles] Harvard Univ, Sch Med, Renal Unit, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wolf, M (reprint author), Harvard Univ, Sch Med, Renal Unit, Dept Med,Massachusetts Gen Hosp, Bartlett 917 55 Fruit St, Boston, MA 02114 USA. EM mswolf@partners.org FU NCRR NIH HHS [M01RR01066, K23 RR017376, K30RR02229207, M01 RR001066, K23RR17376]; NIDDK NIH HHS [R01 DK076116, R01DK076116] NR 43 TC 94 Z9 100 U1 0 U2 2 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 MAR PY 2008 VL 19 IS 3 BP 615 EP 623 DI 10.1681/ASN.2007060673 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 270AD UT WOS:000253691200028 PM 18216315 ER PT J AU Howieson, DB Carlson, NE Moore, MM Wasserman, D Abendroth, CD Payne-Murphy, J Kaye, JA AF Howieson, Diane B. Carlson, Nichole E. Moore, M. Milar Wasserman, Dara Abendroth, Cena D. Payne-Murphy, Jessica Kaye, Jeffrey A. TI Trajectory of mild cognitive impairment onset SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the American-Academy-of-Neurology CY APR 28-MAY 05, 2007 CL Boston, MA SP Amer Acad Neurol DE dementia; Alzheimer disease; aging; aged 80 and over; episodic memory; longitudinal studies ID PRECLINICAL ALZHEIMERS-DISEASE; HEALTHY OLDEST-OLD; APOLIPOPROTEIN-E; DEMENTIA; DECLINE; PREDICTORS AB The objective was to identify the trajectories of onset of memory and other cognitive loss in persons destined to develop mild cognitive impairment (MCI) or dementia. Healthy, community dwelling, cognitively intact elders (if 156. mean a,,e at entry = 83 years) were examined annually for ail average of greater than 7 years. Those who developed at least two consecutive Clinical Dementia Ratings >= 0.5 were classified as having MCI. Longitudinal mixed effects models with a change point were used to model the aging process in those with and without an MCI diagnosis during follow-up and to model the rate of change relative to the age of onset of MCI. MCI had a preclinical stage of accelerated cognitive loss that was observed 3 to 4 years before the diagnosis of MCI on tests of verbal memory, animal trial fluency, and visuospatial constructions. Evidence from memory performance before the change point suggests that a slow decline in memory precedes the period of accelerated decline in the development of MCI. Aging transitions leading to MCI and dementia are characterized by unique linear and nonlinear cognitive changes in several domains that precede the diagnosis of MCI and dementia by at least several years. C1 [Howieson, Diane B.; Moore, M. Milar; Wasserman, Dara; Abendroth, Cena D.; Payne-Murphy, Jessica; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Carlson, Nichole E.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. [Kaye, Jeffrey A.] Portland VA Med Ctr, Portland, OR USA. RP Howieson, DB (reprint author), Oregon Hlth & Sci Univ, Dept Neurol CR131, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM howiesod@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [MO1 RR00334]; NIA NIH HHS [P30 AG008017] NR 30 TC 74 Z9 75 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAR PY 2008 VL 14 IS 2 BP 192 EP 198 DI 10.1017/S1355617708080375 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 338VJ UT WOS:000258537200002 PM 18282317 ER PT J AU Edwards, CL Bennett, GG Wolin, KY Johnson, S Fowler, S Whitfield, KE Askew, S MacKinnon, D McDougald, C Hubbard, R Wellington, C Feliu, M Robinson, E AF Edwards, Christopher L. Bennett, Gary G. Wolin, Kathleen Y. Johnson, Stephanie Fowler, Sherrye Whitfield, Keith E. Askew, Sandy MacKinnon, Dorene McDougald, Camela Hubbard, Robert Wellington, Chante Feliu, Miriam Robinson, Elwood TI Misestimation of peer tobacco use: Understanding disparities in tobacco use SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE tobacco; health disparities; African Americans; knowledge, attitudes & beliefs; historically black colleges and universities ID AFRICAN-AMERICAN YOUTH; COLLEGE-STUDENTS; ADOLESCENT SMOKING; CIGARETTE-SMOKING; SUBSTANCE USE; ALCOHOL; PREVALENCE; NORMS; PREDICTORS; BEHAVIOR AB Blacks experience disproportionately elevated rates of tobacco-related morbidity and mortality. Blacks experience delayed smoking initiation relative to other racial/ethnic groups, highlighting the importance of examining smoking correlates occurring in late adolescence/early adulthood. The current study reports data collected as part of an ongoing collaborative effort to assess alcohol and drug use on the campuses of historically black colleges and universities (HBCUs). Two-thousand, two-hundred, seventy-seven African-American subjects, aged 20.3 +/- 3.9 (range 18-53), completed the CORE Alcohol and Drug survey and a brief demographic questionnaire. Results indicated that 90% of all subjects overestimated the rate of smoking among their peers. Overestimating was associated with a >80% increase in the risk of smoking. These data highlight the need to correct misinformation regarding smoking norms among students at some HBCUs. C1 [Edwards, Christopher L.; Hubbard, Robert; Wellington, Chante; Feliu, Miriam] Duke Univ, Med Ctr,Dept Psychiat & Behav Sci, Biofeedback & Pediat Neuropsychol Serv, Chron Pain Management Program, Durham, NC 27705 USA. [Edwards, Christopher L.; Feliu, Miriam] Duke Univ, Med Ctr, Pain & Palliat Care Ctr, Durham, NC 27705 USA. [Edwards, Christopher L.] Duke Univ, Med Ctr, Dept Med, Div Hematol, Durham, NC 27705 USA. [Bennett, Gary G.] Harvard Univ, Sch Med, Dept Soc Human Dev & Hlth, Boston, MA USA. [Bennett, Gary G.; Askew, Sandy] Dana Faber Canc Inst, Ctr Commun Based Res, Boston, MA USA. [Wolin, Kathleen Y.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Wolin, Kathleen Y.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA. [Fowler, Sherrye] N Carolina Governors Inst Alcohol & Subst Abuse, Durham, NC USA. [Johnson, Stephanie] Amer Psychol Assoc, Durham, NC USA. [Whitfield, Keith E.] Duke Univ, Dept Psychol, Durham, NC 27706 USA. [MacKinnon, Dorene] Univ N Carolina, Sch Educ, Chapel Hill, NC 27599 USA. [Robinson, Elwood] N Carolina Cent Univ, Dept Psychol, Durham, NC USA. RP Edwards, CL (reprint author), Duke Univ, Med Ctr,Dept Psychiat & Behav Sci, Biofeedback & Pediat Neuropsychol Serv, Chron Pain Management Program, 932 Morreene Rd,Room 170, Durham, NC 27705 USA. EM christopher.edwards@duke.edu NR 37 TC 6 Z9 6 U1 3 U2 3 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD MAR PY 2008 VL 100 IS 3 BP 299 EP 302 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 282ED UT WOS:000254549500004 PM 18390023 ER PT J AU Jaroszewski, DE Huh, J Chu, D Malaisrie, SC Riffel, AD Gordon, HS Wang, XL Bakaeen, F AF Jaroszewski, Dawn E. Huh, Joseph Chu, Danny Malaisrie, S. Chris Riffel, Anthony D. Gordon, Howard S. Wang, Xing Li Bakaeen, Faisal TI Utility of detailed preoperative cardiac testing and incidence of post-thoracotomy myocardial infarction SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Western-Thoracic-Surgical-Association CY JUN 27-30, 2007 CL Santa Ana Pueblo, NM SP Western Thorac Surg Assoc ID PERIOPERATIVE CARDIOVASCULAR EVALUATION; MAJOR VASCULAR-SURGERY; NONCARDIAC SURGERY; RISK; REVASCULARIZATION; GUIDELINES; INDEX AB Objective: Recent literature has questioned the efficacy of routine detailed preoperative cardiac ischemia testing and preoperative cardiac intervention before noncardiac surgical procedures. Methods: We performed a retrospective review of patients undergoing thoracotomy (n = 294) between January of 1999 and January of 2005. Results: The median age was 62 years. Detailed preoperative cardiac testing was performed on 184 patients (63%) and went beyond a thorough history, physical examination, and electrocardiogram to include at least one of the following: dobutamine stress echo (n = 116), nuclear stress test (n = 66), treadmill test (n = 8), and coronary angiogram (n = 40). Evidence for coronary disease was detected in 43% of tests (99/230) performed. Revascularization was performed in 10% of all patients (4/40) who underwent coronary angiography. Postoperative myocardial infarction occurred in 7 patients (2.4%) with 4 myocardial infarction-related mortalities. No significant difference was found in the incidence of myocardial infarction in patients with (n = 184) or without (n = 110) detailed preoperative cardiac testing (3.3% vs 0.9%, P = .29). Of the 4 patients (1.4%) who underwent revascularization to treat coronary lesions identified during prethoracotomy workup, 2 had a myocardial infarction, 1 of which was caused by thrombosis of a coronary stent. In the subset of patients who underwent lobectomy (n = 149), detailed cardiac testing was performed on 107 patients (72%). The incidence of myocardial infarction was similar in tested and untested patients (2.8% vs 2.4% respectively, P = 1.0). Conclusion: Selective use of detailed preoperative cardiac testing refines risk stratification and identifies patients for corrective cardiac interventions; however, it did not prove fully protective against myocardial infarction after thoracotomy in our study. C1 [Jaroszewski, Dawn E.; Huh, Joseph; Chu, Danny; Malaisrie, S. Chris; Riffel, Anthony D.; Gordon, Howard S.; Wang, Xing Li; Bakaeen, Faisal] Baylor Coll Med, Dept Cardiothorac Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Jaroszewski, Dawn E.] Mayo Clin, Phoenix, AZ USA. RP Bakaeen, F (reprint author), Baylor Coll Med, Dept Cardiothorac Surg, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM fbakaeen@bcm.edu RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 21 TC 6 Z9 6 U1 0 U2 0 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 MAR PY 2008 VL 135 IS 3 BP 648 EP 655 DI 10.1016/j.jtcvs.2007.09.021 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 272LG UT WOS:000253860300034 PM 18329488 ER PT J AU Akins, CW AF Akins, Cary W. TI Mortimer J. Buckley, MD - Obituary SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Cardiac Surg, White 503-55 Fruit St, Boston, MA 02114 USA. EM cakins@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 2008 VL 135 IS 3 BP 711 EP 712 DI 10.1016/j.jtcvs.2007.12.003 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 272LG UT WOS:000253860300055 ER PT J AU Hirsh, V Major, PP Lipton, A Cook, RJ Langer, CJ Smith, MR Brown, JE Coleman, RE AF Hirsh, Vera Major, Pierre P. Lipton, Allan Cook, Richard J. Langer, Corey J. Smith, Matthew R. Brown, Janet E. Coleman, Robert E. TI Zoledronic acid and survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE bone markers; non-small cell lung cancer; N-telopeptide of type I collagen; survival; zoledronic acid ID SKELETAL-RELATED EVENTS; LONG-TERM EFFICACY; PROSTATE-CANCER; SOLID TUMORS; DOUBLE-BLIND; PHASE-III; BISPHOSPHONATES; COMPLICATIONS; CARCINOMA; TURNOVER AB Introduction: Bone metastases from non-small cell lung cancer (NSCLC) are associated with skeletal-related events (SREs) and elevated levels of N-telopeptide of type I collagen (NTX) in some patients. Zoledronic acid (ZOL) reduces SRE risk and NTX levels. Methods: To assess effects of baseline variables, including NTX levels (normal = NTX < 64 nmol/mmol creatinine; high = NTX >= 64 nmol/mmol creatinine), on treatment effects in NSCLC patients, a retrospective analysis was performed in NSCLC patients with bone metastases (N = 382) treated with ZOL or placebo every 3 weeks in a 21-month randomized clinical trial in patients with NSCLC or other solid tumors. Cox proportional hazards models assessed relative risks (RRs) of SREs, bone lesion progression death. Multivariate models analyzed covariate effects on survival. Results: For both placebo- and ZOL-treated patients, high baseline NTX correlated with increased SRE risk (p = 0.068 and 0.012, respectively). Although high versus normal baseline NTX correlated with more than twofold increased risks of bone lesion progression and death in the placebo group (p = 0.039 and 0.001, respectively), correlations were weaker in the ZOL group (RR = 1.38; p = 0.0186 and RR = 1.27; p = 0.142, respectively), suggesting an interaction effect of ZOL and baseline NTX. Among patients with high baseline NTX, ZOL significantly reduced the RR of death by 35% versus placebo (p = 0.024). Per multivariate analysis, ZOL treatment (P = 0.005), higher lymphocyte count (p = 0.011), performance status 0 to 1 (p = 0.012), and absence of narcotic use (p = 0.0 16) correlated with improved survival. Conclusions: This retrospective analysis revealed statistically significant correlations between ZOL and increased survival versus placebo in NSCLC patients and high baseline NTX levels. C1 [Major, Pierre P.] McMaster Univ, Hamilton Reg Canc Ctr, Hamilton, ON, Canada. [Lipton, Allan] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Cook, Richard J.] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Langer, Corey J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Brown, Janet E.] Univ Leeds, Leeds, W Yorkshire, England. [Coleman, Robert E.] Univ Sheffield, Weston Pk Hosp, Canc Res Ctr, Sheffield, S Yorkshire, England. RP Hirsh, V (reprint author), McGill Univ, Ctr Hlth, Royal Victoria Hosp, Dept Med, Room E3-53,687 Pine Ave W, Montreal, PQ H3A 1A1, Canada. EM vera.hirsh@muhc.mcgill.ca FU Cancer Research UK [10048] NR 37 TC 101 Z9 104 U1 0 U2 2 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 MAR PY 2008 VL 3 IS 3 BP 228 EP 236 DI 10.1097/JTO.0b013e3181651c0e PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 280GR UT WOS:000254414300005 PM 18317064 ER PT J AU Alam, HB AF Alam, Hasan B. TI Regional and local brain oxygenation during hemorrhagic shock: A prospective experimental study on the effects of small-volume resuscitation with norepinephrine - Comment SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Editorial Material ID FLUID RESUSCITATION C1 [Alam, Hasan B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Alam, HB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAR PY 2008 VL 64 IS 3 BP 648 EP 649 PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 274JE UT WOS:000253996800018 ER PT J AU Blehar, DJ Gaspari, RJ Montoya, A Calderon, R AF Blehar, David J. Gaspari, Romolo J. Montoya, Anthony Calderon, Richard TI Correlation of visual axis and coronal axis measurements of the optic nerve sheath diameter SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE measurement; optic nerve; optic nerve sheath; sonography ID TRANSORBITAL SONOGRAPHIC EVALUATION; INTRACRANIAL HYPERTENSION; PRESSURE; FUNDAMENTALS; ULTRASOUND; EXPANSION; PATIENT AB Objective. There are several approaches to sonographic imaging and measurement of the optic nerve sheath diameter (ONSD). In this study, we sought to compare visual axis measurements of the optic nerve sheath (ONS) with traditional coronal axis measurements to assess for correlation. Methods. The ONS was visualized in 2 views on both eyes of healthy volunteers using an 8.5-MHz probe. Coronal axis views were obtained with the probe placed at the lateral canthus directed nasally posterior to the globe. Subsequent imaging was made along the midline visual axis. The diameter in this view was measured at several points posterior to the sclera (2, 3, 6, 9, 12, and 15 mm). Results. Twenty-seven subjects were enrolled (54 scans). There was a significant difference between ONSDs measured in each axis, with a coronal axis mean diameter of 3.4 mm and visual axis mean diameters at 2, 3, 6, 9, 12, and 15 mm of 4.28, 4.32, 5.15, 5.74, 6.39, and 7.42 mm, respectively (P <.05). The Pearson coefficient showed no correlation between coronal axis and visual axis measurements, with R values ranging from 0.51 to 0.69. There was a statistically significant increase in the ONSD as the nerve coursed posteriorly when measured in the visual axis. Conclusions. Visual axis measurements do not reliably correlate with coronal axis measurements. The consistently larger diameter measured in the visual axis as well as the gradually increasing diameter posteriorly suggests measurement of an artifactual shadow rather than the true ONS. C1 [Blehar, David J.; Gaspari, Romolo J.; Montoya, Anthony] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01655 USA. [Calderon, Richard] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Blehar, DJ (reprint author), Univ Massachusetts, Sch Med, Dept Emergency Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM blehard@ummhc.org RI Gaspari, Romolo/I-4649-2014 OI Gaspari, Romolo/0000-0002-8411-0308 NR 9 TC 19 Z9 20 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2008 VL 27 IS 3 BP 407 EP 411 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 270AH UT WOS:000253691600010 PM 18314519 ER PT J AU Jeong, JW Shin, DC Do, SH Blanco, C Klipfel, NE Holmes, DR Hovanessian-Larsen, LJ Marmarelis, VZ AF Jeong, Jeong-Won Shin, Dae C. Do, Syn-Ho Blanco, Cesar Klipfel, Nancy E. Holmes, Dennis R. Hovanessian-Larsen, Linda J. Marmarelis, Vasilis Z. TI Differentiation of cancerous lesions in excised human breast specimens using multiband attenuation profiles from ultrasonic transmission tomography SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE breast cancers; frequency-dependent attenuation; mastectomy specimens; multiband profile; soft tissue differentiation; ultrasonic transmission tomography ID TISSUE CHARACTERIZATION; SCREENING MAMMOGRAPHY; ACTIVE CONTOURS; SEGMENTATION; CLASSIFICATION; DIAGNOSIS; IMAGES; EDGES AB Objective. This study examines the tissue differentiation capability of the recently developed high-resolution ultrasonic transmission tomography (HUTT) system in the context of differentiating between benign and malignant tissue types in mastectomy specimens. Methods. Eight mastectomy patients provided breast specimens with benign and malignant lesions. The specimens were scanned by the HUTT system with a pair of either 8- or 4-MHz transducers. Multilband HUTT images over the frequency range from 2 to 10 MHz provide characteristic profiles of frequency-dependent attenuation, termed "multiband profiles," at individual pixels, These features are classified through a novel algorithm of "segment-wise classification" that identifies the disjoint segments of various tissue types and subsequently classifies them into respective diagnostic categories using a measure of proximity to the respective multiband profile templates that have been previously obtained from reference data. Results. We preformed intraspecimen and interspecimen analyses of 108 slices from 8 mastectomy specimens for which "ground truth" was provided by pathology reports. The average performance indices for 2-way classification (malignant versus nonmalignant tissue) in these intraspecimen (interspecimen) specimen studies were found to be sensitivity of 81.9% (89.6%), specificity of 92.9% (92.1%), and accuracy of 89.2% (89.4%), whereas the indices for the 3-way classification were moderately lower. Conclusions. The results have shown the potential of the HUTT technology for reliable differentiation of cancerous lesions from benign changes and normal tissue in mastectomy specimens using frequency-dependent ultrasound attenuation profiles. C1 [Jeong, Jeong-Won; Shin, Dae C.; Blanco, Cesar] Univ So Calif, Alfred E Mann Inst Biomed Engn, Los Angeles, CA 90089 USA. [Klipfel, Nancy E.] Univ So Calif, Dept Clin Pathol, Los Angeles, CA 90089 USA. [Holmes, Dennis R.] Univ So Calif, Dept Clin Surg, Los Angeles, CA 90089 USA. [Hovanessian-Larsen, Linda J.] Univ So Calif, Dept Radiol, Los Angeles, CA 90089 USA. [Marmarelis, Vasilis Z.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. [Marmarelis, Vasilis Z.] Univ So Calif, Viterbi Sch Engn, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Do, Syn-Ho] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jeong, JW (reprint author), Univ So Calif, Alfred E Mann Inst Biomed Engn, 1042 W 36th Pl,DRB B21, Los Angeles, CA 90089 USA. EM jeongwon.jeong@gmail.com NR 18 TC 12 Z9 12 U1 0 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2008 VL 27 IS 3 BP 435 EP 451 PG 17 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 270AH UT WOS:000253691600013 PM 18314522 ER PT J AU Sengupta, S Amling, C D'Amico, AV Blute, ML AF Sengupta, Shomik Amling, Christopher D'Amico, Anthony V. Blute, Michael L. TI Prostate specific antigen kinetics in the management of prostate cancer SO JOURNAL OF UROLOGY LA English DT Review DE prostatic neoplasms; prostate-specific antigen; prostatectomy; radiotherapy; survival ID PSA DOUBLING TIME; EXTERNAL-BEAM RADIATION; RADICAL PROSTATECTOMY; BIOCHEMICAL FAILURE; HORMONAL-THERAPY; LOCAL RECURRENCE; INCREASING PSA; VELOCITY; RADIOTHERAPY; PREDICTORS AB Purpose: We review the usefulness of prostate specific antigen kinetics (ie prostate specific antigen velocity and doubling time) in the treatment of patients with prostate cancer. Materials and Methods: The MEDLINE database was searched to identify studies investigating prostate specific antigen kinetics in patients with prostate cancer. Results: Various techniques are available for estimating prostate specific antigen kinetics, but to minimize the impact of prostate specific antigen variability on such calculations at least a 90-day period and preferably more than 2 measurements should be used. There is little to suggest which measure of prostate specific antigen kinetics may be superior since both appear to provide useful prognostic information. Prostate specific antigen velocity is easier to calculate but prostate specific antigen doubling time may have greater biological justification. Retrospective studies show that before treatment prostate specific antigen kinetics provide prognostic information regarding the risk of treatment failure and subsequent death from cancer. Additionally, in patients treated surgically preoperative prostate specific antigen kinetics predict the risk of adverse pathology, while in those undergoing conservative treatment prostate specific antigen kinetics are associated with the risk of progression and need for intervention. In patients with biochemical failure after therapy prostate specific antigen kinetics predict the risk and potential site of clinical recurrence, the likely response to salvage therapy, and the risk of death from cancer. Preliminary assessments also suggest that prostate specific antigen kinetics may serve as a surrogate end point to replace cancer specific mortality. Conclusions: Although prospective studies are lacking, the current literature suggests that prostate specific antigen kinetics provide valuable prognostic information, and should be further evaluated in clinical decision making and as a surrogate end point for future trials. C1 [Sengupta, Shomik; Blute, Michael L.] Mayo Clin, Dept Urol, Rochester, MN 55905 USA. [Amling, Christopher] Univ Alabama, Dept Urol, Birmingham, AL USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Blute, ML (reprint author), Mayo Clin, Dept Urol, 200 1st St SW, Rochester, MN 55905 USA. EM Blute.Michael@mayo.edu OI Sengupta, Shomik/0000-0003-3357-1216 NR 49 TC 13 Z9 13 U1 1 U2 4 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 MAR PY 2008 VL 179 IS 3 BP 821 EP 826 DI 10.1016/j.juro.2007.10.023 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 262VL UT WOS:000253176000007 PM 18221963 ER PT J AU Choueiri, TK Dreicer, R Paciorek, A Carroll, PR Konety, B AF Choueiri, Toni K. Dreicer, Robert Paciorek, Alan Carroll, Peter R. Konety, Badrinath TI A model that predicts the probability of positive imaging in prostate cancer cases with biochemical failure after initial definitive local therapy SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; recurrence; kinetics; magnetic resonance imaging; prostate-specific antigen ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; BONE-SCINTIGRAPHY; ANTIGEN; RADIOTHERAPY; RECURRENCE; TRIAL; MEN; PSA AB Purpose: Managing biochemical failure in patients following initial treatment of localized prostate cancer is a relatively common clinical problem. Imaging studies to document metastatic disease are frequently obtained but are often uninformative. In this study we identified clinical parameters that were predictive of positive imaging studies. Materials and Methods: From CaPSURE, a national disease registry, all patients with a detectable prostate specific antigen after definitive therapy with radical prostatectomy or radiation therapy and who had undergone at least 1 imaging study (bone scan, computerized tomography or magnetic resonance imaging of the abdomen and pelvis) were identified. Patient characteristics, trigger prostate specific antigen (prostate specific antigen before the imaging), prostate specific antigen doubling time and velocity prior to imaging for association with a positive imaging test were analyzed. The results were incorporated into a predictive model. Results: We identified 292 patients (66% radical prostatectomy and 34% radiation therapy) who had recurrence and had available imaging data, and 31 (11%) patients had a positive imaging study. On multivariate analysis age, imaging type, trigger prostate specific antigen and prostate specific antigen doubling time were significantly associated with imaging results. A multivariate model including age (younger than 60 vs 60 to 69 vs 70 years or older), primary imaging type (bone scan vs computerized tomography vs magnetic resonance imaging), trigger prostate specific antigen (5 or less vs more than 5 ng/ml) and prostate specific antigen doubling time (less than 10 vs 10 or more months) had a concordance index of 84% in predicting positive imaging. Conclusions: Age, imaging type, trigger prostate specific antigen and prostate specific antigen doubling time were significantly associated with imaging results. Imaging studies are unlikely to be useful when trigger prostate specific antigen is 5 or less ng/ml and prostate specific antigen doubling time is 10 or more months. C1 [Choueiri, Toni K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. [Dreicer, Robert] Cleveland Clin, Taussing Canc Ctr, Cleveland, OH 44106 USA. [Paciorek, Alan; Carroll, Peter R.; Konety, Badrinath] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, 44 Binney St, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu NR 17 TC 50 Z9 52 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2008 VL 179 IS 3 BP 906 EP 910 DI 10.1016/j.juro.2007.10.059 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 262VL UT WOS:000253176000033 PM 18207194 ER PT J AU Dahl, DM AF Dahl, Douglas M. TI 3-year actuarial biochemical recurrence-free survival following laparoscopic radical prostatectomy: Experience from a tertiary referral center in the United States - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Dahl, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 MAR PY 2008 VL 179 IS 3 BP 921 EP 922 DI 10.1016/j.juro.2007.10.114 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 262VL UT WOS:000253176000038 ER PT J AU Stenstrom, DA Muldoon, LL Armijo-Medina, H Watnick, S Doolittle, ND Kaufman, JA Peterson, DR Bubalo, J Neuwelt, EA AF Stenstrom, David A. Muldoon, Leslie L. Armijo-Medina, Hector Watnick, Suzanne Doolittle, Nancy D. Kaufman, John A. Peterson, Darryl R. Bubalo, Joseph Neuwelt, Edward A. TI N-acetylcysteine use to prevent contrast medium-induced nephropathy: Premature phase III trials SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; RADIOCONTRAST-INDUCED NEPHROPATHY; PERFORMANCE LIQUID-CHROMATOGRAPHY; AGENT-ASSOCIATED NEPHROTOXICITY; RENAL-FUNCTION; RADIOGRAPHIC-CONTRAST; CORONARY-ANGIOGRAPHY; CARDIAC-CATHETERIZATION; ORAL ACETYLCYSTEINE; INTRAVENOUS ROUTE AB To date there has been no general consensus regarding the effectiveness of N-acetylcysteine as a protective therapy against contrast medium-induced nephropathy. Several phase III clinical trials have been conducted without a proper understanding of N-acetylcysteine pharmacology, particularly with regard to first-pass hepatic metabolism. A review was conducted of the literature concerning contrast medium-induced nephropathy and new studies of human N-acetylcysteine pharmacology were performed. After an analysis was performed, it was concluded that further phase I and phase 11 trials are needed. The efficacy of N-acetylcysteine in the prevention of contrast medium-induced nephropathy may be demonstrated with the use of higher doses than used in earlier studies, in combination with parenteral administration. C1 [Stenstrom, David A.; Muldoon, Leslie L.; Armijo-Medina, Hector; Doolittle, Nancy D.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97239 USA. [Muldoon, Leslie L.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA. [Kaufman, John A.] Oregon Hlth & Sci Univ, Dept Angiog, Portland, OR 97239 USA. [Bubalo, Joseph] Oregon Hlth & Sci Univ, Dept Pharm, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. [Watnick, Suzanne] Div Hosp & Specialty Med, Nephrol Sect, Portland, OR USA. [Peterson, Darryl R.] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pkwy,L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU NINDS NIH HHS [NS44687, NS33618] NR 75 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2008 VL 19 IS 3 BP 309 EP 318 DI 10.1016/j.jvir.2007.11.003 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 271KV UT WOS:000253788200001 PM 18295688 ER PT J AU Sobkin, PR Bloom, AI Wilson, MW LaBerge, JM Hastings, GS Gordon, RL Brody, LA Sawhney, R Kerlan, RK AF Sobkin, Paul R. Bloom, Allan I. Wilson, Mark W. LaBerge, Jeanne M. Hastings, Geoff S. Gordon, Roy L. Brody, Lynn A. Sawhney, Rajiv Kerlan, Robert K., Jr. TI Massive abdominal wall hemorrhage from injury to the inferior epigastric artery: A retrospective review SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID PSEUDOANEURYSM; PARACENTESIS; COMPLICATION; ANGIOGRAPHY; MANAGEMENT; DIAGNOSIS; HEMATOMA AB PURPOSE: To identify the etiology of inferior epigastric artery injury (IEAI) in patients referred to the interventional radiology service and determine the efficacy of diagnostic imaging and embolization in these patients. MATERIALS AND METHODS: A retrospective review of patients referred to the interventional radiology departments at three university-affiliated hospitals from 1995 through 2007 was performed. Patients were identified and data were extracted from case log books and the electronic medical record. RESULTS: Twenty IEAIs were identified in 19 patients. The etiology of arterial injury was paracentesis in eight (40%), surgical trauma in three (15%), percutaneous drain placement in three (15%), blunt trauma in two (10%), subcutaneous injection in one (5%), stabbing in one (5%), and unknown in two (10%). Fifteen of 19 patients (79%) had an underlying coagulopathy. The diagnosis was confirmed by contrast medium-enhanced computed tomography (CT) in 14 (70%), tagged red blood cell scan in two (10%), and noncontrast CT in one (5%). Three patients (15%) had no diagnostic imaging. Contrast medium-enhanced CT showed active extravasation in nine of 14 patients (64%) and 13 of 14 exhibited active extravasation on subsequent arteriography. The sensitivity and specificity of contrast medium-enhanced CT for demonstrating active arterial bleeding were 70% and 100%, respectively. All 20 IEAIs were treated With transcatheter embolization, with an overall success rate of 90% and no complications. CONCLUSIONS: IEAI is most often an iatrogenic injury in a coagulopathic patient. Contrast medium-enhanced CT can be diagnostic for active bleeding, but in the setting of ongoing hemorrhage a negative study result should not preclude arteriography. Embolization is an effective means to control hemorrhage. C1 [Sobkin, Paul R.; Bloom, Allan I.; LaBerge, Jeanne M.; Gordon, Roy L.; Brody, Lynn A.; Kerlan, Robert K., Jr.] Univ Calif San Francisco, Dept Radiol, Sect Intervent Radiol, San Francisco, CA 94143 USA. [Wilson, Mark W.] San Francisco Gen Hosp, Sect Intervent Radiol, San Francisco, CA 94110 USA. [Sawhney, Rajiv] San Francisco Vet Adm Med Ctr, Sect Intervent Radiol, San Francisco, CA USA. [Hastings, Geoff S.] Kaiser Permanente Med Ctr, Sect Intervent Radiol, Oakland, CA USA. RP Bloom, AI (reprint author), Hassadah Univ, Med Ctr, Dept Radiol, POB 12000, IL-91120 Jerusalem, Israel. EM allan@hassadah.org.il NR 14 TC 12 Z9 12 U1 0 U2 0 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 MAR PY 2008 VL 19 IS 3 BP 327 EP 332 DI 10.1016/j.jvir.2007.11.004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 271KV UT WOS:000253788200003 PM 18295690 ER PT J AU d'Othe, BJ Faintuch, S Reedy, AW Nickerson, CF Rosen, MP AF d'Othe, Bertrand Janne Faintuch, Salomao Reedy, Allen W. Nickerson, Carl F. Rosen, Max P. TI Retrievable versus permanent caval filter procedures: When are they cost-effective for interventional radiology? SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID INFERIOR VENA-CAVA; MULTICENTER; EXPERIENCE; REGISTRY AB PURPOSE: Because many retrievable inferior vena cava (IVC) filters are placed without ever being removed, placement of a retrievable device that is not removed incurs greater technical cost for the institution than a cheaper permanent filter (PF), with no clinical benefit for the patient and no additional professional or technical revenue for the interventional radiologist and institution. The purposes of this study are to identify patient characteristics associated with lack of removal of a retrievable filter (RF) and to develop a cost-effective strategy for placement of a retrievable IVC filter. MATERIALS AND METHODS: A retrospective evaluation of 160 consecutive patients who underwent IVC filter placement with or without removal in our interventional radiology (IR) unit over a period of 31 months was performed. Patient characteristics were identified that were associated with lack of removal of retrievable IVC filters, and the cost savings were calculated in the event that a PF had been substituted for an RF in these patients. RESULTS: A total of 160 consecutive IVC filters were placed during the study period. Of these, 42 (26%) were PFs and 118 (74%) were RFs. During the study period, only 27 of the 118 RFs (23%) were subsequently removed. Factors associated with lack of removal of an RF included patient age (P =.003), presence of ongoing malignancy (P =.04), and indication for filter placement (P =.01). Retrospectively, the use of retrievable devices only in the presence of two of the three selection criteria (ie, age <65 years, no ongoing malignancy, prophylactic indication) would have resulted in a net incremental benefit of $59,562 for the IR service. CONCLUSIONS: The preferential use of retrievable versus permanent devices for filter placement is financially advantageous for an IR unit only if at least 41% of them are eventually removed. The use of clinical criteria to select device type allows significant cost savings. C1 [d'Othe, Bertrand Janne; Faintuch, Salomao; Reedy, Allen W.; Nickerson, Carl F.; Rosen, Max P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. RP d'Othe, BJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Beth Israel Deaconess Med Ctr, 55 Fruit St,GRB-290, Boston, MA 02114 USA. EM bjannedothee@partners.org RI Janne d'Othee, Bertrand/E-8467-2010 NR 15 TC 17 Z9 17 U1 0 U2 0 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 MAR PY 2008 VL 19 IS 3 BP 384 EP 392 DI 10.1016/j.jvir.2007.09.024 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 271KV UT WOS:000253788200011 ER PT J AU Joseph, A Zheng, JH Follenzi, A DiLorenzo, T Sango, K Hyman, J Chen, K Piechocka-Trocha, A Brander, C Hooijberg, E Vignali, DA Walker, BD Goldstein, H AF Joseph, Aviva Zheng, Jian Hua Follenzi, Antonia DiLorenzo, Teresa Sango, Kaori Hyman, Jaime Chen, Ken Piechocka-Trocha, Alicja Brander, Christian Hooijberg, Erik Vignali, Dario A. Walker, Bruce D. Goldstein, Harris TI Lentiviral vectors encoding human immunodeficiency virus type I (HIV-1)-specific T-cell receptor genes efficiently convert peripheral blood CD8 T lymphocytes into cytotoxic T lymphocytes with potent in vitro and in vivo HIV-1-specific inhibitory activity SO JOURNAL OF VIROLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HIV-INFECTED PATIENTS; LOW VIRAL LOAD; DISEASE PROGRESSION; ADOPTIVE IMMUNOTHERAPY; EFFECTOR FUNCTIONS; 1-INFECTED CELLS; IMMUNE-RESPONSES; TCR; REPLICATION AB The human immunodeficiency virus type I (HIV-1)-specific CD8 cytotoxic T-lymphocyte (CTL) response plays a critical role in controlling HIV-1 replication. Augmenting this response should enhance control of HIV-1 replication and stabilize or improve the clinical course of the disease. Although cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection in immunocompromised patients can be treated by adoptive transfer of ex vivo-expanded CMV- or EBV-specific CTLs, adoptive transfer of ex vivo-expanded, autologous HIV-1-specific CTLs had minimal effects on HIV-1 replication, likely a consequence of the inherently compromised qualitative function of HIV-1-specific CTLs derived from HIV-1-infected individuals. We hypothesized that this limitation could be circumvented by using as an alternative source of HIV-1-specific CTLs, autologous peripheral CD8(+) T lymphocytes whose antigen specificity is redirected by transduction with lentiviral vectors encoding HIV-1-specific T-cell receptor (TCR) alpha and beta chains, an approach used successfully in cancer therapy. To efficiently convert peripheral CD8 lymphocytes into HIV-1-specific CTLs that potently suppress in vivo HIV-1 replication, we constructed lentiviral vectors encoding the HIV-1-specific TCR alpha and TCR beta chains cloned from a CTL clone specific for an HIV Gag epitope, SL9, as a single transcript linked with a self-cleaving peptide. We demonstrated that transduction with this lentiviral vector efficiently converted primary human CD8 lymphocytes into HIV-1-specific CTLs with potent in vitro and in vivo HIV-1-specific activity. Using lentiviral vectors encoding an HIV-1-specific TCR to transform peripheral CD8 lymphocytes into HIV-1-specific CTLs with defined specificities represents a new immunotherapeutic approach to augment the HIV-1-specific immunity of infected patients. C1 [Joseph, Aviva; Zheng, Jian Hua; Goldstein, Harris] Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. [Joseph, Aviva; DiLorenzo, Teresa; Sango, Kaori; Hyman, Jaime; Goldstein, Harris] Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Follenzi, Antonia] Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. [DiLorenzo, Teresa] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Chen, Ken] Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. [Piechocka-Trocha, Alicja; Brander, Christian; Walker, Bruce D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Piechocka-Trocha, Alicja; Brander, Christian; Walker, Bruce D.] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. [Piechocka-Trocha, Alicja; Brander, Christian; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. [Hooijberg, Erik] Vrije Univ Amsterdam Med Ctr, NL-1081 HV Amsterdam, Netherlands. [Vignali, Dario A.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA. RP Goldstein, H (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Forchheimer Bldg,Room 408,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM hgoldste@aecom.yu.edu RI Hooijberg, Erik/F-4503-2011 FU NIAID NIH HHS [P30 AI051519, AI51519, AI67136, R01 AI067136] NR 70 TC 52 Z9 55 U1 2 U2 8 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 MAR PY 2008 VL 82 IS 6 BP 3078 EP 3089 DI 10.1128/JV1.01812-07 PG 12 WC Virology SC Virology GA 270AB UT WOS:000253691000046 PM 18184707 ER PT J AU Blutt, SE Warfield, KL Estes, MK Conner, ME AF Blutt, Sarah E. Warfield, Kelly L. Estes, Mary K. Conner, Margaret E. TI Differential requirements for T cells in viruslike particle- and rotavirus-induced protective immunity SO JOURNAL OF VIROLOGY LA English DT Article ID INTRANASAL IMMUNIZATION; EPITHELIAL-CELLS; CAPSID PROTEINS; VP6 PROTEIN; INFECTION; MICE; DISEASE; LYMPHOCYTES; EXPRESSION; EFFICACY AB Correlates of protection from rotavirus infection are controversial. We compared the roles of B and T lymphocytes in protective immunity induced either by intranasally administered nonreplicating viruslike particles or inactivated virus or by orally administered marine rotavirus. We found that protection induced by nonreplicating vaccines requires CD4(+) T cells and CD40/CD40L. In contrast, T cells were not required for short-term protective immunity induced by infection, but both T-cell-dependent and -independent mechanisms contributed to long-term maintenance of protection. Our findings indicate that more than one marker of protective immunity exists and that these markers depend on the vaccine that is administered. C1 [Blutt, Sarah E.; Warfield, Kelly L.; Estes, Mary K.; Conner, Margaret E.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Blutt, Sarah E.; Conner, Margaret E.] Michael E Debakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Conner, ME (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mconner@bcm.edu FU NIAID NIH HHS [AI10604, F32 AI010604, R01 AI080656, R21 AI024998, R01 AI024998]; NIDDK NIH HHS [P30 DK056338, DK56338] NR 24 TC 11 Z9 11 U1 0 U2 0 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 MAR PY 2008 VL 82 IS 6 BP 3135 EP 3138 DI 10.1128/JVI.01727-07 PG 4 WC Virology SC Virology GA 270AB UT WOS:000253691000052 PM 18184712 ER PT J AU Yerly, D Heckerman, D Allen, TM Chisholm, JV Faircloth, K Linde, CH Frahm, N Timm, J Pichler, WJ Cerny, A Brander, C AF Yerly, Daniel Heckerman, David Allen, Todd M. Chisholm, John V., III Faircloth, Kellie Linde, Caitlyn H. Frahm, Nicole Timm, Joerg Pichler, Werner J. Cerny, Andreas Brander, Christian TI Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-RESPONSES; ESCAPE MUTATIONS; CELL RECOGNITION; VIRAL CLEARANCE; INFECTION; PERSISTENCE; EVOLUTION; SELECTION; HIV-1; CD8 AB Hepatitis C virus (HCV) clearance has been associated with reduced viral evolution in targeted cytotoxic T-lymphocyte (CTL) epitopes, suggesting that HCV clearers may mount CTL responses with a superior ability to recognize epitope variants and prevent viral immune escape. Here, 40 HCV-infected subjects were tested with 406 10-mer peptides covering the vast majority of the sequence diversity spanning a 197-residue region of the NS3 protein. HCV clearers mounted significantly broader CTL responses of higher functional avidity and with wider variant cross-recognition capacity than nonclearers. These observations have important implications for vaccine approaches that may need to induce high-avidity responses in vivo. C1 [Yerly, Daniel; Allen, Todd M.; Chisholm, John V., III; Faircloth, Kellie; Linde, Caitlyn H.; Frahm, Nicole; Brander, Christian] Massachusetts Gen Hosp, Charlestown, MA 02143 USA. [Yerly, Daniel; Allen, Todd M.; Chisholm, John V., III; Faircloth, Kellie; Linde, Caitlyn H.; Frahm, Nicole; Brander, Christian] Harvard Univ, Sch Med, Partners AIDS Res Ctr, Charlestown, MA 02143 USA. [Yerly, Daniel; Pichler, Werner J.] Univ Bern, Clin Rheumatol & Clin Immunol Allergol, CH-3010 Bern, Switzerland. [Heckerman, David] Microsoft Res, Redmond, WA 98052 USA. [Timm, Joerg] Univ Hosp Essen, Inst Virol, Essen, Germany. [Cerny, Andreas] Osped Reg Lugano, Dept Med, CH-6903 Lugano, Switzerland. RP Brander, C (reprint author), Massachusetts Gen Hosp, MGH E 5239,149 13th St, Charlestown, MA 02143 USA. EM cbrander@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778 NR 29 TC 36 Z9 38 U1 0 U2 0 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 MAR PY 2008 VL 82 IS 6 BP 3147 EP 3153 DI 10.1128/JVI.02252-07 PG 7 WC Virology SC Virology GA 270AB UT WOS:000253691000054 PM 18184704 ER PT J AU Kasprowicz, V Wiesch, JSZ Kuntzen, T Nolan, BE Longworth, S Berical, A Blum, J McMahon, C Reyor, LL Elias, N Kwok, WW McGovern, BG Freeman, G Chung, RT Klenerman, P Lewis-Ximenez, L Walker, BD Allen, TM Kim, AY Lauer, GM AF Kasprowicz, Victoria Wiesch, Julian Schulze zur Kuntzen, Thomas Nolan, Brian E. Longworth, Steven Berical, Andrew Blum, Jenna McMahon, Cory Reyor, Laura L. Elias, Nahel Kwok, William W. McGovern, Barbara G. Freeman, Gordon Chung, Raymond T. Klenerman, Paul Lewis-Ximenez, Lia Walker, Bruce D. Allen, Todd M. Kim, Arthur Y. Lauer, Georg M. TI High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8(+) and CD4(+) T cells during acute HCV infection, irrespective of clinical outcome SO JOURNAL OF VIROLOGY LA English DT Article ID UP-REGULATION; DYSFUNCTION; EXHAUSTION AB We monitored expression of PD-1 (a mediator of T-cell exhaustion and viral persistence) on hepatitis C virus (HCV)-specific CD8(+) and CD4(+) T cells from blood and liver during acute and chronic infections and after the resolved infection stage. PD-1 expression on HCV-specific T cells was high early in acute infection irrespective of clinical outcome, and most cells continued to express PD-1 in resolved and chronic stages of infection; intrahepatic expression levels were especially high. Our results suggest that an analysis of PD-1 expression alone is not sufficient to predict infection outcome or to determine T-cell functionality in HCV infection. C1 [Kasprowicz, Victoria; Wiesch, Julian Schulze zur; Kuntzen, Thomas; Nolan, Brian E.; Longworth, Steven; Berical, Andrew; Blum, Jenna; McMahon, Cory; Reyor, Laura L.; Elias, Nahel; Walker, Bruce D.; Allen, Todd M.; Kim, Arthur Y.; Lauer, Georg M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Wiesch, Julian Schulze zur] Univ Hamburg, Med Klin 1, Hamburg, Germany. [Elias, Nahel] Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. [Kwok, William W.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [McGovern, Barbara G.] Lemuel Shattuck Hosp, Boston, MA USA. [McGovern, Barbara G.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Freeman, Gordon] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Surg, Gastrointestinal Unit, Boston, MA 02114 USA. [Klenerman, Paul] Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. [Lewis-Ximenez, Lia] Fiocruz MS, Inst Oswaldo Cruz, Dept Virol, BR-21045900 Rio De Janeiro, Brazil. [Wiesch, Julian Schulze zur; Elias, Nahel; Chung, Raymond T.; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Lauer, GM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,6th Floor,Room 6001, Charlestown, MA 02129 USA. EM glauer@partners.org RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [R01 AI067926, K23 AI054379, K23-AI054379-05, R01 AI031563, R01-AI031563-13, R01-AI067926-01, U19 AI066345, U19-AI066345-02]; Wellcome Trust NR 14 TC 98 Z9 108 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 6 BP 3154 EP 3160 DI 10.1128/JVI.02474-07 PG 7 WC Virology SC Virology GA 270AB UT WOS:000253691000055 PM 18160439 ER PT J AU Crawford, H Prado, JG Leslie, A Hue, S Honeyborne, I Reddy, S Van der Stok, M Mncube, Z Brander, C Rousseau, C Mullins, JI Kaslow, R Goepfert, P Allen, S Hunter, E Mulenga, J Kiepiela, P Walker, BD Goulder, PJR AF Crawford, Hayley Prado, Julia G. Leslie, Alasdair Hue, Stephane Honeyborne, Isobella Reddy, Sharon van der Stok, Mary Mncube, Zenele Brander, Christian Rousseau, Christine Mullins, James I. Kaslow, Richard Goepfert, Paul Allen, Susan Hunter, Eric Mulenga, Joseph Kiepiela, Photini Walker, Bruce D. Goulder, Philip J. R. TI Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLA-B*5703-restrieted gag epitope in chronic human immunodeficiency virus type 1 infection (vol 81, pg 8346, 2007) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Univ Oxford, Dept Pediat, Oxford OX1 3SY, England. Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. Massachusetts Gen Hosp East, Partners AIDS Res Ctr, Boston, MA 02129 USA. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. Univ Alabama, Birmingham, AL 35294 USA. Zambia Emory HIV Res Grp, Lusaka, Zambia. Zambia Blood Transfus Serv, Lusaka, Zambia. Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Crawford, H (reprint author), Univ Oxford, Dept Pediat, Peter Medawar Bldg Pathogen Res,S Pk Rd, Oxford OX1 3SY, England. NR 1 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 2008 VL 82 IS 6 BP 3161 EP 3161 DI 10.1128/JV1.02750-07 PG 1 WC Virology SC Virology GA 270AB UT WOS:000253691000056 ER PT J AU Waisbren, SE Bowles, H Hasan, T Zou, KH Emans, SJ Goldberg, C Gould, S Levine, D Lieberman, E Loeken, M Longtine, J Nadelson, C Patenaude, AF Quinn, D Randolph, AG Solet, JM Ullrich, N Walensky, R Weitzman, P Christou, H AF Waisbren, Susan E. Bowles, Hannah Hasan, Tayaba Zou, Kelly H. Emans, S. Jean Goldberg, Carole Gould, Sandra Levine, Deborah Lieberman, Ellice Loeken, Mary Longtine, Janina Nadelson, Carol Patenaude, Andrea Farkas Quinn, Deborah Randolph, Adrienne G. Solet, Jo M. Ullrich, Nicole Walensky, Rochelle Weitzman, Patricia Christou, Helen TI Gender differences in research grant applications and funding outcomes for medical school faculty SO JOURNAL OF WOMENS HEALTH LA English DT Article ID ACADEMIC MEDICINE; WOMEN; COMPENSATION; ADVANCEMENT; SCIENCE; CAREER; EQUITY AB Purpose: To evaluate whether there were differences in acquisition of research grant support between male and female faculty at eight Harvard Medical School-affiliated institutions. Methods: Data were obtained from the participating institutions on all research grant applications submitted by full-time faculty from 2001 through 2003. Data were analyzed by gender and faculty rank of applicant, source of support ( federal or nonfederal), funding outcome, amount of funding requested, and amount of funding awarded. Results: Data on 6319 grant applications submitted by 2480 faculty applicants were analyzed. Women represented 29% of investigators and submitted 26% of all grant requests. There were significant gender differences in the mean number of submissions per applicant (women 2.3, men 2.7), success rate (women 41%, men 45%), number of years requested (women 3.1, men 3.4), median annual amount requested (women $115,325, men $ 150,000), mean number of years awarded (women 2.9, men 3.2), and median annual amount awarded (women $ 98,094, men $ 125,000). After controlling for academic rank, grant success rates were not significantly different between women and men, although submission rates by women were significantly lower at the lowest faculty rank. Although there was no difference in the proportion of money awarded to money requested, women were awarded significantly less money than men at the ranks of instructor and associate professor. More men than women applied to the National Institutes of Health, which awarded higher dollar amounts than other funding sources. Conclusions: Gender disparity in grant funding is largely explained by gender disparities in academic rank. Controlling for rank, women and men were equally successful in acquiring grants. However, gender differences in grant application behavior at lower academic ranks also contribute to gender disparity in grant funding for medical science. C1 [Waisbren, Susan E.; Emans, S. Jean; Goldberg, Carole; Randolph, Adrienne G.; Ullrich, Nicole; Christou, Helen] Childrens Hosp, Boston, MA 02115 USA. [Bowles, Hannah] Harvard Univ, Kennedy Sch Govt, Cambridge, MA 02138 USA. [Zou, Kelly H.; Longtine, Janina; Nadelson, Carol; Walensky, Rochelle; Weitzman, Patricia; Christou, Helen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zou, Kelly H.; Gould, Sandra; Longtine, Janina; Nadelson, Carol; Walensky, Rochelle; Weitzman, Patricia; Christou, Helen] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zou, Kelly H.; Lieberman, Ellice; Walensky, Rochelle; Christou, Helen] Harvard Univ, Sch Med, Boston, MA USA. [Levine, Deborah] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Loeken, Mary] Joslin Diabet Ctr, Boston, MA 02215 USA. [Patenaude, Andrea Farkas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Solet, Jo M.] Cambridge Hlth Alliance, Boston, MA USA. RP Waisbren, SE (reprint author), Childrens Hosp, 1 Autumn St 525, Boston, MA 02115 USA. EM susan.waisbren@childrens.harvard.edu RI Levine, Deborah/K-2819-2012; OI Emans, S. Jean/0000-0002-4535-7850; Levine, Deborah/0000-0001-7761-6493; Walensky, Rochelle P./0000-0002-8795-379X; Randolph, Adrienne/0000-0002-3084-3071; Loeken, Mary/0000-0002-8056-9816 NR 20 TC 32 Z9 32 U1 0 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2008 VL 17 IS 2 BP 207 EP 214 DI 10.1089/jwh.2007.0412 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 284VM UT WOS:000254734700005 PM 18321172 ER PT J AU Seaver, MR Freund, KM Wright, LM Tjia, J Frayne, SM AF Seaver, Margaret R. Freund, Karen M. Wright, Leslie M. Tjia, Jennifer Frayne, Susan M. TI Healthcare preferences among lesbians: A focus group analysis SO JOURNAL OF WOMENS HEALTH LA English DT Article ID QUALITATIVE RESEARCH; WOMENS SATISFACTION; NATIONAL CENTERS; GYNECOLOGIC CARE; BISEXUAL WOMEN; POPULATION; EXCELLENCE; OUTCOMES; NEEDS; RISK AB Objective: The healthcare needs of lesbians are not well understood. We sought to characterize lesbians' experiences with, and preferences for, women's healthcare. Methods: We conducted three age-stratified focus groups (18-29, 30-50, and > 50 years) with a total of 22 participants using a semistructured interview guide to elicit lesbians' experiences and preferences. We analyzed transcripts of these audiotaped sessions using the constant comparative method of grounded theory. Community-dwelling women who self-identified as lesbian and responded to advertisements were selected on first-come basis. Results: Participants voiced experiences and preferences for healthcare that emerged into three themes: desired models of care, desired processes of care, and desired patient-provider relationship. Each theme was further developed into multiple subthemes. Within the subthemes we identified issues that were specific to lesbians and those that were general women's health issues. Participants preferred, but did not always receive, care that is comprehensive in scope, person centered, nondiscriminatory, and inclusive of them as lesbians. Conclusions: Healthcare providers, institutions, and society should adopt an inviting, person-centered approach toward lesbians seeking healthcare, assure them access to healthcare information, and establish healthcare delivery systems that take all aspects of health into account. C1 [Seaver, Margaret R.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Seaver, Margaret R.; Freund, Karen M.; Wright, Leslie M.] Boston Univ, Sch Med, Natl Ctr Excellence Womens Hlth, Boston, MA 02118 USA. [Seaver, Margaret R.; Freund, Karen M.; Wright, Leslie M.] Boston Univ, Med Ctr, Dept Med,Womens Hlth Unit, Gen Internal Med Sect, Boston, MA USA. [Tjia, Jennifer] Univ Penn, Dept Med, Div Geriatr Med, Philadelphia, PA 19104 USA. [Frayne, Susan M.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Internal Med, Palo Alto, CA 94304 USA. [Frayne, Susan M.] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA. RP Seaver, MR (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 11PCC WHC, Boston, MA 02130 USA. EM margrsea@massmed.org OI Freund, Karen/0000-0002-9049-5574 NR 42 TC 19 Z9 19 U1 3 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2008 VL 17 IS 2 BP 215 EP 225 DI 10.1089/jwh.2007.0083 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 284VM UT WOS:000254734700006 PM 18321173 ER PT J AU Suggs, JF Hanson, GR Park, SE Moynihan, AL Li, G AF Suggs, Jeremy F. Hanson, George R. Park, Sang Eun Moynihan, Angela L. Li, Guoan TI Patient function after a posterior stabilizing total knee arthroplasty: cam-post engagement and knee kinematics SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Article DE knee; arthroplasty; knee replacement; biomechanics; kinematics; humans ID VIVO FLUOROSCOPIC ANALYSIS; HIGH-FLEXION; FEMORAL ROLLBACK; MOBILE-BEARING; FOLLOW-UP; MOTION; RANGE; DESIGN; REPLACEMENT; SYSTEM AB Even though posterior substituting total knee arthroplasty has been widely used in surgery, how the cam-post mechanism (posterior substituting mechanism) affects knee joint kinematics and function in patients is not known. The objective of the present study was to investigate posterior femoral translation, internal tibial rotation, tibiofemoral contact, and cam-post engagement of total knee arthroplasty patients during in vivo weight-bearing flexion. Twenty-four knees with a PS TKA were investigated while performing a single leg weight-bearing lunge from full extension to maximum flexion as images were recorded using a dual fluoroscopic system. The in vivo knee position at each targeted flexion angle was reproduced using 3D TKA models and the fluoroscopic images. The kinematics of the knee was measured from the series of the total knee arthroplasty models. The cam-post engagement was determined when the surface model of the femoral cam overlapped with that of the tibial post. The mean maximum flexion angle for all the subjects was 112.5 +/- 13.1 degrees. The mean flexion angle where cam-post engagement was observed was 91.1 +/- 10.9 degrees. The femur moved anteriorly from 0 degrees to 30 degrees and posteriorly through the rest of the flexion range. The internal tibial rotation increased approximately 6 degrees from full extension to 90 degrees of flexion and decreased slightly with further flexion. Both the medial and lateral contact point moved posteriorly from 0 degrees to 30 degrees, remained relatively constant from 30 degrees to 90 degrees, and then moved further posterior from 90 degrees to maximum flexion. The in vivo cam-post engagement corresponded to increased posterior translation and reduced internal tibial rotation at high flexion of the posterior substituting total knee arthroplasty. The initial cam-post engagement was also mildly correlated with the maximum flexion angle of the knee (R = 0.51, p = 0.019). A later cam-post engagement might indicate an environment conducive to greater flexion. If the factors that affect cam-post engagement timing can be established, proper manipulation of those factors may improve the function of the knee after posterior substituting total knee arthroplasty. C1 [Suggs, Jeremy F.; Hanson, George R.; Moynihan, Angela L.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Suggs, Jeremy F.; Hanson, George R.; Moynihan, Angela L.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Suggs, Jeremy F.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Suggs, Jeremy F.] Exponent Inc, Philadelphia, PA USA. [Park, Sang Eun] Dongguk Univ Int Hosp, Dept Orthopaed Surg, Goyang, South Korea. RP Li, G (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM jsuggs@exponent.com; gli1@partners.org NR 29 TC 30 Z9 33 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-2056 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD MAR PY 2008 VL 16 IS 3 BP 290 EP 296 DI 10.1007/s00167-007-0467-9 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 269CO UT WOS:000253627300013 PM 18196219 ER PT J AU Harrington, D Gail, MH AF Harrington, David Gail, Mitchell H. TI Harry S. (Sam) Wieand SO LIFETIME DATA ANALYSIS LA English DT Biographical-Item C1 [Harrington, David] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Harrington, D (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2008 VL 14 IS 1 BP 1 EP 5 DI 10.1007/s10985-008-9081-5 PG 5 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 259ND UT WOS:000252945100001 PM 18219575 ER PT J AU Soh, CH Harrington, DP Zaslavsky, AM AF Soh, Chang-Heok Harrington, David P. Zaslavsky, Alan M. TI Reducing bias in parameter estimates from stepwise regression in proportional hazards regression with right-censored data SO LIFETIME DATA ANALYSIS LA English DT Article DE stepwise regression; bias reduction; bootstrap; proportional hazards model ID VARIABLE SELECTION; SURVIVAL-DATA; MODELS; BOOTSTRAP AB When variable selection with stepwise regression and model fitting are conducted on the same data set, competition for inclusion in the model induces a selection bias in coefficient estimators away from zero. In proportional hazards regression with right-censored data, selection bias inflates the absolute value of parameter estimate of selected parameters, while the omission of other variables may shrink coefficients toward zero. This paper explores the extent of the bias in parameter estimates from stepwise proportional hazards regression and proposes a bootstrap method, similar to those proposed by Miller (Subset Selection in Regression, 2nd edn. Chapman & Hall/CRC, 2002) for linear regression, to correct for selection bias. We also use bootstrap methods to estimate the standard error of the adjusted estimators. Simulation results show that substantial biases could be present in uncorrected stepwise estimators and, for binary covariates, could exceed 250% of the true parameter value. The simulations also show that the conditional mean of the proposed bootstrap bias-corrected parameter estimator, given that a variable is selected, is moved closer to the unconditional mean of the standard partial likelihood estimator in the chosen model, and to the population value of the parameter. We also explore the effect of the adjustment on estimates of log relative risk, given the values of the covariates in a selected model. The proposed method is illustrated with data sets in primary biliary cirrhosis and in multiple myeloma from the Eastern Cooperative Oncology Group. C1 [Soh, Chang-Heok] Genentech Inc, San Francisco, CA 94080 USA. [Harrington, David P.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Harrington, David P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Soh, CH (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. EM csoh@post.harvard.edu; dph@jimmy.harvard.edu; zaslavsk@hcp.med.harvard.edu FU NIAID NIH HHS [AI052817] NR 21 TC 2 Z9 2 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2008 VL 14 IS 1 BP 65 EP 85 DI 10.1007/s10985-007-9078-5 PG 21 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 259ND UT WOS:000252945100009 PM 18189162 ER PT J AU Lentz, MR Westmoreland, SV Lee, V Ratai, EM Halpern, EF Gonzalez, RG AF Lentz, Margaret R. Westmoreland, Susan V. Lee, Vallent Ratai, Eva-Maria Halpern, Elkan F. Gonzalez, R. Gilberto TI Metabolic markers of neuronal injury correlate with SIVCNS disease severity and inoculum in the macaque model of NeuroAIDS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE SIV; HIV; encephalitis; MRS ID SIMIAN IMMUNODEFICIENCY VIRUS; MAGNETIC-RESONANCE-SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; BRAIN-METABOLITES; INFECTED MACAQUES; MR SPECTROSCOPY; HIV DEMENTIA; PROTON; AIDS; MONKEYS AB In vivo MR spectroscopy (MRS) studies have shown reductions in NAA/Cr levels in patients with severe neurocognitive deficits due to AIDS dementia complex (ADC), also known as neuroAIDS. The relationship between the cellular changes within the brain during neuroAIDS and the role of NAA/Cr as a metabolic marker remains unclear. In order to clarify the relationship between NAA/Cr and disease severity we utilized the simian immunodeficiency virus (SIV)/macaque model of encephalitis. High-field proton MRS was performed on extracted metabolites from frontal cortex tissue samples of 29 rhesus macaques (6 healthy, 23 moribund with AIDS). Neuropathologic determination of encephalitis severity for each animal was completed and was found to correlate with NAA/Cr levels. Decreases in Glu/Cr and GABA/Cr may indicate that both excitatory and inhibitory neurons are affected. Highly significant correlations between NAA/Cr, Glu/Cr, and GABA/Cr were observed. These neuronal metabolites were also decreased in the absence of classical SIV encephalitis (SIVE). At any disease classification, animals inoculated with SIVmac251 were found to have lower levels of NAA/Cr than-animals inoculated with SIVmac239. In considering therapy for neuroAIDS the findings here support prevention of the encephalitic process, but suggest that suppressing the formation of multinucleated giant cells alone would be insufficient to prevent neuronal injury. C1 [Lentz, Margaret R.; Lee, Vallent; Ratai, Eva-Maria; Halpern, Elkan F.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Neuroradiol Div, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Westmoreland, Susan V.] New England Primate Res Ctr, Southborough, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, AA Martinos Ctr Biomed Imaging, 55 Friut St, Boston, MA 02114 USA. EM rggonzalez@partners.org FU NCRR NIH HHS [RR00168-39, K26 RR000168, P41 RR014075, P41 RR14075, K01 RR000150, P51 RR000168, RR13213, P41 RR00995, RR000150]; NINDS NIH HHS [K25 NS051129-04, K25 NS051129, NS051129, NS050041, R01 NS034626, R01 NS050041, NS34626] NR 40 TC 13 Z9 13 U1 0 U2 2 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 MAR PY 2008 VL 59 IS 3 BP 475 EP 484 DI 10.1002/mrm.21556 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 272SX UT WOS:000253881200006 PM 18306400 ER PT J AU Kerwin, WS Oikawa, M Yuan, C Jarvik, GP Hatsukami, TS AF Kerwin, W. S. Oikawa, M. Yuan, C. Jarvik, G. P. Hatsukami, T. S. TI MR imaging of adventitial vasa vasorum in carotid atherosclerosis SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE dynamic contrast-enhanced MRI; atherosclerosis; vasa vasorum; kinetic model; carotid artery ID CONTRAST-ENHANCED MRI; IN-VIVO; KINETIC-PARAMETERS; PLAQUE MORPHOLOGY; HIGH-RESOLUTION; FIBROUS-CAP; NEOVASCULARIZATION; ANGIOGENESIS; INFLAMMATION; LESIONS AB Vasa vasorum in the adventitia of atherosclerotic arteries may play a role in plaque progression. In this investigation, a method for characterizing vasa vasorum in the carotid artery is proposed, in which the perfusion properties of the adventitia are probed via dynamic contrast-enhanced (DCE) MRI. A parametric "vasa vasorum image" is automatically generated that depicts the plasma volume (v(p)) and transfer constant (K-trans). The average K-trans within the adventitia is proposed as a quantitative measurement related to the extent of the vasa vasorum. In 25 subjects with lesions meeting the requirements for carotid endarterectomy (CEA) significantly higher adventitial K-trans of 0.155 +/- 0.045 min(-1) was observed, compared to 0.122 +/- 0.029 min(-1) in the remaining 20 subjects with moderate disease (P < 0.01). In the 25 subjects with endarterectomy specimens, histological evaluation showed that adventitial K-trans was significantly correlated with the amount of neovasculature (R = 0.41; P = 0.04) and macrophages (R = 0.49; P = 0.01) in the excised plaque. In the remaining 20 subjects without histology, elevated adventitial Ktrans was significantly correlated with the log of C-reactive protein (CRP) levels (R = 0.57, P = 0.01) and was elevated in active smokers compared to nonsmokers (0.141 +/- 0.036 vs. 0.111 +/- 0.017 min(-1); P = 0.02). Because these factors are all associated with higher risk of atherosclerotic complications, these results suggest that adventitial K-trans may be a marker of risk as well. C1 [Kerwin, W. S.; Oikawa, M.; Yuan, C.] Univ Washington, Dept Radiol, Seattle, WA 98109 USA. [Jarvik, G. P.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Hatsukami, T. S.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Hatsukami, T. S.] NIH, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kerwin, WS (reprint author), Univ Washington, Dept Radiol, 815 Mercer St,Box 358050, Seattle, WA 98109 USA. EM bkerwin@u.washington.edu RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 FU NHLBI NIH HHS [R01 HL067406, P01 HL072262, R01 HL073401] NR 40 TC 95 Z9 101 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 MAR PY 2008 VL 59 IS 3 BP 507 EP 514 DI 10.1002/mrm.21532 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 272SX UT WOS:000253881200010 PM 18306402 ER PT J AU Hong, R Cima, MJ Weissleder, R Josephson, L AF Hong, Rui Cima, Michael J. Weissleder, Ralph Josephson, Lee TI Magnetic microparticle aggregation for viscosity determination by MR SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic particle; nanoparticle; aggregation; relaxivity; viscosity ID SUPERPARAMAGNETIC PARTICLES; MOLECULAR-INTERACTIONS; TRANSVERSE RELAXATION; H-1-NMR DETECTION; CONTRAST AGENTS; NMR; FIELD; NANOPARTICLES; SPECTROSCOPY; NANOSENSORS AB Micron-sized magnetic particles were induced to aggregate when placed in homogeneous magnetic fields, like those of MR imagers and relaxometers, and then spontaneously returned to their dispersed state when removed from the field. Associated with the aggregation and dispersion of the magnetic particles were time-dependent increases and decreases in the spin-spin relaxation time (T-2) of the water. Magnetic nanoparticles, with far smaller magnetic moments per particle, did not undergo magnetically induced aggregation and exhibited time-indpendent values of T-2. The rate of T-2 change associated with magnetic microparticle aggregation was used to determine the viscosity of liquid samples, providing a method that can be of particular advantage for determining the viscosity of small volumes of potentially biohazardous samples of blood or blood plasma. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Cima, Michael J.] MIT, Dept Mat Sci, Cambridge, MA 02139 USA. RP Josephson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. EM josephso@helix.mgh.harvard.edu FU NIBIB NIH HHS [R01-EB004626, R01 EB004626, R01-EB00662, R01 EB000662, R01 EB004626-03] NR 37 TC 18 Z9 19 U1 0 U2 6 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 MAR PY 2008 VL 59 IS 3 BP 515 EP 520 DI 10.1002/mrm.21526 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 272SX UT WOS:000253881200011 PM 18306403 ER PT J AU Liu, CL Zaslavsky, AM Ganz, ML Perrin, J Gortmaker, S McCormick, MC AF Liu, Chia-Ling Zaslavsky, Alan M. Ganz, Michael L. Perrin, James Gortmaker, Steven McCormick, Marie C. TI The financial implications of availability and quality of a usual source of care for children with special health care needs SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE CSHCN; usual source of care; access to care; quality of care; medical home; medical expenditures; MEPS ID MEDICAL HOME; CASE-MANAGEMENT; EXPENDITURES; ACCESS; SERVICES; PROGRAM; ASSOCIATION; ADOLESCENTS; POPULATION; DEFINITION AB Objective To examine the relationship of availability and quality of a usual source of care (USC) to medical expenditures overall and for various types of health care services for children with special health care needs (CSHCN), as a group and by four diagnostic subgroups (asthma, non-asthmatic physical conditions, mental retardation, other mental illnesses). Methods Generalized linear models were used to estimate the annual average per capita medical expenditures (APCME) based on data from 820 CSHCN in the 1995 National Health Interview Survey on Disability and 1996 Medical Expenditure Panel Survey. Results In 1996, 92% of non-institutionalized CSHCN in the United States had a USC. Of these, 52% were classified as receiving accessible care, 95% received comprehensive care, and 69% received satisfactory care. Approximately 89% of CSHCN had expenditures on health care in 1996 and the APCME was $1,344 for CSHCN as a group. Having a USC was associated with higher expenditures overall and for almost all types of health care services for CSHCN across conditions. Receiving comprehensive care was associated with lower total medical expenditures for CSHCN with asthma, whereas receiving satisfactory care was associated with higher total medical expenditures for CSHCN with non-asthma physical conditions. Conclusion Having a regular care provider is associated with higher expenditures for CSHCN across diagnosis. Among CSHCN with a USC, quality of care is associated with medical expenditures, although specific associations vary by the quality characteristic and the condition of the child. These results may mask heterogeneity in severity of condition and quality of care over time. C1 [Liu, Chia-Ling; Ganz, Michael L.; Gortmaker, Steven; McCormick, Marie C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Perrin, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Liu, CL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,Kresge Bldg 6th Floor, Boston, MA 02115 USA. EM liu_chialing@yahoo.com; zaslavsk@hcp.med.harvard.edu; mganz@hsph.harvard.edu; jperrin@partners.org; sgortmak@hsph.harvard.edu; mmccormi@hsph.harvard.edu OI Ganz, Michael/0000-0002-9702-2999; McCormmick, Marie/0000-0002-3938-1707 NR 62 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD MAR PY 2008 VL 12 IS 2 BP 243 EP 259 DI 10.1007/s10995-007-0233-0 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 252TN UT WOS:000252469600012 PM 17557198 ER PT J AU Larson, BT Mynderse, LA Somers, VK Jaff, MR Evans, WP Larson, TR AF Larson, Benjamin T. Mynderse, Lance A. Somers, Virend K. Jaff, Michael R. Evans, William P. Larson, Thayne R. TI Blood pressure surges during office-based transurethral microwave therapy for the prostate SO MAYO CLINIC PROCEEDINGS LA English DT Article ID HYPERTENSIVE PATIENTS; HEART-DISEASE; RISK-FACTORS; EARTHQUAKE; INCREASES; STRESS; HUMANS; STROKE AB OBJECTIVE: To investigate the occurrence of adverse blood pressure (BP) events during transurethral microwave therapy (TUMT) for benign prostatic hyperplasia. PATIENTS AND METHODS: We conducted a retrospective study of the vital signs of 185 consecutive patients who received TUMT (via 6 devices) at 4 institutions from March 1, 2003, to September 18, 2005. Maximum change, percent change in systolic BP, diastolic BP, mean arterial pressures, heart rate, and oxygen saturation were evaluated. RESULTS: Of the 185 patients, 77 patients (42%; 95% confidence interval [CI], 35%-49%) experienced an increase in systolic BP of more than 30 mm Hg during TUMT; 30 patients (16%; 95% CI, 12%,-22%), an increase of more than 50 mm Hg; and 10 patients (5%; 95% CI, 3%-10%), an increase of more than 70 mm Hg. A greater than 20% change in systolic BP from baseline was observed In 95 patients (51%; 95% CI, 44%-58%). Many men experienced multiple events, with an average time of onset of 15.9 minutes into treatment. Significant differences were noted among the devices. CONCLUSION: This retrospective study demonstrates a significant number of BP surges during TUMT for benign prostatic hyperplasia. These BP changes represent a potential risk of cardiovascular events in patients with known or occult cardiovascular disease. Our study is the first to recognize the incidence of this BP response. Until further studies identify the mechanisms responsible for these surges in BP, the results of this study suggest that BP should be monitored, treatment adjusted, and antihypertensive medications continued during all TUMT. C1 [Mynderse, Lance A.] Mayo Clin, Dept Urol, Rochester, MN 55905 USA. [Somers, Virend K.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. [Larson, Benjamin T.] Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Cleveland, OH 44106 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Evans, William P.] SW Florida Urol Assoc, Ft Myers, FL USA. [Larson, Thayne R.] Inst Med Res, Scottsdale, AZ USA. RP Mynderse, LA (reprint author), Mayo Clin, Dept Urol, 200 1st St SW, Rochester, MN 55905 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 2008 VL 83 IS 3 BP 309 EP 312 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 267MJ UT WOS:000253512800009 PM 18315997 ER PT J AU Aw, S Adams, DS Qiu, DY Levin, M AF Aw, Sherry Adams, Dany S. Qiu, Dayong Levin, Michael TI H,K-ATPase protein localization and Kir4.1 function reveal concordance of three axes during early determination of left-right asymmetry SO MECHANISMS OF DEVELOPMENT LA English DT Review DE H,K-ATPase; ion flow; left-right asymmetry; laterality; ion pumps; Kir4.1; polarity ID LEFT-RIGHT AXIS; 1ST CLEAVAGE PLANE; RECTIFYING POTASSIUM CHANNEL; DEVELOPING XENOPUS-EMBRYOS; DORSAL-VENTRAL AXIS; H-K-ATPASE; EARLY STEP; DROSOPHILA OOCYTE; CELL POLARITY; UNCONVENTIONAL MYOSIN AB Consistent laterality is a fascinating problem, and study of the Xenopus embryo has led to molecular characterization of extremely early steps in left-right patterning: bioelectrical signals produced by ion pumps functioning upstream of asymmetric gene expression. Here, we reveal a number of novel aspects of the H+/K+-ATPase module in chick and frog embryos. Maternal H+/K+-ATPase subunits are asymmetrically localized along the left-right, dorso-ventral, and animal-vegetal axes during the first cleavage stages, in a process dependent on cytoskeletal organization. Using a reporter domain fused to molecular motors, we show that the cytoskeleton of the early frog embryo can provide asymmetric, directional information for subcellular transport along all three axes. Moreover, we show that the Kir4.1 potassium channel, while symmetrically expressed in a dynamic fashion during early cleavages, is required for normal LR asymmetry of frog embryos. Thus, Kir4.1 is an ideal candidate for the K+ ion exit path needed to allow the electroneutral H+/K+-ATPase to generate voltage gradients. in the chick embryo, we show that H+/K+-ATPase and Kir4.1 are expressed in the primitive streak, and that the known requirement for H+/K+-ATPase function in chick asymmetry does not function through effects on the circumferential expression pattern of Connexin43. These data provide details crucial for the mechanistic modeling of the physiological events linking subcellular processes to large-scale patterning and suggest a model where the early cytoskeleton sets up asymmetric ion flux along the left-right axis as a system of planar polarity functioning orthogonal to the apical-basal polarity of the early blastomeres. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Aw, Sherry; Adams, Dany S.; Qiu, Dayong; Levin, Michael] Forsyth Ctr Regenerat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. [Levin, Michael] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Forsyth Ctr Regenerat & Dev Biol, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCI NIH HHS [CO6RR11244]; NIDCR NIH HHS [1K22-DE016633, K22 DE016633, K22 DE016633-04]; NIGMS NIH HHS [GM-067227, GM07742, R01 GM067227, R01 GM077425, R01 GM077425-01A2] NR 159 TC 60 Z9 60 U1 5 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAR-APR PY 2008 VL 125 IS 3-4 BP 353 EP 372 DI 10.1016/j.mod.2007.10.011 PG 20 WC Developmental Biology SC Developmental Biology GA 278RK UT WOS:000254303800014 PM 18160269 ER PT J AU Alegria, M Polo, A Gao, S Santana, L Rothstein, D Jimenez, A Hunter, ML Mendieta, F Oddo, V Normand, SL AF Alegria, Margarita Polo, Antonio Gao, Shan Santana, Luz Rothstein, Dan Jimenez, Aida Hunter, Mary Lyons Mendieta, Frances Oddo, Vanessa Normand, Sharon-Lise TI Evaluation of a patient activation and empowerment intervention in mental health care SO MEDICAL CARE LA English DT Article DE retention; attendance; mental health; patient activation; ethnic minorities ID THERAPEUTIC ALLIANCE; DECISION-MAKING; PHYSICIAN RELATIONSHIP; OUTPATIENT TREATMENT; COMMUNICATION; RETENTION; PREDICTORS; DROPOUT; SATISFACTION; PREFERENCES AB Background: Evidence suggests that minority populations have lower levels of attendance and retention in mental health care than non-Latino whites. Patient activation and empowerment interventions may be effective in increasing minority patients' attendance and retention. Objectives: This study developed and evaluated a patient self-reported activation and empowerment strategy in mental health care. Research Design: The Right Question Project-Mental Health (RQP-MH) trainings consisted of 3 individual sessions using a pre/post test comparison group design with patients from 2 community mental health clinics. The RQP-MH intervention taught participants to identify questions that would help them consider their role, process and reasons behind a decision; and empowerment strategies to better manage their care. Subjects: A total of 231 participated, completing at least the pretest inter-view (n = 141 intervention site, 90 comparison site). Measures: Four main outcomes were linked to the intervention: changes in self-reported patient activation; changes in self-reported patient empowerment; treatment attendance; and retention in treatment. Results: Findings show that intervention participants were over twice as likely to be retained in treatment and over 3 times more likely than comparison participants to have scheduled at least I visit during the 6-month follow-up period. Similarly, intervention participants demonstrated 29% more attendance to scheduled visits than comparison patients. There was no evidence of an effect on self-reported patient empowerment, only on self-reported patient activation. Conclusions: Results demonstrate the intervention's potential to increase self-reported patient activation, retention, and attendance in mental health care for minority populations. By facilitating patient-provider communication, the RQP-MH intervention may help minorities effectively participate in mental health care. C1 [Alegria, Margarita; Gao, Shan; Jimenez, Aida; Mendieta, Frances; Oddo, Vanessa] Cambridge Hlth Alliance, Ctr Multicultural Mental Hlth Res, Somerville, MA 02143 USA. [Alegria, Margarita] Harvard Univ, Sch Med, Dept Psychiat, Somerville, MA USA. [Normand, Sharon-Lise] Harvard Univ, Sch Med, Dept Hlth Care Policy, Somerville, MA USA. [Polo, Antonio] De Paul Univ, Dept Psychol, Chicago, IL 60614 USA. [Santana, Luz; Rothstein, Dan] Right Quest Project Inc, Cambridge, MA USA. [Hunter, Mary Lyons] Massachusetts Gen Hosp, Chelsea Healthcare Ctr, Chelsea, MA USA. RP Alegria, M (reprint author), Cambridge Hlth Alliance, Ctr Multicultural Mental Hlth Res, 120 Beacon St,4th Floor, Somerville, MA 02143 USA. EM malegria@charesearch.org FU NIMHD NIH HHS [P20 MD000537] NR 41 TC 93 Z9 94 U1 7 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2008 VL 46 IS 3 BP 247 EP 256 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 269QX UT WOS:000253665200004 PM 18388839 ER PT J AU Lamont, EB Herndon, JE Weeks, JC Henderson, IC Lilenbaum, R Schilsky, RL Christakis, NA AF Lamont, Elizabeth B. Herndon, James E., II Weeks, Jane C. Henderson, I. Craig Lilenbaum, Rogerio Schilsky, Richard L. Christakis, Nicholas A. CA Canc Leukemia Grp B TI Measuring clinically significant chemotherapy-related toxicities using medicare claims from cancer and leukemia group B (CALGB) trial participants SO MEDICAL CARE LA English DT Article DE elderly; chemotherapy; Medicare; validation; toxicity; cancer ID POPULATION-BASED ASSESSMENT; BREAST-CANCER; LUNG-CANCER; OLDER; AGE; HOSPITALIZATIONS; SURVIVAL; VALIDITY; SURGERY AB Background: Because the elderly are underrepresented on clinical trials, physicians have few sources of information to estimate the risks (ie, toxicities) and benefits of chemotherapy administration to the elderly. Objective: Our goal was to determine whether the standard measures of toxicity used in clinical trials could be captured from observational Medicare claims data. Methods: We identified 175 elderly clinical trial patients treated on 2 Cancer and Leukemia Group B (CALGB) trials (9344, adjuvant breast study and 9730, advanced lung cancer study) and merged participants' CALGB data with their Medicare data. From CALGB data, we identified the most frequent Extended Clinical Toxicity Critieria grade III/IV toxicitics. We reviewed diagnostic and procedure codes from Medicare manuals, developed algorithms to measure the toxicities, and then finalized the algorithms after empiric review of patients' codes. We compared results of Medicare algorithms to gold standard CALGB toxicity information to calculate test characteristics. Results: CALGB data documented that 15 grade III/IV chemotherapy-related toxicities occurred in :3% of the 175 patients: white blood cell, hemoglobin, platelets, anorexia, nausea, vomiting, diarrhea, stomatitis, sensory neuropathy, motor neuropathy, motor or sensory neuropathy, dyspnea, hyperglycemia, infection, and malaise. Vomiting was the only toxicity identified by the Medicare-based algorithm with a sensitivity, specificity, and area under the receiver operator curve of >= 80%. Conclusions: The results of this preliminary study suggest that Medicare diagnostic and procedure codes may be of only limited value in measuring clinically significant chemotherapy-related toxicities in elderly Medicare beneficiaries. Future research includes confirming these findings in a larger and more diverse sample. C1 [Lamont, Elizabeth B.; Schilsky, Richard L.; Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lamont, Elizabeth B.; Weeks, Jane C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herndon, James E., II] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Henderson, I. Craig] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Lilenbaum, Rogerio] Mt Sinai Canc Ctr, Dept Med, Miami Beach, FL USA. [Schilsky, Richard L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Lamont, EB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180A Longwood Ave, Boston, MA 02115 USA. EM elamont@partners.org RI Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 FU NCI NIH HHS [U10 CA032102, CA31946, CA32291, CA33601, CA41287, CA47577, CA60138, CA93892, K07 CA093892, N01 CA032102, U10 CA003927, U10 CA023318, U10 CA025224, U10 CA031946, U10 CA032291, U10 CA033601, U10 CA035091, U10 CA035113, U10 CA035279, U10 CA035421, U10 CA041287, U10 CA045389, U10 CA045418, U10 CA045564, U10 CA045808, U10 CA047559, U10 CA047577, U10 CA047642, U10 CA052784, U10 CA071323, U10 CA074811, U10 CA077440, U10 CA077597, U10 CA077658] NR 23 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2008 VL 46 IS 3 BP 303 EP 308 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 269QX UT WOS:000253665200010 PM 18388845 ER PT J AU Ross, JS Keyhani, S Keenan, PS Bernheim, SM Penrod, JD Boockvar, KS Krumhoz, HM Siu, AL AF Ross, Joseph S. Keyhani, Salomeh Keenan, Patricia S. Bernheim, Susannah M. Penrod, Joan D. Boockvar, Kenneth S. Krumhoz, Harlan M. Siu, Albert L. TI Dual use of veterans affairs services and use of recommended ambulatory care SO MEDICAL CARE LA English DT Article DE quality of health care; United States Department of Veterans Affairs; preventive health services; chronic disease; ambulatory care ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; MEDICARE HMOS; PREVENTIVE SERVICES; SYSTEM UTILIZATION; DIABETES CARE; HEALTH; VA; ACCESS; CANCER AB Background: Use of more than one health care system to obtain care is common among adults receiving care within the Veterans Affairs (VA) medical system. It is not known what effect using care from multiple sources has on the quality of care patients receive. Objectives: To examine whether use of recommended ambulatory care services differs between exclusive and dual VA users. Methods: Cross-sectional analysis of the 2004 Behavior Risk Factor Surveillance System, a nationally-representative survey of community-dwelling adults aged 18 years or older. Our outcome measures were self-reported use of 18 recommended services for cancer prevention, cardiovascular risk reduction, diabetes management, and infectious disease prevention. We used multivariable logistic regression to examine the association between exclusive and dual VA use and use of recommended ambulatory services. Results: There were 3470 exclusive VA users and 4523 dual VA users. Dual users were significantly more likely to be older and white, have higher incomes, have graduated from college, and be insured when compared with exclusive VA users. In unadjusted analyses, dual users received higher rates of recommended services. After adjustment for patient characteristics, use of recommended services was largely similar among exclusive and dual VA users. Exclusive VA users reported 14% greater use of breast cancer screening and 10% greater use of cholesterol monitoring among patients with hypercholesterolemia, and 6% lower use of prostate cancer screening and 7% lower use of influenza vaccination. Conclusions: After adjustment for patient characteristics, exclusive and dual VA users reported similar rates of recommended ambulatory service use. C1 [Ross, Joseph S.; Keyhani, Salomeh; Penrod, Joan D.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters Vet Adm Med Ctr, HSR&D Targeted Res Enhancement Program, Bronx, NY 10468 USA. [Ross, Joseph S.; Keyhani, Salomeh; Penrod, Joan D.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Ross, Joseph S.; Penrod, Joan D.; Boockvar, Kenneth S.; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY USA. [Keenan, Patricia S.; Krumhoz, Harlan M.] Yale Univ, Sch Med, Div Hlth Policy& Adm, Dept Epidemiol & Publ Hlth, New Haven, CT USA. [Bernheim, Susannah M.] Yale Univ, Sch Med, Sect Geriatr, Dept Internal Med, New Haven, CT USA. [Krumhoz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Krumhoz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, Dept Internal Med, New Haven, CT USA. [Krumhoz, Harlan M.] Yale New Haven Hosp Ctr Outcomes Res & Evaluat, New Haven, CT USA. RP Ross, JS (reprint author), James J Peters Vet Adm Med Ctr, HSR&D Targeted Res Enhancement Program, 130 W Kingsbridge Rd,Room 4A-17, Bronx, NY 10468 USA. EM joseph.ross@va.gov OI Boockvar, Kenneth/0000-0003-1165-5558 NR 54 TC 15 Z9 15 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2008 VL 46 IS 3 BP 309 EP 316 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 269QX UT WOS:000253665200011 PM 18388846 ER PT J AU Donner, TW Flammer, KM AF Donner, Thomas W. Flammer, Kristin M. TI Diabetes management in the hospital SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID INTENSIVE INSULIN THERAPY; GLYCEMIC CONTROL; ACUTE HYPERGLYCEMIA; CRITICALLY-ILL; SLIDING SCALE; MYOCARDIAL-INFARCTION; GLUCOSE CONTROL; MELLITUS; MORTALITY; COMPLICATIONS AB Hyperglycemia is an increasingly common and often complex condition to manage in the inpatient setting. Numerous clinical trials have demonstrated associations between uncontrolled diabetes and poor clinical outcomes in a number of inpatient settings. Insulin remains the treatment of choice for the majority of hyperglycemic hospitalized patients and should be prescribed in a physiologic manner, employing basal and bolus insulin. Intravenous insulin should be used liberally in the ICU setting where randomized studies have demonstrated improved outcomes. Recommendations for insulin use in the inpatient setting are provided. C1 [Donner, Thomas W.; Flammer, Kristin M.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Donner, Thomas W.] Univ Maryland, Sch Med, Joslin Diabet Ctr, Baltimore, MD 21201 USA. RP Donner, TW (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 22 S Greene St,Room N3W130, Baltimore, MD 21201 USA. EM tdonner@medicine.umaryland.edu NR 58 TC 9 Z9 10 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 2008 VL 92 IS 2 BP 407 EP + DI 10.1016/j.mcna.2007.10.001 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 279IS UT WOS:000254349500010 PM 18298986 ER PT J AU Levy, AG Hershey, JC AF Levy, Andrea Gurmankin Hershey, John C. TI Value-induced bias in medical decision making SO MEDICAL DECISION MAKING LA English DT Article DE value-induced bias; cognitive dissonance; subjective probability; risk perception; wishful thinking ID PROSTATE-CANCER; PROBABILITY; INTERNET; EVENTS AB Background. People who exhibit value-induced bias - distorting relevant probabilities to justify medical decisions - may make suboptimal decisions. Objective. The authors examined whether and in what conditions people exhibit value-induced bias. Design. Volunteers on the Web imagined having a serious illness with 2 possible diagnoses and a treatment with the same "small probability" of success for each diagnosis. The more serious diagnosis was designed as a clear-cut decision to motivate most subjects to choose treatment; the less serious diagnosis was designed to make the treatment a close-call choice. Subjects were randomized to estimate the probability of treatment success before or after learning their diagnosis. The "after group" had the motivation and ability to distort the probability of treatment success to justify their treatment preference. In study 1, subjects learned they had the more serious disease. Consistent with value-induced bias, the after group was expected to give higher probability judgments than the "before group." In study 2, subjects learned they had the less serious disease, and the after group was expected to inflate the probability if they desired treatment and to reduce it if they did not, relative to the before group. Results. In study 1, there was no difference in the mean probability judgment between groups, suggesting no distortion of probability. In study 2, the slope of probability judgment regressed on desire for treatment was steeper for the after group, indicating that distortion of probability did occur. Conclusion. In close-call but not clear-cut medical decisions, people may distort relevant probabilities to justify their preferred choices. C1 [Levy, Andrea Gurmankin] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Levy, Andrea Gurmankin] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Hershey, John C.] Univ Penn, Wharton Sch, Operat & Informat Management Dept, Philadelphia, PA 19104 USA. [Hershey, John C.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Levy, AG (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,SM253, Boston, MA 02115 USA. EM adg11@cornell.edu NR 25 TC 13 Z9 13 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAR-APR PY 2008 VL 28 IS 2 BP 269 EP 276 DI 10.1177/0272989X07311754 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 283HO UT WOS:000254627500011 PM 18349431 ER PT J AU Boldea, V Sharp, GC Jiang, SB Sarrut, D AF Boldea, Vlad Sharp, Gregory C. Jiang, Steve B. Sarrut, David TI 4D-CT lung motion estimation with deformable registration: Quantification of motion nonlinearity and hysteresis SO MEDICAL PHYSICS LA English DT Article DE 4D-CT; lung; motion; deformable registration; hysteresis; nonlinearity ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; IMAGE REGISTRATION; TUMOR MOTION; RADIATION-THERAPY; ORGAN MOTION; BREATH-HOLD; RADIOTHERAPY; MODEL; STRATEGIES; ACCURACY AB In this article, our goal is twofold. First, we propose and compare two methods which process deformable registration to estimate patient specific lung and tumor displacements and deformation during free breathing from four-dimensional computed tomography (4D-CT) data. Second, we propose techniques to quantify the physiological parameters of motion nonlinearity and hysteresis. A Frechet distance-based criterion is introduced to measure the motion hysteresis. Experiments were conducted with 4D-CT data of five patients treated in radiotherapy for non-small cell lung cancer. The accuracy of deformation fields assessed against expert-selected landmarks was found to be within image voxel tolerance. The second method gave slightly better results in terms of accuracy and consistency, although the differences were not statistically significant between the two methods. Lung motion nonlinearity and hysteresis are patient specific, and vary across regions within the lung during respiration. For all patients, motion between end-exhale and end-inhale was well approximated with a straight line trajectory for the majority of lung points. Hysteresis was found to be globally correlated with trajectory length. The main limitation to the proposed method is that intensity-based deformable registration is dependent on image quality and image resolution. Another limitation is the absence of gold standard which makes the validation of the computed motion difficult. However, the proposed tools provide patient specific motion information which, in radiotherapy for example, can ease the definition of precise internal margins. In the future, the integration of physiological information from multiple patients could help to create a general lung atlas with different clinical applications. (c) 2008 American Association of Physicists in Medicine. C1 Univ Lyon 2, LIRIS Lab, F-69008 Bron, France. [Boldea, Vlad; Sarrut, David] Ctr Leon Berard, Dept Radiotherapy, F-69008 Lyon, France. [Sharp, Gregory C.; Jiang, Steve B.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Sarrut, David] Inst Natl Sci Appl, CREATIS Lab, F-69621 Villeurbanne, France. RP Boldea, V (reprint author), Univ Lyon 2, LIRIS Lab, 5 Av P Mendes France, F-69008 Bron, France. EM vboldea@gmail.com RI Sarrut, David/F-4849-2010 OI Sarrut, David/0000-0002-4854-4141 NR 39 TC 87 Z9 93 U1 1 U2 6 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 MAR PY 2008 VL 35 IS 3 BP 1008 EP 1018 DI 10.1118/1.2839103 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 267XL UT WOS:000253542400019 PM 18404936 ER PT J AU Kawasaki, T Ohnishi, M Nosho, K Suemoto, Y Kirkner, GJ Meyerhardt, JA Fuchs, CS Ogino, S AF Kawasaki, Takako Ohnishi, Mutsuko Nosho, Katsuhiko Suemoto, Yuko Kirkner, Gregory J. Meyerhardt, Jeffrey A. Fuchs, Charles S. Ogino, Shuji TI CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci SO MODERN PATHOLOGY LA English DT Article DE colon cancer; CpG island methylator phenotype; DNA methylation; promoter; MethyLight; CIMP-low ID POPULATION-BASED SAMPLE; DNA METHYLATION; MICROSATELLITE INSTABILITY; BRAF MUTATION; COLON-CANCER; HYPERMETHYLATION; EXPRESSION; SURVIVAL; ADENOCARCINOMA; 5-FLUOROURACIL AB The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct phenotype in colorectal cancer. However, the concept of CIMP-low with less extensive CpG island methylation is still evolving. Our aim is to examine whether density of methylation in individual CpG islands was different between CIMP-low and CIMP-high tumors. Utilizing MethyLight technology and 889 population-based colorectal cancers, we quantified DNA methylation (methylation index, percentage of methylated reference) at 14 CpG islands, including 8 CIMP-high-specific loci (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1). Methylation positivity in each locus was defined as methylation index > 4. Low-level methylation (methylation index > 0, <20) in each CIMP-high-specific locus was significantly more common in 340 CIMP-low tumors (1/8-5/8 methylation-positive loci) than 133 CIMP-high tumors (>= 6/8 methylation-positive loci) and 416 CIMP-0 tumors (0/8 methylation-positive loci) (P <= 0.002). In the other six loci (CHFR, HIC1, IGFBP3, MGMT, MINT31 and WRN), which were not highly specific for CIMP-high, low-level methylation, was not persistently more prevalent in CIMP-low tumors. In conclusion, compared to CIMP-high and CIMP-0 tumors, CIMP-low colorectal cancers show not only few methylated CIMP-high-specific CpG islands, but also more frequent low-level methylation at individual loci. Our data may provide supporting evidence for a difference in pathogenesis of DNA methylation between CIMP-low and CIMP-high tumors. C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kawasaki, Takako; Ohnishi, Mutsuko; Nosho, Katsuhiko; Suemoto, Yuko; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kirkner, Gregory J.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA87969, P01 CA55075] NR 40 TC 35 Z9 36 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2008 VL 21 IS 3 BP 245 EP 255 DI 10.1038/modpathol.3800982 PG 11 WC Pathology SC Pathology GA 266CU UT WOS:000253409800003 PM 18204436 ER PT J AU Yan, X Shen, H Jiang, HJ Zhang, CS Hu, D Wang, J Wu, XQ AF Yan, Xin Shen, Hua Jiang, Hongjian Zhang, Chengsheng Hu, Dan Wang, Jun Wu, Xinqi TI External Qi of Yan Xin Qigong induces G2/M arrest and apoptosis of androgen-independent prostate cancer cells by inhibiting Akt and NF-kappa B pathways SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Akt; NF-kappa B; prostate cancer; G2; M arrest; apoptosis; external Qi of Yan Xin Qigong ID SIGNALING PATHWAY; CARCINOMA-CELLS; 3-KINASE/AKT PATHWAY; TRANSCRIPTION FACTOR; CASPASE ACTIVATION; GROWTH ARREST; PC3 CELLS; BCL-XL; KINASE; SURVIVAL AB Long-term clinical observations and ongoing studies have shown antitumor effects of external Qi of Yan Xin Qigong (YXQG-EQ) that originated from traditional Chinese medicine (TCM). In order to understand the molecular mechanisms underlying the antitumor effects of YXQG-EQ, we investigate the effects of YXQG-EQ on growth and apoptosis in androgen-independent prostate cancer PC3 cells. We found that exposure to YXQG-EQ led to G2/M arrest associated with reduced cyclin B1 expression and apoptosis in PC3 cells. YXQG-EQ treatment inhibited constitutive and epidermal growth factor-induced Akt phosphorylation, basal and TNF-alpha-induced NF-kappa B activation, and downregulated anti-apoptotic Bcl-2 and Bcl-xL expression. In contrast, exposure to YXQG-EQ increased phosphorylation of Akt and Erk1/2 in human umbilical vein endothelial cells (HUVEC), and had no cytotoxic effect on either HUVEC or peripheral blood mononuclear cells (PBMC). These results indicate that YXQG-EQ has profound effects on growth and apoptosis of prostate cancer cells by targeting survival pathways including the Akt and NF-kappa B pathways. C1 [Jiang, Hongjian; Wu, Xinqi] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Yan, Xin] Inst Chongqing Tradit Chinese Med, Chongqing, Peoples R China. [Yan, Xin; Shen, Hua; Wang, Jun] New Med Sci Res Inst, New York, NY USA. [Zhang, Chengsheng] McMaster Univ, Hamilton, ON, Canada. [Hu, Dan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wu, XQ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. EM xwu1@partners.org RI Hu, Dan/D-9642-2015 NR 52 TC 14 Z9 14 U1 2 U2 26 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 2008 VL 310 IS 1-2 BP 227 EP 234 DI 10.1007/s11010-007-9684-2 PG 8 WC Cell Biology SC Cell Biology GA 267SE UT WOS:000253528700024 PM 18080802 ER PT J AU Zhang, Y Kwon, S Yamaguchi, T Cubizolles, F Rousseaux, S Kneissel, M Cao, C Li, N Cheng, HL Chua, K Lombard, D Mizeracki, A Matthias, G Alt, FW Khochbin, S Matthias, P AF Zhang, Yu Kwon, SoHee Yamaguchi, Teppei Cubizolles, Fabien Rousseaux, Sophie Kneissel, Michaela Cao, Chun Li, Na Cheng, Hwei-Ling Chua, Katrin Lombard, David Mizeracki, Adam Matthias, Gabriele Alt, Frederick W. Khochbin, Saadi Matthias, Patrick TI Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID II HISTONE DEACETYLASES; CELL MOTILITY; ALPHA-TUBULIN; IN-VIVO; HDAC6; ACETYLATION; MICROTUBULES; EXPRESSION; UBIQUITINATION; IDENTIFICATION AB Posttranslational modifications play important roles in regulating protein structure and function. Histone deacetylase 6 (HDAC6) is a mostly cytoplasmic class II HDAC, which has a unique structure with two catalytic domains and a domain binding ubiquitin with high affinity. This enzyme was recently identified as a multisubstrate protein deacetylase that can act on acetylated histone tails, alpha-tubulin and Hsp90. To investigate the in vivo functions of HDAC6 and the relevance of tubulin acetylation/deacetylation, we targeted the HDAC6 gene by homologous recombination in embryonic stem cells and generated knockout mice. HDAC6-deficient mice are viable and fertile and show hyperacetylated tubulin in most tissues. The highest level of expression of HDAC6 is seen in the testis, yet development and function of this organ are normal in the absence of HDAC6. Likewise, lymphoid development is normal, but the immune response is moderately affected. Furthermore, the lack of HDAC6 results in a small increase in cancellous bone mineral density, indicating that this deacetylase plays a minor role in bone biology. HDAC6-deficient mouse embryonic fibroblasts show apparently normal microtubule organization and stability and also show increased Hsp90 acetylation correlating with impaired Hsp90 function. Collectively, these data demonstrate that mice survive well without HDAC6 and that tubulin hyperacetylation is not detrimental to normal mammalian development. C1 [Zhang, Yu; Kwon, SoHee; Yamaguchi, Teppei; Cubizolles, Fabien; Cao, Chun; Li, Na; Mizeracki, Adam; Matthias, Gabriele; Matthias, Patrick] Novartis Res Fdn, Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland. [Kneissel, Michaela] Novartis Inst Biomed Res, Basel, Switzerland. [Cheng, Hwei-Ling; Chua, Katrin; Lombard, David; Alt, Frederick W.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Childrens Hosp,Howard Hughes Med Inst, Boston, MA 02115 USA. [Rousseaux, Sophie; Khochbin, Saadi] INSERM, U309, Inst Albert Bonniot, Fac Med, F-38706 La Tronche, France. RP Matthias, P (reprint author), Novartis Res Fdn, Friedrich Miescher Inst Biomed Res, POB 2543,Maulbeerstr 66, CH-4058 Basel, Switzerland. EM patrick.matthias@fmi.ch RI Khochbin, Saadi/M-8090-2013; Rousseaux, Sophie/G-1697-2013; OI Cubizolles, Fabien/0000-0002-9822-4074 NR 42 TC 220 Z9 226 U1 5 U2 34 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 MAR PY 2008 VL 28 IS 5 BP 1688 EP 1701 DI 10.1128/MCB.01154-06 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 268TS UT WOS:000253603100023 PM 18180281 ER PT J AU Lo, ASY Taylor, JR Farzaneh, F Kemeny, DM Dibb, NJ Maher, J AF Lo, Agnes Shuk Yee Taylor, Jessica Rhiannon Farzaneh, Farzin Kemeny, David Michael Dibb, Nicholas John Maher, John TI Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation SO MOLECULAR IMMUNOLOGY LA English DT Article DE CSF-1; c-fms; T-cell; adoptive immunotherapy ID FACTOR-I RECEPTOR; GYNECOLOGIC MALIGNANCIES; SIGNAL-TRANSDUCTION; DENDRITIC CELLS; KINASE-ACTIVITY; DOWN-REGULATION; OVARIAN-CANCER; BREAST-CANCER; DIFFERENTIATION; PROLIFERATION AB Aberrant growth factor production is a prevalent mechanism in tumourigenesis. If T-cells responded positively to a cancer-derived cytokine, this might result in selective enhancement of function within the tumour microenvironment. Here, we have chosen colony-stimulating factor-1 (CSF-1) as a candidate to test this concept. CSF-1 is greatly overproduced in many cancers but has no direct effects upon T-lymphocytes, which do not express the c-fms-encoded CSF-1 receptor. To confer CSF-1-responsiveness, we have expressed the human c fins gene in immortalized and primary T-cells. Addition of soluble CSF-1 resulted in synergistic enhancement of IL-2-driven T-cell proliferation. CSF-1 also co-stimulated the production of interferon (IFN)-gamma by activated T-cells. These effects required Y809 of the CSF-1R and activation of the Ras-MEK-MAP kinase cascade, but were independent of PI3K signalling. T-cells that express c-fins are also responsive to membrane-anchored CSF-1 (mCSF-1) which, unlike its soluble counterpart, could co-stimulate IL-2 production. CSF-1 promoted chemotaxis of c-fms-expressing primary human T-cells and greatly augmented proliferation mediated by a tumour-targeted chimeric antigen receptor, with preservation of tumour cytolytic activity. Taken together, these data establish that T-cells may be genetically modified to acquire responsiveness to CSF-1 and provide proof-of-principle for a novel strategy to enhance the effectiveness of adoptive T-cell immunotherapy. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Maher, John] Kings Coll London, Breast Canc Biol Grp, Div Canc Studies, London SE1 9RT, England. [Lo, Agnes Shuk Yee] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Taylor, Jessica Rhiannon] Breakthrough Breast Canc Res Ctr, Canc Genet & Epigenet, Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. [Farzaneh, Farzin] Kings Coll London, Dept Haematol Med, Rayne Inst, London SE5 9NU, England. [Kemeny, David Michael] Natl Univ Singapore, Immunol Programme, Singapore 117597, Singapore. [Kemeny, David Michael] Natl Univ Singapore, Dept Microbiol, Singapore 117597, Singapore. [Dibb, Nicholas John] Univ London Imperial Coll Sci Technol & Med, IRDB, London W12 0NN, England. RP Maher, J (reprint author), Kings Coll London, Breast Canc Biol Grp, Div Canc Studies, Guys Hosp Campus,St Thomas St, London SE1 9RT, England. EM john.maher@kcl.ac.uk RI Farzaneh, Farzin/B-4902-2009 OI Farzaneh, Farzin/0000-0002-9275-2415 NR 57 TC 12 Z9 12 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 MAR PY 2008 VL 45 IS 5 BP 1276 EP 1287 DI 10.1016/j.molimm.2007.09.010 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 260SF UT WOS:000253030000009 PM 17950877 ER PT J AU Mora, JR von Andrian, UH AF Mora, J. R. von Andrian, U. H. TI Differentiation and homing of IgA-secreting cells SO MUCOSAL IMMUNOLOGY LA English DT Review ID A-DEFICIENT RATS; GROWTH-FACTOR-BETA; CD8(+) T-CELLS; VASOACTIVE-INTESTINAL-PEPTIDE; CLASS SWITCH RECOMBINATION; HIGH ENDOTHELIAL VENULES; TRANS-RETINOIC ACID; LYMPHOCYTE-ASSOCIATED ANTIGEN; MUCOSAL VASCULAR ADDRESSIN; INFLAMMATORY-BOWEL-DISEASE AB Most antibody-secreting cells (ASCs) in mucosal tissues produce immunoglobulin A (IgA), the most abundant immunoglobulin in the body and the main class of antibody found in secretions. IgA-ASCs differentiate in the mucosal-associated lymphoid tissues and are usually considered as a homogeneous population of cells. However, IgA-ASCs that travel to the small intestine have unique characteristics in terms of their migratory requirements. These IgA-ASCs require the homing molecules alpha 4 beta 7 and CCR9 to interact with their ligands, mucosal addressin cell adhesion molecule-1 and CCL25, which are constitutively expressed in the small intestine. Indeed, recent work has shown that IgA-ASCs specific for the small bowel are generated under different conditions as compared with IgA-ASCs in other mucosal compartments. Moreover, the mechanisms inducing IgA class switching may also vary according to the tissue where IgA-ASCs differentiate. Here we describe the mechanisms involved in the differentiation of IgA-ASCs in mucosal compartments, in particular those involved in the generation of gut-homing IgA-ASCs. C1 [Mora, J. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. [von Andrian, U. H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [von Andrian, U. H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Mora, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. EM j_rodrigo_mora@harvard.hms.edu; uva@harvard.hms.edu RI von Andrian, Ulrich/A-5775-2008 FU Crohn's & Colitis Foundation of America (CCFA); Cancer Research Institute (CRI); Center for the Study of Inflammatory Bowel Disease [DK43351]; NIH FX We are grateful to Susan Davis for valuable editorial assistance and to Drs Scott Snapper and Andrea Cerutti for critical reading of this manuscript. JRM is indebted to Ingrid Ramos for constant support. JRM is supported by grants from Crohn's & Colitis Foundation of America (CCFA), Cancer Research Institute (CRI) and Center for the Study of Inflammatory Bowel Disease (CSIBD, DK43351). UHvA is supported by grants from the NIH. NR 199 TC 95 Z9 98 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAR PY 2008 VL 1 IS 2 BP 96 EP 109 DI 10.1038/mi.2007.14 PG 14 WC Immunology SC Immunology GA 366HF UT WOS:000260470600004 PM 19079167 ER PT J AU Goyette, P Lefebvre, C Ng, A Brant, SR Cho, JH Duerr, RH Silverberg, MS Taylor, KD Latiano, A Aumais, G Deslandres, C Jobin, G Annese, V Daly, MJ Xavier, RJ Rioux, JD AF Goyette, P. Lefebvre, C. Ng, A. Brant, S. R. Cho, J. H. Duerr, R. H. Silverberg, M. S. Taylor, K. D. Latiano, A. Aumais, G. Deslandres, C. Jobin, G. Annese, V. Daly, M. J. Xavier, R. J. Rioux, J. D. TI Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis SO MUCOSAL IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; MACROPHAGE-STIMULATING PROTEIN; GENOME-WIDE ASSOCIATION; RECEPTOR TYROSINE KINASE; HEPATOCYTE GROWTH-FACTOR; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; BETA-CHAIN; ULCERATIVE-COLITIS; INTESTINAL MACROPHAGES AB Association mapping and candidate gene studies within inflammatory bowel diseases (IBD) linkage regions, as well as genome-wide association studies in Crohn's disease (CD) have led to the discovery of multiple risk genes, but these explain only a fraction of the genetic susceptibility observed in IBD. We have thus been pursuing a region on chromosome 3p21-22 showing linkage to CD and ulcerative colitis (UC) using a gene-centric association mapping approach. We identified 12 functional candidate genes by searching for literature cocitations with relevant keywords and for gene expression patterns consistent with immune/intestinal function. We then performed an association study composed of a screening phase, where tagging single nucleotide polymorphisms (SNPs) were evaluated in 1,020 IBD patients, and an independent replication phase in 745 IBD patients. These analyses identified and replicated significant association with IBD for four SNPs within a 1.2 Mb linkage disequilibrium region. We then identified a non-synonymous coding variant (rs3197999, R689C) in the macrophage-stimulating 1 (MST1) gene (P-value 3.62x10(-6)) that accounts for the association signal, and shows association with both CD and UC. MST1 encodes macrophage-stimulating protein (MSP), a protein regulating the innate immune responses to bacterial ligands. R689C is predicted to interfere with MSP binding to its receptor, suggesting a role for this gene in the pathogenesis of IBD. C1 [Goyette, P.; Lefebvre, C.; Rioux, J. D.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Goyette, P.; Lefebvre, C.; Rioux, J. D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Ng, A.; Xavier, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Ng, A.; Xavier, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Brant, S. R.] Johns Hopkins Univ, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD USA. [Cho, J. H.] Yale Univ, Dept Med, Div Gastroenterol, New Haven, CT 06520 USA. [Duerr, R. H.] Univ Pittsburgh, Sch Med, Div Gastroenterol, Dept Med Hepatol & Nutr, Pittsburgh, PA USA. [Silverberg, M. S.] Univ Toronto, Mt Sinai Hosp, IBD Ctr, Toronto, ON M5G 1X5, Canada. [Taylor, K. D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Taylor, K. D.] Cedars Sinai Med Ctr, IBD Ctr, Los Angeles, CA 90048 USA. [Latiano, A.; Annese, V.] CSS RCCS Hosp, Gastrointestinal Unit, San Giovanni Rotondo, Italy. [Latiano, A.; Annese, V.] CSS RCCS Hosp, Endoscopy Unit, San Giovanni Rotondo, Italy. [Aumais, G.; Jobin, G.] Hop Maison Neuve Rosemont, Dept Gastroenterol, Montreal, PQ H1T 2M4, Canada. [Deslandres, C.] Hop St Justine, Dept Gastroenterol, Montreal, PQ H3T 1C5, Canada. [Daly, M. J.; Rioux, J. D.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Daly, M. J.; Xavier, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. RP Rioux, JD (reprint author), Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. EM rioux@inflammgen.org RI Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015; Latiano, Anna/R-1965-2016; OI Rioux, John/0000-0001-7560-8326; Latiano, Anna/0000-0003-3719-2061; Duerr, Richard/0000-0001-6586-3905 FU National Institutes of Diabetes, Digestive and Kidney diseases (NIDDK) [DK62431, DK62422/DK62429, DK62420, DK62432, DK62423, DK62413]; NIDDK [DK064869]; NIAID [AI062773] FX The North American IBD Genetics Consortium is funded by multiple grants from the National Institutes of Diabetes, Digestive and Kidney diseases (NIDDK): DK62431 (S.R.B.), DK62422/DK62429 (J.H.C.), DK62420 (R.H.D.), DK62432 (J.D.R.), DK62423 (M.S.S.), and DK62413 (K.D.T.). The current work was funded by an NIDDK Grant (DK064869) to J.D.R and an NIAID Grant (AI062773) to R.J.X.A.N. is the recipient of a fellowship from the Crohn's and Colitis Foundation of America. We thank Catherine Labbe for her contribution to the genotying performed as part of this project. NR 59 TC 58 Z9 59 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAR PY 2008 VL 1 IS 2 BP 131 EP 138 DI 10.1038/mi.2007.15 PG 8 WC Immunology SC Immunology GA 366HF UT WOS:000260470600007 PM 19079170 ER PT J AU Deutsch, EW Ball, CA Berman, JJ Bova, GS Brazma, A Bumgarner, RE Campbell, D Causton, HC Christiansen, JH Daian, F Dauga, D Davidson, DR Gimenez, G Goo, YA Grimmond, S Henrich, T Herrmann, BG Johnson, MH Korb, M Mills, JC Oudes, AJ Parkinson, HE Pascal, LE Pollet, NI Quackenbush, J Ramialison, M Ringwald, M Salgado, D Sansone, SA Sherlock, G Stoeckert, CJ Swedlow, J Taylor, RC Walashek, L Warford, A Wilkinson, DG Zhou, Y Zon, LI Liu, AY True, LD AF Deutsch, Eric W. Ball, Catherine A. Berman, Jules J. Bova, G. Steven Brazma, Alvis Bumgarner, Roger E. Campbell, David Causton, Helen C. Christiansen, Jeffrey H. Daian, Fabrice Dauga, Delphine Davidson, Duncan R. Gimenez, Gregory Goo, Young Ah Grimmond, Sean Henrich, Thorsten Herrmann, Bernhard G. Johnson, Michael H. Korb, Martin Mills, Jason C. Oudes, Asa J. Parkinson, Helen E. Pascal, Laura E. Pollet, N. Icolas Quackenbush, John Ramialison, Mirana Ringwald, Martin Salgado, David Sansone, Susanna-Assunta Sherlock, Gavin Stoeckert, Christian J., Jr. Swedlow, Jason Taylor, Ronald C. Walashek, Laura Warford, Anthony Wilkinson, David G. Zhou, Yi Zon, Leonard I. Liu, Alvin Y. True, Lawrence D. TI Minimum information specification for in situ hybridization and immunohistochemistry experiments (MISFISHIE) SO NATURE BIOTECHNOLOGY LA English DT Article ID PROSTATE-CANCER METASTASIS; FUNCTIONAL GENOMICS; BREAST-CANCER; BIOCHEMICAL RECURRENCE; RESISTANCE PROTEIN; ANDROGEN RECEPTOR; SYSTEMS BIOLOGY; MICROARRAY DATA; SMOOTH-MUSCLE; OBJECT MODEL AB One purpose of the biomedical literature is to report results in sufficient detail that the methods of data collection and analysis can be independently replicated and verified. Here we present reporting guidelines for gene expression localization experiments: the minimum information specification for in situ hybridization and immunohistochemistry experiments (MISFISHIE). MISFISHIE is modeled after the Minimum Information About a Microarray Experiment (MIAME) specification for microarray experiments. Both guidelines define what information should be reported without dictating a format for encoding that information. MISFISHIE describes six types of information to be provided for each experiment: experimental design, biomaterials and treatments, reporters, staining, imaging data and image characterizations. This specification has benefited the consortium within which it was developed and is expected to benefit the wider research community. We welcome feedback from the scientific community to help improve our proposal. C1 [Deutsch, Eric W.; Campbell, David; Goo, Young Ah; Johnson, Michael H.; Korb, Martin; Oudes, Asa J.; Pascal, Laura E.; Walashek, Laura; Liu, Alvin Y.] Inst Syst Biol, Seattle, WA 98103 USA. [Ball, Catherine A.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. [Berman, Jules J.] Assoc Pathol Informat, Bethesda, MD 20814 USA. [Bova, G. Steven] Johns Hopkins Univ, Sch Med, PELICAN Lab, Dept Pathol, Baltimore, MD 21287 USA. [Bova, G. Steven] Johns Hopkins Univ, Sch Med, PELICAN Lab, Dept Hlth Informat Sci, Baltimore, MD 21287 USA. [Bova, G. Steven] Johns Hopkins Univ, Sch Med, PELICAN Lab, Dept Med Genet, Baltimore, MD 21287 USA. [Bova, G. Steven] Johns Hopkins Univ, Sch Med, PELICAN Lab, Dept Oncol, Baltimore, MD 21287 USA. [Bova, G. Steven] Johns Hopkins Univ, Sch Med, PELICAN Lab, Dept Urol, Baltimore, MD 21287 USA. [Brazma, Alvis; Sansone, Susanna-Assunta] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Bumgarner, Roger E.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Causton, Helen C.] Imperial Coll Sch Med, MRC, Clin Sci Ctr Microarray Ctr, London W12 0NN, England. [Christiansen, Jeffrey H.; Davidson, Duncan R.] Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Daian, Fabrice; Dauga, Delphine; Gimenez, Gregory; Salgado, David] Univ Aix Marseille 2, CNRS, Inst Biol Dev Marseille, UMR 6216, F-13288 Marseille 9, France. [Goo, Young Ah; Oudes, Asa J.; Pascal, Laura E.; Walashek, Laura; Liu, Alvin Y.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Grimmond, Sean] Univ Queensland, Inst Mol Biosci, Inchon 402751, South Korea. [Henrich, Thorsten; Ramialison, Mirana] EMBL Heidelberg, D-69117 Heidelberg, Germany. [Herrmann, Bernhard G.] Max Planck Inst Mol Genet, Inst Med Genet, D-14195 Berlin, Germany. [Herrmann, Bernhard G.] Max Planck Inst Mol Genet, Dept Dev Genet, D-14195 Berlin, Germany. [Mills, Jason C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Pollet, N. Icolas] Univ Paris 11, CNRS, UMR 8080, F-91405 Orsay, France. [Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ringwald, Martin] Jackson Lab, Bar Harbor, ME 04609 USA. [Sherlock, Gavin] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Stoeckert, Christian J., Jr.] Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. [Stoeckert, Christian J., Jr.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Swedlow, Jason] Univ Dundee, Div Gene Regulat & Express, Wellcome Trust Bioctr, Dundee DD1 5EH, Scotland. [Taylor, Ronald C.] Pacific NW Natl Lab, Computat Biol & Bioinformat Grp, Richland, WA 99352 USA. [Warford, Anthony] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Wilkinson, David G.] Natl Inst Med Res, Div Dev Neurobiol, London NW7 1AA, England. [Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Stem Cell Program, Boston, MA 02115 USA. [Zhou, Yi; Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [True, Lawrence D.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Deutsch, EW (reprint author), Inst Syst Biol, 1441 N 34th St, Seattle, WA 98103 USA. EM edeutsch@systemsbiology.org RI Sherlock, Gavin/B-1831-2009; Sherlock, Gavin/E-9110-2012; Pollet, Nicolas/A-4746-2013; Bumgarner, Roger/K-3531-2015; Smith, Barry/A-9525-2011; Grimmond, Sean/J-5304-2016; SALGADO, David/A-1417-2014; OI Ramialison, Mirana/0000-0001-6315-4777; Swedlow, Jason/0000-0002-2198-1958; Taylor, Ronald/0000-0001-9777-9767; Sherlock, Gavin/0000-0002-1692-4983; Brazma, Alvis/0000-0001-5988-7409; Pollet, Nicolas/0000-0002-9975-9644; Bumgarner, Roger/0000-0002-8168-6985; Smith, Barry/0000-0003-1384-116X; Grimmond, Sean/0000-0002-8102-7998; Wilkinson, David/0000-0001-6757-7080; Sansone, Susanna-Assunta/0000-0001-5306-5690; Christiansen, Jeffrey/0000-0002-8146-1225; Parkinson, Helen/0000-0003-3035-4195 FU Biotechnology and Biological Sciences Research Council [BB/E025080/1]; Medical Research Council [MC_U117532048, MC_U127527203]; NHLBI NIH HHS [R33 HL073712]; NIDDK NIH HHS [DK63328, DK63400, DK63481, DK63483, DK63630, R01 DK063400, R01 DK079798, R01 DK079798-01A2, U01 DK063328, U01 DK063481, U01 DK063483, U01 DK063630] NR 70 TC 66 Z9 65 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2008 VL 26 IS 3 BP 305 EP 312 DI 10.1038/nbt1391 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 276EF UT WOS:000254123400023 PM 18327244 ER PT J AU Osafune, K Caron, L Borowiak, M Martinez, RJ Fitz-Gerald, CS Sato, Y Cowan, CA Chien, KR Melton, DA AF Osafune, Kenji Caron, Leslie Borowiak, Malgorzata Martinez, Rita J. Fitz-Gerald, Claire S. Sato, Yasunori Cowan, Chad A. Chien, Kenneth R. Melton, Douglas A. TI Marked differences in differentiation propensity among human embryonic stem cell lines SO NATURE BIOTECHNOLOGY LA English DT Article ID ENDODERM; DISTINCT; LIVER; GENE; MICE AB The differentiation potential of 17 human embryonic stem (hES) cell lines was compared. Some lines exhibit a marked propensity to differentiate into specific lineages, often with > 100-fold differences in lineage-specific gene expression. For example, HUES 8 is best for pancreatic differentiation and HUES 3 for cardiomyocyte generation. These non-trivial differences in developmental potential among hES cell lines point to the importance of screening and deriving lines for lineage-specific differentiation. C1 [Osafune, Kenji; Caron, Leslie; Borowiak, Malgorzata; Martinez, Rita J.; Fitz-Gerald, Claire S.; Cowan, Chad A.; Chien, Kenneth R.; Melton, Douglas A.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. [Borowiak, Malgorzata; Martinez, Rita J.; Fitz-Gerald, Claire S.; Melton, Douglas A.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Osafune, Kenji] Japan Sci & Technol Agcy, ICORP Organ Regenerat Project, Meguro Ku, Tokyo 1538902, Japan. [Caron, Leslie; Cowan, Chad A.; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Sato, Yasunori] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Cowan, Chad A.] Stowers Med Inst, Boston, MA 02114 USA. [Chien, Kenneth R.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Melton, DA (reprint author), Harvard Univ, Stem Cell Inst, 42 Church St, Cambridge, MA 02138 USA. EM dmelton@harvard.edu FU Howard Hughes Medical Institute NR 15 TC 427 Z9 439 U1 3 U2 38 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2008 VL 26 IS 3 BP 313 EP 315 DI 10.1038/nbt1383 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 276EF UT WOS:000254123400024 PM 18278034 ER PT J AU Wagner, BK Kitami, T Gilbert, TJ Peck, D Ramanathan, A Schreiber, SL Golub, TR Mootha, VK AF Wagner, Bridget K. Kitami, Toshimori Gilbert, Tamara J. Peck, David Ramanathan, Arvind Schreiber, Stuart L. Golub, Todd R. Mootha, Vamsi K. TI Large-scale chemical dissection of mitochondrial function SO NATURE BIOTECHNOLOGY LA English DT Article ID HUMAN SKELETAL-MUSCLE; GENE-EXPRESSION; SMALL MOLECULES; OXIDATIVE-PHOSPHORYLATION; INSULIN-RESISTANCE; DIABETES-MELLITUS; BIOGENESIS; DISEASE; RHABDOMYOLYSIS; TOXICITY AB Mitochondrial oxidative phosphorylation ( OXPHOS) is under the control of both mitochondrial ( mtDNA) and nuclear genomes and is central to energy homeostasis. To investigate how its function and regulation are integrated within cells, we systematically combined four cell-based assays of OXPHOS physiology with multiplexed measurements of nuclear and mtDNA gene expression across 2,490 small-molecule perturbations in cultured muscle. Mining the resulting compendium revealed, first, that protein synthesis inhibitors can decouple coordination of nuclear and mtDNA transcription; second, that a subset of HMG-CoA reductase inhibitors, combined with propranolol, can cause mitochondrial toxicity, yielding potential clues about the etiology of statin myopathy; and, third, that structurally diverse microtubule inhibitors stimulate OXPHOS transcription while suppressing reactive oxygen species, via a transcriptional mechanism involving PGC-1 alpha and ERR alpha, and thus may be useful in treating age-associated degenerative disorders. Our screening compendium can be used as a discovery tool both for understanding mitochondrial biology and toxicity and for identifying novel therapeutics. C1 [Wagner, Bridget K.; Kitami, Toshimori; Gilbert, Tamara J.; Peck, David; Ramanathan, Arvind; Schreiber, Stuart L.; Golub, Todd R.; Mootha, Vamsi K.] MIT, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Kitami, Toshimori; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. RP Mootha, VK (reprint author), MIT, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM vamsi@hms.harvard.edu FU Howard Hughes Medical Institute; NIDDK NIH HHS [R24 DK080261, R24 DK080261-01] NR 49 TC 126 Z9 130 U1 3 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2008 VL 26 IS 3 BP 343 EP 351 DI 10.1038/nbt1387 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 276EF UT WOS:000254123400028 PM 18297058 ER PT J AU Young, AP Schlisio, S Minamishima, YA Zhang, Q Li, LJ Grisanzio, C Signoretti, S Kaelin, WG AF Young, Arthur P. Schlisio, Susanne Minamishima, Yoji Andrew Zhang, Qing Li, Lianjie Grisanzio, Chiara Signoretti, Sabina Kaelin, William G., Jr. TI VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400 SO NATURE CELL BIOLOGY LA English DT Article ID CELLULAR SENESCENCE; TUMOR SUPPRESSION; E1A; INACTIVATION; PROTEINS; GENE; P53; ACTIVATION; INDUCTION; APOPTOSIS AB Germline von Hippel-Lindau tumour suppressor gene (VHL) mutations cause renal cell carcinomas, haemangioblastomas and phaeochromocytomas in humans(1). Mutations in VHL also occur in sporadic renal cell carcinomas. The protein encoded by VHL, VHL, is part of the ubiquitin ligase that downregulates the heterodimeric transcription factor Hif under well-oxygenated conditions(1). Here we show that acute VHL inactivation causes a senescent-like phenotype in vitro and in vivo. This phenotype was independent of p53 and Hif but dependent on the retinoblastoma protein (Rb) and the SWI2/SNF2 chromatin remodeller p400. Rb activation occurred through a decrease in Skp2 messenger RNA, which resulted in the upregulation of p27 in a Hif-independent fashion. Our results suggest that senescence induced by VHL inactivation is a tumour-suppressive mechanism that must be overcome to develop VHL-associated neoplasias. C1 [Young, Arthur P.; Schlisio, Susanne; Minamishima, Yoji Andrew; Zhang, Qing; Li, Lianjie; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Grisanzio, Chiara; Signoretti, Sabina] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Grisanzio, Chiara; Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Li, Lianjie; Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu RI Minamishima, Yoji/E-5380-2010; OI Minamishima, Yoji/0000-0001-7995-9318; Schlisio, Susanne/0000-0002-2605-3771 NR 32 TC 140 Z9 144 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2008 VL 10 IS 3 BP 361 EP U115 DI 10.1038/ncb1699 PG 21 WC Cell Biology SC Cell Biology GA 271HA UT WOS:000253778300019 PM 18297059 ER PT J AU Ramakrishna, N AF Ramakrishna, Naren TI The role of fractionated radiotherapy and stereotactic radiosurgery for pituitary adenomas SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE pituitary adenoma; radiotherapy; radiosurgery; recurrence ID EFFICACY C1 Harvard Univ, Dept Radiat Oncol, Sch Med, Brigham & Womens Hosp,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ramakrishna, N (reprint author), Harvard Univ, Dept Radiat Oncol, Sch Med, Brigham & Womens Hosp,Dana Farber Canc Inst, ASBI-L2,75 Francis St, Boston, MA 02115 USA. EM nramakrishna@Iroc.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD MAR PY 2008 VL 4 IS 3 BP 138 EP 139 DI 10.1038/ncpendmet0746 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 264VE UT WOS:000253317700009 PM 18212762 ER PT J AU Hur, C Yachimski, P AF Hur, C. Yachimski, P. TI How useful is histologic confirmation of intestinal metaplasia in patients with long-segment Barrett's esophagus? SO NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material DE Barrett's esophagus; biopsy; detection; endoscopy; intestinal metaplasia C1 [Hur, C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hur, C.] Harvard Univ, Sch Med, Boston, MA USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 101 Merrimac St, Boston, MA 02114 USA. EM chur@partners.org OI Hur, Chin/0000-0002-2819-7576 FU NCI NIH HHS [K07 CA107060, K07 CA107060-03] NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4378 J9 NAT CLIN PRACT GASTR JI Nat. Clin. Pract. Gastroenterol. Hepatol. PD MAR PY 2008 VL 5 IS 3 BP 140 EP 141 DI 10.1038/ncpgasthep1056 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 268MB UT WOS:000253582800009 PM 18212774 ER PT J AU Nachtigall, LB Shih, HA AF Nachtigall, L. B. Shih, H. A. TI Fractionated radiotherapy versus stereotactic radiosurgery for pituitary adenomas SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material C1 [Nachtigall, L. B.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02116 USA. [Nachtigall, L. B.; Shih, H. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Nachtigall, LB (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Zero Emerson Pl,Suite 112, Boston, MA 02116 USA. EM Inachtigall@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD MAR PY 2008 VL 4 IS 3 BP 134 EP 135 DI 10.1038/ncpneuro0711 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 269FG UT WOS:000253634300007 PM 18227826 ER PT J AU Heissmeyer, V Rao, A AF Heissmeyer, Vigo Rao, Anjana TI Itching to end NF-kappa B SO NATURE IMMUNOLOGY LA English DT Editorial Material ID ACTIVATION; MICE; UBIQUITINATION; PROTEINS; LIGASE AB Both activation and termination of transcription factor NF-kappa B signaling require ubiquitin modification of pathway components. The E3 ligase Itch teams up with the NF-kappa B inhibitor A20 to edit the composition of ubiquitin chains on the signaling adaptor RIP, thereby limiting inflammatory responses. C1 [Heissmeyer, Vigo] Helmholtz Ctr Munich, German Res Ctr Environm Hlth, Inst Mol Immunol, D-81377 Munich, Germany. [Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA. RP Heissmeyer, V (reprint author), Helmholtz Ctr Munich, German Res Ctr Environm Hlth, Inst Mol Immunol, D-81377 Munich, Germany. EM vigo.heissmeyer@helmholtz-muenchen.de NR 13 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2008 VL 9 IS 3 BP 227 EP 229 DI 10.1038/ni0308-227 PG 5 WC Immunology SC Immunology GA 266BQ UT WOS:000253406700005 PM 18285770 ER PT J AU Rollins, BJ AF Rollins, Barrett J. TI Innocents abroad: regulating where naive T cells go SO NATURE IMMUNOLOGY LA English DT Editorial Material ID QUIESCENCE; THYMOCYTE; LKLF AB Kruppel-like factor 2 is now shown to regulate chemokine receptor expression in lymphocytes, which leads to their homing to nonlymphoid organs after they leave the thymus. C1 [Rollins, Barrett J.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rollins, Barrett J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM barrett_rollins@dfci.harvard.edu NR 7 TC 4 Z9 5 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2008 VL 9 IS 3 BP 233 EP 235 DI 10.1038/ni0308-233 PG 4 WC Immunology SC Immunology GA 266BQ UT WOS:000253406700008 PM 18285773 ER PT J AU Henrickson, SE Mempel, TR Mazo, IB Liu, B Artyomov, MN Zheng, H Peixoto, A Flynn, MP Senman, B Junt, T Wong, HC Chakraborty, AK von Andrian, UH AF Henrickson, Sarah E. Mempel, Thorsten R. Mazo, Irina B. Liu, Bai Artyomov, Maxim N. Zheng, Huan Peixoto, Antonio Flynn, Michael P. Senman, Balimkiz Junt, Tobias Wong, Hing C. Chakraborty, Arup K. von Andrian, Ulrich H. TI T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation SO NATURE IMMUNOLOGY LA English DT Article ID LYMPH-NODES; IN-VIVO; IMMUNOLOGICAL SYNAPSE; RECEPTOR MICROCLUSTERS; CROSS-PRESENTATION; STOP SIGNAL; TOLERANCE; IMMUNITY; DYNAMICS; NAIVE AB After homing to lymph nodes, CD8(+) T cells are primed by dendritic cells (DCs) in three phases. During phase one, T cells undergo brief serial contacts with DCs for several hours, whereas phase two is characterized by stable T cell-DC interactions. We show here that the duration of phase one and T cell activation kinetics correlated inversely with the number of complexes of cognate peptide and major histocompatibility complex (pMHC) per DC and with the density of antigen-presenting DCs per lymph node. Very few pMHC complexes were necessary for the induction of full-fledged T cell activation and effector differentiation. However, neither T cell activation nor transition to phase two occurred below a threshold antigen dose determined in part by pMHC stability. Thus, phase one permits T cells to make integrated 'measurements' of antigen dose that determine subsequent T cell participation in immune responses. C1 [Henrickson, Sarah E.; Mempel, Thorsten R.; Mazo, Irina B.; Peixoto, Antonio; Flynn, Michael P.; Senman, Balimkiz; Junt, Tobias; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Henrickson, Sarah E.; Mempel, Thorsten R.; Mazo, Irina B.; Peixoto, Antonio; Flynn, Michael P.; Senman, Balimkiz; Junt, Tobias; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Liu, Bai; Wong, Hing C.] Altor Biosci, Miramar, FL 33025 USA. [Zheng, Huan; Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Artyomov, Maxim N.; Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NCI NIH HHS [P01 CA071932-11A2, P01 CA071932]; NHLBI NIH HHS [HL066987, HL07623, T32 HL007623, T32 HL066987]; NIAID NIH HHS [AI069259, AI072252, P01 AI071195, P01 AI071195-01, R01 AI069259, R01 AI072252]; NIGMS NIH HHS [T32 GM007753] NR 54 TC 216 Z9 219 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2008 VL 9 IS 3 BP 282 EP 291 DI 10.1038/ni1559 PG 10 WC Immunology SC Immunology GA 266BQ UT WOS:000253406700014 PM 18204450 ER PT J AU Kashiwagi, S Tsukada, K Xu, L Miyazaki, J Kozin, SV Tyrrell, JA Sessa, WC Gerweck, LE Jain, RK Fukumura, D AF Kashiwagi, Satoshi Tsukada, Kosuke Xu, Lei Miyazaki, Junichi Kozin, Sergey V. Tyrrell, James A. Sessa, William C. Gerweck, Leo E. Jain, Rakesh K. Fukumura, Dai TI Perivascular nitric oxide gradients normalize tumor vasculature SO NATURE MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MURAL CELL RECRUITMENT; SYNTHASE; ANGIOGENESIS AB Normalization of tumor vasculature is an emerging strategy to improve cytotoxic therapies. Here we show that eliminating nitric oxide (NO) production from tumor cells via neuronal NO synthase silencing or inhibition establishes perivascular gradients of NO in human glioma xenografts in mice and normalizes the tumor vasculature, resulting in improved tumor oxygenation and response to radiation treatment. Creation of perivascular NO gradients may be an effective strategy for normalizing abnormal vasculature. C1 [Kashiwagi, Satoshi; Tsukada, Kosuke; Xu, Lei; Miyazaki, Junichi; Kozin, Sergey V.; Tyrrell, James A.; Gerweck, Leo E.; Jain, Rakesh K.; Fukumura, Dai] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Sessa, William C.] Yale Univ, Sch Med, Dept Pharmacol, Boyer Ctr Mol Med, New Haven, CT 06536 USA. [Kashiwagi, Satoshi; Tsukada, Kosuke; Xu, Lei; Miyazaki, Junichi; Kozin, Sergey V.; Tyrrell, James A.; Gerweck, Leo E.; Jain, Rakesh K.; Fukumura, Dai] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu RI Tyrrell, James/A-6359-2010; Sessa, William/B-6844-2011 FU NCI NIH HHS [P01-CA80124, R01 CA096915, R01-CA96915] NR 15 TC 66 Z9 71 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2008 VL 14 IS 3 BP 255 EP 257 DI 10.1038/nm1730 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 271VB UT WOS:000253815700030 PM 18278052 ER PT J AU Hilton, MJ Tu, XL Wu, XM Bai, ST Zhao, HB Kobayashi, T Kronenberg, HM Teitelbaum, SL Ross, FP Kopan, R Long, FX AF Hilton, Matthew J. Tu, Xiaolin Wu, Ximei Bai, Shuting Zhao, Haibo Kobayashi, Tatsuya Kronenberg, Henry M. Teitelbaum, Steven L. Ross, F. Patrick Kopan, Raphael Long, Fanxin TI Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation SO NATURE MEDICINE LA English DT Article ID EMBRYONIC LETHALITY; CELL-DIFFERENTIATION; VASCULAR DEVELOPMENT; MICE LACKING; DEFECTS; EXPRESSION; SKELETAL; PRESENILIN-1; ACTIVATION; REQUIRES AB Postnatal bone marrow houses mesenchymal progenitor cells that are osteoblast precursors. These cells have established therapeutic potential, but they are difficult to maintain and expand in vitro, presumably because little is known about the mechanisms controlling their fate decisions. To investigate the potential role of Notch signaling in osteoblastogenesis, we used conditional alleles to genetically remove components of the Notch signaling system during skeletal development. We found that disruption of Notch signaling in the limb skeletogenic mesenchyme markedly increased trabecular bone mass in adolescent mice. Notably, mesenchymal progenitors were undetectable in the bone marrow of mice with high bone mass. As a result, these mice developed severe osteopenia as they aged. Moreover, Notch signaling seemed to inhibit osteoblast differentiation through Hes or Hey proteins, which diminished Runx2 transcriptional activity via physical interaction. These results support a model wherein Notch signaling in bone marrow normally acts to maintain a pool of mesenchymal progenitors by suppressing osteoblast differentiation. Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway. C1 [Hilton, Matthew J.; Tu, Xiaolin; Wu, Ximei; Long, Fanxin] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Bai, Shuting; Zhao, Haibo; Teitelbaum, Steven L.; Ross, F. Patrick] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kopan, Raphael; Long, Fanxin] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA. RP Long, FX (reprint author), Washington Univ, Sch Med, Dept Med, 660 S Euclid Ave, St Louis, MO 63110 USA. EM flong@wustl.edu OI Hilton, Matthew/0000-0003-3165-267X; Teitelbaum, Steven/0000-0002-4054-6679; Wu, Ximei/0000-0002-3316-893X FU NIAMS NIH HHS [AR046523, 5T32AR07033, AR046852, R01 AR046523, R01 AR046852, R37 AR046523, T32 AR007033]; NICHD NIH HHS [HD044056, R01 HD044056, R01 HD044056-05]; NIDDK NIH HHS [DK065789, DK11794, R01 DK065789, R01 DK065789-05] NR 46 TC 260 Z9 275 U1 3 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2008 VL 14 IS 3 BP 306 EP 314 DI 10.1038/nm1716 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 271VB UT WOS:000253815700037 PM 18297083 ER PT J AU Kawasaki, Y Xu, ZZ Wang, X Park, JY Zhuang, ZY Tan, PH Gao, YJ Roy, K Corfas, G Lo, EH Ji, RR AF Kawasaki, Yasuhiko Xu, Zhen-Zhong Wang, Xiaoying Park, Jong Yeon Zhuang, Zhi-Ye Tan, Ping-Heng Gao, Yong-Jing Roy, Kristine Corfas, Gabriel Lo, Eng H. Ji, Ru-Rong TI Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain SO NATURE MEDICINE LA English DT Article ID SPINAL NERVE LIGATION; ACTIVATED PROTEIN-KINASE; MECHANICAL ALLODYNIA; RAT MODEL; MICROGLIA; CONTRIBUTES; NEURONS; CORD; HYPERSENSITIVITY; INFLAMMATION AB Treatment of neuropathic pain, triggered by multiple insults to the nervous system, is a clinical challenge because the underlying mechanisms of neuropathic pain development remain poorly understood(1-4). Most treatments do not differentiate between different phases of neuropathic pain pathophysiology and simply focus on blocking neurotransmission, producing transient pain relief. Here, we report that early- and late-phase neuropathic pain development in rats and mice after nerve injury require different matrix metalloproteinases (MMPs). After spinal nerve ligation, MMP-9 shows a rapid and transient upregulation in injured dorsal root ganglion (DRG) primary sensory neurons consistent with an early phase of neuropathic pain, whereas MMP-2 shows a delayed response in DRG satellite cells and spinal astrocytes consistent with a late phase of neuropathic pain. Local inhibition of MMP-9 by an intrathecal route inhibits the early phase of neuropathic pain, whereas inhibition of MMP-2 suppresses the late phase of neuropathic pain. Further, intrathecal administration of MMP-9 or MMP-2 is sufficient to produce neuropathic pain symptoms. After nerve injury, MMP-9 induces neuropathic pain through interleukin-1 beta cleavage and microglial activation at early times, whereas MMP-2 maintains neuropathic pain through interleukin-1b cleavage and astrocyte activation at later times. Inhibition of MMP may provide a novel therapeutic approach for the treatment of neuropathic pain at different phases. C1 [Kawasaki, Yasuhiko; Xu, Zhen-Zhong; Park, Jong Yeon; Zhuang, Zhi-Ye; Tan, Ping-Heng; Gao, Yong-Jing; Ji, Ru-Rong] Brigham & Womens Hosp, Dept Anesthesiol, Pain Res Ctr, Boston, MA 02115 USA. [Kawasaki, Yasuhiko; Xu, Zhen-Zhong; Park, Jong Yeon; Zhuang, Zhi-Ye; Tan, Ping-Heng; Gao, Yong-Jing; Roy, Kristine; Corfas, Gabriel; Ji, Ru-Rong] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Roy, Kristine; Corfas, Gabriel] Harvard Univ, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. RP Ji, RR (reprint author), Brigham & Womens Hosp, Dept Anesthesiol, Pain Res Ctr, 75 Francis St, Boston, MA 02115 USA. EM rrji@zeus.bwh.harvard.edu RI GAO, YONG-JING/E-6939-2015; OI GAO, YONG-JING/0000-0002-7432-7458; Park, Jong Yeon/0000-0003-0588-1903; Ji, Ru-Rong/0000-0002-9355-3688 FU FIC NIH HHS [R03 TW007180-03, R03 TW007180, TW7180]; NIDCR NIH HHS [R01 DE017794, R01 DE017794-02, R01-DE17794]; NINDS NIH HHS [F30 NS054362, P01 NS055104, P01-NS55104, P50 NS010828, P50-NS10828, R01 NS035884, R01 NS037074, R01 NS037074-08, R01 NS048422, R01 NS048422-03, R01 NS054932, R01 NS054932-01A1, R01 NS056458, R01 NS056458-02, R01-NS37074, R01-NS48422, R01-NS54362, R01-NS56458, R37 NS037074] NR 29 TC 305 Z9 314 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2008 VL 14 IS 3 BP 331 EP 336 DI 10.1038/nm1723 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 271VB UT WOS:000253815700040 PM 18264108 ER PT J AU Anderson, SM Famous, KR Sadri-Vakili, G Kumaresan, V Schmidt, HD Bass, CE Terwilliger, EF Cha, JHJ Pierce, RC AF Anderson, Sharon M. Famous, Katie R. Sadri-Vakili, Ghazaleh Kumaresan, Vidhya Schmidt, Heath D. Bass, Caroline E. Terwilliger, Ernest F. Cha, Jang-Ho J. Pierce, R. Christopher TI CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking SO NATURE NEUROSCIENCE LA English DT Article ID DEPENDENT PROTEIN-KINASE; VENTRAL TEGMENTAL AREA; RECEPTOR STIMULATION INCREASES; INDUCED BEHAVIORAL SENSITIZATION; PRIMING-INDUCED REINSTATEMENT; NUCLEUS-ACCUMBENS; AMPA RECEPTOR; SYNAPTIC PLASTICITY; DRUG-SEEKING; SURFACE EXPRESSION AB Increases in dopamine and glutamate transmission in the nucleus accumbens independently promote the reinstatement of cocaine seeking, an animal model of relapse. Here we have tested whether cocaine reinstatement in rats depends on interactions between accumbal dopamine and glutamate systems that are mediated by Ca2+/calmodulin-mediated kinase II (CaMKII). We show that stimulation of D1-like dopamine receptors in the nucleus accumbens shell reinstates cocaine seeking by activating L-type Ca2+ channels and CaMKII. Cocaine reinstatement is associated with D1-like dopamine receptor-dependent increases in accumbens shell CaMKII phosphorylated on Thr286 and glutamate receptor 1 (GluR1) phosphorylated on Ser831 (a known CaMKII phosphorylation site), in addition to increases in cell-surface expression of GluR1-containing AMPA receptors in the shell. Consistent with these findings, cocaine reinstatement is attenuated by intra-shell administration of AAV10-GluR1-C99, a vector that impairs the transport of GluR1-containing AMPA receptors. Thus, CaMKII may be an essential link between accumbens shell dopamine and glutamate systems involved in the neuronal plasticity underlying cocaine craving and relapse. C1 [Anderson, Sharon M.; Famous, Katie R.; Kumaresan, Vidhya; Schmidt, Heath D.; Pierce, R. Christopher] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. [Pierce, R. Christopher] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Bass, Caroline E.; Terwilliger, Ernest F.] Beth Israel Deaconess Med Ctr, Harvard Inst Med, Div Expt Med, Boston, MA 02115 USA. [Terwilliger, Ernest F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pierce, RC (reprint author), Boston Univ, Sch Med, Dept Pharmacol, 715 Albany St, Boston, MA 02118 USA. EM rcpierce@bu.edu OI Bass, Caroline/0000-0002-5856-6387 FU NIDA NIH HHS [DA16824, F30 DA19304, F32 DA017543, K02 DA18678, R01 DA15214, R21 DA18333]; NIGMS NIH HHS [T32 GM008541-7] NR 50 TC 170 Z9 176 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAR PY 2008 VL 11 IS 3 BP 344 EP 353 DI 10.1038/nn2054 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 267ZS UT WOS:000253548300018 PM 18278040 ER PT J AU Breakefield, XO Blood, AJ Li, YQ Hallett, M Hanson, PI Standaert, DG AF Breakefield, Xandra O. Blood, Anne J. Li, Yuqing Hallett, Mark Hanson, Phyllis I. Standaert, David G. TI The pathophysiological basis of dystonias SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID DEEP-BRAIN-STIMULATION; FOCAL HAND DYSTONIA; TYROSINE-HYDROXYLASE GENE; STRIATAL CHOLINERGIC INTERNEURONS; HEREDITARY PROGRESSIVE DYSTONIA; MARKED DIURNAL FLUCTUATION; EPSILON-SARCOGLYCAN GENE; DOPA-RESPONSIVE DYSTONIA; TRANSGENIC MOUSE MODEL; GTP CYCLOHYDROLASE-I AB Dystonias comprise a group of movement disorders that are characterized by involuntary movements and postures. Insight into the nature of neuronal dysfunction has been provided by the identification of genes responsible for primary dystonias, the characterization of animal models and functional evaluations and in vivo brain imaging of patients with dystonia. The data suggest that alterations in neuronal development and communication within the brain create a susceptible substratum for dystonia. Although there is no overt neurodegeneration in most forms of dystonia, there are functional and microstructural brain alterations. Dystonia offers a window into the mechanisms whereby subtle changes in neuronal function, particularly in sensorimotor circuits that are associated with motor learning and memory, can corrupt normal coordination and lead to a disabling motor disorder. C1 [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA. [Breakefield, Xandra O.; Blood, Anne J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Li, Yuqing; Standaert, David G.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Li, Yuqing; Standaert, David G.] Univ Alabama Birmingham, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. [Hanson, Phyllis I.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Blood, Anne J.] Massachusetts Gen Hosp, Dept Psychiat & Neurol & Athinoula, A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu RI Li, Yuqing/G-1596-2011; Hanson, Phyllis/E-9420-2012; OI Li, Yuqing/0000-0003-1211-5529; Standaert, David/0000-0003-2921-8348 FU Intramural NIH HHS; NINDS NIH HHS [NS047692, NS050717, NS37409, P50 NS037409, R01 NS050717, R01 NS052368, R21 NS046348, R21 NS047692] NR 129 TC 245 Z9 247 U1 3 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAR PY 2008 VL 9 IS 3 BP 222 EP 234 DI 10.1038/nrn2337 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 266CD UT WOS:000253408000015 PM 18285800 ER PT J AU Park, SY Shoelson, SE AF Park, Sang Youn Shoelson, Steven E. TI When a domain is not a domain SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID PHOSPHOTYROSINE-DEPENDENT INTERACTION; INSULIN-RECEPTOR; CRYSTAL-STRUCTURE; TYROSINE KINASE; IRS-1; SUBSTRATE; DISTINCT; MEDIATE; REGION; SHC AB The kinase regulatory-loop binding (KRLB) region of insulin receptor substrate 2 was originally thought to be a new type of domain with binding properties similar to phosphotyrosine binding (PTB) domains. A crystallographic study now shows that KRLB is actually a short peptide segment that binds to the insulin receptor using an extended series of contacts that mimic both autoinhibitory loop and ATP binding to its catalytic cleft. C1 [Park, Sang Youn; Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Park, Sang Youn; Shoelson, Steven E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM steven.shoelson@joslin.harvard.edu NR 13 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAR PY 2008 VL 15 IS 3 BP 224 EP 226 DI 10.1038/nsmb0308-224 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 271UY UT WOS:000253815400005 PM 18319738 ER PT J AU Tinaz, S Schendan, HE Stern, CE AF Tinaz, Sule Schendan, Haline E. Stern, Chantal E. TI Fronto-striatal deficit in Parkinson's disease during semantic event sequencing SO NEUROBIOLOGY OF AGING LA English DT Article DE dopamine; basal ganglia; dorsolateral prefrontal cortex; executive functions; fMRI ID WORKING-MEMORY; DOPAMINERGIC MODULATION; COGNITIVE DEFICITS; PET ACTIVATION; BRAIN; LOBE; TASK; DEMENTIA; CORTEX; ADULTS AB Studies of Parkinson's disease (PD) suggest that cognitive deficits accompany the classically recognized motor symptoms, and that these cognitive deficits may result from damage to frontal-basal ganglia circuits. PD patients are impaired on ordering events and action components into coherent sequences. In this study, we examined early-stage, nondemented, medicated PD subjects and matched control subjects during a semantic event sequencing task using functional MRI (fMRI). The task required subjects to examine four pictures of meaningful events, determine the correct temporal relationship between each picture, and re-order the pictures into a coherent sequence. There were two main findings. First, we found abnormal activation within the prefrontal cortex (PFC) and the "default" network in the PD group. Distinct areas of the PFC showed both hypoactivation and hyperactivation, whereas the "default" network showed reduced levels of resting activation in PD. Secondly, we observed left caudate hyperactivation in the PD group. The findings are discussed in relationship to how more activation may be compensatory, but does not necessarily mean efficient and correlated brain function. (C) 2006 Elsevier Inc. All rights reserved. C1 [Tinaz, Sule; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [Schendan, Haline E.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Schendan, Haline E.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Stern, CE (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St,Rm 109, Boston, MA 02215 USA. EM chantal@bu.edu OI Schendan, Haline/0000-0001-8925-5605 FU NCRR NIH HHS [P41 RR014075, P41 RR014075-09, P41RR14075]; NIA NIH HHS [F32 AG005914, F32 AG05914]; NIMH NIH HHS [R21 MH066213-01, R21 MH066213, R21 MH066213-02]; NINDS NIH HHS [R01 NS052914] NR 52 TC 31 Z9 31 U1 5 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2008 VL 29 IS 3 BP 397 EP 407 DI 10.1016/j.neurobiolaging.2006.10.025 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 266LJ UT WOS:000253436400008 PM 17157417 ER PT J AU Yacoubian, TA Cantuti-Castelvetri, I Bouzou, B Asteris, G McLean, PJ Hyman, BT Standaert, DG AF Yacoubian, Talene A. Cantuti-Castelvetri, Ippolita Bouzou, Berengere Asteris, Georgios McLean, Pamela J. Hyman, Bradley T. Standaert, David G. TI Transcriptional dysregulation in a transgenic model of Parkinson disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Parkinson disease; alpha-synuclein; Microarray; substantia nigra; laser capture microdissection; mouse; transcription ID HUMAN ALPHA-SYNUCLEIN; DOPAMINE NEURON DEATH; REAL-TIME PCR; GENE-EXPRESSION; LEWY BODIES; SUBSTANTIA-NIGRA; 14-3-3 PROTEINS; ANIMAL-MODELS; GENDER; MICE AB Alpha-synuclein has been implicated in Parkinson disease, yet the mechanism by which alpha-synuclein causes cell injury is not understood. Using a transgenic mouse model, we evaluated the effect of alpha-synuclein overexpression on gene expression in the substantia nigra. Nigral mRNA from wild type and alpha-synuclein transgenic mice was analyzed using Affymetrix gene arrays. At 3 months, before pathological changes are apparent, we observed modest alterations in gene expression. However, nearly 200 genes were altered in expression at 9 months, when degenerative changes are more apparent. Functional genomic analysis revealed that the genes altered at 9 months were predominantly involved in gene transcription. As in human Parkinson disease, gene expression changes in the transgenic model were also modulated by gender. These data demonstrate that alterations of gene expression are widespread in this animal model, and suggest that transcriptional dysregulation may be a disease mechanism that can be targeted therapeutically. (c) 2007 Elsevier Inc. All rights reserved. C1 [Yacoubian, Talene A.; Standaert, David G.] Univ Alabama, Dept Neurol, Ctr Neurodegenerat Expt & Therapeut, Birmingham, AL 35294 USA. [Yacoubian, Talene A.; Cantuti-Castelvetri, Ippolita; McLean, Pamela J.; Hyman, Bradley T.; Standaert, David G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Bouzou, Berengere; Asteris, Georgios] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Ctr Interdisciplinary Informat, Charlestown, MA 02129 USA. RP Yacoubian, TA (reprint author), Univ Alabama, Dept Neurol, Ctr Neurodegenerat Expt & Therapeut, Birmingham, AL 35294 USA. EM tyacoub@uab.edu OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [P50 NS038372, NS38372, P50 NS038372-05] NR 60 TC 40 Z9 40 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAR PY 2008 VL 29 IS 3 BP 515 EP 528 DI 10.1016/j.nbd.2007.11.008 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 270CG UT WOS:000253696900013 PM 18191405 ER PT J AU Kuperberg, GR Sitnikova, T Lakshmanan, BM AF Kuperberg, Gina R. Sitnikova, Tatiana Lakshmanan, Balaji M. TI Neuroanatomical distinctions within the semantic system during sentence comprehension: Evidence from functional magnetic resonance imaging SO NEUROIMAGE LA English DT Review ID EVENT-RELATED POTENTIALS; RIGHT CEREBRAL HEMISPHERES; SYNTACTIC POSITIVE SHIFT; LEFT PREFRONTAL CORTEX; MEDIAL TEMPORAL-LOBE; LANGUAGE COMPREHENSION; BRAIN POTENTIALS; CORTICAL SURFACE; TIME-COURSE; THEMATIC RELATIONSHIPS AB To make sense of a sentence, we must compute morphosyntactic and semantic-thematic relationships between its verbs and arguments and evaluate the resulting propositional meaning against any preceding context and our real-world knowledge. Recent electrophysiological studies suggest that, in comparison with non-violated verbs (e.g. "...at breakfast the boys would eat..."), animacy semantic-thematically violated verbs (e.g. "...at breakfast the eggs would eat...") and morphosyntactically violated verbs (e.g. "...at breakfast the boys would eats...") evoke a similar neural response. This response is distinct from that evoked by verbs that only violate real-world knowledge (e.g. "...at breakfast the boys would plant..."). Here we used fMRI to examine the neuroanatomical regions engaged in response to these three violations. Real-world violations, relative to other sentence types, led to increased activity within the left anterior inferior frontal cortex, reflecting participants' increased and prolonged efforts to retrieve semantic knowledge about the likelihood of events occurring in the real world. In contrast, animacy semantic-thematic violations of the actions depicted by the central verbs engaged a frontal/inferior parietal/basal ganglia network known to mediate the execution and comprehension of goal-directed action. We suggest that the recruitment of this network reflected a semantic-thematic combinatorial process that involved an attempt to determine whether the actions described by the verbs could be executed by their NP Agents. Intriguingly, this network was also activated to morphosyntactic violations between the verbs and their subject NP arguments. Our findings support the pattern of electrophysiological findings in suggesting (a) that a clear division within the semantic system plays out during sentence comprehension, and (b) that semantic-thematic and syntactic violations of verbs within simple active sentences are treated similarly by the brain. (c) 2008 Published by Elsevier Inc. C1 [Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Kuperberg, Gina R.; Sitnikova, Tatiana; Lakshmanan, Balaji M.] MGH MIT HMS, A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Sitnikova, Tatiana] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM kuperber@nmr.mgh.harvard.edu FU NIMH NIH HHS [R01 MH 071635, R01 MH071635, R01 MH071635-03] NR 122 TC 67 Z9 70 U1 3 U2 8 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 MAR 1 PY 2008 VL 40 IS 1 BP 367 EP 388 DI 10.1016/j.neuroimage.2007.10.009 PG 22 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 265MC UT WOS:000253362100036 PM 18248739 ER PT J AU Fortier, CB LaFleche, G Disterhoft, JF Steffen, EM Venne, JR McGlinchey, RE AF Fortier, Catherine Brawn LaFleche, Ginette Disterhoft, John F. Steffen, Elizabeth M. Venne, Jonathan R. McGlinchey, Regina E. TI Delay discrimination and reversal eyeblink classical conditioning in abstinent chronic alcoholics SO NEUROPSYCHOLOGY LA English DT Article DE alcohol; eyeblink classical conditioning; discrimination; reversal ID CHOLINERGIC BASAL FOREBRAIN; TEMPORAL-LOBE AMNESIA; STORED ODOR MEMORIES; PROACTIVE-INTERFERENCE; WHITE-MATTER; QUANTITATIVE-ANALYSIS; COGNITIVE FUNCTIONS; BRAIN TRANSPLANTS; CEREBRAL-CORTEX; WORKING-MEMORY AB Evidence has shown that alcoholism leads to volume reductions in brain regions critical for associative learning using the eyeblink classical conditioning paradigm (EBCC). Evidence indicates that cerebellar shrinkage causes impairment in simple forms of EBCC, whereas changes in forebrain structures result in impairment in more complex tasks. In this study, the ability of abstinent alcoholics and matched control participants to acquire learned responses during delay discrimination and discrimination reversal was examined and related to severity of drinking history and neuropsychological performance. During discrimination learning, one tone (CS+) predicted the occurrence of an airpuff (unconditioned stimulus), and another tone (CS-) served as a neutral stimulus; then the significance of the tones was reversed. Alcoholics who learned the initial discrimination were impaired in acquiring the new CS+ after the tones reversed; this is a function that has previously been linked to forebrain structures. It is suggested that a factor important to alcoholic addiction may be the presence of alcoholic-related associative responses that interfere with the ability to learn new more adaptive associations. C1 [Fortier, Catherine Brawn; Steffen, Elizabeth M.; Venne, Jonathan R.; McGlinchey, Regina E.] Vet Affairs Boston Healthcare Syst, GRECC, Boston, MA 02130 USA. [Fortier, Catherine Brawn; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [LaFleche, Ginette] Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02215 USA. [Disterhoft, John F.] Northwestern Univ, Dept Physiol, Feinberg Sch Med, Evanston, IL 60208 USA. RP Fortier, CB (reprint author), VA Boston Healthcare Syst, GRECC 182, 150 S Huntington Ave, Boston, MA 02130 USA. EM cbrawn@bu.edu RI McGlinchey, Regina/R-1971-2016; OI Disterhoft, John/0000-0002-8817-7913 FU NIA NIH HHS [AG08796, R37 AG008796]; NIAAA NIH HHS [R01 AA014205, R01 AA014205-01A2]; NIMH NIH HHS [MH53673] NR 75 TC 26 Z9 26 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAR PY 2008 VL 22 IS 2 BP 196 EP 208 DI 10.1037/0894-4105.22.2.196 PG 13 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 272RV UT WOS:000253878300007 PM 18331162 ER PT J AU McGlinchey, RE Fortier, CB Capozzi, SM Disterhoft, JF AF McGlinchey, Regina E. Fortier, Catherine Brawn Capozzi, Stephen M. Disterhoft, John F. TI Procedural memory system supports single cue trace eyeblink conditioning in medial temporal lobe amnesia SO NEUROPSYCHOLOGY LA English DT Article DE associative learning; Pavlovian conditioning; bitemporal amnesia ID INTERSTIMULUS-INTERVAL; QUANTITATIVE-ANALYSIS; RESPONSES; DISCRIMINATION; RABBITS; DELAY; AGE AB A number of studies investigating trace eyeblink conditioning have found impaired, but not eliminated, acquisition of conditioned responses (CRs) in both animals and humans with hippocampal removal or damage. The underlying mechanism of this residual learning is unclear. The present study investigated whether the impaired level of learning is the product of residual hippocampal function or whether it is mediated by another memory system that has been shown to function normally in delay eyeblink conditioning. Performance of bilateral medial temporal lobe amnesic patients who had a prior history of participating in eyeblink conditioning studies was compared to a control group with a similar training history and to an untrained control group in a series of single cue trace conditioning tasks with 500 ms, 250 ins, and 0 ms trace intervals. Overall, patients acquired CRs to a level similar to the untrained controls, but were significantly impaired compared to the trained controls. The pattern of acquisition suggests that amnesic patients may be relying on the expression of previously acquired, likely cerebellar based, procedural memory representations in trace conditioning. C1 [McGlinchey, Regina E.; Fortier, Catherine Brawn] Vet Affairs Boston Healthcare Syst, GRECC, Boston, MA USA. [McGlinchey, Regina E.; Fortier, Catherine Brawn] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Capozzi, Stephen M.] Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02215 USA. [Disterhoft, John F.] Northwestern Univ, Dept Physiol, Evanston, IL 60208 USA. RP McGlinchey, RE (reprint author), VA Boston Healthcare Syst, GRECC 182, 150 S Huntington Ave, Boston, MA 02130 USA. EM Regina_McGlinchey@hms.harvard.edu RI McGlinchey, Regina/R-1971-2016; OI Disterhoft, John/0000-0002-8817-7913 FU NIA NIH HHS [AG08796, R01 AG021501, R37 AG008796]; NIAAA NIH HHS [R01 AA014205, R01 AA014205-01A2]; NIMH NIH HHS [MH 53673]; NINDS NIH HHS [P50 NS026985] NR 18 TC 3 Z9 4 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAR PY 2008 VL 22 IS 2 BP 278 EP 282 DI 10.1037/0894-4105.22.2.278 PG 5 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 272RV UT WOS:000253878300016 PM 18331171 ER PT J AU Streeter, CC Terhune, DB Whitfield, TH Gruber, S Sarid-Segal, O Silveri, MM Tzilos, G Afshar, M Rouse, ED Tian, H Renshaw, PF Ciraulo, DA Yurgelun-Todd, DA AF Streeter, Chris C. Terhune, Devin B. Whitfield, Theodore H. Gruber, Staci Sarid-Segal, Ofra Silveri, Marisa M. Tzilos, Golfo Afshar, Maryam Rouse, Elizabeth D. Tian, Hua Renshaw, Perry F. Ciraulo, Domenic A. Yurgelun-Todd, Deborah A. TI Performance on the Stroop predicts treatment compliance in cocaine-dependent individuals SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cocaine; prefrontal; Stroop; compliance; neuropsychological testing; executive function ID ANTERIOR CINGULATE CORTEX; ATTENTIONAL BIAS; SCREENING TRIAL; NEUROPSYCHOLOGICAL PERFORMANCE; TREATMENT OUTCOMES; ALCOHOL ABUSERS; GABA LEVELS; WORD TEST; INTERFERENCE; ABSTINENCE AB Treatment dropout is a problem of great prevalence and stands as an obstacle to recovery in cocaine-dependent (CD) individuals. Treatment attrition in CD individuals may result from impairments in cognitive control, which can be reliably measured by the Stroop color-word interference task. The present analyses contrasted baseline performance on the color-naming, word-reading, and interference subtests of the Stroop task in CD subjects who completed a cocaine treatment trial (completers: N = 50) and those who dropped out of the trial before completion (non-completers: N = 24). A logistic regression analysis was used to predict trial completion using three models with the following variables: the Stroop task subscale scores (Stroop model); the Hamilton depression rating scale (HDRS) scores (HDRS model); and both the Stroop task subscale scores and HDRS scores (Stroop and HDRS model). Each model was able to significantly predict group membership (completers vs non-completers) better than a model based on a simple constant (HDRS model p = 0.02, Stroop model p = 0.006, and Stroop and HDRS model p = 0.003). Models using the Stroop preformed better than the HDRS model. These findings suggest that the Stroop task can be used to identify cocaine-dependent subjects at risk for treatment dropout. The Stroop task is a widely available, reliable, and valid instrument that can be easily employed to identify and tailor interventions of at risk individuals in the hope of improving treatment compliance. C1 Boston Univ Med Sch, Div Psychiat, Boston, MA 02118 USA. McLean Hosp, Brain Imaging Ctr, Boston, MA USA. Harvard Med Sch, Dept Psychiat, Boston, MA USA. Biostat Solutions Consulting, Boston, MA USA. Boston VA Healthcare Syst, Dept Psychiat, Boston, MA USA. Wayne State Univ, Dept Psychol, Detroit, MI USA. RP Streeter, CC (reprint author), Boston Univ Med Sch, Div Psychiat, 85 E Newton St, Boston, MA 02118 USA. EM streeter@bu.edu OI Ciraulo, Domenic/0000-0001-7706-8765; Terhune, Devin/0000-0002-6792-4975 FU NIAAA NIH HHS [K23AA13149]; NIDA NIH HHS [DA15116, DA09448, DA50038] NR 82 TC 81 Z9 83 U1 5 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2008 VL 33 IS 4 BP 827 EP 836 DI 10.1038/sj.npp.1301465 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 261OW UT WOS:000253090900012 PM 17568399 ER PT J AU Farrell, CJ Hoh, BL Pisculli, ML Henson, JW Barker, FG Curry, WT AF Farrell, Christopher J. Hoh, Brian L. Pisculli, Mary L. Henson, John W. Barker, Fred G. Curry, William T., Jr. TI Limitations of diffusion-weighted imaging in the diagnosis of postoperative infections SO NEUROSURGERY LA English DT Article DE brain abscess; craniotomy; diffusion-weighted imaging; infection; magnetic resonance imaging ID BRAIN-ABSCESS; DIFFERENTIAL-DIAGNOSIS; TUMORS; MR; DISCRIMINATION; COEFFICIENT; RESECTION; FEATURES; LESIONS; IMAGES AB OBJECTIVE: Diffusion-weighted imaging (DWI) has assumed a rapidly emerging role in the diagnosis of intracranial infection; however, its usefulness in the recognition of postoperative infection has been largely unexplored. We sought to determine the ability of DWI to accurately detect a broad range of postneurosurgical infections as well as identify individual factors that may limit its applicability. METHODS: We retrospectively identified 65 patients who had undergone surgery for the confirmed diagnosis of infection between August 2001 and February 2005 and had received preoperative magnetic resonance imaging evaluation, including DWI. Fifty patients developed infections after a primary neurosurgical procedure ("postoperative" infections), whereas 15 infections occurred without antecedent intervention ("spontaneous" infections). Logistic regression analysis was-used to identify factors associated with false-negative DWI findings. Additionally, we investigated the false-positive rate of DWI by retrospectively reviewing a series of 30 consecutive patients who underwent craniotomy and received postoperative DWI. RESULTS: Spontaneously developing cranial infections exhibited evidence of restricted diffusion in 14 out of 15 (93%) patients; however, infections that occurred postoperatively were associated with a significant false-negative rate using DWI (36%; P < 0.01). Within the subset of patients with postoperative infection, location of infection significantly correlated with the DWI false-negative rate. Infections located extradurally were less likely to demonstrate restricted diffusion compared with those located primarily within the subdural or intraparenchymal spaces. Additionally, false-positive DWI findings were observed in 11 of the 30 patients (37%) who had DWI obtained postoperatively in the absence of infection. CONCLUSION: Utilization of DWI for the diagnosis of infection after primary neurosurgical intervention is associated with an elevated false-negative rate. The absence of restricted diffusion is not sufficient to exclude the presence of pyogenic postcraniotomy infection and should not be used as the principle determinant of patient management in this clinical setting. C1 [Barker, Fred G.; Curry, William T., Jr.] Harvard Univ, Stephen E & Catherine Pappas Ctr Neurooncol, Sch Med, Massachusetts Gen Hosp,Dept Neurosurg, Boston, MA 02114 USA. [Hoh, Brian L.] Univ Florida, Dept Neurosurg, Gainesville, FL USA. [Pisculli, Mary L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Henson, John W.] Harvard Univ, Stephen E & Catherine Pappas Ctr Neurooncol, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Boston, MA 02114 USA. [Henson, John W.] Harvard Univ, Stephen E & Catherine Pappas Ctr Neurooncol, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Boston, MA 02114 USA. RP Curry, WT (reprint author), Harvard Univ, Stephen E & Catherine Pappas Ctr Neurooncol, Sch Med, Massachusetts Gen Hosp,Dept Neurosurg, 55 Fruit St,Y9E, Boston, MA 02114 USA. EM wcurry@partners.org NR 22 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 2008 VL 62 IS 3 BP 577 EP 582 DI 10.1227/01.NEU.0000297089.10744.55 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 292LV UT WOS:000255268500007 PM 18301347 ER PT J AU Botbol, YR Raghavendra, NK Rahman, S Engelman, A Lavigne, M AF Botbol, Yair R. Raghavendra, Nidhanapati K. Rahman, Shaila Engelman, Alan Lavigne, Marc TI Chromatinized templates reveal the requirement for the LEDGF/p75 PWWP domain during HIV-1 integration in vitro SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HISTONE ACETYLTRANSFERASE COMPLEXES; TRANSCRIPTIONAL COACTIVATOR P75; DNA INTEGRATION; RETROVIRAL INTEGRATION; CDNA INTEGRATION; BINDING DOMAINS; SITE SELECTION; HUMAN GENOME; HUMAN-CELLS AB Integration is an essential step in the retroviral lifecycle, and the lentiviral integrase binding protein lens epithelium-derived growth factor (LEDGF)/p75 plays a crucial role during human immunodeficiency virus type 1 (HIV-1) cDNA integration. In vitro, LEDGF/p75 stimulates HIV-1 integrase activity into naked target DNAs. Here, we demonstrate that this chromatin-associated protein also stimulates HIV-1 integration into reconstituted polynucleosome templates. Activation of integration depended on the LEDGF/p75-integrase interaction with either type of template. A differential requirement for the dominant DNA and chromatin-binding elements of LEDGF/p75 was however observed when using naked DNA versus polynucleosomes. With naked DNA, the complete removal of these N-terminal elements was required to abate cofactor function. With polynucleosomes, activation mainly depended on the PWWP domain, and to a lesser extent on nearby AT-hook DNA-binding motifs. GST pull-down assays furthermore revealed a role for the PWWP domain in binding to nucleosomes. These results are completely consistent with recent ex vivo studies that characterized the PWWP and integrase-binding domains of LEDGF/p75 as crucial for restoring HIV-1 infection to LEDGF-depleted cells. Our studies therefore establish novel in vitro conditions, highlighting chromatinized DNA as target acceptor templates, for physiologically relevant studies of LEDGF/p75 in lentiviral cDNA integration. C1 [Raghavendra, Nidhanapati K.; Rahman, Shaila; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Raghavendra, Nidhanapati K.; Rahman, Shaila; Engelman, Alan] Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. [Botbol, Yair R.; Lavigne, Marc] Inst Pasteur, Dept Virol, Unit Struct Virol, F-75724 Paris, France. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu; mlavigne@pasteur.fr FU NIAID NIH HHS [AI39394, R37 AI039394, R01 AI039394] NR 50 TC 39 Z9 43 U1 0 U2 6 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 MAR PY 2008 VL 36 IS 4 BP 1237 EP 1246 DI 10.1093/nar/gkm1127 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 272KD UT WOS:000253857400024 PM 18174227 ER PT J AU Taylor, AB Meyer, B Leal, BZ Kottter, P Schirf, V Demeler, B Hart, PJ Entian, KD Wohnert, J AF Taylor, Alexander B. Meyer, Britta Leal, Belinda Z. Koettter, Peter Schirf, Virgil Demeler, Borries Hart, P. John Entian, Karl-Dieter Woehnert, Jens TI The crystal structure of Nep1 reveals an extended SPOUT-class methyltransferase fold and a pre-organized SAM-binding site SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEEP TREFOIL KNOT; RIBOSOMAL-RNA; ANGSTROM RESOLUTION; POSTTRANSCRIPTIONAL MODIFICATIONS; MESSENGER-RNA; ACTIVE-SITE; SUBUNIT; PROTEIN; YEAST; METHYLATION AB Ribosome biogenesis in eukaryotes requires the participation of a large number of ribosome assembly factors. The highly conserved eukaryotic nucleolar protein Nep1 has an essential but unknown function in 18S rRNA processing and ribosome biogenesis. In Saccharomyces cerevisiae the malfunction of a temperature-sensitive Nep1 protein ( nep1-1(ts)) was suppressed by the addition of S-adenosylmethionine (SAM). This suggests the participation of Nep1 in a methyltransferase reaction during ribosome biogenesis. In addition, yeast Nep1 binds to a 6-nt RNA-binding motif also found in 18S rRNA and facilitates the incorporation of ribosomal protein Rps19 during the formation of pre-ribosomes. Here, we present the X-ray structure of the Nep1 homolog from the archae-bacterium Methanocaldococcus jannaschii in its free form (2.2A resolution) and bound to the S-adenosylmethionine analog S-adenosylhomocysteine (SAH, 2.15 angstrom resolution) and the antibiotic and general methyltransferase inhibitor sinefungin ( 2.25 angstrom resolution). The structure reveals a fold which is very similar to the conserved core fold of the SPOUT-class methyltransferases but contains a novel extension of this common core fold. SAH and sinefungin bind to Nep1 at a preformed binding C1 [Taylor, Alexander B.; Leal, Belinda Z.; Schirf, Virgil; Demeler, Borries; Hart, P. John; Woehnert, Jens] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, X Ray Crystallog Core Lab, San Antonio, TX 78229 USA. [Meyer, Britta; Koettter, Peter; Entian, Karl-Dieter] Univ Frankfurt, Excellence Ctr Macromol Complexes, D-60438 Frankfurt, Germany. [Meyer, Britta; Koettter, Peter; Entian, Karl-Dieter] Univ Frankfurt, Inst Mol Biowissenschaften, D-60438 Frankfurt, Germany. [Schirf, Virgil; Demeler, Borries] Univ Texas Hlth Sci Ctr San Antonio, Ctr Analyt Ultracentrifugat Macromol Assemblies, San Antonio, TX USA. [Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Wohnert, J (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM entian@bio.uni-frankfurt.de; jewoe@biochem.uthscsa.edu RI Entian, Karl-Dieter/D-3080-2011 NR 57 TC 22 Z9 26 U1 0 U2 1 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 MAR PY 2008 VL 36 IS 5 BP 1542 EP 1554 DI 10.1093/nar/gkm1172 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 278NY UT WOS:000254294800021 PM 18208838 ER PT J AU Allen, M Lezzoni, LI Huang, AN Huang, LC Leveille, SG AF Allen, Marybeth Lezzoni, Lisa I. Huang, Annong Huang, Linchang Leveille, Suzanne G. TI Improving patient-clinician communication about chronic conditions - Description of an Internet-based nurse e-coach intervention SO NURSING RESEARCH LA English DT Article DE internet; nursing; primary healthcare ID DISABLED OLDER PERSONS; SELF-MANAGEMENT; PRIMARY-CARE; CHRONIC DISEASE; DEPRESSION; EXPERIENCE; COMMUNITY; RECOVERY; EFFICACY; OUTCOMES AB Background: Studies show that patients who have higher self-efficacy and participate actively in their care have better disease management. Patient-provider Internet portals offer an exciting new venue for empowering and engaging patients in better management of chronic conditions. Objectives: To describe development of an Internet-based health coaching intervention. Approach: An Internet-based health coaching intervention to enhance patient-provider communication regarding three common conditions, chronic pain, depression, and impaired mobility, was developed. Using principles of self-management, the intervention aimed to engage and empower patients to collaborate with their primary care physician in managing their health conditions. Delivered online by nurse electronic coaches (e-coaches), the intervention involved a standardized set of e-mails and worksheets targeting self-efficacy, patient education, and motivation I to improve health. Results: Participants in the intervention (N = 121) primarily used the automated elements of the program, although 35% exchanged e-mails with the nurse e-coach. Most patients (88%) who contacted the e-coach were interested in further coaching. Patients who viewed the online worksheets did so repeatedly; 42 patients opened the worksheets 107 times prior to the visit. Discussion: The Internet-based coaching intervention departs substantially from usual nursing care but warrants further study given its potential to offer considerable benefits to large numbers of patients. Several challenges were identified to providing patient coaching and self-management support via the Internet, but this efficient and low-cost approach offers an innovative opportunity to improve patient clinician partnerships in managing chronic conditions. As patients become more accustomed to electronic communication, nurses can play an important role, joining efforts to develop this new realm to promote patients as partners in managing their health conditions. C1 [Allen, Marybeth; Lezzoni, Lisa I.; Huang, Annong; Leveille, Suzanne G.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. [Lezzoni, Lisa I.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Huang, Linchang] Beth Israel Deaconess Med Ctr, Dept Informat Syst, Boston, MA USA. RP Leveille, SG (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 1309 Beacon St,Rm 219, Brookline, MA 02446 USA. EM sleveill@bidmc.barvard.edu NR 31 TC 48 Z9 48 U1 5 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2008 VL 57 IS 2 BP 107 EP 112 DI 10.1097/01.NNR.0000313478.47379.98 PG 6 WC Nursing SC Nursing GA 279RJ UT WOS:000254372000006 PM 18347482 ER PT J AU Strandberg, L Mellstrom, D Ljunggren, O Grundberg, E Karlsson, MK Holmberg, AH Orwoll, ES Eriksson, AL Svedberg, J Bengtsson, M Ohlsson, C Jansson, JO AF Strandberg, Louise Mellstrom, Dan Ljunggren, Osten Grundberg, Elin Karlsson, Magnus K. Holmberg, Anna H. Orwoll, Eric S. Eriksson, Anna L. Svedberg, Johan Bengtsson, Magnus Ohlsson, Claes Jansson, John-Olov TI IL6 and IL1B Polymorphisms are associated with fat mass in older men: The MrOS study Sweden SO OBESITY LA English DT Article ID MATURE-ONSET OBESITY; INTERLEUKIN-1-BETA GENE; PROMOTER; MICE; EXPRESSION; TRANSCRIPTION; DISEASES; LEPTIN; SYSTEM AB There is growing evidence that immune functions are linked to the regulation of body fat. Our studies of knockout mice indicate that both endogenous interleukin (IL)-6 and IL-1 can suppress mature-onset obesity. We now investigated whether four common polymorphisms of the IL6 and IL1 systems are associated with the fat mass measured with dual-energy X-ray absorptiometry (DXA) in elderly men (n = 3,014). The study subjects were from the Swedish part of the MrOS multicenter population study and 69-81 years of age. The IL6-174 G>C (Minor allele frequency (MAF) = 48%) gene promoter polymorphism was associated with the primary outcome total fat mass (P = 0.006) and regional fat masses, but not with lean body mass. The IL1B-31T>C (MAF = 34%) polymorphism was also associated with total fat (P = 0.007) and regional fat masses, but not lean body mass. The IL-1 receptor antagonist (IL-1ra) gene (IL1RN) + 2018 T>C (MAF = 27%) polymorphism (in linkage disequilibrium (LD) with a well-studied variable number tandem repeat of 86 base pair (bp)) and IL1B + 3953 C>T (MAF = 26%) polymorphism were not associated with total fat mass. In conclusion, the IL-1 and IL-6 systems, shown to suppress mature-onset obesity in experimental animals, contain gene polymorphisms that are associated with fat, but not lean, mass in elderly men. C1 [Strandberg, Louise; Svedberg, Johan; Bengtsson, Magnus; Jansson, John-Olov] Univ Gothenburg, Inst Neurosci & Physiol Endocrinol, Sahlgrenska Acad, Gothenburg, Sweden. [Mellstrom, Dan; Eriksson, Anna L.; Ohlsson, Claes] Sahlgrens Univ Hosp, Sahlgrenska Acad, Ctr Bone Res, Gothenburg, Sweden. [Ljunggren, Osten; Grundberg, Elin] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Karlsson, Magnus K.; Holmberg, Anna H.] Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden. [Karlsson, Magnus K.; Holmberg, Anna H.] Malmo Univ Hosp, Dept Orthopaed, Malmo, Sweden. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Portland, OR 97201 USA. [Orwoll, Eric S.] Portland VA Med Ctr, Portland, OR USA. RP Jansson, JO (reprint author), Univ Gothenburg, Inst Neurosci & Physiol Endocrinol, Sahlgrenska Acad, Gothenburg, Sweden. EM JOJ@medic.gu.se OI Grahnemo, Louise/0000-0001-5276-6612; Orwoll, Eric/0000-0002-8520-7355 NR 22 TC 24 Z9 25 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAR PY 2008 VL 16 IS 3 BP 710 EP 713 DI 10.1038/oby.2007.95 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 271YA UT WOS:000253823400031 PM 18239554 ER PT J AU Gardner, R Raemer, DB AF Gardner, Roxane Raemer, Daniel B. TI Simulation in obstetrics and gynecology SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID VIRTUAL-REALITY SIMULATION; HUMAN PATIENT SIMULATOR; SHOULDER DYSTOCIA; OPERATING-ROOM; RESIDENT PERFORMANCE; OBJECTIVE EVALUATION; LAPAROSCOPIC SKILLS; TECHNICAL SKILLS; TRAINING DEVICES; MANAGEMENT AB Simulation is a practical and safe approach to the acquisition and maintenance of task-oriented and behavioral skills across the spectrum of medical specialties, including obstetrics and gynecology. Since the 1990s, the profession of obstetrics and gynecology has come to appreciate the value of simulation and major steps are being taken toward incorporating this technique into specialty-specific training, evaluation, and credentialing programs. This article provides an overview of simulators and simulation in health care and describes the scope of their current use and anticipated applications in the field of obstetrics and gynecology. C1 [Gardner, Roxane; Raemer, Daniel B.] Ctr Med Simulat, Cambridge, MA 02139 USA. [Gardner, Roxane] Brigham & Womens Hosp, Dept Obstet Gynecol, Boston, MA 02115 USA. [Gardner, Roxane; Raemer, Daniel B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raemer, Daniel B.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Gardner, R (reprint author), Ctr Med Simulat, 65 Landsdowne St, Cambridge, MA 02139 USA. EM rgardner1@partners.org NR 147 TC 46 Z9 48 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD MAR PY 2008 VL 35 IS 1 BP 97 EP + DI 10.1016/j.ogc.2007.12.008 PG 32 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 287SS UT WOS:000254937400010 PM 18319131 ER PT J AU Khaleque, M Bharti, A Gong, J Gray, PJ Sachdev, V Ciocca, DR Stati, A Fanelli, M Calderwood, SK AF Khaleque, Ma Bharti, A. Gong, J. Gray, P. J. Sachdev, V. Ciocca, D. R. Stati, A. Fanelli, M. Calderwood, S. K. TI Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1 SO ONCOGENE LA English DT Article DE heat shock factor; metastasis; associated protein ID METASTASIS-ASSOCIATED PROTEIN-1; C-FOS; GENE; CANCER; EXPRESSION; PHOSPHORYLATION; 14-3-3-EPSILON; CHAPERONES; COMPLEXES; APOPTOSIS AB Heat shock factor 1 (HSF1), the transcriptional activator of the heat shock genes, is increasingly implicated in cancer. We have shown that HSF1 binds to the corepressor metastasis-associated protein 1 (MTA1) in vitro and in human breast carcinoma samples. HSF1-MTA1 complex formation was strongly induced by the transforming ligand heregulin and complexes incorporated a number of additional proteins including histone deacetylases (HDAC1 and 2) and Mi2 alpha, all components of the NuRD corepressor complex. These complexes were induced to assemble on the chromatin of MCF7 breast carcinoma cells and associated with the promoters of estrogen-responsive genes. Such HSF1 complexes participate in repression of estrogen-dependent transcription in breast carcinoma cells treated with heregulin and this effect was inhibited by MTA1 knockdown. Repression of estrogen-dependent transcription may contribute to the role of HSF1 in cancer. C1 [Khaleque, Ma; Gray, P. J.; Calderwood, S. K.] Harvard Univ, Sch Med, Dept Radiat Oncol, BIDMC, Boston, MA 02215 USA. [Khaleque, Ma] NS Univ, Dept Biochem, Dhaka, Bangladesh. [Bharti, A.; Gong, J.; Sachdev, V.; Calderwood, S. K.] Boston Univ, Dept Med, Mendoza, Argentina. [Ciocca, D. R.; Stati, A.; Fanelli, M.] Inst Expt Med & Biol Cuyo, Lab Oncol, Mendoza, Argentina. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, BIDMC, 21-27 Burlington Ave,5th Floor, Boston, MA 02215 USA. EM scalderw@bidmc.harvard.edu FU NCI NIH HHS [CA077465] NR 24 TC 46 Z9 52 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2008 VL 27 IS 13 BP 1886 EP 1893 DI 10.1038/sj.onc.1210834 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 276NZ UT WOS:000254150600008 PM 17922035 ER PT J AU Mehta, S Thiagalingam, S Zembowicz, A Hatton, MP AF Mehta, Sonia Thiagalingam, Sureka Zembowicz, Artur Hatton, Mark P. TI Endocrine mucin-producing sweat gland carcinoma of the eyelid SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB A 70-year-old woman was examined for a 4-mm bluish nodule in the left upper eyelid. The lesion was excised and pathology showed it to be endocrine mucin-producing sweat gland carcinoma with positive margins. She underwent Mobs surgery and reconstruction of the resulting defect. Clinicians should be aware of this entity given its association with invasive mucinous adenocarcinoma, a locally aggressive tumor with metastatic potential. C1 [Mehta, Sonia] Boston Univ, Sch Med, Boston, MA 02215 USA. [Thiagalingam, Sureka; Zembowicz, Artur; Hatton, Mark P.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Zembowicz, Artur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zembowicz, Artur] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Hatton, MP (reprint author), Boston Inc, 50 Stainford St Suite, Boston, MA 02114 USA. EM mphatton@eyeboston.com NR 6 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2008 VL 24 IS 2 BP 164 EP 165 DI 10.1097/IOP.0b013e3181659c96 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 280QQ UT WOS:000254441700025 PM 18356733 ER PT J AU Dunphy, RW Wentzolf, JN Subramanian, M Conlin, PR Pasquale, LR AF Dunphy, Robert W. Wentzolf, Jeffrey N. Subramanian, Manju Conlin, Paul R. Pasquale, Louis R. TI Structural features anterior to the retina represented in panoramic scanning laser fundus images SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article AB Using the Optos Panoramic200 Scanning Laser Ophthalmoscope (Optos, Scotland, United Kingdom), clinically relevant findings anterior to the retinal surface, represented in digital ultra-wide field fundus images, were identified. Examples in this series demonstrate the potential for findings at the level of the crystalline lens and the full depth of the vitreous when imaging of the retina and choroid complex is undertaken. Clinicians interpreting these images should be aware of the potential contribution of information from anterior segment structures and the vitreous cavity. The information derived from anterior segment structures may enhance the diagnostic potential of the instrument. C1 [Wentzolf, Jeffrey N.; Pasquale, Louis R.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Glaucoma Serv, Boston, MA USA. [Dunphy, Robert W.] New England Coll Optometry, Boston, MA USA. [Conlin, Paul R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Subramanian, Manju] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. RP Pasquale, LR (reprint author), VA Boston Ocular TeleHlth Ctr, VA Boston Healthcare Syst, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. NR 5 TC 8 Z9 8 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD MAR-APR PY 2008 VL 39 IS 2 BP 160 EP 163 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 277RC UT WOS:000254231400015 PM 18435345 ER PT J AU Kumar, ATN Raymond, SB Bacskai, BJ Boas, DA AF Kumar, Anand T. N. Raymond, Scott B. Bacskai, Brian J. Boas, David A. TI Comparison of frequency-domain and time-domain fluorescence lifetime tomography SO OPTICS LETTERS LA English DT Article ID TURBID MEDIA; RESOLUTION AB We compare frequency-and time-domain formulations of deep-tissue fluorescence imaging of turbid media. Simulations are used to show that time-domain fluorescence tomography, implemented via the asymptotic lifetime-based approach, offers a significantly better separability of multiple lifetime targets than a frequency-domain approach. We also demonstrate experimentally, using complex-shaped phantoms, the advantages of the asymptotic time-domain approach over a Fourier-based approach for analyzing time-domain fluorescence data. (C) 2008 Optical Society of America. C1 [Kumar, Anand T. N.; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Raymond, Scott B.] Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. [Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu OI Raymond, Scott/0000-0001-7008-8974 FU NIA NIH HHS [R01 AG026240, AG 026240, R01 AG026240-05]; NIBIB NIH HHS [EB 000768, R01 EB000768] NR 13 TC 40 Z9 40 U1 0 U2 1 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 MAR 1 PY 2008 VL 33 IS 5 BP 470 EP 472 DI 10.1364/OL.33.000470 PG 3 WC Optics SC Optics GA 282KE UT WOS:000254565700020 PM 18311295 ER PT J AU Smullin, SE Faquin, W Susarla, SM Kaban, LB AF Smullin, Steven E. Faquin, William Susarla, Srinivas M. Kaban, Leonard B. TI Peripheral desmoplastic ameloblastoma: report of a case and literature review (vol 105, pg 37, 2008) SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Correction C1 [Smullin, Steven E.; Faquin, William; Susarla, Srinivas M.; Kaban, Leonard B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smullin, SE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 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 MAR PY 2008 VL 105 IS 3 BP 406 EP 406 DI 10.1016/j.tripleo.2008.01.001 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 268TW UT WOS:000253603600024 ER PT J AU Dunwoody, CJ Krenzischek, DA Pasero, C Rathmell, JP Polomano, RC AF Dunwoody, Colleen J. Krenzischek, Dina A. Pasero, Chris Rathmell, James P. Polomano, Rosemary C. TI Assessment, physiological monitoring, and consequences of inadequately treated acute pain SO PAIN MANAGEMENT NURSING LA English DT Article ID INTENSIVE-CARE-UNIT; POSTOPERATIVE PAIN; POSITION STATEMENT; OLDER-ADULTS; MANAGEMENT; ANALGESIA; PATIENT; HYPERGLYCEMIA; VALIDATION; INFUSION AB Postoperative pain is a major health care issue. Several factors have contributed to inadequate postoperative pain control, including a lack of understanding of preemptive pain management strategies, mistaken beliefs and expectations of patients, inconsistencies in pain assessment practices, use of as-needed analgesics that patients must request, and lack of analgesic regimens that account for interindividual differences and requirements. Untreated acute pain has the potential to produce acute neurohumoral changes, neuronal remodeling, and long-lasting psychologic and emotional distress and may lead to prolonged chronic pain states. To effectively manage postoperative pain, nurses must be able to adequately assess pain severity in diverse patient populations, understand how to monitor physiologic changes associated with pain and its treatment, be prepared to address the psychosocial experiences accompanying pain, and know the consequences of inadequate analgesia. It is important for nurses to be aware of relevant research and evidence-based guidelines that are available to guide pain assessments and patient monitoring practices. (C) 2008 by the American Society for Pain Management Nursing. C1 [Polomano, Rosemary C.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Dunwoody, Colleen J.] UPMC Presbyterian, Pittsburgh, PA USA. [Krenzischek, Dina A.] Johns Hopkins Univ Hosp, Dept Surg Nursing, Dept Anesthesia & Crit Care, Same Day Prep Post Anesthesia Care Unit, Baltimore, MD 21287 USA. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr, Boston, MA USA. RP Polomano, RC (reprint author), Univ Penn, Sch Nursing, Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM polomanr@nursing.upenn.edu NR 53 TC 23 Z9 23 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1524-9042 J9 PAIN MANAG NURS JI Pain Manag. Nurs. PD MAR PY 2008 VL 9 IS 1 SU 1 BP S11 EP S21 DI 10.1016/j.pmn.2007.11.006 PG 11 WC Nursing SC Nursing GA 278KU UT WOS:000254285200003 PM 18294590 ER PT J AU Krenzischek, DA Dunwoody, CJ Polomano, RC Rathmell, JP AF Krenzischek, Dina A. Dunwoody, Colleen J. Polomano, Rosemary C. Rathmell, James P. TI Pharmacotherapy for acute pain: Implications for practice SO PAIN MANAGEMENT NURSING LA English DT Article ID PATIENT-CONTROLLED ANALGESIA; POSTOPERATIVE PAIN; MANAGEMENT; ANESTHESIA; CARE; MORPHINE; OPIOIDS; SAFETY AB Effective treatment of perioperative acute pain requires that information about the patient's goals for pain relief, previous history with analgesics, and type of surgical procedure is used to guide decisions about analgesic regimens. Analgesics are selected based on the location of surgery, degree of anticipated pain, and patient characteristics (such as comorbidities), and routes of administration and dosing schedules are determined to maximize the effectiveness and safety of analgesia while minimizing the potential for adverse events. Pain management therapy is then extended into the postsurgical phase of recovery. To accomplish this, nurses must have a thorough understanding of the pharmacology of analgesics. This article provides useful information for commonly used analgesics, primarily nonsteroidal antfinflammatory drugs (NSAIDs), opioids, and local anesthetics for control of acute postoperative pain. (C) 2008 by the American Society for Pain Management Nursing. C1 [Krenzischek, Dina A.] Johns Hopkins Univ Hosp, Dept Surg Nursing, Dept Anesthesia & Crit Care, Same Day Prep Post Anesthesia Care Unit, Baltimore, MD 21287 USA. [Dunwoody, Colleen J.] UPMC Presbyterian, Pittsburgh, PA USA. [Polomano, Rosemary C.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, MGH Pain Ctr, Boston, MA 02114 USA. [Rathmell, James P.] Harvard Univ, Sch Med, Boston, MA USA. RP Krenzischek, DA (reprint author), Johns Hopkins Univ Hosp, Dept Surg Nursing, Dept Anesthesia & Crit Care, Same Day Prep Post Anesthesia Care Unit, Baltimore, MD 21287 USA. EM dkrenzis@jhmi.edu NR 38 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1524-9042 J9 PAIN MANAG NURS JI Pain Manag. Nurs. PD MAR PY 2008 VL 9 IS 1 SU 1 BP S22 EP S32 DI 10.1016/j.pmn.2007.11.003 PG 11 WC Nursing SC Nursing GA 278KU UT WOS:000254285200004 PM 18294591 ER PT J AU Polomano, RC Rathmell, JP Krenzischek, DA Dunwoody, CJ AF Polomano, Rosemary C. Rathmell, James P. Krenzischek, Dina A. Dunwoody, Colleen J. TI Emerging trends and new approaches to acute pain management SO PAIN MANAGEMENT NURSING LA English DT Article ID PATIENT-CONTROLLED ANALGESIA; RELEASE EPIDURAL MORPHINE; IONTOPHORETIC TRANSDERMAL SYSTEM; ACUTE POSTOPERATIVE PAIN; PERIPHERAL-NERVE BLOCKS; PREEMPTIVE ANALGESIA; ORTHOPEDIC-SURGERY; SURGICAL-PATIENTS; OPIOID ANALGESIA; CONTROLLED-TRIAL AB New approaches to the management of acute perioperative pain have focused on ways to improve the risk/benefit profile of various analgesics, enhance the consistency of pain control, address interpatient differences in responses to pain and treatments, and avoid periods of ineffective pain relief (analgesic gaps). Although intravenous patient-controlled analgesia has been the "gold standard" for acute pain management, there are now more analgesic options and compelling data to support combinations of analgesics or multimodal therapy, timing of analgesic interventions, and the use of newer drug delivery systems. Maximizing pain control with preemptive analgesia and multimodal therapy and the availability of transdermal fentanyl by iontophoresis and of extended-release epidural morphine have expanded the armamentarium of effective options for perioperative pain control. This article explores emerging trends in acute pain therapy and discusses their implications for improving patient care. (C) 2008 by the American Society for Pain Management Nursing. C1 [Polomano, Rosemary C.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,MGH Pain Ctr, Boston, MA USA. [Krenzischek, Dina A.] Johns Hopkins Univ Hosp, Dept Surg Nursing, Dept Anesthesia & Crit Care, Same Day Prep Post Anesthesia Care Unit, Baltimore, MD 21287 USA. [Dunwoody, Colleen J.] UPMC Presbyterian, Pittsburgh, PA USA. RP Polomano, RC (reprint author), Univ Penn, Sch Nursing, Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM polomanr@nursing.upenn.edu NR 53 TC 4 Z9 4 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1524-9042 J9 PAIN MANAG NURS JI Pain Manag. Nurs. PD MAR PY 2008 VL 9 IS 1 SU 1 BP S33 EP S41 DI 10.1016/j.pmn.2007.11.005 PG 9 WC Nursing SC Nursing GA 278KU UT WOS:000254285200005 PM 18294592 ER PT J AU Polomano, RC Dunwoody, CJ Krenzischek, DA Rathmell, JP AF Polomano, Rosemary C. Dunwoody, Colleen J. Krenzischek, Dina A. Rathmell, James P. TI Perspective on pain management in the 21st century SO PAIN MANAGEMENT NURSING LA English DT Article ID POSTOPERATIVE PAIN; POSTSURGICAL PAIN; QUALITY; SURGERY; IMPACT AB Pain is a predictable consequence of surgery or trauma. Untreated, it is associated with significant physiologic, emotional, mental, and economic consequences. Despite the vast amount of current knowledge, uncontrolled postoperative pain is reported by approximately 50% of patients. Thus, techniques for effective acute pain management (APM) represent unmet educational needs. The significance of this unmet need is reflected in the number of journal and textbook publications dedicated to disseminating research, evidence-based guidelines, and clinical information. Acknowledging the importance of APM, health care accrediting agencies and professional societies have become increasingly focused on ensuring that patients receive prompt and acceptable pain relief. (C) 2008 by the American Society for Pain Management Nursing. C1 [Polomano, Rosemary C.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Dunwoody, Colleen J.] UPMC Presbyterian, Pittsburgh, PA USA. [Krenzischek, Dina A.] Johns Hopkins Univ Hosp, Dept Surg Nursing, Dept Anesthesia & Crit Care, Same Day Prep Post Anesthesia Care Unit, Baltimore, MD 21287 USA. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Pain Ctr, Boston, MA USA. RP Polomano, RC (reprint author), Univ Penn, Sch Nursing, Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM polomanr@nursing.upenn.edu NR 30 TC 16 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1524-9042 J9 PAIN MANAG NURS JI Pain Manag. Nurs. PD MAR PY 2008 VL 9 IS 1 SU 1 BP S3 EP S10 DI 10.1016/j.pmn.2007.11.002 PG 8 WC Nursing SC Nursing GA 278KU UT WOS:000254285200002 PM 18294589 ER PT J AU Chetty, A Cao, GJ Manzo, N Nielsen, HC Waxman, A AF Chetty, Anne Cao, Gong-Jee Manzo, Nicholas Nielsen, Heber C. Waxman, Aaron TI The role of IL-6 and IL-11 in hyperoxic injury in developing lung SO PEDIATRIC PULMONOLOGY LA English DT Article DE hyperoxia; lung injury; IL-6 and IL-11 ID TUMOR-NECROSIS-FACTOR; BRONCHOPULMONARY DYSPLASIA; PROLONGED HYPEROXIA; ENDOTHELIAL-CELLS; PRETERM INFANTS; FACTOR RECEPTOR; NEONATAL-RATS; EXPRESSION; APOPTOSIS; INTERLEUKIN-6 AB We examined the cytoprotective effect of interleukin-6 (IL-6) and interleukin-11 (IL-11) during oxidant injury in neonatal lung and the regulators of cell death in vitro and in vivo after oxidant exposure. Type 11 cells from day 21 fetal neonatal rat lungs were treated with varying concentrations of either IL-6 or IL-11 for 24 hr prior to exposure to H2O2. Three-day-old transgenic lung-specific IL-11 and IL-6 overexpressing and wild type (WT) mouse pups were exposed to hyperoxia or room air for 3 days. Type 11 cells exposed to either IL-6 or IL-11 prior to oxidant injury exhibited improved survival compared to controls, 67% +/- 2.6 survivals in IL-6 pretreated cells compared to 48% +/- 1.6 in control; 63% +/- 3 survivals in IL-11 pretreated cells compared to 49% +/- 2.6 in control. The number of TUNEL positive cells in hyperoxia-exposed lungs was increased compared to room air animals (27 +/- 0.9 vs. 4 +/- 0.4; mean +/- SEM; P<0.05). In contrast, the number of TUNEL positive cells was reduced in hyperoxia-exposed lungs from IL-11 (+)mice (15.2 +/- 2.2; mean +/- SEM; P< 0.05). There was an enhanced accumulation of Bcl-2 and reduction of Bax protein in hyperoxia-exposed IL-11 (+) compared to room air-exposed mice. This was not seen in hyperoxia-exposed IL-6 (+) pups. An increase in caspase-3 was seen in hyperoxia-exposed lungs of WT pups compared to IL-11 (+) pups. IL-11 and IL-6 provide protective effects against oxidant-mediated injury in fetal type 11 cells and IL-11 provides protection in vivo by down-regulation of caspase-mediated cell death. C1 [Chetty, Anne; Cao, Gong-Jee; Nielsen, Heber C.] Tufts Univ, New England Med Ctr, Dept Pediat, Floating Hosp Children, Boston, MA 02111 USA. [Manzo, Nicholas; Waxman, Aaron] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02115 USA. RP Chetty, A (reprint author), Tufts Univ, New England Med Ctr, Dept Pediat, Floating Hosp Children, Box 44,750 Washington St, Boston, MA 02111 USA. EM achetty@tufts-neme.org OI Nielsen, Heber/0000-0002-9382-0539 FU NHLBI NIH HHS [R01 HL037930, HL 074859, HL 37930, HL 67089] NR 28 TC 10 Z9 17 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD MAR PY 2008 VL 43 IS 3 BP 297 EP 304 DI 10.1002/ppul.20777 PG 8 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 276ZY UT WOS:000254183400012 PM 18214944 ER PT J AU Holland, N Dong, J Garnett, E Shaikh, N Huen, K Harmatz, P Olive, A Winter, HS Gold, BD Cohen, SA Baldassano, RN Kirschner, BS Heyman, MB AF Holland, Nina Dong, Jing Garnett, Elizabeth Shaikh, Nishat Huen, Karen Harmatz, Paul Olive, Anthony Winter, Harland S. Gold, Benjamin D. Cohen, Stanley A. Baldassano, Robert N. Kirschner, Barbara S. Heyman, Melvin B. TI Reduced intracellular T-Helper 1 interferon-gamma in blood of newly diagnosed children with Crohn's disease and age-related changes in Th1/Th2 cytokine profiles SO PEDIATRIC RESEARCH LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; IFN-GAMMA; T-CELLS; INTERLEUKIN-12; EXPRESSION; SECRETION; RELEVANCE; PATTERNS; COLITIS; CD4(+) AB Abnormal cytokine production by T-helper 1 (Th1)/T-helper 2 (Th2) lymphocytes has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined Th1/Th2 cytokine status in pediatric IBD patients, and results have been inconsistent. We used flow cytometric detection of intracellular IFN-gamma/IL-4 cytokine production to investigate CD4(+), Th1, and Th2 cells in the peripheral blood of children with untreated, newly diagnosed Crohn's disease (CD) (n = 23) and matched healthy controls (n = 49). Th1 cytokine levels were lower in CD patients compared with controls (p = 0.006) and strongly correlated with levels of albumin and hematocrit (r = 0.51, p = 0.007 and r = 0.35, p = 0.052, respectively). An age-dependent increase in Th1 cells was observed (P < 0.0005); however, no correlation was found between age, clinical end points, %CD4(+), or Th2 cell numbers. In conclusion, the Th1 cytokine levels in blood are lower in early onset CD patients than in healthy children and are directly associated with disease-related clinical parameters. In future studies of pediatric IBD patients, it will be critical to consider the effect of age and disease progression on cytokine status in. intestinal mucosa and peripheral blood. C1 [Holland, Nina; Dong, Jing; Shaikh, Nishat; Huen, Karen] Univ Calif San Francisco, Sch Publ Hlth, San Francisco, CA 94143 USA. [Garnett, Elizabeth; Heyman, Melvin B.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Harmatz, Paul] Childrens Hosp & Res Ctr Oakland, Oakland, CA 94609 USA. [Olive, Anthony] Baylor Coll Med, Texas Childrens Hosp Clin Care Ctr, Houston, TX 77030 USA. [Winter, Harland S.] MassGen Hosp Children, Boston, MA 02114 USA. [Gold, Benjamin D.; Cohen, Stanley A.] Emory Clin, Atlanta, GA 30322 USA. [Baldassano, Robert N.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kirschner, Barbara S.] Univ Chicago, Chicago, IL 60637 USA. RP Holland, N (reprint author), Univ Calif Berkeley, 733 Univ Hall, Berkeley, CA 94720 USA. EM ninah@berkeley.edu FU NCRR NIH HHS [M01 RR001271, M01 RR01271]; NIDDK NIH HHS [K24 DK060617, K24 DK060617-03, K24 DK60617, R03 DK063187-01A1, R03 DK063187] NR 38 TC 9 Z9 13 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAR PY 2008 VL 63 IS 3 BP 257 EP 262 PG 6 WC Pediatrics SC Pediatrics GA 267OM UT WOS:000253518400008 PM 18287963 ER PT J AU Gonder-Frederick, L Zrebiec, J Bauchowitz, A Lee, J Cox, D Ritterband, L Kovatchev, B Clarke, W AF Gonder-Frederick, Linda Zrebiec, John Bauchowitz, Andrea Lee, Jarim Cox, Daniel Ritterband, Lee Kovatchev, Boris Clarke, William TI Detection of hypoglycemia by children with type 1 diabetes 6 to 11 years of age and their parents: A field study SO PEDIATRICS LA English DT Article DE pediatric type 1 diabetes; hypoglycemia detection ID BLOOD-GLUCOSE AWARENESS; YOUNG-ADULTS; ADOLESCENTS; ACCURACY; SYMPTOMS; IDDM AB OBJECTIVES. The objectives of this study were to ( 1) assess accuracy of hypoglycemia detection in children with type 1 diabetes and their parents, using personal digital assistant technology to collect glucose estimates and meter readings, ( 2) identify demographic, clinical, and psychological predictors of individual differences in accuracy, and ( 3) test whether poor hypoglycemia detection is a risk factor for severe hypoglycemia in children. METHODS. Sixty-one children aged 6 to 11 and their parents completed 70 trials, over 1 month, of a survey programmed on a personal digital assistant, which asked them to rate symptoms, estimate current blood glucose level, and then measure blood glucose level. For the subsequent 6 months, parents reported children's severe hypoglycemia episodes bimonthly. RESULTS. Both parents and children showed poor ability to recognize high or low blood glucose levels, making clinically significant errors as frequently as clinically accurate estimates. Parents failed to recognize >50% of readings <3 mmol/ L (<55 mg/dL) and made potentially dangerous errors such as believing the blood glucose level was high when it was low 17% of the time. Children were significantly more accurate at recognizing their hypoglycemia but still failed to detect >40% of episodes. Higher depression scores for children related to lower accuracy. Children who were less accurate at detecting hypoglycemia subsequently experienced more severe hypoglycemia. CONCLUSIONS. Ability to recognize hypoglycemia is a significant problem for children with type 1 diabetes and their parents. For children, poor ability to detect low blood glucose levels may be a significant and underappreciated risk factor for severe hypoglycemia. More effort is needed to provide education and training designed to improve hypoglycemia detection in this population. C1 [Gonder-Frederick, Linda; Bauchowitz, Andrea; Cox, Daniel; Ritterband, Lee; Kovatchev, Boris] Univ Virginia Hlth Syst, Behav Med Ctr, Dept Psychiat & Neurobehav Sci, Charlottesville, VA USA. [Zrebiec, John; Lee, Jarim] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA. [Clarke, William] Univ Virginia, Dept Pediat, Charlottesville, VA 22908 USA. RP Gonder-Frederick, L (reprint author), Univ Virginia, Behav Med Ctr, Box 800223, Charlottesville, VA 22908 USA. EM lag3g@virginia.edu RI Ritterband, Lee/G-7810-2011 OI Ritterband, Lee/0000-0001-7624-5213 FU NIDDK NIH HHS [R01 DK60039] NR 20 TC 16 Z9 16 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2008 VL 121 IS 3 BP E489 EP E495 DI 10.1542/peds.2007-0808 PG 7 WC Pediatrics SC Pediatrics GA 271HS UT WOS:000253780100051 PM 18310169 ER PT J AU Ogura, E Kageyama, K Hanada, K Kasckow, J Suda, T AF Ogura, Eriko Kageyama, Kazunori Hanada, Komaki Kasckow, John Suda, Toshihiro TI Effects of estradiol on regulation of corticotropin-releasing factor gene and interleukin-6 production via estrogen receptor type beta in hypothalamic 4B cells SO PEPTIDES LA English DT Article DE estradiol; corticotropin-releasing factor; interleukin-6; gene transcription; hypothalamus; stress ID PITUITARY-ADRENAL AXIS; MONOPHOSPHATE-RESPONSIVE ELEMENT; HORMONE PROMOTER ACTIVITY; MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; RAT HYPOTHALAMUS; PLASMA INTERLEUKIN-6; ER-ALPHA; VASOPRESSIN; PATHWAY AB Corticotropin-releasing factor (CRF) is produced in the hypothalamic paraventricular nucleus (PVN) in response to stress and stimulates the release of adrenocorticotropic hormone in the corticotrophs. Estrogens acting centrally are able to modulate the stress responses. In fact, direct estrogenic regulation of CRF gene expression has been demonstrated in various tissues. However, the mechanisms responsible for the actions of estrogens on CRF regulation in the PVN remain undetermined. We investigated whether estradiol (E2) contributes to the regulation of CRF gene and promoter activity in hypothalamic 4B cells. Furthermore, the involvement of E2 in the regulation of interleukin (IL)-6 and its role in hypothalamic 4B cells was explored. We demonstrated the dominant expression of estrogen receptor type beta (ER beta) and found that a physiologically relevant dose of E2 and an ER beta agonist stimulated CRF gene transcription in hypothalamic 4B cells. E2 stimulated IL-6 transcriptional activity via ER beta, and subsequently the levels of IL-6 mRNA and protein. We also found that treatment with IL-6 significantly reduced cell viability. Thus, these data suggest the important effects of E2 on the regulation of CRF gene and IL-6 production via ER beta in hypothalamic 4B cells. (c) 2007 Elsevier Inc. All rights reserved. C1 [Kasckow, John] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15206 USA. [Kasckow, John] Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15206 USA. [Ogura, Eriko; Kageyama, Kazunori; Hanada, Komaki; Suda, Toshihiro] Hirosaki Univ, Grad Sch Med, Dept Endocrinol & Metab, Hirosaki, Aomori 0368562, Japan. RP Kageyama, K (reprint author), Hirosaki Univ, Grad Sch Med, Dept Endocrinol & Metab, 5 Zaifu Cho, Hirosaki, Aomori 0368562, Japan. EM kkageyama@hkg.odn.ne.jp NR 45 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAR PY 2008 VL 29 IS 3 BP 456 EP 464 DI 10.1016/j.peptides.2007.11.007 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 287JE UT WOS:000254912600018 PM 18160129 ER PT J AU Nguyen, SI Eaton, SA Bain, AM Rahman, AP Payne, KD Bedimo, R Herrington, JD Maclayton, DO Rodriguez-Barradas, MC Busti, AJ AF Nguyen, Scan I. Eaton, Susan A. Bain, Amy M. Rahman, Anita P. Payne, Kenna D. Bedimo, Roger Herrington, Jon D. Maclayton, Darego O. Rodriguez-Barradas, Maria C. Busti, Anthony J. TI Lipid-lowering efficacy and safety after switching to atazanavir-ritonavir-based highly active Antiretroviral therapy in patients with human immunodeficiency virus SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Annual Scientific Sessions of the National-Lipid-Association CY MAY 31-JUN 04, 2007 CL Scottsdale, AZ SP Natl Lipid Assoc DE atazanavir; ritonavir; protease inhibitor; human immunodeficiency virus; HIV; dyslipidemia; antiretroviral therapy ID PROTEASE INHIBITOR THERAPY; HIV-INFECTED PATIENTS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; PERIPHERAL LIPODYSTROPHY; METABOLIC ABNORMALITIES; INCREASED RISK; HYPERLIPIDEMIA; LIPOPROTEIN AB Study Objective. To evaluate the efficacy, safety, and lipid-lowering effects after switching from a non-atazanavir-containing, protease inhibitor-based highly active antiretroviral therapy (HAART) to atazanavir-ritonavir-based HAART in patients infected with human immunodeficiency virus (HIV). Design. Multicenter, noncontrolled, retrospective study. Setting. Three tertiary teaching hospitals. Patients. Thirty-six patients with HIV infection, aged 18 years or older, who were receiving non-atazanavir-containing, protease inhibitor-based HAART that was switched to atazanavir 300 mg-ritonavir 100 mg-based HAART without changes in nucleoside reverse transcriptase inhibitors and confounders known to Alter serum lipid levels. Measurements and Main Results. Lipid profiles measured 4 weeks-6 months before the switch, as well as follow-up lipid profiles measured 4 weeks-6 months after receiving the new HAART regimen, were evaluated. The switch resulted in the following changes in lipid levels: total cholesterol -9% (p=0.002), low-density lipoprotein cholesterol -13% (p<0.001), high-density lipoprotein cholesterol (HDL) -2% (p=0.431), triglycerides -23% (p=0.007), non-HDL -11% (p=0.002), total cholesterol:HDL ratio -10% (p=0.004), and triglyceride:HDL ratio -24% (p=0.019). A subgroup analysis was conducted on the lipid profiles of nine patients who stilt met the strict inclusion and exclusion criteria up to 9 months after the switch; it showed that the reductions in their lipid profiles were sustained. In addition, 33% more patients achieved their National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III cholesterol goals. No significant changes were noted in median (interquartile range) CD4(+) counts (372 [236-551] and 361 [217-464] cells/mm(3), p=0.118) or in number of patients with undetectable HIV viral loads ([defined as < 50 copies/ml] 32/36 and 31/36 patients, p>0.05) between baseline and after the switch, respectively Conclusion. Switching to an atazanavir-ritonavir-based HAART regimen was associated with significant improvement in lipid profiles, similar to those seen in clinical trials, without compromising safety or viral and immunologic control. In addition, more patients were able to achieve their NCEP ATP III goals. C1 [Nguyen, Scan I.; Eaton, Susan A.; Bain, Amy M.; Rahman, Anita P.; Payne, Kenna D.; Busti, Anthony J.] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dallas, TX 75216 USA. [Bain, Amy M.; Rahman, Anita P.; Payne, Kenna D.; Bedimo, Roger; Busti, Anthony J.] N Texas Vet Affairs Med Ctr, Dallas, TX USA. [Bedimo, Roger] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Herrington, Jon D.] Scott & White Mem Hosp & Clin, Temple, TX 76508 USA. [Maclayton, Darego O.] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA. [Maclayton, Darego O.; Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Maclayton, Darego O.; Rodriguez-Barradas, Maria C.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Busti, AJ (reprint author), Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dallas Ft Worth Reg Campus,4500 S Lancaster Rd,Bl, Dallas, TX 75216 USA. EM anthony.busti@ttuhsc.edu NR 41 TC 21 Z9 21 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAR PY 2008 VL 28 IS 3 BP 323 EP 330 DI 10.1592/phco.28.3.323 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 269PM UT WOS:000253661400006 PM 18294112 ER PT J AU Katyar, SK Meleth, S Sharma, SD AF Katyar, Santosh K. Meleth, Sreelatha Sharma, Som D. TI Silymarin, a flavonoid from milk thistle (Silybum marianum L.), inhibits UV-induced oxidative stress through targeting infiltrating CD11b(+) cells in mouse skin SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID TEA POLYPHENOL (-)-EPIGALLOCATECHIN-3-GALLATE; TYPE-3 COMPLEMENT RECEPTOR; ANTIGEN-PRESENTING CELLS; ULTRAVIOLET-RADIATION; INFLAMMATORY CELLS; IMMUNE SUPPRESSION; IRRADIATED SKIN; TUMOR-GROWTH; IN-VIVO; PHOTOCARCINOGENESIS AB Phytochemicals have shown promise in inhibiting UV-induced oxidative stress, and therefore are considered as potent inhibitors of UV-induced oxidative stress-mediated skin diseases. We have shown previously that topical treatment of sillymarin, a flavonoid from milk thistle (Silybum marianum), inhibits UV-induced oxidative stress in mouse skin. However, the cellular targets responsible for the inhibition of UV-induced oxidative stress by silymarin are not clearly defined. To address this issue, C3H/HeN mice were UV irradiated (go mJ cm(-2)) with or without topical treatment with silymarin (1 mg cm(-2) skin area). Mice were killed 48 h later and skin samples collected. Flow cytometric analysis of viable dermal cells revealed that the number of infiltrating CD11b+ cells were the major source of oxidative stress (31.8%) in UV-irradiated skin compared with non-UV-exposed skin (0.4%). Treatment of sillymarin inhibited UV-induced oxidative stress through inhibition of infiltrating CD11b+ cells. The analysis of myeloperoxidase also indicated that silymarin significantly (P < 0.001) decreased UV-induced infiltration of leukocytes, and this effect of sillymarin was similar to that of intraperitoneal treatment of mice with monoclonal antibodies to CD11b. The inhibitory effect of silymarin, regardless of whether it is topically treated before or after UV irradiation, was of similar magnitude. Intraperitoneal administration of monoclonal antibodies to CD11b (rat IgG2b) to C3H/HeN mice inhibited UVB-induced oxidative stress generated by both epidermal and dermal cells as is evident by relative fluorescence intensity of oxidized rhodamine. Similar to the effect of anti-CD11b, sillymarin also inhibited UV-induced oxidative stress in both epidermal and dermal cells. Further, CD11b+ and CD11b- cell subsets from UV-treated or silymarin + UV-treated mice were separated by immunomagnetic cell isolation technique from total epidermal and dermal single cell suspensions and analyzed for reactive oxygen species (ROS)/H2O2 production. Analytic data revealed that CD11b+ cell population from UV-irradiated skin resulted in significantly higher production of ROS in both epidermis and dermis than CD11b- cell population, and that silymarin inhibited UV-induced oxidative stress through targeting infiltrating the CD11b+ cell type in the skin. C1 [Katyar, Santosh K.; Sharma, Som D.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. [Katyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Katyar, SK (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu NR 28 TC 0 Z9 0 U1 2 U2 5 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR-APR PY 2008 VL 84 IS 2 BP 266 EP 271 DI 10.1111/j.1751-1097.2007.00241.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 270UZ UT WOS:000253747000003 ER PT J AU Yusuf, N Katiyar, SK Elmets, CA AF Yusuf, Nabiha Katiyar, Santosh K. Elmets, Craig A. TI The immunosuppressive effects of phthalocyanine photodynamic therapy in mice are mediated by CD4(+) and CD8(+) T cells and can be adoptively transferred to naive recipients SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID POPULATIONS; INDUCTION; ABSENCE AB Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors but it is also immunosuppressive which may reduce its therapeutic efficacy. The purpose of our study was to elucidate the role of CD4(+) and CD8(+) T cells in PDT immunosuppression. Using silicon phthalocyanine 4 (Pc4) as photosensitizer, nontumor-bearing CD4 knockout (CD4(-/-)) mice and their wild type (WT) counterparts were subjected to Pc4-PDT in a manner identical to that used for tumor regression (1 cm spot size, 0.5 mg kg(-1) Pc4, 110 J cm(-2) light) to assess the effect of Pc4-PDT on cell-mediated immunity. There was a decrease in immunosuppression in CD4(-/-) mice compared with WT mice. We next examined the role of CD8(+) T cells in Pc4-PDT-induced immunosuppression using CD8(-/-) mice following the same treatment regimen used for CD4(-/-) mice. Similar to CD4(-/-) mice, CD8(-/-) mice exhibited less immunosuppression than WT mice. Pc4-PDT-induced immunosuppression could be adoptively transferred with spleen cells from Pc4-PDT treated donor mice to syngenic naive recipients (P < 0.05) and was mediated primarily by T cells, although macrophages were also found to play a role. Procedures that limit PDT-induced immunosuppression but do not affect PDT-induced regression of tumors may prove superior to PDT alone in promoting long-term antitumor responses. C1 [Yusuf, Nabiha; Katiyar, Santosh K.; Elmets, Craig A.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Yusuf, Nabiha; Katiyar, Santosh K.; Elmets, Craig A.] Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA. [Yusuf, Nabiha; Katiyar, Santosh K.; Elmets, Craig A.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Elmets, CA (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM celmets@uab.edu NR 22 TC 16 Z9 17 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR-APR PY 2008 VL 84 IS 2 BP 366 EP 370 DI 10.1111/j.1751-1097.2007.00270.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 270UZ UT WOS:000253747000014 PM 18208456 ER PT J AU Peled, ZM Warren, AG Johnston, P Yaremchuk, MJ AF Peled, Ziv M. Warren, Anne G. Johnston, Patrick Yaremchuk, Michael J. TI The Use of Alloplastic Materials in Rhinoplasty Surgery: A Meta-Analysis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Background: Conventional wisdom regarding the use of alloplastic materials in rhinoplastic surgery would advise against their use because of safety and aesthetic concerns. However, autogenous tissue harvest is not without associated morbidity and may be inadequate or insufficient in some clinical situations. Prior studies examining this issue have not provided definitive recommendations regarding implant selection, ideal locations in which to use specific implants, and necessary follow-up. Methods: First, the authors systematically reviewed the available literature on alloplastic implant use in rhinoplastic surgery by searching the MEDLINE database (from 1966 through September of 2005). Bibliographies from retrieved articles were searched for additional references. All data were independently extracted by two coauthors. Second, the authors performed a meta-analysis of the three most commonly used implant types. Results: Although a wide variety of alloplastic materials have been used historically and are still currently available, the most commonly used materials are silicone, expanded polytetrafluoroethylene (Gore-Tex), and porous high-density polyethylene (Medpor). In our meta-analysis, the removal rate for both Gore-Tex and Medpor implants was 3.1 percent, whereas the removal rate for silicone implants was significantly higher at 6.5 percent. Conclusions: Alloplastic implants in rhinoplastic surgery have acceptable complication rates and can be used when autogenous materials are unavailable or insufficient. Outcomes with Medpor or Gore-Tex implants may be slightly better than those with silicone. Improved reporting of implant failures and follow-up times in future studies are needed to better define specific guidelines for the use of these materials. (Plast. Reconstr. Surg. 121: 85e, 2008.) C1 [Peled, Ziv M.] Univ Arizona, Inst Peripheral Nerve Surg & Plast Surg, Tucson, AZ 85749 USA. Harvard Univ, Sch Med, Childrens Hosp, Clin Res Program, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Peled, ZM (reprint author), Univ Arizona, Inst Peripheral Nerve Surg & Plast Surg, 3170 N Swan Rd, Tucson, AZ 85749 USA. EM zpeled@hotmail.com NR 55 TC 41 Z9 41 U1 1 U2 3 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 MAR PY 2008 VL 121 IS 3 BP 85E EP 92E DI 10.1097/01.prs.0000299386.73127.a7 PG 8 WC Surgery SC Surgery GA V13KX UT WOS:000207666800008 PM 18317090 ER PT J AU Greene, AK May, JW AF Greene, Arin K. May, James W., Jr. TI Applying to plastic surgery residency: Factors associated with medical student career choice SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Background: Applications to plastic surgery residency increased 34 percent from 2002 to 2005, despite decreasing applications to other surgical subspecialties. During this period, medical education, reimbursement, work hours, and media coverage have changed. Methods: To determine factors responsible for rising applications to plastic surgery residencies, medical student applicants to plastic surgery residencies for 2005 were surveyed. Applicants recorded exposure to plastic surgery during medical school and graded the influence of personality, lifestyle, income potential, and media coverage on their decision to choose plastic surgery training. To further study the effects of plastic surgery exposure on career choice, the percentage of graduating students applying to plastic surgery residency was compared between medical schools with and without plastic surgery training programs. Results: Medical schools that provided greater exposure to plastic surgery and schools with plastic surgery training programs had a higher percentage of graduates applying to plastic surgery residency (p < 0.001). Applicants rated compatibility with the personality of plastic surgeons as a significant factor in their career choice. Lifestyle and income potential were moderately important, whereas media coverage minimally affected career decision. Applicants typically decided on a plastic surgical career during the third year of medical school. Conclusions: Medical student exposure to plastic surgery is the most influential factor in a student's decision to pursue a career in plastic surgery. To continue the increasing applicant trend toward plastic surgery, plastic surgeon engagement of medical students should be emphasized, ideally before the third year of medical school. C1 [Greene, Arin K.; May, James W., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP May, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, 15 Fruit St, Boston, MA 02114 USA. EM jwmay@partners.org NR 9 TC 24 Z9 24 U1 0 U2 4 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 MAR PY 2008 VL 121 IS 3 BP 1049 EP 1053 DI 10.1097/01.prs.0000299454.10281.33 PG 5 WC Surgery SC Surgery GA 268GA UT WOS:000253566000036 PM 18317155 ER PT J AU Pilcher, CD Wong, JK Pillai, SK AF Pilcher, Christopher D. Wong, Joseph K. Pillai, Satish K. TI Inferring HIV transmission dynamics from phylogenetic sequence relationships SO PLOS MEDICINE LA English DT Editorial Material ID INFECTION; RESISTANCE; TYPE-1; RATES C1 [Pilcher, Christopher D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wong, Joseph K.; Pillai, Satish K.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Pilcher, CD (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM cpilcher@php.ucsf.edu FU NIDA NIH HHS [K01 DA024654]; NIMH NIH HHS [R01 MH068686]; NINDS NIH HHS [R01 NS051132] NR 14 TC 2 Z9 3 U1 0 U2 0 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 MAR PY 2008 VL 5 IS 3 BP 350 EP 352 AR 069 DI 10.1371/journal.pmed.0050069 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 287PL UT WOS:000254928900006 PM 18351799 ER PT J AU Niedre, M Ntziachristos, V AF Niedre, Mark Ntziachristos, Vasilis TI Elucidating structure and function in vivo with hybrid fluorescence and magnetic resonance imaging SO PROCEEDINGS OF THE IEEE LA English DT Article DE dual modality; fluorescence; imaging; magnetic resonance imaging (MRI); optical ID DIFFUSE OPTICAL SPECTROSCOPY; LAPLACIAN-TYPE REGULARIZATION; NEAR-INFRARED TOMOGRAPHY; SINGULAR-VALUE ANALYSIS; CONTRAST AGENT; MOLECULAR TOMOGRAPHY; BREAST-CANCER; TURBID MEDIA; QUANTUM DOTS; HUMAN BRAIN AB While the mathematics, physics, and technology behind magnetic resonance (MR) and fluorescence image formation are distinctively different, the two modalities have significant complementary features to impart strong preclinical and clinical application synergies. Traditionally, hybrid MR and fluorescence imaging implied the use of a system where optical and MR signals can be concurrently acquired. in this case, the common geometry allows for the superposition of fluorescence images of cellular and subcellular processes onto anatomical and functional MR images. More recently, a different hybrid imaging paradigm is strongly evolving by utilizing hybrid MR-fluorescence nanoparticles. This approach offers a second paradigm of hybrid visualization where the common underlying contrast enables the coregistration of MR and fluorescence images acquired under different geometries. we review herein progress with the evolving field of multimodality MR and fluorescence imaging and discuss how these strategies offer a highly promising outlook in established and in novel preclinical and clinical applications. C1 [Niedre, Mark] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. [Ntziachristos, Vasilis] Tech Univ Munich, Inst Biol & Med Imaging, Chair Biol Imaging, D-80333 Munich, Germany. RP Niedre, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. EM mniedre@mgh.harvard.edu; v.ntziachristos@tum.de NR 88 TC 22 Z9 23 U1 1 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9219 J9 P IEEE JI Proc. IEEE PD MAR PY 2008 VL 96 IS 3 BP 382 EP 396 DI 10.1109/JPROC.2007.913498 PG 15 WC Engineering, Electrical & Electronic SC Engineering GA 264PB UT WOS:000253299600003 ER PT J AU Hammad, SM Crellin, HG Wu, BX Melton, J Anelli, V Obeid, LM AF Hammad, Samar M. Crellin, Heather G. Wu, Bill X. Melton, Jessica Anelli, Viviana Obeid, Lina M. TI Dual and distinct roles for sphingosine kinase 1 and sphingosine 1 phosphate in the response to inflammatory stimuli in RAW macrophages SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Article DE sphingosine kinase; sphingosine 1 phosphate; inflammation; TNF; LPS; apoptosis ID SIGNAL-TRANSDUCTION; MONOCYTIC CELLS; TNF-ALPHA; KAPPA-B; KINASE; ACTIVATION; RECEPTORS; 1-PHOSPHATE; SURVIVAL; EXPRESSION AB Sphingosine kinase 1 (SK1) and its product sphingosine-1-phosphate (SIP) have been implicated in the regulation of many cellular processes including growth regulation, protection from apoptosis, stimulation of angiogenesis, and most recently as mediators of the TNF-alpha inflammatory response. In this study we set out to examine the role of SK1/S1P in the RAW macrophage response to the potent inflammatory stimulus lipopolysaccharide (LPS). We show that LPS increases cellular levels of SK1 message and protein. This increase is at the transcriptional level and is accompanied by increased SK activity and generation of S1P. S1P is able to cause increases in COX-2 and PGE2 levels in RAW cells. Knockdown of SK1 using siRNA is able to inhibit the TNF but not the LPS inflammatory response. Moreover, knockdown of SK1 enhances both TNF- and LPS-induced apoptosis. These data indicate that there is a dual and distinct role for SK1 and S1P in the TNF and the LPS inflammatory pathways. (C) 2007 Elsevier Inc. All rights reserved. C1 [Obeid, Lina M.] Med Univ S Carolina, Dept Med, Div Gen Internal Med Geriatr, Charleston, SC 29403 USA. [Obeid, Lina M.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Hammad, Samar M.] Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29403 USA. [Crellin, Heather G.; Wu, Bill X.; Anelli, Viviana; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29403 USA. [Melton, Jessica] Med Univ S Carolina, Coll Grad Studies, Summer Undergrad Res Program, Charleston, SC 29403 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med Geriatr, POB 250779, Charleston, SC 29403 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01 CA097132, P01 CA097132-01A10003]; NIGMS NIH HHS [R01 GM062887-07, R01 GM062887] NR 37 TC 47 Z9 48 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD MAR PY 2008 VL 85 IS 3-4 BP 107 EP 114 DI 10.1016/j.prostaglandins.2007.11.002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 286CS UT WOS:000254823700005 PM 18166496 ER PT J AU Rush, AJ Kilner, J Fava, M Wisniewski, SR Warden, D Nierenberg, AA Trivedi, MH AF Rush, A. John Kilner, Jon Fava, Maurizio Wisniewski, Stephen R. Warden, Diane Nierenberg, Andrew A. Trivedi, Madhukar H. TI Clinically relevant findings from STAR*D SO PSYCHIATRIC ANNALS LA English DT Article ID MAJOR DEPRESSIVE DISORDER; MEASUREMENT-BASED CARE; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; QUICK INVENTORY; OUTCOMES; SYMPTOMATOLOGY; GUIDELINES; DISEASE; TRIALS C1 [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Fava, Maurizio; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. RP Rush, AJ (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM john.rush@ut-southwestem.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 NR 23 TC 5 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAR PY 2008 VL 38 IS 3 BP 188 EP 193 PG 6 WC Psychiatry SC Psychiatry GA 273JW UT WOS:000253927200006 ER PT J AU Henderson, C Bainbridge, J Keaton, K Kenton, M Guz, M Kanis, B AF Henderson, Claire Bainbridge, Jay Keaton, Kim Kenton, Martha Guz, Meghan Kanis, Becky TI The use of data to assist in the design of a new service system for homeless veterans in new york city SO PSYCHIATRIC QUARTERLY LA English DT Article DE homelessness; veterans; transitional housing AB Objective Operation Home is an agreement between the City of New York and the US Department of Veterans Affairs to design a new service system to help end veteran homelessness in New York City. The authors' task was to obtain data to inform the design of this new system. Methods A variety of methods were used. The group reviewed relevant literature and data from street homeless survey samples, analyzed shelter data, and consulted with VA homeless program staff on the findings. We then surveyed case managers at a veterans' shelter regarding their clients and determined their housing eligibility using a standardized logic model, and led two focus groups of veterans at this shelter regarding their views of the current shelter system and services for homeless veterans and how these might be improved. Results Among those resident in shelters during 2006, 37.2% of self-identified veterans compared to 0.9% of others reported their prior residence as supported housing, suggesting the need for more intensive case management at veterans' supported housing sites to help them sustain their tenure. The lack of interconnectedness among the various information systems made it more difficult to collect and analyze pertinent data. To begin to address this, a data match was undertaken to estimate the proportion of veterans resident in the veterans' shelter who were not in receipt of VA benefits to which they may be entitled. Conclusion The data obtained through collaboration between staff from NYC's Department of Homelessness Services, US Department of Veterans Affairs facilities in the New York/New Jersey region and Common Ground Community led to information that informed the evaluation design of the new system. The identification of gaps in available data on homeless veterans will lead to projects both to improve and share data. C1 [Henderson, Claire] James J Peters VA Med Ctr, VISN MIRECC 3, Bronx, NY 10468 USA. [Keaton, Kim; Guz, Meghan] New York City Dept Homeless Serv, Qual Assurance Program Evaluat & Policy Anal Unit, Div Adult Serv, New York, NY USA. [Kenton, Martha] New York City Dept Homeless Serv, Tech Assistance & Training Div Adult Serv, New York, NY USA. [Kanis, Becky] Common Ground Community, New York, NY USA. RP Henderson, C (reprint author), James J Peters VA Med Ctr, VISN MIRECC 3, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rosalind.Henderson@va.gov NR 5 TC 2 Z9 2 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD MAR PY 2008 VL 79 IS 1 BP 3 EP 17 DI 10.1007/s11126-007-9060-0 PG 15 WC Psychiatry SC Psychiatry GA 270YK UT WOS:000253755900002 PM 18060499 ER PT J AU Henderson, C Bainbridge, J Keaton, K Kenton, M Guz, M Kanis, B AF Henderson, Claire Bainbridge, Jay Keaton, Kim Kenton, Martha Guz, Meghan Kanis, Becky TI The use of data to assist in the design of a new service system for homeless veterans in New York City (vol 79, pg 19, 2008) SO PSYCHIATRIC QUARTERLY LA English DT Correction C1 [Henderson, Claire] James J Peters VA Med Ctr, VISN MIRECC 3, Bronx, NY 10468 USA. [Kenton, Martha; Guz, Meghan] Ney York City Dept Homeless Serv, Qual Assurance Program Evaluat & Policy Anal Unit, Div Adult Serv, New York, NY USA. [Kenton, Martha] Ney York City Dept Homeless Serv, Tech Assistance & Training Div Adult Serv, New York, NY USA. [Kanis, Becky] Common Ground Community, New York, NY USA. RP Henderson, C (reprint author), James J Peters VA Med Ctr, VISN MIRECC 3, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rosalind.Henderson@va.gov RI Henderson, Claire/E-4664-2010 OI Henderson, Claire/0000-0002-6998-5659 NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD MAR PY 2008 VL 79 IS 1 BP 19 EP 19 DI 10.1007/s11126-007-9066-7 PG 1 WC Psychiatry SC Psychiatry GA 270YK UT WOS:000253755900003 ER PT J AU Leontieva, L Dimmock, JA Gately, PW Gallinger, L Ploutz-Snyder, R Batki, SL AF Leontieva, Luba Dimmock, Jacqueline A. Gately, Paul W. Gallinger, Lisa Ploutz-Snyder, Robert Batki, Steven L. TI Voucher-based incentives for naltrexone treatment attendance in schizophrenia and alcohol use disorders SO PSYCHIATRIC SERVICES LA English DT Article ID PATIENT FACTORS; REINFORCEMENT; ABUSE; METAANALYSIS; INDIVIDUALS; DEPENDENCE; ABSTINENCE; ADHERENCE AB Objective: This study assessed the feasibility of voucher-based incentives for attendance for directly observed naltrexone treatment in a controlled trial for alcohol use disorders in schizophrenia. Methods: Cash-value voucher-based incentives were contingent on attendance at three research visits per week over 12 weeks for 61 participants. Vouchers increased in value based on consecutive attendance. Missed visits resulted in reduction of voucher value. Results: Participants attended 82% of all research visits. Average value of vouchers earned was $330 (78% of the maximum possible). Psychotic symptom severity at baseline did not affect the utilization of vouchers, and 94% of participants perceived the incentive system as helpful. Conclusions: The incentive system was well accepted and used despite psychosis severity, and the attendance rate was high, although causality between incentives and attendance could not be examined. A voucherbased incentive system for attendance can be successfully applied in a clinical trial for alcohol dependence treatment in schizophrenia. C1 [Leontieva, Luba; Dimmock, Jacqueline A.; Gately, Paul W.; Gallinger, Lisa] SUNY Syracuse, Upstate Med Ctr, Dept Psychiat, Syracuse, NY 13210 USA. [Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Leontieva, L (reprint author), SUNY Syracuse, Upstate Med Ctr, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM leontiel@upstate.edu FU NIAAA NIH HHS [R01-AA-013655] NR 15 TC 2 Z9 2 U1 2 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2008 VL 59 IS 3 BP 310 EP 314 DI 10.1176/appi.ps.59.3.310 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 271KX UT WOS:000253788400015 PM 18308913 ER PT J AU Zhu, BJ Ascher-Svanum, H Shi, LZ Faries, D Montgomery, W Marder, SR AF Zhu, Baojin Ascher-Svanum, Haya Shi, Lizheng Faries, Douglas Montgomery, William Marder, Stephen R. TI Time to discontinuation of depot and oral first-generation antipsychotics in the usual care of schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article ID HOSPITALIZATION; DRUGS AB Objective: This study compared the time to discontinuation for any reason of first-generation antipsychotics-in oral versus depot formulation-in the usual care of schizophrenia. Methods: This study used data from a three-year, prospective, nonrandomized, noninterventional, multisite study of schizophrenia. Participants initiated on oral haloperidol or fluphenazine (N=202) were compared with those initiated on haloperidol or fluphenazine in depot formulation (N=97) on time to all-cause discontinuation for one year after initiation, by using Kaplan-Meier survival analysis, a Cox proportional hazards regression model, and propensity score-adjusted bootstrap resampling methods. Results: Compared with participants treated with the oral formulation, those treated with depot first-generation antipsychotics had a significantly longer mean time to all-cause medication discontinuation and were twice as likely to stay on the medication. Conclusion: In the usual care of schizophrenia, treatment with first-generation antipsychotics in depot formulation appears to be associated with longer time to all-cause medication discontinuation compared with oral formulation of the same medication. C1 [Zhu, Baojin; Ascher-Svanum, Haya; Faries, Douglas; Montgomery, William] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Shi, Lizheng] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Marder, Stephen R.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. [Marder, Stephen R.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. RP Ascher-Svanum, H (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop 4133, Indianapolis, IN 46285 USA. EM haya@lilly.com NR 10 TC 33 Z9 33 U1 0 U2 0 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 MAR PY 2008 VL 59 IS 3 BP 315 EP 317 DI 10.1176/appi.ps.59.3.315 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 271KX UT WOS:000253788400016 PM 18308914 ER PT J AU Rodriguez, KL Gambino, FJ Butow, PN Hagerty, RG Arnold, RM AF Rodriguez, Ken L. Gambino, Frank J. Butow, Phyllis N. Hagerty, Rebecca G. Arnold, Robert M. TI 'It's going to shorten your life': framing of oncologist-patient communication about prognosis SO PSYCHO-ONCOLOGY LA English DT Article DE communication; prognosis; care : terminal; death; qualitative research ID EARLY BREAST-CANCER; TREATMENT PREFERENCES; CARE; INFORMATION; DIAGNOSIS; MESSAGES; LANGUAGE; DISEASE; WOMEN; TRIAL AB In this qualitative study, we used grounded theory techniques to analyze transcripts of 29 first-time encounters between oncologists and patients referred to them with previously diagnosed, incurable cancer. We found that 23 (79%) of the transcripts included 166 examples of prognostic talk. The language used ranged from general to personal, with 25% of statements mentioning no patients (e.g., 'the tumor will usually come back'), 13% mentioning patients other than the current patient (e.g., 'some patients with tumor response will be around for 2-5 years'), 11% mentioning the current patient in the context of others (e.g., 'on average, people like you live a couple of years'), and 51% directly focusing on the patient (e.g., 'this thing's going to kill you eventually'). More statements pertained to treatment-related prognosis than to disease-related prognosis (67 versus 33%). While 31% of statements focused on negative outcomes (loss framing), the remainder either focused on positive outcomes (gain framing) or discussed a combination of positive and negative outcomes (mixed framing). When discussions focused on negative outcomes, general and indirect language was commonly used, perhaps to buffer the patient from news of the poor prognosis. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Rodriguez, Ken L.] VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA 15240 USA. [Rodriguez, Ken L.; Arnold, Robert M.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Rodriguez, Ken L.; Arnold, Robert M.] Univ Pittsburgh, Ctr Bioeth & Hlth Law, Pittsburgh, PA USA. [Gambino, Frank J.] Carnegie Mellon Univ, Dept English, Pittsburgh, PA 15213 USA. [Butow, Phyllis N.; Hagerty, Rebecca G.] Univ Sydney, Sch Psychol, Med Psychol Res Unit, Sydney, NSW 2006, Australia. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, CHERP, 151C U,Univ Dr C,Bldg 28,Rm,1A115, Pittsburgh, PA 15240 USA. EM Keri.Rodriguez@va.gov FU NCATS NIH HHS [UL1 TR000005]; NCI NIH HHS [3R01 CA100387-03S1] NR 38 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2008 VL 17 IS 3 BP 219 EP 225 DI 10.1002/pon.1223 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 280GJ UT WOS:000254413400002 PM 17575562 ER PT J AU Bober, S Recklitis, C Park, E Diller, L AF Bober, S. Recklitis, C. Park, E. Diller, L. TI Caring for cancer survivors: Preliminary results from a survey of primary care physicians SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Bober, S.; Recklitis, C.; Diller, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Park, E.] 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 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2008 VL 17 IS 3 SU S BP S12 EP S12 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 281PG UT WOS:000254509900022 ER PT J AU Braun, IM Greenberg, DB Pirl, WF AF Braun, I. M. Greenberg, D. B. Pirl, W. F. TI The effect of having survived cancer on fatigue severity: A re-analysis of the literature SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2008 VL 17 IS 3 SU S BP S96 EP S97 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 281PG UT WOS:000254509900179 ER PT J AU Pirl, W Wills, A Mielniczuk, L Solis, J Temel, J Greer, J AF Pirl, W. Wills, A. Mielniczuk, L. Solis, J. Temel, J. Greer, J. TI Risk of developing cancer after major depressive disorder SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Pirl, W.; Wills, A.; Solis, J.; Temel, J.; Greer, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mielniczuk, L.] Univ Ottawa, Ottawa, ON, Canada. 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 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2008 VL 17 IS 3 SU S BP S69 EP S70 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 281PG UT WOS:000254509900128 ER PT J AU Radwin, L Wilkes, G Cabral, H AF Radwin, L. Wilkes, G. Cabral, H. TI Effects of patient-centered oncology care on desired patient outcomes SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Radwin, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilkes, G.] Boston Med Ctr, Boston, MA USA. [Cabral, H.] Boston Univ, Sch Publ Hlth, 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 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2008 VL 17 IS 3 SU S BP S53 EP S53 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 281PG UT WOS:000254509900095 ER PT J AU Recklitis, C Diller, L Li, X Robison, L Zeltzer, L AF Recklitis, C. Diller, L. Li, X. Robison, L. Zeltzer, L. TI The relationship of suicide ideation to physical and emotional health in adult survivors of childhood cancer: A report from the childhood cancer survivor study SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Recklitis, C.; Diller, L.; Li, X.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, X.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Robison, L.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Zeltzer, L.] Univ Calif Los Angeles, Matel Childrens Hosp, Los Angeles, CA 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 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2008 VL 17 IS 3 SU S BP S32 EP S33 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 281PG UT WOS:000254509900058 ER PT J AU Sanchez, VV Ng, A Mauch, P Diller, L Recklitis, C AF Sanchez, Varela V. Ng, A. Mauch, P. Diller, L. Recklitis, C. TI Post-traumatic stress disorder in survivors of Hodgkin's lymphoma: Prevalence and disease correlates SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Sanchez, Varela V.; Ng, A.; Mauch, P.; Diller, L.; Recklitis, C.] Dana Farber Canc Inst, Boston, MA 02115 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 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 2008 VL 17 IS 3 SU S BP S36 EP S37 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 281PG UT WOS:000254509900065 ER PT J AU Hopwood, CJ Morey, LC Edelen, MO Shea, MT Grilo, CM Sanislow, CA McGlashan, TH Daversa, MT Gunderson, JG Zanarini, MC Markowitz, JC Skodol, AE AF Hopwood, Christopher J. Morey, Leslie C. Edelen, Maria Orlando Shea, M. Tracie Grilo, Carlos M. Sanislow, Charles A. McGlashan, Thomas H. Daversa, Maria T. Gunderson, John G. Zanarini, Mary C. Markowitz, John C. Skodol, Andrew E. TI A comparison of interview and self-report methods for the assessment of borderline personality disorder criteria SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE borderline personality disorder; self-report; structured interview; predictive validity ID SCHIZOTYPAL; VALIDITY; AVOIDANT; SAMPLE AB Interview methods are widely regarded as the standard for the diagnosis of borderline personality disorder (BPD), whereas self-report methods are considered a time-efficient alternative. However, the relative validity of these methods has not been sufficiently tested. The current study used data from the Collaborative Longitudinal Personality disorder Study to compare diagnostic base rates and the relative validity of interview and self-report methods for assessing functional outcome in BPD. Although self-report yielded higher base rates of criteria endorsement, results did not support the common assumption that diagnostic interviews are more valid than self-reports, but instead indicated the combined use of these methods optimally identifies BPD criteria. C1 [Hopwood, Christopher J.; Morey, Leslie C.] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Edelen, Maria Orlando; Shea, M. Tracie] Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Edelen, Maria Orlando; Shea, M. Tracie] Brown Med Sch, Providence, RI 02906 USA. [Grilo, Carlos M.; Sanislow, Charles A.; McGlashan, Thomas H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Daversa, Maria T.; Gunderson, John G.; Zanarini, Mary C.] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. [Daversa, Maria T.; Gunderson, John G.; Zanarini, Mary C.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Markowitz, John C.] New York State Psychiat Inst & Hosp, Dept Psychiat, New York, NY 10032 USA. [Markowitz, John C.] Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. [Skodol, Andrew E.] Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ 85721 USA. [Skodol, Andrew E.] Univ Arizona, Mental Hlth Res Inst, Tucson, AZ 85721 USA. RP Hopwood, CJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman WAC 812, Boston, MA 02114 USA. EM chopwood@partners.org RI Morey, Leslie/B-5617-2008 OI Morey, Leslie/0000-0001-7711-5568 FU NIMH NIH HHS [K23 MH073708-03, K23 MH073708, F31MH75543-01A2, MH50840, MH50837, MH50838, K23 MH073708-04, MH50850, MH01654, MH50839, MH073708, K23 MH073708-05] NR 19 TC 54 Z9 54 U1 3 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD MAR PY 2008 VL 20 IS 1 BP 81 EP 85 DI 10.1037/1040-3590.20.1.81 PG 5 WC Psychology, Clinical SC Psychology GA 268GZ UT WOS:000253569000010 PM 18315403 ER PT J AU Kunik, ME Veazey, C Cully, JA Souchek, J Graham, DP Hopko, D Carter, R Sharafkhaneh, A Goepfert, EJ Wray, N Stanley, MA AF Kunik, M. E. Veazey, C. Cully, J. A. Souchek, J. Graham, D. P. Hopko, D. Carter, R. Sharafkhaneh, A. Goepfert, E. J. Wray, N. Stanley, M. A. TI COPD education and cognitive behavioral therapy group treatment for clinically significant symptoms of depression and anxiety in COPD patients: a randomized controlled trial SO PSYCHOLOGICAL MEDICINE LA English DT Article DE anxiety; chronic obstructive pulmonary disease; cognitive behavioral therapy; depression ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; OLDER MEDICAL PATIENTS; GENERALIZED ANXIETY; PRIMARY-CARE; ELDERLY-PATIENTS; HEALTH-STATUS; PREVALENCE; MANAGEMENT; INVENTORY AB Background. Chronic obstructive pulmonary disease (COPD) affects 14 to 20 million Americans and is associated with increased prevalence of affective disorders, contributing significantly to disability. This study compared cognitive behavioral therapy (CBT) group treatment for anxiety and depression with COPI) education for COPI) patients with moderate-to-severe anxiety and/or depressive symptoms. Method. A randomized controlled trial (RCT) was conducted between 11 July 2002 and 30 April 2005 at the Michael E. DeBakey VA Medical Center, Houston, TX. Participants were 238 patients treated for COPD the year before, with forced expiratory value in 1 second (FEV)(1)/forced vital capacity (FVC) < 70% and FEVI < 70% predicted, and symptoms of moderate anxiety and/or moderate depression, who were being treated by a primary care provider or pulmonologist. Participants attended eight sessions of CBT or COPD education. Assessments were at baseline, at 4 and 8 weeks, and 4,8 and 12 months. Primary outcomes were disease-specific and generic quality of life (QoL) [Chronic Respiratory Questionnaire (CRQ) and Medical Outcomes Survey Short Form-36 (SF-36) respectively]. Secondary outcomes were anxiety [Beck Anxiety Inventory (BAI)], depressive symptoms [Beck Depression Inventory-II (BDI-II)], 6-minute walk distance (6MWD) and use of health services. Results. Both treatments significantly improved QoL, anxiety and depression (p<0.005) over 8 weeks; the rate of change did not differ between groups. Improvements were maintained with no significant change during follow-up. Ratios of post- to pretreatment use of health services were equal to 1 for both groups. Conclusions. CBT group treatment and COPD education can achieve sustainable improvements in QoL for COPI) patients experiencing moderate-to-severe symptoms of depression or anxiety. C1 [Kunik, M. E.; Cully, J. A.; Souchek, J.; Graham, D. P.; Wray, N.; Stanley, M. A.] Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. [Kunik, M. E.; Cully, J. A.; Souchek, J.; Graham, D. P.; Sharafkhaneh, A.; Wray, N.; Stanley, M. A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Kunik, M. E.; Cully, J. A.; Graham, D. P.; Goepfert, E. J.; Stanley, M. A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kunik, M. E.; Souchek, J.; Sharafkhaneh, A.; Wray, N.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Veazey, C.] NW State Univ Louisiana, Natchitoches, LA USA. [Hopko, D.] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. [Carter, R.] Texas Tech Univ, Lubbock, TX 79409 USA. RP Kunik, ME (reprint author), Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. EM mkunik@bcm.tmc.edu RI Graham, David /J-1158-2014; Wray, Naomi/C-8639-2015 OI Wray, Naomi/0000-0001-7421-3357 NR 60 TC 85 Z9 88 U1 2 U2 26 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 MAR PY 2008 VL 38 IS 3 BP 385 EP 396 DI 10.1017/S0033291707001687 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 281FF UT WOS:000254481600010 PM 17922939 ER PT J AU Rao, VS Titushkin, IA Moros, EG Pickard, WF Thatte, HS Cho, MR AF Rao, V. S. Titushkin, I. A. Moros, E. G. Pickard, W. F. Thatte, H. S. Cho, M. R. TI Nonthermal effects of radiofrequency-field exposure on calcium dynamics in stem cell-derived neuronal cells: Elucidation of calcium pathways SO RADIATION RESEARCH LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; INTRACELLULAR CALCIUM; CA2+ CHANNELS; GROWTH CONES; ENDOPLASMIC-RETICULUM; BIOLOGICAL TISSUE; HUMAN OSTEOBLASTS; IN-VITRO; DIFFERENTIATION; RECEPTORS AB Intracellular Ca2+ spikes trigger cell proliferation, differentiation and cytoskeletal reorganization. In addition to Ca2+ spiking that can be initiated by a ligand binding to its receptor, exposure to electromagnetic stimuli has also been shown to alter Ca2+ dynamics. Using neuronal cells differentiated from a mouse embryonic stem cell line and a custom-built, frequency-tunable applicator, we examined in real time the altered Ca2+ dynamics and observed increases in the cytosolic Ca2+ in response to nonthermal radiofrequency (RF)-radiation exposure of cells from 700 to 1100 MHz. While about 60% of control cells (not exposed to RF radiation) were observed to exhibit about five spontaneous Ca2+ spikes per cell in 60 min, exposure of cells to an 800 MHz, 0.5 W/kg RF radiation, for example, significantly increased the number of Ca2+ spikes to 15.7 +/- 0.8 (P < 0.05). The increase in the Ca2+ spiking activities was dependent on the frequency but not on the SAR between 0.5 to 5 W/kg. Using pharmacological agents, it was found that both the N-type Ca2+ channels and phospholipase C enzymes appear to be involved in mediating increased Ca2+ spiking. Interestingly, microfilament disruption also prevented the Ca2+ spikes. Regulation of Ca2+ dynamics by external physical stimulation such as RF radiation may provide a noninvasive and useful tool for modulating the Ca2+-dependent cellular and molecular activities of cells seeded in a 3D environment for which only a few techniques are currently available to influence the cells. (C) 2008 by Radiation Research Society. C1 [Rao, V. S.; Titushkin, I. A.; Cho, M. R.] Univ Illinois, Dept Bioengn, Chicago, IL USA. [Moros, E. G.] Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA. [Pickard, W. F.] Washington Univ, Dept Elect & Syst Engn, St Louis, MO USA. [Thatte, H. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Cho, MR (reprint author), 851 S Morgan St,M-C 063, Chicago, IL 60607 USA. EM mcho@uic.edu OI Moros, Eduardo/0000-0003-1964-2460 NR 62 TC 20 Z9 21 U1 2 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAR PY 2008 VL 169 IS 3 BP 319 EP 329 DI 10.1667/RR1118.1 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 267ML UT WOS:000253513000008 PM 18302487 ER PT J AU Catalano, OA Singh, AH Uppot, RN Hahn, PF Ferrone, CR Sahani, DV AF Catalano, Onofrio A. Singh, Anandkumar H. Uppot, Raul N. Hahn, Peter F. Ferrone, Cristina R. Sahani, Dushyant V. TI Vascular and biliary variants in the liver: Implications for liver surgery SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 92nd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 2006 CL Chicago, IL SP Radiol Soc N Amer ID HEPATIC COLORECTAL METASTASES; EXPERT CONSENSUS STATEMENT; ENHANCED MR CHOLANGIOGRAPHY; HELICAL COMPUTED-TOMOGRAPHY; MULTIDETECTOR ROW CT; LAPAROSCOPIC CHOLECYSTECTOMY; PREOPERATIVE EVALUATION; TRANSPLANT DONORS; ARTERIAL INFUSION; RIGHT HEPATECTOMY AB Accurate preoperative assessment of the hepatic vascular and biliary anatomy is essential to ensure safe and successful hepatic surgery. Such surgical procedures range from the more complex, like tumor resection and partial hepatectomy for living donor liver transplantation, to others performed more routinely, like laparoscopic cholecystectomy. Modern noninvasive diagnostic imaging techniques, such as multidetector computed tomography (CT) and magnetic resonance (MR) imaging performed with liver-specific contrast agents with biliary excretion, have replaced conventional angiography and endoscopic cholangiography for evaluation of the hepatic vascular and biliary anatomy. These techniques help determine the best hepatectomy plane and help identify patients in whom additional surgical steps will be required. Preoperative knowledge of hepatic vascular and biliary anatomic variants is mandatory for surgical planning and to help reduce postoperative complications. Multidetector CT and MR imaging, with the added value of allow accurate identification of areas at risk for image postprocessing, venous congestion or devascularization. This information may influence surgical planning with regard to the extent of hepatic resection or the need for vascular reconstruction. (c) RSNA, 2008. C1 [Catalano, Onofrio A.; Singh, Anandkumar H.; Uppot, Raul N.; Hahn, Peter F.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,WHT 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 38 TC 53 Z9 64 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2008 VL 28 IS 2 BP 359 EP 378 DI 10.1148/rg.282075099 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 274IR UT WOS:000253995500003 PM 18349445 ER PT J AU Arellano, RS AF Arellano, Ronald S. TI Spectrum of CT findings after radio-frequency ablation of hepatic tumors - Invited commentary SO RADIOGRAPHICS LA English DT Editorial Material ID HEPATOCELLULAR-CARCINOMA; FOLLOW-UP C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Arellano, RS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2008 VL 28 IS 2 BP 390 EP 392 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 274IR UT WOS:000253995500005 ER PT J AU Levenson, RB Singh, AK Novelline, RA AF Levenson, Robin B. Singh, Ajay K. Novelline, Robert A. TI Fournier gangrene: role of imaging SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 92nd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 2006 CL Chicago, IL SP Radiol Soc N Amer ID CT FINDINGS; MANAGEMENT; EMERGENCY AB Fournier gangrene is a rapidly progressing necrotizing fasciitis involving the perineal, perianal, or genital regions and constitutes a true surgical emergency with a potentially high mortality rate. Although the diagnosis of Fournier gangrene is often made clinically, emergency computed tomography (CT) can lead to early diagnosis with accurate assessment of disease extent. CT not only helps evaluate the perineal structures that can become involved by Fournier gangrene, but also helps assess the retroperitoneum, to which the disease can spread. Findings at CT include asymmetric fascial thickening, subcutaneous emphysema, fluid collections, and abscess formation. Subcutaneous emphysema is the hallmark of Fournier gangrene but is not seen in all cases. Compared with radiography and ultrasonography, CT provides a higher specificity for the diagnosis of Fournier gangrene and superior evaluation of disease extent; however, diagnosis and evaluation can also be performed with these other modalities. The administration of broad-spectrum antibiotics and aggressive surgical debridement of the nonviable tissue are both essential for successful treatment. An awareness of the CT features of Fournier gangrene is imperative for prompt diagnosis and effective treatment planning. (c) RSNA 2008. C1 [Levenson, Robin B.; Singh, Ajay K.] Univ Massachusetts, Mem Med Ctr, Dept Radiol, Worcester, MA 01655 USA. [Singh, Ajay K.; Novelline, Robert A.] Massachusetts Gen Hosp, Div Emergency Radiol, Boston, MA 02114 USA. RP Levenson, RB (reprint author), Univ Massachusetts, Mem Med Ctr, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM RBL500@yahoo.com NR 22 TC 50 Z9 55 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2008 VL 28 IS 2 BP 519 EP 528 DI 10.1148/rg.282075048 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 274IR UT WOS:000253995500015 PM 18349455 ER PT J AU Jagannathan, JP Ramaiya, N Gill, RR Alyea, EP Ros, P AF Jagannathan, Jyothi P. Ramaiya, Nikhil Gill, Ritu R. Alyea, Edwin Pascal, III Ros, Pablo TI Imaging of complications of hematopoietic stem cell transplantation SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE hematopoietic stem cell transplantation; complications; imaging; CT ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; HEPATIC VENOOCCLUSIVE DISEASE; HIGH-RESOLUTION CT; IDIOPATHIC PNEUMONIA SYNDROME; INVASIVE FUNGAL SINUSITIS; PULMONARY COMPLICATIONS; PNEUMATOSIS-INTESTINALIS; RISK-FACTORS; LYMPHOPROLIFERATIVE DISORDER AB Hematopoietic stem cell transplantation is increasingly used for treatment of malignant and nonmalignant disorders, genetic and immunologic disorders, and solid tumors. Although advances in immunosuppressive therapy and management of infections have improved long-term survival, transplant recipients remain at risk for a multitude of complications, many of which are serious and life threatening. Post-transplant complications may be classified either according to the organ system or according to the timeframe following transplantation. Complications may involve the chest, abdominopelvic organs, the central nervous system, or musculoskeletal tissues. This article reviews the various clinical and radiologic findings of key complications following hematopoietic stem cell transplantation and the pertinent differentiating factors. C1 [Ramaiya, Nikhil; Alyea, Edwin Pascal, III] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Jagannathan, Jyothi P.; Ros, Pablo] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Jagannathan, Jyothi P.; Gill, Ritu R.; Ros, Pablo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ramaiya, Nikhil; Alyea, Edwin Pascal, III] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Ros, Pablo] Univ Autonoma Barcelona, Hosp De St Pau, Dept Radiol, Barcelona 08025, Spain. RP Ramaiya, N (reprint author), Dana Farber Canc Inst, Div Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM nramaiya@partners.org NR 75 TC 6 Z9 8 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2008 VL 46 IS 2 BP 397 EP 417 DI 10.1016/j.rcl.2008.04.004 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 338XU UT WOS:000258543500014 PM 18619387 ER PT J AU Hansell, DM Bankier, AA MacMahon, H McLoud, TC Muller, NL Remy, J AF Hansell, David M. Bankier, Alexander A. MacMahon, Heber McLoud, Theresa C. Mueller, Nestor L. Remy, Jacques TI Fleischner Society: Glossary of terms tor thoracic imaging SO RADIOLOGY LA English DT Review ID THIN-SECTION CT; HIGH-RESOLUTION CT; CRYPTOGENIC ORGANIZING PNEUMONIA; DESQUAMATIVE INTERSTITIAL PNEUMONIA; IDIOPATHIC PULMONARY-FIBROSIS; EXOGENOUS LIPOID PNEUMONIA; INFILTRATIVE LUNG-DISEASES; INFLATION-FIXED LUNGS; CRAZY-PAVING PATTERN; REVERSED HALO SIGN AB Members of the Fleischner Society compiled a glossary of terms for thoracic imaging that replaces previous glossaries published on 1984 and 1996 for thoracic radiography and computed tomography (CT), respectively. The need to update the previous versions came from the recognition that new words have emerged, others have become obsolete, and the meaning of some terms has changed. Brief descriptions of some diseases are included, and pictorial examples (chest radiographs and CT scans) are provided for majority of terms. C1 [Hansell, David M.] Royal Brompton Hosp, Dept Radiol, London SW3 6NP, England. [Bankier, Alexander A.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [MacMahon, Heber] Univ Chicago Hosp, Dept Radiol, Chicago, IL 60637 USA. [McLoud, Theresa C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mueller, Nestor L.] Vancouver Gen Hosp, Dept Radiol, Vancouver, BC V5Z 1M9, Canada. [Remy, Jacques] CHRU Lille, Hop Calmette, Dept Radiol, Lille, France. RP Hansell, DM (reprint author), Royal Brompton Hosp, Dept Radiol, Sydney St, London SW3 6NP, England. EM d.hansell@rbht.nhs.uk NR 138 TC 750 Z9 791 U1 1 U2 26 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 MAR PY 2008 VL 246 IS 3 BP 697 EP 722 DI 10.1148/radiol.2462070712 PG 26 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266FN UT WOS:000253420000005 PM 18195376 ER PT J AU Lee, JM Kopans, DB McMahon, PM Halpern, EF Ryan, PD Weinstein, MC Gazelle, GS AF Lee, Janie M. Kopans, Daniel B. McMahon, Pamela M. Halpern, Elkan F. Ryan, Paula D. Weinstein, Milton C. Gazelle, G. Scott TI Breast cancer screening in BRCA1 mutation carriers: Effectiveness of MR imaging - Markov Monte Carlo decision analysis SO RADIOLOGY LA English DT Article ID HIGH FAMILIAL RISK; CARCINOMA IN-SITU; OVARIAN-CANCER; GERMLINE MUTATIONS; RANDOMIZED-TRIALS; WOMEN; MAMMOGRAPHY; SURVEILLANCE; SURVIVAL; ULTRASOUND AB Purpose: To project, intermediate and long-terrn clinical outcomes of magnetic resonance (MR) imaging screening for breast cancer in women with BRCA1 gene mutations. Materials and Methods: A microsimulation model was developed to compare three annual screening strategies versus clinical surveillance: (a) mammography, (b) MR imaging, and (c) combined MR imaging and mammography. Input parameters were obtained from the published medical literature, existing databases, and expert opinion. The model was calibrated to targets from the Surveillance Epidemiology and End Results database (1975-1980) compiled during a period prior to the onset. of widespread mammographic screening. Sensitivity analysis Was Performed to evaluate the effect of uncertainty in parameter estimates. Results: With clinical surveillance, the estimated median diameter of invasive breast cancers at presentation was 2.6 cm. Average lire expectancy was 71.15 years. With annual screening with mammography, MR imaging, or combined mammography and MR imaging, median invasive tumor diameters at. diagnosis decreased to 1.9, 1.3, and 1.1 cm, respectively. Annual screening with mammography, MR imaging, or combined mammography and MR imaging increased average lire expectancy by 0.80 year, 1.10 years, and 1.38 years, respectively, and decreased relative mortality from breast cancer (16.8%, 17.2%, and 22.0%, respectively). Program sensitivity was greater than 50% only with MR imaging screening strategies. The majority or women undergoing screening had one or more, false-positive screening examinations (53.8%, 80.2%, and 84.0% for mammography, ME imaging, and combined mammography and MR imaging, respectively). Many women also underwent one or more biopsies for benign disease (11.3%, 26.3%, and 30.3%, respectively). Results were sensitive to BRCA1 penetrance estimates and to MR imaging sensitivity in the detection of ductal carcinoma in Situ. Conclusion: Annual screening with combined mammography and MR imaging provides BRCA1 mutation carriers with the greatest life expectancy gain and breast cancer mortality reduction. However, an important: trade-off or this strategy is an increased rate of False-positive screening results and biopsies performed for benign disease. C1 [Lee, Janie M.; Kopans, Daniel B.; McMahon, Pamela M.; Halpern, Elkan F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lee, Janie M.; McMahon, Pamela M.; Halpern, Elkan F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Ryan, Paula D.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. [Weinstein, Milton C.; Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Lee, JM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM jlee45@partners.org FU NCI NIH HHS [R25 CA92203, R25 CA092203] NR 40 TC 29 Z9 31 U1 1 U2 2 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 MAR PY 2008 VL 246 IS 3 BP 763 EP 771 DI 10.1148/radiol.2463070224 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266FN UT WOS:000253420000010 PM 18309013 ER PT J AU Gervais, DA Levis, DA Hahn, PF Uppot, RN Arellano, RS Mueller, PR AF Gervais, Debra A. Levis, Diane A. Hahn, Peter F. Uppot, Raul N. Arellano, Ronald S. Mueller, Peter R. TI Adjunctive intrapleural tissue plasminogen activator administered via chest tubes placed with imaging guidance: Effectiveness and risk for hemorrhage SO RADIOLOGY LA English DT Article ID LOCULATED PLEURAL EFFUSIONS; INTRACAVITARY UROKINASE; FIBRINOLYTIC TREATMENT; CONTROLLED-TRIAL; STREPTOKINASE; EMPYEMA; HEMOTHORAX; MANAGEMENT; INFECTION AB Purpose: To retrospectively determine the effectiveness of and risk for hemorrhage with intrapleural adjunctive tissue plasminogen activator (tPA) administered via chest tubes placed with imaging guidance. Materials and Methods: This HWAA-compliant study was approved by the institutional review board of Massachusetts General Hospital, with informed consent waived. A retrospective review of 66 patients (age range, 1-95 years; mean age, 55 years; 44 male. 22 female) who received intrapleural tPA between 2000 and 2006 was performed. Overall effectiveness of tPA was defined as successful drainage without need for additional decortication or video-assisted thoracoscopic surgery. Primary and secondary effectiveness were defined as effectiveness after one and two cycles of tPA, respectively. Imaging findings and complications were recorded. Hemorrhagic complications were noted, and the Fisher exact test was used to show whether concurrent anticoagulation increased bleeding risk. Results: Fifty-seven (86%) of 66 patients underwent complete drainage with tPA without further surgical procedures. Primary effectiveness was seen in 52 (87%) of 60 patients and secondary effectiveness was seen in five (83%) of six. Loculation of fluid was the most common finding in this selected cohort. Number of fluid pockets, pleural heterogeneity, and pleural thickness were not predictors of effectiveness There were live major pleural hemorrhages in four patients across five tPA cycles. Hemorrhages occurred only in patients receiving therapeutic anticoagulation (four of 12) and in none of the other patients (P < .001). No hemorrhages Occurred in the 38 patients receiving prophylactic anticoagulation. Conclusion: Intrapleural tPA is effective in improving drainage of loculated effusions not drained with catheters alone; prophylactic systemic anticoagulation does not increase bleeding risk with intrapleural tPA, but therapeutic anticoagulation is associated with a significantly increased risk of pleural hemorrhage. (c) RSNA, 2008. C1 [Gervais, Debra A.; Levis, Diane A.; Hahn, Peter F.; Uppot, Raul N.; Arellano, Ronald S.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dgervais@partners.org NR 19 TC 17 Z9 17 U1 0 U2 1 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 MAR PY 2008 VL 246 IS 3 BP 956 EP 963 DI 10.1148/radiol.2463070235 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266FN UT WOS:000253420000033 PM 18309017 ER PT J AU Karra, R Wu, SM AF Karra, Ravi Wu, Sean M. TI Multipotent stem cells in cardiac regenerative therapy SO REGENERATIVE MEDICINE LA English DT Review DE cardiac development; cardiac progenitor cells; cardiac regeneration; myocardial infarction; adult stem cells ID ACUTE MYOCARDIAL-INFARCTION; COLONY-STIMULATING FACTOR; BONE-MARROW-CELLS; RANDOMIZED CONTROLLED-TRIAL; PROGENITOR CELLS; SMOOTH-MUSCLE; INTRACORONARY INJECTION; ISCHEMIC-MYOCARDIUM; CLINICAL-TRIAL; SOMATIC-CELLS AB The potential for stem cells to ameliorate or cure heart diseases has galvanized a cadre of cardiovascular translational and clinical scientists to take a 'first-in-man' approach using autologous stem cells from a variety of tissues. However, recent clinical trial data show that when these cells are given by intracoronary infusion or direct myocardial injection, limited improvement in heart function occurs with no evidence of cardiomyogenesis. These studies illustrate the great need to understand the logic of cell-lineage commitment and the principles of cardiac differentiation. Recent identification of stem/progenitor cells of embryological origin with intrinsic competence to differentiate into multiple lineages within the heart offers new possibilities for cardiac regeneration. When combined with developments in nuclear reprogramming and provided that tumor risks and other challenges of embryonic cell transplantation can be overcome, the prospect of achieving autologous, cardiomyogenic, stem cell-based therapy may be within reach. C1 [Karra, Ravi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wu, Sean M.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Wu, Sean M.] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. RP Wu, SM (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM rkarra@partners.org; smwu@partners.org FU NHLBI NIH HHS [K08 HL081086-02, K08 HL081086, HL081086] NR 71 TC 2 Z9 3 U1 0 U2 15 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0751 J9 REGEN MED JI Regen. Med. PD MAR PY 2008 VL 3 IS 2 BP 189 EP 198 DI 10.2217/17460751.3.2.189 PG 10 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA 331EH UT WOS:000257995000013 PM 18307403 ER PT J AU Janik, JE Hoeft, MA Ajar, AH Alsofrom, GF Borrello, MT Rathmell, JP AF Janik, James E. Hoeft, Mark A. Ajar, Amir H. Alsofrom, Gary F. Borrello, Michael T. Rathmell, James P. TI Variable osteology of the sixth cervical vertebra in relation to stellate ganglion block SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article DE stellate ganglion; complex regional pain syndrome; anatomy; computed tomography; Chassaignac's tubercle ID SPREAD AB Background and Objectives: Stellate ganglion block is often carried out using palpation of surface landmarks to guide needle placement. However, anatomic variation of the surface landmarks used is common and block failure has been reported in as many as 30% of patients, even when the surface landmarks that guide needle placement can be easily identified. Methods: Computed tomography (CT) images of the cervical spine of 70 adult patients were examined to measure the distances in the coronal and sagittal planes between various points on the cricoid cartilage, anterior tubercle, posterior tubercle, and nadir of the vertebral gutter. The width of the tubercle in the caudal and cephalad plane was determined through multiplanar reformatted CT images in 6 randomly chosen patients. Results: The mean distance from the lateral margin of the cricoid cartilage laterally to the anterior tubercle was 13 +/- 5 mm (range 3-22 mm) in men and 12 +/- 3 mm (range 6-22 mm) in women. The mean depth of the anterior tubercle as measured posteriorly from the midpoint of the trachea was 20 +/- 4 (range 10-33 mm) in men and 19 +/- 4 mm (range 9-33 mm) in women. The maximal and minimal cephalad-caudad dimensions of the transverse process of C6 were 9.3 +/- 0.3 mm, and 6.7 +/- 0.3 mm, respectively. Conclusions: Large variability was observed in the size and location of the landmarks used for needle placement during stellate ganglion block. Placement of the needle medially where the transverse process joins the lateral margin of the vertebral body provides a larger bony target that may potentially provide a safer, more reliable block. C1 [Janik, James E.; Hoeft, Mark A.; Ajar, Amir H.; Borrello, Michael T.] Univ Vermont, Coll Med, Dept Anesthesiol, Burlington, VT USA. [Alsofrom, Gary F.] Univ Vermont, Coll Med, Dept Radiol, Burlington, VT USA. [Rathmell, James P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RP Rathmell, JP (reprint author), MGH Pain Ctr, 15Parkman St,WACC 333, Boston, MA 02114 USA. EM jratlimell@partners.org NR 15 TC 8 Z9 12 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAR-APR PY 2008 VL 33 IS 2 BP 102 EP 108 DI 10.1016/j.rapm.2007.08.013 PG 7 WC Anesthesiology SC Anesthesiology GA 271II UT WOS:000253781700003 PM 18299089 ER PT J AU Hess, DR AF Hess, Dean R. TI Change in editor. Some things change: Many things remain the same SO RESPIRATORY CARE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 4 TC 2 Z9 2 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAR PY 2008 VL 53 IS 3 BP 308 EP 310 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 273FP UT WOS:000253916100001 PM 18291044 ER PT J AU Shih, HA Loeffler, JS AF Shih, Helen A. Loeffler, Jay S. TI Radiation therapy in acromegaly SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE radiation; radiation therapy; stereotactic radiotherapy; stereotactic radiosurgery; gamma knife; proton radiation ID GAMMA-KNIFE RADIOSURGERY; LONG-TERM EFFICACY; GROWTH-FACTOR-I; PITUITARY-ADENOMAS; STEREOTACTIC RADIOSURGERY; CONFORMAL RADIOTHERAPY; CAVERNOUS SINUS; CRANIAL NERVES; HORMONE; IRRADIATION AB Radiation therapy is generally not a primary treatment modality for growth hormone-secreting pituitary adenomas. However, in patients with acromegaly refractory to medical and/or surgical interventions, radiation can offer durable tumor control and often biochemical remission. Technique of radiation therapy delivery and dose vary by adenoma size and extrasellar extension. Radiation can be delivered in a single sitting by stereotactic radiosurgery or in fractionated form of smaller doses delivered over typically 5-6 weeks in 25-30 treatments. A brief overview of forms of radiation modalities is reviewed followed by discussion of the role for radiation therapy, rationale of delivery method, and potential adverse effects. C1 [Shih, Helen A.; Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM hshih@partners.org; jloeffler@partners.org NR 37 TC 11 Z9 12 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD MAR PY 2008 VL 9 IS 1 BP 59 EP 65 DI 10.1007/s11154-007-9065-x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 260FK UT WOS:000252996000006 PM 18080837 ER PT J AU Baid-Agrawal, S Pascual, M Moradpour, D Frei, U Tolkoff-Rubin, N AF Baid-Agrawal, Seema Pascual, Manuel Moradpour, Darius Frei, Ulrich Tolkoff-Rubin, Nina TI Hepatitis C virus infection in haemodialysis and kidney transplant patients SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID STAGE RENAL-DISEASE; PEGYLATED INTERFERON-ALPHA-2B MONOTHERAPY; POSTTRANSPLANT DIABETES-MELLITUS; DIALYSIS-ASSOCIATED DISEASES; ACUTE HUMORAL REJECTION; LONG-TERM IMPACT; PLUS RIBAVIRIN; ALLOGRAFT RECIPIENTS; UNITED-STATES; LIVER-TRANSPLANTATION AB Chronic infection with hepatitis C virus (HCV) is an important global health problem. The prevalence of HCV is significantly higher in haemodialysis and kidney transplant patients, as compared to the general population. In spite of the relatively milder liver disease activity reported in HCV-infected haemodialysis patients, HCV infection adversely affects survival. Likewise, HCV has a detrimental effect on both patient and graft survival after kidney transplantation. However, patient survival is significantly better with kidney transplantation compared to remaining on dialysis; therefore, HCV infection alone should not be a contraindication to transplantation. Combination antiviral therapy with pegylated interferon-alpha and low-dose ribavirin is currently evolving in haemodialysis patients. Interferon-alpha (standard/pegylated) is relatively contraindicated after kidney transplantation because of an increased risk of allograft rejection. Therefore, antiviral treatment of transplant candidates while on dialysis remains the best option and may avoid the risk of HCV-associated liver and renal disease after transplantation. Large multi-centre clinical trials are required in HCV-infected haemodialysis and kidney transplant patients in order to define optimal therapeutic strategies before and after transplantation. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 [Baid-Agrawal, Seema; Frei, Ulrich] Charite Univ Med Berlin, Campus Virchow Klinikum, Dept Nephrol & Med Intens Care, D-13353 Berlin, Germany. [Pascual, Manuel] Univ Lausanne Hosp, Transplantat Ctr, Lausanne, Switzerland. [Moradpour, Darius] CHUV, Div Gastroenterol & Hepatol, Lausanne, Switzerland. [Tolkoff-Rubin, Nina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal & Transplantat Units, Boston, MA USA. RP Baid-Agrawal, S (reprint author), Charite Univ Med Berlin, Campus Virchow Klinikum, Dept Nephrol & Med Intens Care, Augustenburger Pl 1, D-13353 Berlin, Germany. EM seema.baid-agrawal@charite.de NR 118 TC 29 Z9 31 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD MAR-APR PY 2008 VL 18 IS 2 BP 97 EP 115 DI 10.1002/rmv.565 PG 19 WC Virology SC Virology GA 277ES UT WOS:000254196100005 PM 18064722 ER PT J AU O'Donnel, CJ Elosua, R AF O'Donnel, Christopher J. Elosua, Roberto TI Cardiovascular risk factors. Insights from Framingham Heart Study SO REVISTA ESPANOLA DE CARDIOLOGIA LA Spanish DT Review DE cardiovascular disease; coronary heart disease; epidemiology; prevention; risk factor ID DENSITY-LIPOPROTEIN-CHOLESTEROL; BODY-MASS INDEX; AMERICAN-DIABETES-ASSOCIATION; LONG-TERM CORONARY; BLOOD-PRESSURE; PHYSICAL-ACTIVITY; SERUM-CHOLESTEROL; FOLLOW-UP; SYSTOLIC HYPERTENSION; SCIENTIFIC STATEMENT AB Epidemiology involves the study of disease frequency and its determinants within the population. Cardiovascular epidemiology began in the 1930s as a result of changes observed in the causes of death. In the 1950s, several epidemiological studies were set in motion with the aim of clarifying the cause of cardiovascular disease. Four years after the Framingham Heart Study started, researchers had identified high cholesterol and high blood pressure levels as important factors in the development of cardiovascular disease. In subsequent years, the Framingham study and other epidemiological studies have helped to identify other risk factors, which are now considered classical risk factors. By coining the expression << risk factor >>, the Framingham Heart Study helped to bring about a change in the way medicine is practiced. Today, a risk factor is defined as a measurable characteristic that is causally associated with increased disease frequency and that is a significant independent predictor of an increased risk of presenting with the disease. This wide-ranging overview describes some of the most important insights into the causes of cardiovascular disease to have come from the Framingham Heart Study. The emphasis is on the identification of risk factors, and the assessment of their predictive ability and their implications for disease prevention. C1 [O'Donnel, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [O'Donnel, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Elosua, Roberto] Inst Municipal Invest Med, Hosp Mar, Unidad Lipidos Epidemiol Cardiovasc, E-08003 Barcelona, Spain. [Elosua, Roberto] CIBERESP, Barcelona, Spain. RP O'Donnel, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. OI ELOSUA, ROBERTO/0000-0001-8235-0095 NR 116 TC 55 Z9 70 U1 2 U2 17 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD MAR PY 2008 VL 61 IS 3 BP 299 EP 310 DI 10.1016/S1885-5857(08)60118-8 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278DV UT WOS:000254265000012 PM 18361904 ER PT J AU Labarere, J Bosson, JL Francois, P Fine, MJ AF Labarere, J. Bosson, J. -L. Francois, P. Fine, M. J. TI Propensity score analysis in observational research: Application to a study of prophylaxis against venous thromboembolism SO REVUE DE MEDECINE INTERNE LA French DT Article DE propensity score; observational studies; adjustment; venous thromboembolism ID OUTCOMES; BIAS; INPATIENTS AB Introduction. - In observational studies, a significant difference in the outcomes between treated and untreated patients may be observed in absence of treatment effect and caused by differences in baseline characteristics. Exegesis. - Propensity score analysis is a post hoe adjustment method which consists in deriving the conditional probability of receiving the treatment for a patient given his measured baseline characteristics (i.e., the propensity score). Matching each treated patient to an untreated one who has the nearest propensity score tends to balance baseline characteristics between the two groups and reduce the risk for overt bias. Then, the outcomes can be compared between matched treated and untreated patients. Conclusion. - Propensity score analysis is relevant for clinical conditions and treatments for which randomized controlled trials are unlikely to be conducted. However, propensity analysis cannot adjust for unmeasured characteristics and sensitivity analysis should be performed to assess how sensitive the conclusions are to potential confounding factors. (C) 2007 Publie par Elsevier Masson SAS. C1 [Labarere, J.; Bosson, J. -L.; Francois, P.] Univ Grenoble 1, Lab THEMAS, TIMC, CNRS,UMR 5525,Ctr Hosp, F-38043 Grenoble, France. [Labarere, J.; Francois, P.] Univ Grenoble 1, Ctr Hosp, Unite Evaluat Med, F-38043 Grenoble, France. [Fine, M. J.] Univ Pittsburgh, VA Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Fine, M. J.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15240 USA. RP Labarere, J (reprint author), Univ Grenoble 1, Lab THEMAS, TIMC, CNRS,UMR 5525,Ctr Hosp, F-38043 Grenoble, France. EM jlabarere@chu-grenoble.fr RI Labarere, Jose/N-1688-2014; OI Labarere, Jose/0000-0001-7621-6586 NR 12 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0248-8663 J9 REV MED INTERNE JI Rev. Med. Interne PD MAR PY 2008 VL 29 IS 3 BP 255 EP 258 DI 10.1016/j.revmed.2007.08.001 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 274XQ UT WOS:000254036500020 PM 17976869 ER PT J AU Ojikutu, B Zheng, H Walensky, RP Lu, ZG Losina, E Giddy, J Freedberg, KA AF Ojikutu, Bisola Zheng, Hui Walensky, Rochelle P. Lu, Zhigang Losina, Elena Giddy, Janet Freedberg, Kenneth A. TI Predictors of mortality in patients initiating antiretroviral therapy in Durban, South Africa SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1-INFECTED PATIENTS AB Objective. To identify predictors of mortality in patients initiating antiretroviral therapy (ART) in Durban, South Africa. Design. We conducted a retrospective cohort study analysing data on patients who presented to McCord Hospital, Durban, and started ART between 1 January 1999 and 29 February 2004. We performed univariate and multivariate analysis and constructed Kaplan-Meier curves to assess predictors. Results. Three hundred and nine patients were included. Forty-nine (16%) had died by the conclusion of the study. In univariate analysis, the strongest predictors of mortality were a CD4 cell count <50/mu l (hazard ratio (HR) 3.70, 95% confidence interval (CI) 1.96 - 7.14), a haemoglobin concentration <= 8 g/dl (FIR 1.23, 95% CI 1.08 - 1.40), a history of oral candidiasis (HR 3.17, 95% CI 1.70 - 5.87) and a history of cryptococcal meningitis (FIR 2.76,95% CI 1.80 - 19.2). A CD4 cell count <50/mu l (HR 3.08, 95% CI 1.54 - 5.88) and a history of oral candidiasis (HR 2.58, 95% CI 1.37 - 4.88) remained significant in multivariate analysis. A history of tuberculosis was not a significant predictor of mortality. Conclusions. Simple clinical and laboratory data independently predict mortality and allow for risk stratification in patients initiating ART in South Africa. Interventions enabling patients to be identified before they develop these clinical markers and earlier initiation of ART will help to ensure maximum benefits of therapy. C1 [Ojikutu, Bisola; Zheng, Hui; Walensky, Rochelle P.; Lu, Zhigang; Freedberg, Kenneth A.] Harvard Univ, Sch Med, CFAR, Harvard Ctr AIDS Res, Boston, MA 02115 USA. [Ojikutu, Bisola; Zheng, Hui; Walensky, Rochelle P.; Lu, Zhigang; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. [Ojikutu, Bisola] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Walensky, Rochelle P.; Lu, Zhigang; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Giddy, Janet] McCord Hosp, Durban, South Africa. RP Ojikutu, B (reprint author), Harvard Univ, Sch Med, CFAR, Harvard Ctr AIDS Res, Boston, MA 02115 USA. EM bojikutu@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [K24 AI062476-04, AI 058736, K23 AI001794, K23 AI001794-05, K23 AI01794, K24 AI01794, K24 AI062476, K25 AI050436, K25 AI050436-05, K25 AI50436, P30 AI060354, P30 AI060354-03, R01 AI058736, R01 AI058736-04]; PHS HHS [P30 060354] NR 13 TC 15 Z9 15 U1 0 U2 1 PU SA MEDICAL ASSOC PI PRETORIA PA BLOCK F CASTLE WALK CORPORATE PARK, NOSSOB STREET, ERASMUSKLOOF EXT3, PRETORIA, 0002, SOUTH AFRICA SN 0256-9574 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD MAR PY 2008 VL 98 IS 3 BP 204 EP 208 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 288NV UT WOS:000254994000019 PM 18350223 ER PT J AU Swartz, MS Wagner, HR Swanson, JW Stroup, IS McEvoy, JP Reimherr, F Miller, DD Mcgee, M Khan, A Canive, JM Davis, SM Hsiao, JK Lieberman, JA Adler, L Bari, M Belz, I Bland, R Blocher, T Bolyard, B Buffenstein, A Burruss, J Byerly, M Canive, J Caroff, S Casat, C Chavez-Rice, E Csernansky, J Delgado, P Douyon, R D'Souza, C Glick, I Goff, D Gratz, S Grossberg, GT Hale, M Hamner, M Jaffe, R Jeste, D Kablinger, A Khan, A Lamberti, S Levy, MT Lieberman, J Maguire, G Manschreck, T McEvoy, J McGee, M Meltzer, H Miller, A Miller, DD Nasrallah, H Nemeroff, C Olson, S Oxenkrug, GF Patel, J Reimher, F Riggio, S Risch, S Saltz, B Simpatico, T Simpson, G Smith, M Sommi, R Steinbook, RM Stevens, M Torres, R Weiden, P Wolberg, J AF Swartz, Marvin S. Wagner, H. Ryan Swanson, Jeffrey W. Stroup, I. Scott McEvoy, Joseph P. Reimherr, Fred Miller, Del D. McGee, Mark Khan, Ahsan Canive, Jose M. Davis, Sonia M. Hsiao, John K. Lieberman, Jeffrey A. Adler, Lawrence Bari, Mohammed Belz, Irving Bland, Raymond Blocher, Thomas Bolyard, Brent Buffenstein, Alan Burruss, John Byerly, Matthew Canive, Jose Caroff, Stanley Casat, Charles Chavez-Rice, Eugenio Csernansky, John Delgado, Pedro Douyon, Richard D'Souza, Cyril Glick, Ira Goff, Donald Gratz, Silvia Grossberg, George T. Hale, Mahlon Hamner, Mark Jaffe, Richard Jeste, Dilip Kablinger, Anita Khan, Ahsan Lamberti, Steve Levy, Michael T. Lieberman, Jeffrey Maguire, Gerald Manschreck, Theo McEvoy, Joseph McGee, Mark Meltzer, Herbert Miller, Alexander Miller, Del D. Nasrallah, Henry Nemeroff, Charles Olson, Stephen Oxenkrug, Gregory F. Patel, Jayendra Reimher, Frederick Riggio, Silvana Risch, Samuel Saltz, Bruce Simpatico, Thomas Simpson, George Smith, Michael Sommi, Roger Steinbook, Richard M. Stevens, Michael Torres, Rafael Weiden, Peter Wolberg, James CA CATIE Investigators TI The effectiveness of antipsychotic medications in patients who use or avoid illicit substances: Results from the CATIE study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; antipsychotics; substance abuse; dual disorders ID INTERVENTION EFFECTIVENESS CATIE; SEVERE MENTAL-ILLNESS; CHRONIC-SCHIZOPHRENIA; USE DISORDERS; NIMH CATIE; DUAL DIAGNOSIS; ABUSE; TRIAL; RISPERIDONE; PREVALENCE AB Objective: This double-blind study compared a second generation (atypical) antipsychotic drugs compared to a representative older agent for patients with schizophrenia who use or avoid illicit substances. Methods: Schizophrenic subjects were recruited at 57 U.S. sites and randomly assigned to olanzapine, perphenazine, quetiapine, risperidone or ziprasidone for up to 18 months. The primary aim of this analysis was to delineate differences between the overall effectiveness of these five treatments among patients who used or did not use illicit substances. Results: There were no significant differences between treatment groups in time to all-cause treatment discontinuation among patients who use illicit drugs (median 3.3 to 6.8 months). Among non-users time to treatment discontinuation was significantly longer for patients treated with olanzapine (median 13.0 months) than perphenazine (5.9 months), risperidone(5.6 months), or quetiapine(5.0 months); time to discontinuation for ziprasidone(4.3 months) was even shorter, although the latter difference was not significant. The difference between risperidone and quetiapine, although small, was significant. All remaining differences were non-significant. Similar results were found for discontinuation due to inefficacy. There were no differences between illicit users and non-users in symptom reduction and global improvement, after adjustment for differential duration of treatment. Differences in discontinuation results were attenuated by non-compliance, but the trends persisted after controlling for treatment compliance. Conclusions: Among patients with chronic schizophrenia who avoid use of illicit drugs, olanzapine was more effective than other antipsychotics as reflected by longer time to all-cause discontinuation, but illicit substance abuse attenuated this advantage, reinforcing the need for concurrent substance abuse treatment. (C) 2007 Elsevier B.V. All rights reserved. C1 [Swartz, Marvin S.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC 27710 USA. [Stroup, I. Scott] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Reimherr, Fred] Univ Utah, Med Ctr, Dept Psychiat, Salt Lake City, UT USA. [McGee, Mark] Appalachian Behav Healthcare Syst, Athens, OH USA. [Davis, Sonia M.] Quintiles Inc, Res Triangle Pk, NC USA. [Miller, Del D.] Univ Iowa, Sch Med, Dept Psychiat, Iowa City, IA 52242 USA. [Khan, Ahsan] Inst Psychiat Res, Wichita, KS USA. [Canive, Jose M.] Albuquerque Vet Adm, Med Ctr, Dept Psychiat, Albuquerque, NM USA. [Canive, Jose M.] Univ New Mexico, Albuquerque, NM 87131 USA. [Hsiao, John K.] NIMH, NIH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Lieberman, Jeffrey A.] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY USA. [Adler, Lawrence] Clin Insights, Glen Burnie, MD USA. [Bari, Mohammed] Synergen Clin Res, Chula Vista, CA USA. [Belz, Irving] Tri Cty MHMR, Conroe, TX USA. [Bland, Raymond] So Illinois Univ, Sch Med, Springfield, IL USA. [Blocher, Thomas] MHMRA Harris Cty, Houston, TX USA. [Bolyard, Brent] Cox N Hosp, Springfield, MO USA. [Burruss, John] Baylor Coll Med, Houston, TX 77030 USA. [Buffenstein, Alan] Queens Med Ctr, Honolulu, HI USA. [Byerly, Matthew] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Canive, Jose] Albuquerque VA Med Ctr, Albuquerque, NM USA. [Caroff, Stanley] Behav Hlth Serv, Philadelphia, PA USA. [Casat, Charles] Behav Hlth Ctr, Charlotte, NC USA. [Chavez-Rice, Eugenio] El Paso Community MHMR Ctr, El Paso, TX USA. [Csernansky, John] Washington Univ, Sch Med, St Louis, MO USA. [Douyon, Richard] VA Med Ctr, Miami, FL USA. [D'Souza, Cyril] Connecticut Mental Hlth Ctr, New Haven, CT USA. [Glick, Ira] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Goff, Donald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gratz, Silvia] Eastern Penn Psychiat Inst, Philadelphia, PA USA. [Grossberg, George T.] St Louis Univ, Sch Med, Wohl Inst, St Louis, MO USA. [Hale, Mahlon] New Britain Gen Hosp, New Britain, CT USA. [Hamner, Mark] Med Univ S Carolina, Charleston, SC 29425 USA. [Hamner, Mark] Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Jaffe, Richard] Belmont Ctr Comprehens Treatment, Philadelphia, PA USA. [Jeste, Dilip] Univ Calif San Diego, VA Med Ctr, San Diego, CA USA. [Kablinger, Anita] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA USA. [Khan, Ahsan] Univ Kansas, Sch Med, Wichita, KS 67214 USA. [Lamberti, Steve] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Levy, Michael T.] Staten Isl Univ Hosp, Staten Isl, NY USA. [Lieberman, Jeffrey] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Maguire, Gerald] Univ Calif Irvine, Orange, CA 92668 USA. [Manschreck, Theo] Corrigan Mental Hlth Ctr, Fall River, MA USA. [McEvoy, Joseph] Duke Univ, Med Ctr, Durham, NC USA. [McGee, Mark] Appalachian Behav Healthcare, Athens, OH USA. [Meltzer, Herbert] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Miller, Alexander] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Miller, Del D.] Univ Iowa, Iowa City, IA USA. [Nasrallah, Henry] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Nemeroff, Charles] Emory Univ, Sch Med, Atlanta, GA USA. [Olson, Stephen] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Oxenkrug, Gregory F.] St Elizabeths Med Ctr, Boston, MA USA. [Patel, Jayendra] Univ Mass Hlth CAre, Worcester, MA USA. [Reimher, Frederick] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Riggio, Silvana] Bronx VA Med Ctr, Mt Sinai Med Ctr, Bronx, NY USA. [Risch, Samuel] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Saltz, Bruce] Henderson Mental Hlth Ctr, Boca Raton, FL USA. [Simpatico, Thomas] Northwestern Univ, Chicago, IL 60611 USA. [Simpson, George] Univ So Calif, Med Ctr, Los Angeles, CA USA. [Smith, Michael] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Sommi, Roger] Univ Missouri, Kansas City, MO 64110 USA. [Steinbook, Richard M.] Univ Miami, Sch Med, Miami, FL USA. [Stevens, Michael] Valley Mental Hlth, Salt Lake City, UT USA. [Torres, Rafael] Univ Mississippi, Jackson, MS 39216 USA. [Weiden, Peter] SUNY Downstate Med Ctr, Brooklyn, NY 11203 USA. [Wolberg, James] Mt Sinai Med Ctr, New York, NY 10029 USA. RP Swartz, MS (reprint author), Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Med Ctr, DUMC Box 3173, Durham, NC 27710 USA. EM swart001@mc.duke.edu RI Meltzer, Herbert/E-8131-2013; Stroup, Thomas/F-9188-2014 OI Adler, Lawrence/0000-0002-6619-2493; Stroup, Thomas/0000-0002-3123-0672 FU NCRR NIH HHS [M01 RR000046]; NIMH NIH HHS [N01 MH90001] NR 46 TC 27 Z9 27 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2008 VL 100 IS 1-3 BP 39 EP 52 DI 10.1016/j.schres.2007.11.034 PG 14 WC Psychiatry SC Psychiatry GA 284RB UT WOS:000254722400004 PM 18191383 ER PT J AU van Erp, TGM Lesh, TA Knowlton, BJ Bearden, CE Hardt, M Karlsgodt, KH Shirinyan, D Rao, V Green, MF Subotnik, KL Nuechterlein, K Cannon, TD AF van Erp, Theo G. M. Lesh, Tyler A. Knowlton, Barbara J. Bearden, Carrie E. Hardt, Molly Karlsgodt, Katherine H. Shirinyan, David Rao, Vikas Green, Michael F. Subotnik, Kenneth L. Nuechterlein, Keith Cannon, Tyrone D. TI Remember and know judgments during recognition in chronic schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; psychosis; chronic; memory; episodic; recognition; recollection; familiarity; context; remember; know ID SIGNAL-DETECTION-THEORY; CONSCIOUS RECOLLECTION; DECISION-PROCESSES; MEMORY; FAMILIARITY; METAANALYSIS; IMPAIRMENT; MECHANISMS; AWARENESS; DEFICITS AB Deficits in learning and memory are among the most robust correlates of schizophrenia. It has been hypothesized that these deficits are in part due to reduced conscious recollection and increased reliance on familiarity assessment as a basis for retrieval. The Remember-Know (R-K) paradigm was administered to 35 patients with chronic schizophrenia and 35 healthy controls. In addition to making "remember" and "know" judgments, the participants were asked to make forced-choice recognition judgments with regard to details about the learning episode. Analyses comparing response types showed a significant reduction in "remember" responses and a significant increase in "know" responses in schizophrenia patients relative to controls. Both patients and controls recalled more details of the learning episode for "remember" compared to "know" responses, although, in particular for "remember" responses, patients recalled fewer details compared with controls. Notably, patients recognized fewer inter-item but not intra-item stimulus features compared with controls. These findings suggest deficits in organizing and integrating relational information during the learning episode and/or using relational information for retrieval. A Dual-Process Signal Detection interpretation of these findings suggests that recollection in chronic schizophrenia is significantly reduced, while familiarity is not. Additionally, a unidimensional Signal Detection Theory interpretation suggests that chronic schizophrenia patients show a reduction in memory strength, and an altered criterion on the memory strength distribution for detecting new compared with old stimuli but not for detecting stimuli that are remembered versus familiar. Taken together, these findings are consistent with a deficit in recollection and increased reliance on familiarity in making recognition memory judgments in chronic schizophrenia. (C) 2007 Elsevier B.V All rights reserved. C1 [van Erp, Theo G. M.; Lesh, Tyler A.; Knowlton, Barbara J.; Bearden, Carrie E.; Hardt, Molly; Karlsgodt, Katherine H.; Shirinyan, David; Rao, Vikas; Nuechterlein, Keith; Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Bearden, Carrie E.; Green, Michael F.; Nuechterlein, Keith; Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP van Erp, TGM (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM vanerp@psych.ucla.edu RI Karlsgodt, Katherine/H-2964-2013; OI Karlsgodt, Katherine/0000-0003-3332-4231; Lesh, Tyler/0000-0002-6160-3927 FU NCRR NIH HHS [RR021992, U24 RR021992]; NIGMS NIH HHS [GM072978]; NIMH NIH HHS [MH066286, MH65079, P50 MH066286, P50 MH066286-01A1, P50 MH066286-01A10002, R01 MH065079, R01 MH065079-01A1] NR 48 TC 32 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2008 VL 100 IS 1-3 BP 181 EP 190 DI 10.1016/j.schres.2007.09.021 PG 10 WC Psychiatry SC Psychiatry GA 284RB UT WOS:000254722400017 PM 17964760 ER PT J AU Hoggard, J Saad, T Schon, D Vesely, TM Royer, T AF Hoggard, Jeffrey Saad, Theodore Schon, Don Vesely, Thomas M. Royer, Tim TI Guidelines for venous access in patients with chronic kidney disease SO SEMINARS IN DIALYSIS LA English DT Article ID INSERTED CENTRAL CATHETERS AB At the time of hemodialysis vascular access evaluation, many chronic kidney disease patients already have iatrogenic injury to their veins which impedes the surgical construction of an arteriovenous fistula (AVF). Achieving the important goal of a greater prevalence of arteriovenous fistulae in the US hemodialysis population will require identification of those patients prior to reaching end-stage renal disease and an educational and procedural system for preserving their veins. C1 [Hoggard, Jeffrey] Eastern Nephrol Associates PLLC, Greenville, NC USA. [Saad, Theodore] Nephrol Christiana Care Hlth Syst, Dept Med, Nephrol Associates PA, Newark, DE USA. [Schon, Don] Arizona Kidney Dis & Hypertens Surg Ctr, Phoenix, AZ USA. [Vesely, Thomas M.] Vascular Access Ctr, Frontenac, MO USA. [Royer, Tim] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Hoggard, J (reprint author), 1776 Blue Banks Fram Rd, Greenville, NC 27834 USA. EM jhoggard@suddenlink.net NR 16 TC 40 Z9 40 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 2008 VL 21 IS 2 BP 186 EP 191 DI 10.1111/j.1525-139X.2008.00421.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 277DS UT WOS:000254193500017 PM 18364015 ER PT J AU Hough, S AF Hough, Sigmund TI Untitled SO SEXUALITY AND DISABILITY LA English DT Editorial Material C1 VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, W Roxbury, MA 02132 USA. RP Hough, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Sigmund_Hough@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD MAR PY 2008 VL 26 IS 1 BP 1 EP 1 DI 10.1007/s11195-007-9070-8 PG 1 WC Rehabilitation SC Rehabilitation GA 262FG UT WOS:000253133800001 ER PT J AU DenBoer, JW AF DenBoer, John W. TI The facts of life -and more: Sexuality and intimacy for people with intellectual disabilities SO SEXUALITY AND DISABILITY LA English DT Book Review C1 [DenBoer, John W.] Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston Consortium Psychol Training Program, Boston, MA 02130 USA. [DenBoer, John W.] Boston Univ, Sch Med, Boston, MA 02130 USA. RP DenBoer, JW (reprint author), Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston Consortium Psychol Training Program, 150 S Huntington Ave, Boston, MA 02130 USA. EM jwdenboer@yahoo.com NR 3 TC 0 Z9 0 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD MAR PY 2008 VL 26 IS 1 BP 51 EP 53 DI 10.1007/s11195-007-9065-5 PG 3 WC Rehabilitation SC Rehabilitation GA 262FG UT WOS:000253133800007 ER PT J AU Conhaim, RL Kluesner, KA Watson, KE Munoz-del-Rio, A Heisey, DM Harms, BA AF Conhaim, Robert L. Kluesner, Karr A. Watson, Kai E. Munoz-del-Rio, Alejandro Heisey, Dennis M. Harms, Bruce A. TI Hemorrhage progressively disturbs interalveolar perfusion in the lungs of rats SO SHOCK LA English DT Article DE pulmonary circulation; microvascular perfusion; perfusion distribution; dispersion index analysis ID PULMONARY BLOOD-FLOW; SHOCK; HETEROGENEITY AB Acute hemorrhage is often followed by devastating lung injury. However, why blood loss should lead to lung injury is not known. One possibility is that hemorrhage rapidly disturbs the distribution of microvascular perfusion at the alveolar level, which may be a triggering event for subsequent injury. We showed previously that a 30% blood loss in rats caused significant maldistribution of interalveolar perfusion within 45 min (J Trauma 60:158, 2006). In this report, we describe results of further exploration of this phenomenon. We wanted to know if perfusion distribution was disturbed at 15 min, when vascular pressures were significantly reduced by the blood loss, compared with those at 45 min, when the pressures had returned substantially toward normal. We hemorrhaged rats by removing 30% of their blood volume. We quantified interalveolar perfusion distribution by statistically analyzing the trapping patterns of 4-mu m-diameter fluorescent latex particles infused into the pulmonary circulation 15 (red particles) and 45 min (green particles) after blood removal. We used confocal fluorescence microscopy to digitally image the trapping patterns in sections of the air-dried lungs and used pattern analysis to quantify the patterns in tissue image volumes that ranged from 1,300 alveoli to less than 1 alveolus. LogDI, a measure of perfusion maldistribution, increased from 1.00 +/- 0.15 at 15 min after blood loss to 1.62 +/- 0.24 at 45 min (P < 0.001). These values were 0.86 +/- 0.22 (15 min) and 1.12 +/- 0.24 (45 min) in control rats (P = 0.03). Hemorrhage caused the green (45 min)-to-red (15 min) particle distance to decrease from 35.9 +/- 6.5 to 28.0 +/- 5.1 mu m (P = 0.024) and the red-to-green particle distance to remain unchanged (30.2 +/- 5.7 mu m [red]; 31.5 +/- 10.0 mu m [green] [n.s.]). We conclude that hemorrhage caused a progressive increase in interalveolar perfusion maldistribution over 45 min that did not correspond to reduced arterial pressures or altered blood gases. Our particle distance measurements led us to further conclude that this maldistribution occurred in areas that were perfused at 15 min rather than in previously unperfused areas. C1 [Conhaim, Robert L.; Kluesner, Karr A.; Watson, Kai E.; Munoz-del-Rio, Alejandro; Heisey, Dennis M.; Harms, Bruce A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. [Conhaim, Robert L.; Kluesner, Karr A.; Watson, Kai E.; Munoz-del-Rio, Alejandro; Heisey, Dennis M.; Harms, Bruce A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Conhaim, RL (reprint author), H5-301-BX3236,600 Highland Ave, Madison, WI 53792 USA. EM conhaim@surgery.wisc.edu NR 19 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD MAR PY 2008 VL 29 IS 3 BP 410 EP 416 DI 10.1097/shk.0b013618145042 PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 265VZ UT WOS:000253391100016 PM 17704732 ER PT J AU Sheah, K Ouellette, HA Torriani, M Nielsen, GP Kattapuram, S Bredella, MA AF Sheah, Kenneth Ouellette, Hugue A. Torriani, Martin Nielsen, G. Petur Kattapuram, Susan Bredella, Miriam A. TI Metastatic myxoid liposarcomas: imaging and histopathologic findings SO SKELETAL RADIOLOGY LA English DT Article DE myxoid liposarcoma; metastasis; magnetic resonance imaging; positron emission tomography; computed tomography ID SOFT-TISSUE TUMORS; OF-THE-LITERATURE; SKELETAL METASTASES; TLS-CHOP; EXTREMITY AB Objective The objective was to describe the imaging and histopathologic characteristics of metastatic myxoid liposarcomas. Materials and methods This retrospective study was approved by the institutional review board and complied with HIPAA guidelines. The study group comprised 12 patients with metastatic myxoid liposarcoma who underwent MRI, CT, or FDG-PET. The location and imaging characteristics of the metastatic lesions were recorded, and the histopathology of all metastatic lesions was reviewed. Results There were 23 histologically proven metastases in 12 patients. Based on imaging criteria, there were 41 metastases. The mean time from the diagnosis of primary tumor to the first metastasis was 4.4 years. Sixty-seven percent of patients had bone and soft tissue metastases, 33% had pulmonary metastases, 33% had liver metastases, 25% had intra-abdominal, and 16% retroperitoneal metastases. CT demonstrated well-defined lobulated masses with soft tissue attenuation in all cases, without macroscopic fat component. In cases of osseous metastases, CT showed mixed lytic and sclerotic foci, with bone destruction in advanced cases. MRI demonstrated fluid-like signal intensity with mild heterogeneous enhancement in cases of soft tissue metastases. In osseous metastases, MRI showed avid heterogeneous enhancement. FDG-PET showed no significant FDG uptake for all metastases. MRI was the most useful imaging modality for osseous and soft tissue metastases. Conclusion Myxoid liposarcomas are soft tissue sarcomas, with a high prevalence of extrapulmonary metastases. The bones and soft tissues were the most common site of involvement, followed by the lungs and liver. MRI was the most sensitive modality in the detection of osseous and soft tissue metastases, and is the recommended modality for the diagnosis and follow-up of bone and soft tissue involvement. C1 [Sheah, Kenneth; Ouellette, Hugue A.; Torriani, Martin; Kattapuram, Susan; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sheah, Kenneth] Singapore Gen Hosp, Dept Radiol, Singapore 169608, Singapore. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,YAW 6E, Boston, MA 02114 USA. EM mbredella@partners.org NR 21 TC 29 Z9 33 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 2008 VL 37 IS 3 BP 251 EP 258 DI 10.1007/s00256-007-0424-1 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 255SI UT WOS:000252677300010 PM 18097662 ER PT J AU Brzczinski, WA Basile, J AF Brzczinski, Walter A. Basile, Jan TI Effect of angiotensin receptor blockade and anti hypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: A randomized trial SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material C1 [Brzczinski, Walter A.; Basile, Jan] Med Univ S Carolina, Dept Med, Ralph H Johnson VA Med Ctr, Div Gen Internal Med,Primary Care Serv Line, Charleston, SC 29401 USA. RP Basile, J (reprint author), Med Univ S Carolina, Dept Med, Ralph H Johnson VA Med Ctr, Div Gen Internal Med,Primary Care Serv Line, 109 Bee St, Charleston, SC 29401 USA. 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 0038-4348 J9 SOUTH MED J JI South.Med.J. PD MAR PY 2008 VL 101 IS 3 BP 220 EP 221 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 272OI UT WOS:000253868700002 ER PT J AU Benisty, S Hernandez, K Viswanathan, A Reyes, S Kurtz, A O'Sullivan, M Bousser, MG Dichgans, M Chabriat, H AF Benisty, Sarah Hernandez, Karen Viswanathan, Anand Reyes, Sonia Kurtz, Annie O'Sullivan, Michael Bousser, Marie-Germaine Dichgans, Martin Chabriat, Hugues TI Diagnostic criteria of vascular dementia in CADASIL SO STROKE LA English DT Article DE CADASIL; diagnostic criteria; leukoariosis; vascular dementia ID COGNITIVE IMPAIRMENT; NINDS-AIREN; CLINICAL-CRITERIA; INSTRUMENTAL ACTIVITIES; LACUNAR LESIONS; DSM-IV; DISEASE; STROKE; MRI; DISABILITY AB Background and Purpose - Subcortical ischemic vascular dementia ( SIVD) is a major subtype of vascular dementia ( VaD). Recently, the diagnostic criteria of VaD have been modified to encompass this entity. Application of these criteria in CADASIL, a genetic model of SIVD, may help to better assess their significance. The aim of this study was to compare different sets of diagnostic criteria of VaD in a population of CADASIL patients. Methods - Different sets of diagnostic criteria of VaD ( DSMIV, ICD10, standard NINDS-AIREN, modified NINDS-AIREN for SIVD) were applied to 115 CADASIL patients. Diagnosis of VaD was made through 2 steps: ( 1) diagnosis of dementia and ( 2) association of dementia to lesions of vascular origin. The percentage of patients satisfying the different sets and the concordance between these criteria was analyzed. Results - At least 1 set of criteria was satisfied for diagnosis in 29 subjects with dementia. In this group of patients, the sensitivity of the DSM IV, ICD 10, and standard NINDS-AIREN criteria for VaD was, respectively, 79%, 72%, and 45%. In contrast, the sensitivity of the NINDS-AIREN criteria for SIVD was 90%. The incomplete sensitivity of these last criteria was related to the absence of focal signs in some patients. The neuroimaging criteria were satisfied in all patients with dementia. Conclusions - The modified NINDS-AIREN criteria of SIVD are the most sensitive VaD criteria in CADASIL. Among these criteria, the neuroimaging criteria, although poorly specific to dementia, have a complete sensitivity. In contrast, focal signs were inconstant in CADASIL patients with dementia. C1 [Hernandez, Karen; Reyes, Sonia; Kurtz, Annie; Bousser, Marie-Germaine; Chabriat, Hugues] Univ Paris 07, Dept Neurol, F-75010 Paris, France. [Benisty, Sarah] Univ Paris 07, Dept Geriatr Med, Paris, France. [Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Viswanathan, Anand] Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. [Viswanathan, Anand] Harvard Univ, Sch Med, Boston, MA 02115 USA. [O'Sullivan, Michael; Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. RP Chabriat, H (reprint author), Univ Paris 07, Dept Neurol, 2 Rue Ambroise Pare, F-75010 Paris, France. EM hugues.chabriat@lrb.aphp.fr RI O'Sullivan, Michael/A-1796-2010; Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 NR 39 TC 17 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2008 VL 39 IS 3 BP 838 EP 844 DI 10.1161/STROKEAHA.107.490672 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 267XP UT WOS:000253542800017 PM 18258841 ER PT J AU Hjort, N Wu, O Ashkanian, M Solling, C Mouridsen, K Christensen, S Gyldensted, C Andersen, G Ostergaard, L AF Hjort, Niels Wu, Ona Ashkanian, Mahmoud Solling, Christine Mouridsen, Kim Christensen, Soren Gyldensted, Carsten Andersen, Grethe Ostergaard, Leif TI MRI detection of early blood-brain barrier disruption - Parenchymal enhancement predicts focal hemorrhagic transformation after thrombolysis SO STROKE LA English DT Article DE blood brain barrier; brain infarction; imaging; intracerebral hemorrhage; MRI; thrombolysis ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC-STROKE AB Background and Purpose - Blood-brain barrier disruption may be a predictor of hemorrhagic transformation (HT) in ischemic stroke. We hypothesize that parenchymal enhancement (PE) on postcontrast T1-weighted MRI predicts and localizes subsequent HT. Methods - In a prospective study, 33 tPA-treated stroke patients were imaged by perfusion-weighted imaging, T1 and FLAIR before thrombolytic therapy and after 2 and 24 hours. Results - Postcontrast T1 PE was found in 5 of 32 patients (16%) 2 hours post-thrombolysis. All 5 patients subsequently showed HT compared to 11 of 26 patients without PE (P = 0.043, specificity 100%, sensitivity 31%), with exact anatomic colocation of PE and HT. Enhancement of cerebrospinal fluid on FLAIR was found in 4 other patients, 1 of which developed HT. Local reperfusion was found in 4 of 5 patients with PE, whereas reperfusion was found in all cases of cerebrospinal fluid hyperintensity. Conclusions - PE detected 2 hours after thrombolytic therapy predicts HT with high specificity. Contrast-enhanced MRI may provide a tool for studying HT and targeting future therapies to reduce risk of hemorrhagic complications. C1 [Hjort, Niels; Wu, Ona; Ashkanian, Mahmoud; Solling, Christine; Mouridsen, Kim; Christensen, Soren; Gyldensted, Carsten; Ostergaard, Leif] Aarhus Univ Hosp, Ctr Functionally Integrat Neurosci, Dept Neuroradiol, DK-8000 Aarhus C, Denmark. [Hjort, Niels; Andersen, Grethe] Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus, Denmark. [Wu, Ona] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Hjort, N (reprint author), Aarhus Univ Hosp, Ctr Functionally Integrat Neurosci, Dept Neuroradiol, Norrebrogade 44,Bldg 30, DK-8000 Aarhus C, Denmark. EM niels@pet.auh.dk RI Mouridsen, Kim/B-2104-2008; Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 NR 8 TC 59 Z9 64 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2008 VL 39 IS 3 BP 1025 EP 1028 DI 10.1161/STROKEAHA.107.497719 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 267XP UT WOS:000253542800044 PM 18258832 ER PT J AU Locicero, A Sinclair, SJ AF Locicero, Alice Sinclair, Samuel J. TI Terrorism and terrorist leaders: Insights from developmental and ecological psychology SO STUDIES IN CONFLICT & TERRORISM LA English DT Article ID SUICIDE TERRORISM AB A recent increase in terrorist actions where the terrorist's death is planned and intentional has raised interest in the psychological functioning, motivation, and reasoning of those who engage in terrorism and those who support it. No consensus exists among Western] psychologists regarding terrorists who plan to die in their attack, and no Western psychological perspective has thus far contributed substantively to explaining or predicting it. Although most agree that groups engaging in such actions typically have a wider network of support, the psychology of supporters is also unexplained. This article proposes a developmental psychological model of the conditions that favor focused terrorist actions that have publicly discernible goals ascribed to a political or religious cause. The article describes a common pattern of cognitive complexity among terrorist leaders, using Osama bin Laden as a model, where entrenched cognitive simplicity in one key ideological domain (religious or political) is coupled with behavior reflecting the capacity for far greater complexity in other domains (organizational skills, planning, problem-solving.) This pattern, in specifiable historical and ecological context, makes terrorist tactics, including those in which the attacker intentionally dies, more likely, and increases the challenges associated with attempts at diplomacy or negotiated peace. C1 [Sinclair, Samuel J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Sinclair, Samuel J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Locicero, Alice] Endicott Coll, Social Sci Div, Beverly, MA USA. RP Sinclair, SJ (reprint author), 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM jsincl@post.harvard.edu NR 62 TC 5 Z9 5 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1057-610X J9 STUD CONFL TERROR JI Stud. Confl. Terror. PD MAR PY 2008 VL 31 IS 3 BP 227 EP 250 DI 10.1080/10576100701879638 PG 24 WC International Relations; Political Science SC International Relations; Government & Law GA 273BN UT WOS:000253905500004 ER PT J AU Pennell, NA Daniels, GH Haddad, RI Ross, DS Evans, T Wirth, LJ Fidias, PH Temel, JS Gurubhagavatula, S Heist, RS Clark, JR Lynch, TJ AF Pennell, Nathan A. Daniels, Gilbert H. Haddad, Robert I. Ross, Douglas S. Evans, Tracey Wirth, Lori J. Fidias, Panos H. Temel, Jennifer S. Gurubhagavatula, Sarada Heist, Rebecca Suk Clark, John R. Lynch, Thomas J. TI A phase II study of gefitinib in patients with advanced thyroid cancer SO THYROID LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; DOXORUBICIN PLUS CISPLATIN; SOLID TUMORS; CARCINOMA; TRIAL; CHEMOTHERAPY; COMBINATION; MUTATIONS; PAPILLARY AB Objective: To determine the efficacy of gefitinib in patients with advanced thyroid cancer. Design: In this open-label phase II trial, 27 patients with radioiodine-refractory, locally advanced, or metastatic thyroid cancer were treated with 250mg of daily gefitinib. Histologic subtypes included papillary (41%), follicular (22%), anaplastic (19%), medullary (15%), and Hurthle cell carcinomas (4%). The primary endpoint was overall response rate. Secondary endpoints were toxicity, progression-free survival (PFS), and overall survival (OS). Main outcomes: There were no objective responses among the 25 patients evaluated. After 3, 6, and 12 months of treatment, 48%, 24%, and 12% of patients had stable disease (SD), respectively. Median PFS and OS were 3.7 and 17.5 months, respectively. Five patients with SD had a decrease in thyroglobulin (Tg) to < 90% of baseline that was maintained for at least 3 months. Conclusions: Although gefitinib therapy did not result in any tumor responses, 32% of patients had reductions in tumor volume that did not meet criteria for partial response rate. Along with falling Tg levels and prolonged SD in a subset of patients, this may indicate biologic activity. C1 [Pennell, Nathan A.; Daniels, Gilbert H.; Ross, Douglas S.; Fidias, Panos H.; Temel, Jennifer S.; Gurubhagavatula, Sarada; Heist, Rebecca Suk; Clark, John R.; Lynch, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Haddad, Robert I.; Wirth, Lori J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Evans, Tracey] Univ Penn, Philadelphia, PA 19104 USA. RP Pennell, NA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,POB Room 221, Boston, MA 02114 USA. EM npennell@partners.org NR 32 TC 116 Z9 123 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAR PY 2008 VL 18 IS 3 BP 317 EP 323 DI 10.1089/thy.2007.0120 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282PN UT WOS:000254579800008 PM 17985985 ER PT J AU Davis, A Mandal, R Johnson, M Makar, R Stowell, C Dzik, S AF Davis, Amanda Mandal, Rajni Johnson, Matthew Makar, Robert Stowell, Christopher Dzik, Sunny TI A touch of TRALI SO TRANSFUSION LA English DT Article ID ACUTE LUNG INJURY; LOOK-BACK; CIRCULATORY OVERLOAD; LEUKOCYTE ANTIBODIES; RECIPIENTS; DONORS; BLOOD AB Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-associated morbidity and mortality. The National Heart, Lung, and Blood Institute (NHLBI) and Canadian Consensus Conference definitions of TRALI exclude cases of mild TRALI. As a result, many cases of mild TRALI are likely to be missed. Three cases are reported in which patients experienced the acute onset of breathlessness in association with transfusion of blood components containing human leukocyte antigen (HLA) antibodies reactive with recipient HLA antigens. Despite the sudden onset of a pulmonary syndrome in association with transfusion, clinicians caring for these patients did not consider TRALI, and no case would meet recent consensus definitions. Nevertheless, supporting clinical and serologic evidence for TRALI was found in each case. Benefits in recognizing mild cases of TRALI include quantifying the true incidence of TRALI, understanding the physiology of mild versus severe TRALI, and preventing subsequent cases of TRALI due to donors found to have HLA antibodies. C1 [Davis, Amanda; Mandal, Rajni; Johnson, Matthew; Makar, Robert; Stowell, Christopher; Dzik, Sunny] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. RP Davis, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, 55 Fruit St,GRJ 148, Boston, MA 02114 USA. EM akdavis@partners.org NR 14 TC 31 Z9 34 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2008 VL 48 IS 3 BP 541 EP 545 DI 10.1111/j.1537-2995.2007.01567.x PG 5 WC Hematology SC Hematology GA 267CA UT WOS:000253484900019 PM 18067496 ER PT J AU Surman, OS Saidi, R Purtilo, R Simmerling, M Ko, D Burke, TF AF Surman, O. S. Saidi, R. Purtilo, R. Simmerling, M. Ko, D. Burke, T. F. TI The market of human organs: A window into a poorly understood global business SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Joint Meeting of the International-Xenotransplantation-Association/International-Pancreas-and -Islet-Transplant-Association/Cell-Transplant-Society CY SEP 15-20, 2007 CL Minneapolis, MN SP Int Xenotransplantat Assoc, Int Pancreas & Islet Transplant Assoc, Cell Transplant Soc ID UNRELATED KIDNEY DONORS; LIVER-TRANSPLANTATION; IRANIAN MODEL; UNITED-STATES; DONATION; CHINA; PAID AB The global demand for human organs has set the stage, for an exploding and poorly understood global business in human organs. Whenever there is demand for a product, the opportunity for business arises. The form that a business takes is dependent on a complex network of inputs and outputs, each affecting the others. Historically, the details of any specific market are drastically underestimated. Nowhere is this truer than in the market of human organs. The drivers, which propel the "goods" of human organs, form a flourishing business. Critical analysis is essential to understanding of the supply and demand sides and to determine the role of government in regulating the industry. Governmental groups have dismissed formation of a regulated market for organ sales. The concept is nonetheless a topic of active discussion, motivated by the suffering of patients in need of organs and exploitation of the victims of human trafficking. Ethical principles have been invoked on each side of the ensuing debate. Theory in the absence of sufficient data is shaky ground for enactment of new policy. The Aristotelian concept of "practical wisdom" and the pragmatism of William James illuminate the importance of scientific investigation as guide to policy formation. How will stakeholders benefit or lose? What impact might be anticipated in regard to organized medicine's social contract? What can we learn about cross-cultural differences and their effect on the global landscape? C1 [Surman, O. S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Burke, T. F.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Surman, O. S.; Saidi, R.; Ko, D.] Massachusetts Gen Hosp, Transplantat Serv, Boston, MA 02114 USA. [Purtilo, R.] Yale Univ, Dept Bioeth, New Haven, CT 06520 USA. [Simmerling, M.] Cornell Univ, CECT, Ithaca, NY 14853 USA. [Simmerling, M.] Cornell Univ, Dept Bioeth, Ithaca, NY 14853 USA. RP Surman, OS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 29 TC 3 Z9 3 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD MAR PY 2008 VL 40 IS 2 BP 491 EP 493 DI 10.1016/j.transproceed.2008.02.019 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 284GT UT WOS:000254695600052 PM 18374111 ER PT J AU Diswall, M Angstrom, J Schuurman, HJ Dor, FJMF Rydberg, L Breimer, ME AF Diswall, M. Angstroem, J. Schuurman, H. -J. Dor, F. J. M. F. Rydberg, L. Breimer, M. E. TI Glycolipid studies in small intestine and pancreas of alpha 1,3-galactosyltransferase knockout miniature swine: alpha 1,3GALT-KO animals lack alpha GAL antigens and contain novel blood group H compounds SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Joint Meeting of the International-Xenotransplantation-Association/International-Pancreas-and -Islet-Transplant-Association/Cell-Transplant-Society CY SEP 15-20, 2007 CL Minneapolis, MN SP Int Xenotransplantat Assoc, Int Pancreas & Islet Transplant Assoc, Cell Transplant Soc ID PIGS; BABOONS; DONORS AB Background. To avoid hyperacute rejection of xeno-organs, alpha 1,3-galactosyltransferase knock-out (GalT-KO) pigs have been produced. However, Gal alpha 1,3Gal (Gal) determinant elimination may expose cryptic carbohydrate antigens and/or generate new antigens that might interfere with the human immune response. Methods. Glycolipids isolated from small intestine and pancreas of two GalT-KO and one wild-type (WT) pig were tested for immune reactivity with antibodies on thin-layer chromatograms after separation by high-performance liquid chromatography, and selected fractions were analysed by proton NMR spectroscopy. Results. Immunostaining using purified human anti-Gal Abs revealed that tissues from WT animals express large amounts of Gal-antigens whereas GalT-KO tissues lacked these antigens. Proton NMR spectroscopy on small intestine fractions revealed both linear and branched nona- and decaglycosylceramides, respectively, with terminal Gal-epitopes. In corresponding GalT-KO fractions, Gal-epitopes seemed to be replaced by terminal alpha 1,2fucoses. Two novel branched blood group H compounds was found in the GalT-KO intestine. Conclusions. The structural complexity of alpha Gal-terminating antigens in the WT organs is very high. Knockout of alpha 1,3GalT by gene-targeting results in elimination of Gal-determinants. In addition structurally novel alpha 1,2fucose-terminated blood group H compounds were identified in the GalT-KO tissue. These compounds are not expected to be recognized by the human immune system. C1 [Diswall, M.; Rydberg, L.] Sahlgrens Univ Hosp, Dept Clin Chem & Transfus Med, S-41345 Gothenburg, Sweden. [Diswall, M.; Angstroem, J.; Breimer, M. E.] Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden. [Schuurman, H. -J.] Immerge Biotherapeut Inc, Cambridge, MA USA. [Dor, F. J. M. F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Dor, F. J. M. F.] Erasmus MC, Dept Surg, Rotterdam, Netherlands. RP Diswall, M (reprint author), Sahlgrens Univ Hosp, Dept Clin Chem & Transfus Med, Campus Sahlgrenska, S-41345 Gothenburg, Sweden. EM mette.diswall@gu.se RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 10 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD MAR PY 2008 VL 40 IS 2 BP 543 EP 546 DI 10.1016/j.transproceed.2008.01.032 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 284GT UT WOS:000254695600065 PM 18374124 ER PT J AU Lohse, MJ Nikolaev, VO Hein, P Hoffmann, C Vilardaga, JP Bunemann, M AF Lohse, Martin J. Nikolaev, Viacheslav O. Hein, Peter Hoffmann, Carsten Vilardaga, Jean-Pierre Buenemann, Moritz TI Optical techniques to analyze real-time activation and signaling of G-protein-coupled receptors SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID RESONANCE ENERGY-TRANSFER; HETEROTRIMERIC G-PROTEINS; BETA-ADRENERGIC-RECEPTOR; LIVING CELLS; CYCLIC-AMP; CARDIAC MYOCYTES; LIVE CELLS; SUBUNIT DISSOCIATION; ADENYLATE-CYCLASE; EPAC ACTIVATION AB The activation of G-protein-coupled receptors (GPCRs) is traditionally measured either by monitoring downstream physiological events or by membrane-based biochemical assays. Neither of these approaches permits detailed kinetic or spatial analysis of receptor activation and signaling. Recently, several optical techniques have been developed to monitor receptor activation either by using purified reconstituted GPCRs or by observing GPCRs, G proteins and second messengers in intact cells. These techniques are providing, literally, new views on both the mechanistic basis of the signaling process and the kinetic and spatial properties of GPCR-mediated signals. They suggest that agonists can activate GPCRs within milliseconds, that different compounds can induce distinct active conformations of GPCRs, that G-protein activation is the rate-limiting step in GPCR signaling, and that cellular signals can be temporally and spatially confined. They are also raising controversial issues, such as whether or not receptors and G proteins are pre-coupled and whether G proteins dissociate during activation. C1 [Lohse, Martin J.; Nikolaev, Viacheslav O.; Hein, Peter; Hoffmann, Carsten; Vilardaga, Jean-Pierre; Buenemann, Moritz] Univ Wurzburg, Inst Pharmacol & Toxicol, D-97078 Wurzburg, Germany. [Lohse, Martin J.; Nikolaev, Viacheslav O.] Univ Wurzburg, DFG Res Ctr Expt Biomed, Rudolf Virchow Ctr, D-97078 Wurzburg, Germany. [Hein, Peter] Univ Calif San Francisco, Dept Pharmacol & Psychiat, San Francisco, CA 94158 USA. [Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Ctr Syst Biol, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lohse, MJ (reprint author), Univ Wurzburg, Inst Pharmacol & Toxicol, D-97078 Wurzburg, Germany. EM lohse@toxi.uni-wuerzburg.de RI Lohse, Martin/A-7160-2012; Hein, Peter/A-7477-2008 OI Lohse, Martin/0000-0002-0599-3510; Hein, Peter/0000-0002-5899-3979 NR 76 TC 86 Z9 87 U1 0 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAR PY 2008 VL 29 IS 3 BP 159 EP 165 DI 10.1016/j.tips.2007.12.002 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 284QW UT WOS:000254721900007 PM 18262662 ER PT J AU Albert, M Song, JS Schultz, D Cormack, RA Ternpany, CM Haker, S Devlin, PM Beard, C Hurwitz, MD Suh, WW Jolesz, F D'Amico, AV AF Albert, Michele Song, Jun S. Schultz, Delray Cormack, Robert A. Ternpany, Clare M. Haker, Steve Devlin, Phillip M. Beard, Clair Hurwitz, Mark D. Suh, Wonsuk W. Jolesz, Ferenc D'Amico, Anthony V. TI Defining the rectal dose constraint for permanent radioactive seed implantation of the prostate SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE prostate cancer; brachytherapy; quality of life ID EXTERNAL-BEAM RADIATION; INTERSTITIAL BRACHYTHERAPY; GASTROINTESTINAL TOXICITY; SELECT PATIENTS; CANCER; THERAPY; COMPLICATIONS; MORBIDITY AB Purpose: This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy. Methods and materials: Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent 1 1 25 radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test. Results: There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment. Conclusions: Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I-125 permanent prostate brachy mono-therapy. Published by Elsevier Inc. C1 [Albert, Michele; Song, Jun S.; Cormack, Robert A.; Devlin, Phillip M.; Beard, Clair; Hurwitz, Mark D.; Suh, Wonsuk W.; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Albert, Michele; Song, Jun S.; Cormack, Robert A.; Ternpany, Clare M.; Haker, Steve; Devlin, Phillip M.; Beard, Clair; Hurwitz, Mark D.; Suh, Wonsuk W.; Jolesz, Ferenc; D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ternpany, Clare M.; Haker, Steve; Jolesz, Ferenc] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Schultz, Delray] Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. RP Albert, M (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM malbert@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 FU NCI NIH HHS [R25 CA089017] NR 21 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAR-APR PY 2008 VL 26 IS 2 BP 147 EP 152 DI 10.1016/j.urolonc.2007.03.026 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 274ZO UT WOS:000254041500006 PM 18312933 ER PT J AU Ruger, JP Emmons, KM AF Ruger, Jennifer Prah Emmons, Karen M. TI Economic evaluations of smoking cessation and relapse prevention programs for pregnant women: A systematic review SO VALUE IN HEALTH LA English DT Review DE economic evaluations; pregnant women; relapse prevention; smoking cessation; systematic review ID COST-EFFECTIVENESS ANALYSIS; HEALTH-EDUCATION; UTILITY ANALYSES; SERVICES; BENEFIT; QUALITY; GUIDELINES; OUTCOMES; HMO AB Objective: Smoking cessation and relapse prevention during and after pregnancy reduces the risk of adverse maternal and infant health outcomes, but the economic evaluations of such programs have not been systematically reviewed. This study aims to critically assess economic evaluations of smoking cessation and relapse prevention programs for pregnant women. Methods: All relevant English-language articles were identified using PubMed (January 1966-2003), the British National Health Service Economic Evaluation Database, and reference lists of key articles. Economic evaluations of smoking cessation and relapse prevention among pregnant women were reviewed. Fifty-one articles were retrieved, and eight articles were included and evaluated. A single reviewer extracted methodological details, study designs, and outcomes into summary tables. All studies were reviewed, and study quality was judged using the criteria recommended by the Panel on Cost-Effectiveness in Health and Medicine and the British Medical Journal (BMJ) checklist for economic evaluations. Results: The search retrieved 51 studies. No incremental cost-effectiveness studies or cost-utility studies were found. A narrative synthesis was conducted on the eight studies thatmet the inclusion criteria. Roughly one-third employed cost-benefit analyses (CBA). Those conducting CBA have found favorable benefit-cost ratios of up to 3:1; for every dollar invested $3 are saved in downstream health-related costs. Conclusions: CBA suggests favorable cost-benefit ratios for smoking cessation among pregnant women, although currently available economic evaluations of smoking cessation and relapse prevention programs for pregnant women provide limited evidence on cost-effectiveness to determine optimal resource allocation strategies. Although none of these studies had been performed in accordance with Panel recommendations or BMJ guidelines, they are, however, embryonic elements of a more systematic framework. Existing analyses suggest that the return on investment will far outweigh the costs for this critical population. There is significant potential to improve the quality of economic evaluations of such programs; therefore, additional analyses are needed. The article concludes with ideas on how to design and conduct an economic evaluation of such programs in accordance with accepted quality standards. C1 [Ruger, Jennifer Prah] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Emmons, Karen M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Ruger, JP (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St,POB 208034, New Haven, CT 06520 USA. EM jennifer.ruger@yale.edu FU NCI NIH HHS [R01 CA073242, R01 CA073242-04]; NIDA NIH HHS [K01 DA016358, K01 DA016358-01] NR 27 TC 24 Z9 24 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAR-APR PY 2008 VL 11 IS 2 BP 180 EP 190 DI 10.1111/j.1524-4733.2007.00239.x PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 282JR UT WOS:000254564300007 PM 17854435 ER PT J AU Ruger, JP Weinstein, MC Hammond, SK Kearney, MH Emmons, KM AF Ruger, Jennifer Prah Weinstein, Milton C. Hammond, S. Katherine Kearney, Margaret H. Emmons, Karen M. TI Cost-effectiveness of motivational interviewing for smoking cessation and relapse prevention among low-income pregnant women: A randomized controlled trial SO VALUE IN HEALTH LA English DT Article DE cost-effectiveness; low-income; pregnant women; relapse prevention; smoking cessation ID SMOKERS; POSTPARTUM; PROGRAM; STRATEGIES; BENEFIT; HMO AB Objective: Low-income women have high rates of smoking during pregnancy, but little is known about the costs, benefits, and cost-effectiveness of motivational interviewing (MI), focused on the medical and psychosocial needs of this population, as an intervention for smoking cessation and relapse prevention. Methods: A sample of 302 low-income pregnant women was recruited from multiple obstetrical sites in the Boston metropolitan area into a randomized controlled trial of a motivational intervention for smoking cessation and relapse prevention versus usual care (UC). The findings of this clinical trial were used to estimate the costs, benefits, and cost-effectiveness of the intervention from a societal perspective, incorporating published quality-adjusted life-year (QALY) and life-year (LY) estimates. Outcomes included smoking cessation and relapse, maternal and infant outcomes, economic costs, LYs and QALYs saved, and incremental cost-effectiveness ratios. Results: The cost-effectiveness of MI for relapse prevention compared to UC was estimated to be $851/LY saved and $628/QALY saved. Including savings in maternal medical costs in sensitivity analyses resulted in cost savings for MI for relapse prevention compared to UC. For smoking cessation, MI cost more but did not provide additional benefit compared to UC. In one-way sensitivity analyses, the incremental cost-effectiveness of MI versus UC would have been $117,100/LY saved and $86,300/QALY saved if 8% of smokers had quit. In two-way sensitivity analyses, MI was still relatively cost-effective for relapse prevention ($17,300/QALY saved) even if it cost as much as $2000/participant and was less effective. For smoking cessation, however, a higher level of effectiveness (9/110) and higher cost ($400/participant) resulted in higher incremental cost-effectiveness ratios ($112,000/QALY). Conclusions: Among low-income pregnant women, MI helps prevent relapse at relatively low cost, and may be cost-saving when net medical cost savings are considered. For smoking cessation, MI cost more but provided no additional benefit compared to UC, but might offer benefits at costs comparable to other clinical preventive interventions if 8-10% of smokers are induced to quit. C1 [Ruger, Jennifer Prah] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Weinstein, Milton C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Weinstein, Milton C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hammond, S. Katherine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Kearney, Margaret H.] Univ Rochester, Sch Nursing, Rochester, NY USA. [Emmons, Karen M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Ruger, JP (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St,POB 208034, New Haven, CT 06520 USA. EM jennifer.ruger@yale.edu OI Kearney, Margaret H/0000-0002-2671-7662 FU NCI NIH HHS [R01 CA073242, R01 CA073242-04]; NIDA NIH HHS [K01 DA016358, K01 DA016358-01] NR 33 TC 35 Z9 35 U1 2 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAR-APR PY 2008 VL 11 IS 2 BP 191 EP 198 DI 10.1111/j.1524-4733.2007.00240.x PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 282JR UT WOS:000254564300008 PM 17854434 ER PT J AU Stokes, ME Thompson, D Montoya, EL Weinstein, MC Winer, EP Earle, CC AF Stokes, Michael E. Thompson, David Montoya, Eduardo L. Weinstein, Milton C. Winer, Eric P. Earle, Craig C. TI Ten-year survival and cost following breast cancer recurrence: Estimates from SEER-Medicare data SO VALUE IN HEALTH LA English DT Article; Proceedings Paper CT 10th Annual International Meeting of the International-Society-for-Pharmacoeconomics-and-Outcomes-Research CY MAY 15-18, 2005 CL Washington, DC SP Int Soc Pharmacoecon & Outcomes Res DE breast cancer recurrence; costs; Kaplan-Meier Sample Average estimator; SEER-Medicare; survival ID RADIATION-THERAPY; STAGE; TAMOXIFEN; CLAIMS; TRIAL AB Objective: A variety of pharmacologic therapies are available or in development for the prevention of breast cancer recurrence. Assessing the value of these treatments is compromised by a paucity of data on the impact of recurrence on economic costs and survival. The purpose of this study was to shed light on these issues. Methods: We conducted a retrospective analysis of linked SEER-Medicare data. All patients in the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry who were diagnosed with nonmetastatic breast cancer during 1991-1993 were identified, and their subsequent Medicare claims were scanned for evidence of further breast cancer events (local or distant recurrence, contralateral breast cancer). Medicare claims were then scanned from the time of the event through 2002 to assess patterns of survival and costs. Results: We identified 10,798 patients in SEER who were diagnosed with nonmetastatic breast cancer during 1991-1993, including 1833 who subsequently had another breast cancer event (local recurrence, 958; distant recurrence, 622; contralateral breast cancer, 253). Median survival was 37 months and 8 months among patients with local and distant recurrence, respectively; 53% of patients with contralateral breast cancer remained alive after all the data were censored at 97 months. Expected 10-year costs (2004 US$, discounted 3%) attributable to distant recurrence, local recurrence, and contralateral breast cancer were $11,450 (SE 2056), $19,596 (SE 1754), and $19,183 (SE 4131), respectively. Conclusions: Breast cancer recurrence and contralateral breast cancer lead to substantial increases in costs, amounting to approximately $11,000-19,000 over 10 years depending on type. The impact of these events on survival also varies considerably by type. C1 [Stokes, Michael E.; Thompson, David; Montoya, Eduardo L.; Weinstein, Milton C.] i3 Innovus, Medford, MA USA. [Weinstein, Milton C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Winer, Eric P.; Earle, Craig C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Thompson, D (reprint author), i3 Innovus, 10 Cabot Rd,Suite 304, Medford, MA USA. EM david.thompson@i3innovus.com NR 20 TC 43 Z9 44 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAR-APR PY 2008 VL 11 IS 2 BP 213 EP 220 DI 10.1111/j.1524-4733.2007.00226.x PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 282JR UT WOS:000254564300011 PM 18380633 ER PT J AU Dominguez, EP Barshes, NR Sherman, V Albo, D Kougias, P Chen, C Sweeney, JF Lin, PH AF Dominguez, Edward P. Barshes, Neal R. Sherman, Vadim Albo, Daniel Kougias, Panagiotis Chen, Changyi Sweeney, John F. Lin, Peter H. TI Effect of catheter-directed arterial embolization and laparoscopic endovascular stapling on stapled vessel integrity in a porcine model SO VASCULAR LA English DT Article DE endovascular staplers; laparoscopic splenectomy; platinum coils; polyvinyl alcohol particles; polyvinyl alcohol embolization particle; splenic artery embolization ID ASSISTED SPLENECTOMY; CONTOUR EMBOLI; COMPLICATIONS; EXPERIENCE; OCCLUSION AB Arterial embolization is a frequently performed adjunctive maneuver prior to laparoscopic splenectomy or nephrectomy to facilitate laparoscopic dissection and reduce intraoperative bleeding. However, little is known regarding the effect of laparoscopic stapling across thrombosed vessels with imbedded embolic materials. This study analyzed the stapled line integrity by comparing visceral arteries treated with either platinum coils or polyvinyl alcohol (PVA) particles. Using a porcine model, 30 visceral vessels including splenic and renal arteries were treated with either coil or PVA embolization, which was followed by laparoscopic stapling. Vessel integrity and bursting pressure analysis was performed using an in vitro flow circuitry. The mean bursting pressure of the coil and the PVA group was 158 +/- 56 and 350 +/- 34 mm Hg, respectively (p < .001). The lowest bursting pressure in the coil and the PVA group was 70 and 280 mm Hg, respectively. The highest bursting pressure in the coil and the PVA group was 225 and 420 mm Hg, respectively. The bursting pressure in the splenic artery between the PVA and the coil group was 345 +/- 29 and 150 +/- 54 mm Hg, respectively (p < .001). Significant difference in the bursting pressure in the renal artery was noted in the PVA and the coil group, which was 350 +/- 40 and 160 +/- 40 mm Hg, respectively (p < .001). Our findings showed that preoperative coil embolization followed by laparoscopic vessel stapling sustained a poor busting pressure. Such a practice appears to be unsafe based on our findings and should be performed with caution in a clinical setting. C1 [Dominguez, Edward P.; Barshes, Neal R.; Sherman, Vadim; Albo, Daniel; Kougias, Panagiotis; Chen, Changyi; Lin, Peter H.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Dominguez, Edward P.; Barshes, Neal R.; Sherman, Vadim; Albo, Daniel; Kougias, Panagiotis; Chen, Changyi; Lin, Peter H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Sweeney, John F.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. RP Lin, PH (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Hauston VAMC 112,2002 Holcomb Blvd, Houston, TX 77030 USA. EM plin@bcm.edu FU NHLBI NIH HHS [HL076345] NR 20 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1708-5381 J9 VASCULAR JI Vascular PD MAR-APR PY 2008 VL 16 IS 2 BP 80 EP 84 DI 10.2310/6670.2008.00016 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 300QS UT WOS:000255840900003 PM 18377836 ER PT J AU Blankfield, RP Iftikhar, I Glickman, E Harris, NS AF Blankfield, Robert P. Iftikhar, Imran Glickman, Ellen Harris, N. Stuart TI Temperature and blood pressure following amlodipine overdose SO WILDERNESS & ENVIRONMENTAL MEDICINE LA English DT Article DE temperature; blood pressure; thermoregulatory-vascular remodeling ID HUMAN HYPERTENSION; INSULIN; SYSTEM AB The cardiovascular system participates in both blood pressure (BP) and temperature regulation. As a result, salt ingestion creates conflict between BP and temperature homeostasis, as vasodilatation that would promptly lower the BP would simultaneously increase cutaneous blood flow, thereby accelerating heat loss. If temperature homeostasis has precedence over blood pressure homeostasis, as postulated by the thermoregulatory-vascular remodeling (TVR) hypothesis, then in order to minimize heat loss, BP remains elevated following salt ingestion until the kidneys excrete the excess salt. A case of amlodipine overdose offered an opportunity to test a corollary of the TVR hypothesis: vasodilators should cause a drop in body temperature and/or an increase in the metabolic rate. Following the ingestion of 1000 mg of amlodipine, the temperature and BP of a single patient were monitored during the initial 36 hours and during the 13th day of hospitalization. The BP dropped markedly between the fifth and seventh hours postingestion, but then rose steadily and normalized by 28 hours postingestion. The temperature was normal at 7 hours postingestion, declined gradually between the seventh and 26th hours postingestion, stabilized between the 26th and 31st hours postingestion, then began to rise. During this case of amlodipine overdose, a modest temperature decline lagged behind a marked BP decline. As the BP rose, the temperature also rose, but lagged behind the BP increases. These findings suggest that there is a relationship between BP and temperature and are consistent with the TVR hypothesis. C1 [Harris, N. Stuart] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Harris, N. Stuart] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Glickman, Ellen] Kent State Univ, Exercise Sci Lab, Kent, OH 44242 USA. [Iftikhar, Imran] Cleveland Clin Syst, Fairview Hosp, Dept Internal Med, Cleveland, OH USA. [Blankfield, Robert P.] Case Western Reserve Univ, Sch Med, Dept Family Med, Cleveland, OH 44106 USA. [Blankfield, Robert P.] Univ Hosp Primary Care Phys Practice, Berea, OH USA. RP Blankfield, RP (reprint author), Berea Hlth Ctr, 201 Front St,Suite 101, Berea, OH 44017 USA. EM blankfield@roadrunner.com RI Iftikhar, Imran/I-7565-2015 NR 14 TC 1 Z9 1 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1080-6032 J9 WILD ENVIRON MED JI Wildern. Environ. Med. PD SPR PY 2008 VL 19 IS 1 BP 39 EP 41 DI 10.1580/07-WEME-CR-112.1 PG 3 WC Public, Environmental & Occupational Health; Sport Sciences SC Public, Environmental & Occupational Health; Sport Sciences GA 279PL UT WOS:000254367000007 PM 18333658 ER PT J AU Bates-Jensen, BM McCreath, HE Pongquan, V Apeles, NCR AF Bates-Jensen, Barbara M. McCreath, Heather E. Pongquan, Voranan Apeles, Neil Christopher R. TI Subepidermal moisture differentiates erythema and stage I pressure ulcers in nursing home residents SO WOUND REPAIR AND REGENERATION LA English DT Article ID BRADEN SCALE; PREDICTIVE-VALIDITY; RISK-FACTORS; SORE RISK; RELIABILITY; QUALITY; CARE; DIAGNOSIS; CLASSIFICATION; MULTISITE AB The objective of this descriptive cohort study was to examine the relationship between subepidermal moisture (SEM) and visual assessment of early pressure ulcers (PUs) in 31 nursing home (NH) residents residing in two NHs. Concurrent visual assessments and SEM were obtained at the sacrum, right and left trochanters, buttocks, and ischium weekly for 20 weeks. Visual assessment was rated as normal, erythema, stage I PU, or stage II+ PU. SEM, measured with a dermal phase meter where higher readings indicate greater SEM (range: 0-999 dermal phase units [DPU]), was modeled as a predictor of concurrent visual assessment of skin damage and erythema and stage I PUs at the sacrum 1 week later with covariate PU risk. Participants had a mean age of 84.1 years, were 83% female, 72% non-Hispanic white. SEM was lowest for normal skin (104 DPU, SD 114), higher for erythema (185 DPU, SD 138), stage I PUs (264 DPU, SD 208), and highest for stage II+ PUs (727 DPU, SD 287) across all sites (all p < 0.01). SEM was responsive to visual assessment changes, differentiated between erythema and stage I PU, and higher SEM predicted greater likelihood of erythema/stage I PU at the sacrum the next week (odds ratio=1.32 for every 100 DPU increase, p=0.03). SEM was associated with concurrent skin damage and future (1 week later) development of sacral erythema/stage I PUs. SEM differentiates between erythema and stage I PUs. SEM may assist in predicting early PU damage, allowing for earlier intervention to prevent PUs. C1 [Bates-Jensen, Barbara M.; Pongquan, Voranan] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Bates-Jensen, Barbara M.; McCreath, Heather E.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Bates-Jensen, Barbara M.] Vet Adm Greater Los Angeles Healthcare Syst, Ctr Clin, Los Angeles, CA USA. [Apeles, Neil Christopher R.] Valley Presbyterian Hosp, Van Nuys, CA USA. RP Bates-Jensen, BM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Sch Nursing, VA Greater Los Angeles,Clin Ctr,CWOCN, 5-594 Factor Bldg,700 Tiverton Ave, Los Angeles, CA 90095 USA. EM bbatesjensen@sonnet.ucla.edu NR 57 TC 13 Z9 14 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2008 VL 16 IS 2 BP 189 EP 197 DI 10.1111/j.1524-475X.2008.00359.x PG 9 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 271AJ UT WOS:000253761000008 PM 18318804 ER PT J AU Kevy, SV Jacobson, MS Heeschen, C AF Kevy, S. V. Jacobson, M. S. Heeschen, C. TI Composition of a bone marrow concentrate determines its regenerative effect: A comparative in vivo study SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 [Kevy, S. V.; Jacobson, M. S.] CBR, Inst Biomed Res, Boston, MA USA. [Heeschen, C.] Univ Munich, Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2008 VL 16 IS 2 MA 52 BP A24 EP A24 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 271AJ UT WOS:000253761000074 ER PT J AU Scherer, SS Pietramaggiori, G Matthews, J Perry, S Assmann, A Seth, A Demcheva, M Vournakis, JN Valeri, CR Hechtman, HB Orgill, DP AF Scherer, Sandra Saja Pietramaggiori, Giorgio Matthews, Jasmine Perry, Samuel Assmann, Anke Seth, Arun Demcheva, Marina Vournakis, John N. Valeri, C. Robert Hechtman, Herbert B. Orgill, Dennis P. TI Biodegradable poly-N-acetyl glucosamine (pGLcNAc) nanofibers enhance wound healing by activating cell migration, angiogenesis and cell proliferation SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 [Scherer, Sandra Saja; Pietramaggiori, Giorgio; Matthews, Jasmine; Perry, Samuel; Orgill, Dennis P.] Harvard Univ, Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. [Assmann, Anke] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Seth, Arun] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Demcheva, Marina; Vournakis, John N.] Marine Polymer Technol, Danvers, MA USA. [Valeri, C. Robert] Naval Blood Res Lab Inc, Boston, MA USA. [Hechtman, Herbert B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2008 VL 16 IS 2 MA 5 BP A11 EP A11 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 271AJ UT WOS:000253761000027 ER PT J AU Zhao, Z Mckee, CJ Kessl, JJ Santos, WL Daigle, JE Engelman, A Verdine, G Kvaratskhelia, M AF Zhao, Zhuojun McKee, Christopher J. Kessl, Jacques J. Santos, Webster L. Daigle, Janet E. Engelman, Alan Verdine, Gregory Kvaratskhelia, Mamuka TI Subunit-specific protein footprinting reveals significant structural Rearrangements and a role for N-terminal Lys-14 of HIV-1 integrase during viral DNA binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHOTO-CROSS-LINKING; INDUCED CONFORMATIONAL-CHANGE; REVERSE-TRANSCRIPTASE; STRAND TRANSFER; RETROVIRAL DNA; NUCLEOCAPSID PROTEIN; CRYSTAL-STRUCTURE; CATALYTIC CORE; ACTIVE-SITE AB To identify functional contacts between HIV-1 integrase ( IN) and its viral DNA substrate, we devised a new experimental strategy combining the following two methodologies. First, disulfide-mediated cross-linking was used to site-specifically link select core and C-terminal domain amino acids to respective positions in viral DNA. Next, surface topologies of free IN and IN-DNA complexes were compared using Lys-and Arg-selective small chemical modifiers and mass spectrometric analysis. This approach enabled us to dissect specific contacts made by different monomers within the multimeric complex. The footprinting studies for the first time revealed the importance of a specific N-terminal domain residue, Lys-14, in viral DNA binding. In addition, a DNA-induced conformational change involving the connection between the core and C-terminal domains was observed. Site-directed mutagenesis experiments confirmed the importance of the identified contacts for recombinant IN activities and virus infection. These new findings provided major constraints, enabling us to identify the viral DNA binding channel in the active full-length IN multimer. The experimental approach described here has general application to mapping interactions within functional nucleoprotein complexes. C1 [Zhao, Zhuojun; McKee, Christopher J.; Kessl, Jacques J.; Verdine, Gregory; Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Santos, Webster L.; Verdine, Gregory] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Daigle, Janet E.; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, Boston, MA 02115 USA. RP Kvaratskhelia, M (reprint author), Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, Ctr Comprehens Canc, Columbus, OH 43210 USA. EM kvaratskhelia.1@osu.edu RI Kessl, Jacques/J-6073-2015; OI Santos, Webster/0000-0002-4731-8548 FU NIAID NIH HHS [R01 AI062520, AI039394, AI062520, R01 AI039394, R37 AI039394]; NIGMS NIH HHS [F32 GM067380, F32 GM067380-03, R01 GM044853, R01 GM044853-15] NR 61 TC 40 Z9 41 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 29 PY 2008 VL 283 IS 9 BP 5632 EP 5641 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266IC UT WOS:000253426700043 PM 18093980 ER PT J AU Campanella, GSV Medoff, BD Manice, LA Colvin, RA Luster, AD AF Campanella, Gabriele S. V. Medoff, Benjamin D. Manice, Lindsay A. Colvin, Richard A. Luster, Andrew D. TI Development of a novel chemokine-mediated in vivo T cell recruitment assay SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE chemokines; cell trafficking; chemotaxis ID IFN-INDUCIBLE PROTEIN-10; RECEPTOR CXCR3; DIFFERENTIAL EXPRESSION; INFLAMMATORY RESPONSES; ALPHA-CHEMOATTRACTANT; ALLOGRAFT-REJECTION; MULTIPLE-SCLEROSIS; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; IP-10 AB Trafficking of leukocytes to sites of inflammation is an important step in the establishment of an immune response. Chemokines are critical regulators of leukocyte trafficking and are widely studied molecules for their important role in disease and for their potential as new therapeutic targets. The ability of chemokines to induce leukocyte recruitment has been mainly measured by in vitro chemotaxis assays, which lack many components of the complex biological process of leukocyte migration and therefore provide incomplete information about chemokine function in vivo. In vivo assays to study the activity of chemokines to induce leukocyte recruitment have been difficult to establish. We describe here the development of a robust in vivo recruitment assay for CD8(+) and CD4(+) T lymphocytes induced by the CXCR3 ligands IP-10 (CXCL10) and I-TAC (CXCL11). For this assay, in vitro activated T lymphocytes were adoptively transferred into the peritoneum of naive mice. Homing of these transferred T lymphocytes into the airways was measured following intratracheal instillation of chemokines. High recruitment indices were achieved that were dependent on chemokine concentration and CXCR3 expression on the transferred lymphocytes. Recruitment was also inhibited by antibodies to the chemokine. The assay models the natural condition of chemokine-mediated lymphocyte migration into the airways as chemokines are expressed in the airways during inflammation. The nature of this model allows flexibility to study wildtype and mutant chemokines and chemokine receptors and the ability to evaluate chemokine antagonists and antibodies in vivo. This assay will therefore help elucidate a deeper understanding of the chemokine system in vivo. (C) 2007 Elsevier B.V. All rights reserved. C1 [Campanella, Gabriele S. V.; Medoff, Benjamin D.; Manice, Lindsay A.; Colvin, Richard A.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Charlestown, MA 02129 USA. [Medoff, Benjamin D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Bldg 149,13th St, Charlestown, MA 02129 USA. EM aluster@mgh.harvard.edu FU NCI NIH HHS [R01 CA069212-11, R01 CA069212, R01 CA069212-10, R01 CA069212-12, R01 CA069212-13, R01-CA69212] NR 34 TC 15 Z9 15 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD FEB 29 PY 2008 VL 331 IS 1-2 BP 127 EP 139 DI 10.1016/j.jim.2007.12.002 PG 13 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 275GH UT WOS:000254059400012 PM 18206159 ER PT J AU Livingston, DM Silver, DP AF Livingston, David M. Silver, Daniel P. TI Cancer - Crossing over to drug resistance SO NATURE LA English DT Editorial Material ID CELLS C1 [Livingston, David M.; Silver, Daniel P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu; daniel_silver@dfci.harvard.edu NR 7 TC 16 Z9 18 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 28 PY 2008 VL 451 IS 7182 BP 1066 EP 1067 DI 10.1038/4511066a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 266RB UT WOS:000253453600030 PM 18305536 ER PT J AU Kinane, TB Grabowski, EF Sharma, A Nimkin, K King, ME Cornell, LD Fracchia, MS Harris, NL Harris, S Hales, CA AF Kinane, T. Bernard Grabowski, Eric F. Sharma, Amita Nimkin, Katherine King, Mary Etta Cornell, Lynn D. Fracchia, Mary Shannon Harris, Nancy Lee Harris, Scott Hales, Charles A. TI Case 7-2008: A 17-year-old girl with chest pain and hemoptysis - Membranous glomerulonephritis with the nephrotic syndrome and pulmonary embolus. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RIGHT-VENTRICULAR DYSFUNCTION; TISSUE-PLASMINOGEN ACTIVATOR; VENOUS THROMBOEMBOLISM; POSTTHROMBOTIC SYNDROME; FOLLOW-UP; NEPHROPATHY; CHILDREN; THROMBOSIS; THERAPY; THROMBOLYSIS C1 [Kinane, T. Bernard; Grabowski, Eric F.; Sharma, Amita; King, Mary Etta] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Nimkin, Katherine] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cornell, Lynn D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kinane, T. Bernard; Grabowski, Eric F.; Sharma, Amita; King, Mary Etta] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Nimkin, Katherine] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Cornell, Lynn D.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Kinane, TB (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 35 TC 1 Z9 1 U1 0 U2 5 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 FEB 28 PY 2008 VL 358 IS 9 BP 941 EP 952 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 266JD UT WOS:000253430200011 PM 18305270 ER PT J AU Gazdzinski, S Durazzo, TC Yeh, PH Hardin, D Banys, P Meyerhoff, DJ AF Gazdzinski, Stefan Durazzo, Timothy C. Yeh, Ping-Hong Hardin, Dawn Banys, Peter Meyerhoff, Dieter J. TI Chronic cigarette smoking modulates injury and short-term recovery of the medial temporal lobe in alcoholics SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE hippocampus; magnetic resonance imaging; magnetic resonance spectroscopy; abstinence from alcohol; learning and memory; recovery ID MAGNETIC-RESONANCE-SPECTROSCOPY; POSTTRAUMATIC-STRESS-DISORDER; CHRONIC ETHANOL-CONSUMPTION; ILLICIT STIMULANT ABUSERS; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; COGNITIVE PERFORMANCE; ABSTINENT ALCOHOLICS; ADULT NEUROGENESIS; METABOLITE CHANGES AB Memory function is largely mediated by the medial temporal lobe (MTL), and its compromise has been observed in alcohol dependence and chronic cigarette smoking. The effects of heavy alcohol consumption and chronic smoking on hippocampal volumes and MTL metabolites and their recovery during abstinence from alcohol have not been assessed. Mate alcoholics in treatment (ALC) [13 smokers (sALC) and 11 non-smokers (nsALC)] underwent quantitative magnetic resonance imaging and short-echo proton magnetic resonance spectroscopic imaging at I week and I month of sobriety. Outcome measures were compared with 14 age-matched, non-smoking light-drinkers and were related to visuospatial learning and memory. Over I month of abstinence, N-acetyl-aspartate, a neuronal marker, and membrane-associated choline-containing metabolites normalized in the MTL of nsALC subjects, but remained low in the MTL of sALC subjects. Metabolite concentration changes in both groups were associated with improvements in visuospatial memory. Hippocampal volumes increased in both groups during abstinence, but increasing volumes correlated with visuospatial memory improvements only in nsALC subjects. In summary, chronic cigarette stroking in alcohol-dependent men appears to have adverse effects on MTL metabolite recovery during short-term sobriety. These data may also have implications for other conditions with established MTL involvement and significant smoking co-morbidity, such as schizophrenia-spectrum and mood disorders. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Gazdzinski, Stefan; Durazzo, Timothy C.; Yeh, Ping-Hong; Hardin, Dawn; Meyerhoff, Dieter J.] San Francisco Vet Adm Med Ctr, Magnet Resonance Unit, San Francisco, CA 94121 USA. [Banys, Peter; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Banys, Peter] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Gazdzinski, S (reprint author), San Francisco Vet Adm Med Ctr, Magnet Resonance Unit, 4150 Clement St 114M, San Francisco, CA 94121 USA. EM spg@itsa.ucsf.edu FU NIAAA NIH HHS [R01 AA010788, AA 10788, R01 AA010788-06, R01 AA010788-07, R01 AA010788-08, R01 AA010788-09, R01 AA010788-10, R01 AA010788-11, R01 AA010788-12] NR 84 TC 38 Z9 38 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD FEB 28 PY 2008 VL 162 IS 2 BP 133 EP 145 DI 10.1016/j.pscychresns.2007.04.003 PG 13 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 272GH UT WOS:000253847400005 PM 18178068 ER PT J AU Abrahm, JL Banffy, MB Harris, MB AF Abrahm, Janet L. Banffy, Michael B. Harris, Mitchel B. TI Spinal cord compression in patients with advanced metastatic cancer - "All I care about is walking and living my life" SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; EPIDURAL METASTASIS; STEREOTACTIC RADIOSURGERY; SURGICAL RESECTION; PROGNOSTIC-FACTORS; RADIATION-THERAPY; NEUROPATHIC PAIN; VERTEBRAL METASTASIS; BREAST-CANCER; RADIOTHERAPY AB As 1 of the 12 700 US cancer patients who, each year, develops metastatic spinal cord compression, Ms H wishes to walk and live her life. Sadly, this wish may be difficult to fulfill. Before diagnosis, 83% to95% of patients experience back pain, which often is referred, obscuring the site( s) of the compression( s). Prediction of ambulation depends on a patient's ambulatory status before therapy and time between developing motor defects and starting therapy. Ambulatory patients with no visceral metastases and more than 15 days between developing motor symptoms and receiving therapy have the best rate of survival. To preserve ambulation and optimize survival, magnetic resonance imaging should be performed for cancer patients with new back pain despite normal neurological findings. At diagnosis, counseling, pain management, and corticosteroids are begun. Most patients are offered radiation therapy. Surgery followed by radiation is considered for selected patients with a single high- grade epidural lesion caused by a radioresistant tumor who also have an estimated survival of more than 3 months. Team discussions with the patient and support network help determine therapy options and include patient goals; assessment of risks, benefits, and burdens of each treatment; and discussion of the odds of preserving prognosis of ambulation and of the effect of therapy on the patient's overall prognosis. Rehabilitation improves impaired function and its associated depression. Clinicians can help patients cope with transitions in self- image, independence, family and community roles, and living arrangements and can help patients with limited prognoses identify their end- of- life goals and preferences about resusitation and entering hospice. C1 [Abrahm, Janet L.] Harvard Univ, Div Psychosocial Oncol & Palliat Care, Dana Farber Canc Inst, Dept Med Oncol,Sch Med, Boston, MA 02115 USA. [Abrahm, Janet L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Banffy, Michael B.] Harvard Univ, Sch Med, Dept Orthoped Surg, Harvard Combined Orthoped Program, Boston, MA 02115 USA. [Harris, Mitchel B.] Harvard Univ, Sch Med, Dept Orthoped Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Abrahm, JL (reprint author), Harvard Univ, Div Psychosocial Oncol & Palliat Care, Dana Farber Canc Inst, Dept Med Oncol,Sch Med, 44 Binney St SW 420, Boston, MA 02115 USA. EM jabrahm@partners.org NR 101 TC 55 Z9 57 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 27 PY 2008 VL 299 IS 8 BP 937 EP 946 DI 10.1001/jama.299.8.937 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 266DZ UT WOS:000253413200022 PM 18314436 ER PT J AU Solowska, JM Morfini, G Falnikar, A Himes, BT Brady, ST Huang, D Baas, PW AF Solowska, Joanna M. Morfini, Gerardo Falnikar, Aditi Himes, B. Timothy Brady, Scott T. Huang, Dongyang Baas, Peter W. TI Quantitative and functional analyses of spastin in the nervous system: Implications for hereditary spastic paraplegia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE microtubule; neuron; axon; spastin; katanin; hereditary spastic paraplegia ID FAST AXONAL-TRANSPORT; MICROTUBULE-SEVERING PROTEIN; INTRAGENIC MODIFIERS; ANDROGEN RECEPTOR; VESICLE MOTILITY; SPG4 MUTATIONS; GENE-MUTATIONS; KATANIN; IDENTIFICATION; EXPRESSION AB Spastin and P60-katanin are two distinct microtubule-severing proteins. Autosomal dominant mutations in the SPG4 locus corresponding to spastin are the most common cause of hereditary spastic paraplegia ( HSP), a neurodegenerative disease that afflicts the adult corticospinal tracts. Here we sought to evaluate whether SPG4-based HSP is best understood as a " loss-of-function" disease. Using various rat tissues, we found that P60-katanin levels are much higher than spastin levels during development. In the adult, P60-katanin levels plunge dramatically but spastin levels decline only slightly. Quantitative data of spastin expression in specific regions of the nervous system failed to reveal any obvious explanation for the selective sensitivity of adult corticospinal tracts to loss of spastin activity. An alternative explanation relates to the fact that the mammalian spastin gene has two start codons, resulting in a 616 amino acid protein called M1 and a slightly shorter protein called M85. We found that M1 is almost absent from developing neurons and most adult neurons but comprises 20-25% of the spastin in the adult spinal cord, the location of the axons that degenerate during HSP. Experimental expression in cultured neurons of a short dysfunctional M1 polypeptide ( but not a short dysfunctional M85 peptide) is deleterious to normal axonal growth. In squid axoplasm, the M1 peptide dramatically inhibits fast axonal transport, whereas the M85 peptide does not. These results are consistent with a " gain-of-function" mechanism underlying HSP wherein spastin mutations produce a cytotoxic protein in the case of M1 but not M85. C1 [Solowska, Joanna M.; Falnikar, Aditi; Himes, B. Timothy; Baas, Peter W.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. [Morfini, Gerardo; Brady, Scott T.; Huang, Dongyang] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA. [Himes, B. Timothy] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Morfini, G (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, 2900 Queen Lane, Philadelphia, PA 19129 USA. EM gmorfini@uic.edu; pbaas@drexelmed.edu FU NINDS NIH HHS [R01 NS023320-17, R01 NS023868, R01 NS023868-21, R01 NS041170, R01 NS023320, R01 NS041170-06] NR 49 TC 51 Z9 52 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 27 PY 2008 VL 28 IS 9 BP 2147 EP 2157 DI 10.1523/JNEUROSCI.3159-07.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 268AC UT WOS:000253549300016 PM 18305248 ER PT J AU Rucker, B Almeida, ME Libermann, TA Zerbini, LF Wink, MR Sarkis, JJF AF Rucker, Barbara Almeida, Manoela E. Libermann, Towia A. Zerbini, Luiz F. Wink, Marcia R. Sarkis, Joao J. F. TI E-NTPDases and ecto-5 '-nucleotidase expression profile in rat heart left ventricle and the extracellular nucleotide hydrolysis by their nerve terminal endings SO LIFE SCIENCES LA English DT Article DE E-NTPDases; ecto-5 '-nucleotidase/CD73; left ventricle; cardiac synaptosomes ID ECTO-ATP-DIPHOSPHOHYDROLASE; NUCLEOSIDE TRIPHOSPHATE DIPHOSPHOHYDROLASE-1; CARDIOVASCULAR-SYSTEM; KINETIC CHARACTERIZATION; BIOCHEMICAL-PROPERTIES; CLONING; APYRASE; NOREPINEPHRINE; INHIBITION; ADENOSINE AB In this study, we have identified the E-NTPDase family members and ecto-5'-nucleotidase/CD73 in rat heart left ventricle. Moreover, we characterize the biochemical properties and enzyme activities from synaptosomes of the nerve terminal endings of heart left ventricle. We observe divalent cation-dependent enzymes that presented optimum PH of 8.0 for ATP and ADP hydrolysis, and 9.5 for AMP hydrolysis. The apparent K-M values are 40 mu M, 90 mu M and 39 mu M and apparent V-max values are 537, 219 and 111 nmol Pi released/min/mg of protein for ATP, ADP and AMP hydrolysis, respectively. Ouabain, orthovanadate, NEM, lanthanum, and levamisole do not affect ATP and ADP hydrolysis in rat cardiac synaptosomes. Oligomycin (2 mu g/mL) and sodium azide (0.1 mM), both mitochondrial ATPase inhibitors, inhibit only the ATP hydrolysis. High concentrations of sodium azide and gadolinium chloride show an inhibition on both, ATP and ADP hydrolysis. Suramin inhibit more strongly ATP hydrolysis than ADP hydrolysis whereas Evans blue almost abolish both hydrolysis. AMP hydrolysis is not affected by levamisole and tetramisole, whereas 0.1 mM ammonium molybdate practically abolish the ecto-5'-nucleotidase activity. RT-PCR analysis from left ventricle tissue demonstrate different levels of expression of Entpd1 (Cd39), Entpd2 (Cd39L1), Entpd3 (Cd39L3), Entpd5 (Cd39L4) Entpd6, (Cd39L2) and 5'-NT/CD73. By quantitative real-time PCR we identify the Entpd2 as the enzyme with the highest expression in rat left ventricle. Our results contribute to the understanding about the control of the extracellular nucleotide levels in and cardiac system. (c) 2007 Elsevier Inc. All rights reserved. C1 [Rucker, Barbara; Almeida, Manoela E.] Univ Fed Rio Grande do Sul, Dept Bioquim, ICBS, BR-90035003 Porto Alegre, RS, Brazil. [Libermann, Towia A.; Zerbini, Luiz F.] BIDMC Genom Ctr, Boston, MA USA. [Libermann, Towia A.; Zerbini, Luiz F.] Harvard Univ, Sch Med, Boston, MA USA. [Wink, Marcia R.] FFFCMPA, Dept Ciencias Fisiol, Porto Alegre, RS, Brazil. RP Rucker, B (reprint author), Univ Fed Rio Grande do Sul, Dept Bioquim, ICBS, Rua Ramiro Barcelos 2600 Predio ANEXO, BR-90035003 Porto Alegre, RS, Brazil. EM barucker@ig.com.br RI Libermann, Towia/F-9866-2010; Zerbini, Luiz /B-7720-2015; OI Libermann, Towia/0000-0002-4006-8179 NR 63 TC 14 Z9 14 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 EI 1879-0631 J9 LIFE SCI JI Life Sci. PD FEB 27 PY 2008 VL 82 IS 9-10 BP 477 EP 486 DI 10.1016/j.lfs.2007.12.003 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 272WH UT WOS:000253891500005 PM 18201730 ER PT J AU Rutter, MK Wilson, PWF Sullivan, LM Fox, CS D'Agostino, RB Meigs, JB AF Rutter, Martin K. Wilson, Peter W. F. Sullivan, Lisa M. Fox, Caroline S. D'Agostino, Ralph B. Meigs, James B. TI Use of alternative thresholds defining insulin resistance to predict incident type 2 diabetes mellitus and cardiovascular disease SO CIRCULATION LA English DT Article DE insulin resistance; cardiovascular diseases; diabetes mellitus; risk factors; prospective studies; prognosis ID HOMEOSTASIS MODEL ASSESSMENT; CORONARY-HEART-DISEASE; METABOLIC SYNDROME; ATHEROSCLEROSIS; SENSITIVITY; GLUCOSE; EVENTS; RISK AB Background- The performance characteristics of surrogate insulin resistance (IR) measures, commonly defined as the top 25% of the measure's distribution, used to predict incident type 2 diabetes mellitus (DM) and cardiovascular disease (CVD) have not been critically assessed in community samples. Methods and Results- Baseline IR was assessed among 2720 Framingham Offspring Study subjects by use of fasting insulin, the homeostasis model assessment of IR (HOMA-IR), and the reciprocal of the Gutt insulin sensitivity index, with 7- to 11-year follow-up for incident DM (130 cases) or CVD (235). Area under the receiver operating characteristic curve, sensitivity, specificity, and positive likelihood ratio were estimated at 12 diagnostic thresholds (quantiles) of IR measures. Positive likelihood ratios for DM or CVD increased in relation to IR quantiles; risk gradients were greater for DM than for CVD, with no 9th to 10th quantile (76th centile) threshold effects. IR had better discrimination for incident DM than for CVD (HOMA-IR area under the receiver operating characteristic curve: DM 0.80 versus CVD 0.63). The HOMA-IR >= 76th centile threshold was associated with these test-performance values: sensitivity (DM 68%, CVD 40%), specificity (DM 77%, CVD 76%), and positive likelihood ratio (DM 3.0, CVD 1.7). The HOMA-IR threshold that yielded > 90% sensitivity was the 6th quantile for DM prediction and the 3rd quantile for CVD. Compared with the >= 76th centile threshold, these alternative thresholds yielded lower specificity (DM 43%, CVD 17%) and positive likelihood ratios (DM 1.6, CVD 1.1). Conclusions- Surrogate IR measures have modest performance at the 76th centile, with no threshold effects. Different centile thresholds might be selected to optimize sensitivity versus specificity for DM versus CVD prediction if surrogate IR measures are used for risk prediction. C1 [Rutter, Martin K.] Univ Manchester, Div Cardiovasc & Endocrine Sci, Cardiovasc Res Grp, Manchester, Lancs, England. [Rutter, Martin K.] Manchester Royal Infirm, Manchester Diabet Ctr, Manchester M13 9WL, Lancs, England. [Wilson, Peter W. F.] Emory Univ, Sch Med, Atlanta, GA USA. [Sullivan, Lisa M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Cunsulting Unit, Boston, MA 02215 USA. [Fox, Caroline S.] NHLBI, Framingham, MA USA. [Fox, Caroline S.; Meigs, James B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol & Metab, Boston, MA 02115 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Dept Med Genet, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Rutter, Martin/0000-0001-6380-539X; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIDDK NIH HHS [K24 DK080140, K24 DK080140-01] NR 22 TC 39 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 26 PY 2008 VL 117 IS 8 BP 1003 EP 1009 DI 10.1161/CIRCULATIONAHA.107.727727 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 267XQ UT WOS:000253542900003 PM 18250267 ER PT J AU Fang, MC Go, AS Chang, Y Borowsky, L Pomernacki, NK Singer, DE AF Fang, Margaret C. Go, Alan S. Chang, Yuchiao Borowsky, Leila Pomernacki, Niela K. Singer, Daniel E. CA ATRIA Study Group TI Comparison of risk stratification schemes to predict thromboembolism in people with nonvalvular atrial fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VON-WILLEBRAND-FACTOR; ISCHEMIC-STROKE; ANTITHROMBOTIC THERAPY; CARDIOVASCULAR EVENTS; ATHEROSCLEROSIS RISK; MULTIPLE BIOMARKERS; VASCULAR EVENTS; ANTICOAGULATION; PREVENTION; WARFARIN AB Objectives We assessed 5 risk stratification schemes for their ability to predict atrial fibrillation (AF)-related thromboembolism in a large community-based cohort. Background Risk schemes can help target anticoagulant therapy for patients at highest risk for AF-related thromboembolism. We tested the predictive ability of 5 risk schemes: the Atria[ Fibrillation Investigators, Stroke Prevention in Atrial Fibrillation, CHADS(2) (Congestive heart failure, Hypertension, Age >= 75 years, Diabetes mellitus, and prior Stroke or transient ischemic attack) index, Framingham score, and the 7th American College of Chest Physicians Guidelines. Methods We followed a cohort of 13,559 adults with AF for a median of 6.0 years. Among non-warfarin users, we identified incident thromboembolism (ischemic stroke or peripheral embolism) and risk factors from clinical databases. Each scheme was divided into low, intermediate, and high predicted risk categories and applied to the cohort. Annualized thromboembolism rates and c-statistics (to assess discrimination) were calculated for each risk scheme. Results We identified 685 validated thromboembolic events that occurred during 32,721 person-years off warfarin therapy. The risk schemes had only fair discriminating ability, with c-statistics ranging from 0.56 to 0.62. The proportion of patients assigned to individual risk categories varied widely across the schemes. The proportion categorized as low risk ranged from 11.7% to 37.1% across schemes, and the proportion considered high risk ranged from 16.4% to 80.4%. Conclusions Current risk schemes have comparable, but only limited, overall ability to predict thromboembolism in persons with AF. Recommendations for antithrombotic therapy may vary widely depending on which scheme is applied for individual patients. Better risk stratification is crucially needed to improve selection of AF patients for anticoagulant therapy. C1 [Fang, Margaret C.; Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Go, Alan S.; Pomernacki, Niela K.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Chang, Yuchiao; Borowsky, Leila; Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Fang, MC (reprint author), 503 Parnassus Ave,Box 0131, San Francisco, CA 94143 USA. EM mfang@medicine.ucsf.edu FU NIA NIH HHS [AG15478, K23 AG028978, K23 AG28978, R01 AG015478] NR 29 TC 193 Z9 199 U1 1 U2 8 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 FEB 26 PY 2008 VL 51 IS 8 BP 810 EP 815 DI 10.1016/j.jacc.2007.09.065 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 266KN UT WOS:000253434200005 PM 18294564 ER PT J AU Niemann, S Landers, JE Churchill, MJ Hosler, B Sapp, P Speed, WC Lahn, BT Kidd, KK Brown, RH Hayashi, Y AF Niemann, S. Landers, J. E. Churchill, M. J. Hosler, B. Sapp, P. Speed, W. C. Lahn, B. T. Kidd, K. K. Brown, R. H., Jr. Hayashi, Y. TI Motoneuron-specific NR3B gene - No association with ALS and evidence for a common null allele SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; SINGLE-NUCLEOTIDE POLYMORPHISMS; NMDA RECEPTORS; LINKAGE DISEQUILIBRIUM; SUBUNIT; EXPRESSION; MUTATIONS; SEQUENCE AB Objective: The GRIN3B gene encodes NR3B, a motoneuron-specific member of the NMDA type of ionotropic glutamate receptors. NR3B reduces the Ca2+- permeability as well as the overall current of the receptor response and may thereby protect motoneurons against glutamate-mediated excitotoxicity. We tested whether genetic dysfunction of GRIN3B is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Methods: We searched for mutations in the GRIN3B coding region (3.1 kb) in 117 individuals with familial ALS and in 46 individuals with sporadic ALS. We genotyped the newly identified GRIN3B null allele and four "tag single nucleotide polymorphisms (SNPs)" at the GRIN3B locus in 342 individuals with sporadic ALS and in 374 matched controls. The GRIN3B null allele frequency was determined in 2,128 individuals from a worldwide panel of 42 populations. We furthermore compared the GRIN3B coding sequence in primates (human - macaque) and rodents (rat - mouse) to evaluate the molecular evolution of GRIN3B. Results: Thirty-two SNPs, including 16 previously unreported SNPs, one 27-bp deletion, a polymorphic CAG repeat, and a 4-bp insertion (insCGTT), were identified. Mutational and case control studies did not reveal variants that cause or modify disease in ALS. Intriguing is an insCGTT variant that truncates the protein at its amino terminus and results in a GRIN3B null allele. We demonstrated a global distribution of the null allele with allele frequencies ranging between 0 and 0.38, and we delineated a null allele specific haplotype of 9.89 kb. Comparative genomic analysis across four taxa demonstrated accelerated evolution of NR3B in primates. Conclusions: Our study supports the conclusions that 1) GRIN3B does not seem to be associated with familial or sporadic ALS, 2) the GRIN3B null allele is a common polymorphism, 3) the GRIN3B null allele has arisen once and early in human evolution, and 4) the GRIN3B gene belongs to a group of nervous system - related genes that have been subjected to faster evolution during evolution. C1 [Niemann, S.; Churchill, M. J.; Hayashi, Y.] MIT, RIKEN, MIT Neurosci Res Ctr, Picower Inst Learning & Memory,Dept Brain & Cogni, Cambridge, MA USA. [Niemann, S.; Landers, J. E.; Hosler, B.; Sapp, P.; Brown, R. H., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mass Gen Inst Neurodegenerat Dis,Cecil B Day Lab, Charlestown, MA USA. [Niemann, S.; Landers, J. E.; Hosler, B.; Sapp, P.; Brown, R. H., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mass Gen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA USA. [Speed, W. C.; Kidd, K. K.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Lahn, B. T.] Univ Chicago, Howard Hughes Med Inst, Dept Human Genet, Chicago, IL 60637 USA. RP Niemann, S (reprint author), Massachusetts Gen Hosp E, Cecil B Day Lab Neuromuscular Res, Bldg 114,16th St, Charlestown, MA 02129 USA. EM Niemann.Stephan@gmail.com RI Hayashi, Yasunori/C-2249-2008 OI Hayashi, Yasunori/0000-0002-7560-3004 FU NIAAA NIH HHS [R01AA009379]; NIDA NIH HHS [R01DA17310]; NIGMS NIH HHS [P01GM057672]; NINDS NIH HHS [1P01NS31248-02, R01NS37912, R21NS46421-02] NR 28 TC 13 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 26 PY 2008 VL 70 IS 9 BP 666 EP 676 DI 10.1212/01.wnl.0000271078.51280.17 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 267XS UT WOS:000253543100003 PM 17687115 ER PT J AU Schmahmann, JD Neal, M MacMore, J AF Schmahmann, Jeremy D. Neal, Marygrace MacMore, Jason TI Evaluation of the assessment and grading of medical students on a neurology clerkship SO NEUROLOGY LA English DT Article ID PERFORMANCE; COMPETENCE; OBSTETRICS AB Objective: To describe a clinical encounter (Bedside Examination Exercise [BEE]) used for assessment and teaching in the Massachusetts General Hospital neurology clerkship; to compare results of the BEE with the Harvard Medical School Subjective Evaluation Form (SEF) and National Board of Medical Examiners Shelf examination (Shelf); and to develop a grading system that assesses multiple skills and reflects proficiency. Methods: The BEE was administered to 409 students. Final grades were compared with those of 71 students evaluated with the SEF alone. We compared results on the SEF, BEE, and Shelf examination in another 132 students. A composite score was developed, weighted SEF 70%, BEE 15%, and Shelf 15%, to derive the final grade. Results: The BEE helped limit grade inflation, but did not predict final grade determined by the SEF. Grades from the three test instruments had normal distributions, but different means and SDs: SEF 84% +/- 10.3%; BEE 83% +/- 9.3%; Shelf 69% +/- 8.4%. There was poor agreement among individual students between different tests, even within core competencies. The 70-15-15 composite score had a normal distribution, 81% +/- 8.5%. Conclusions: The Bedside Examination Exercise (BEE) is useful for assessing and teaching clinical skills. No single test instrument predicts results of another with acceptable accuracy. Use of complimentary assessment tools (BEE, Subjective Evaluation Form, and Shelf) lessens uncertainty in deriving the composite score, and facilitates evaluation of different attributes. The composite score enables a five-tier grading system that recognizes proficiency, rewards excellence, and provides meaningful feedback. This approach could be generalized to other clerkships. C1 [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Suite 340,Charles River Plaza S,55 Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org NR 10 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 26 PY 2008 VL 70 IS 9 BP 706 EP 712 DI 10.1212/01.wnl.0000302179.56679.00 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 267XS UT WOS:000253543100008 PM 18299522 ER PT J AU Hodi, FS Butler, M Oble, DA Seiden, MV Haluska, FG Kruse, A MacRae, S Nelson, M Canning, C Lowy, I Korman, A Lautz, D Russell, S Jaklitsch, MT Ramaiya, N Chen, TC Neuberg, D Allison, JP Mihm, MC Dranoff, G AF Hodi, F. Stephen Butler, Marcus Oble, Darryl A. Seiden, Michael V. Haluska, Frank G. Kruse, Andrea MacRae, Suzanne Nelson, Marybeth Canning, Christine Lowy, Israel Korman, Alan Lautz, David Russell, Sara Jaklitsch, Michael T. Ramaiya, Nikhil Chen, Teresa C. Neuberg, Donna Allison, James P. Mihm, Martin C. Dranoff, Glenn TI Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CTLA-4; regulatory T cells (Tregs); vaccine; GM-CSF ID COLONY-STIMULATING FACTOR; PHASE-I TRIAL; COMBINATION IMMUNOTHERAPY; METASTATIC MELANOMA; CTLA-4 BLOCKADE; MONOCLONAL-ANTIBODY; GM-CSF; CELLS; AUTOIMMUNITY; THERAPY AB Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. The administration of fully human anti-CTLA-4 blocking monoclonal antibodies to advanced-cancer patients increases immune-mediated tumor destruction in some subjects. Nonetheless, patients that respond also frequently manifest serious inflammatory pathologies, raising the possibility that the therapeutic and toxic effects of CTLA-4 blockade might be linked. Here we show that periodic infusions of anti-CTLA-4 antibodies after vaccination with irradiated, autologous tumor cells engineered to secrete GM-CSF (GVAX) generate clinically meaningful antitumor immunity without grade 3 or 4 toxicity in a majority of metastatic melanoma patients. The application of this sequential immunotherapy to advanced ovarian carcinoma patients also revealed that tumor destruction and severe inflammatory pathology could be dissociated, although further refinements are required to increase clinical responses and to minimize toxicity in this population. The extent of therapy-induced tumor necrosis was linearly related to the natural logarithm of the ratio of intratumoral CD8(+) effector T cells to FoxP3(+) regulatory T cells (Tregs) in posttreatment biopsies. Together, these findings help clarify the immunologic and clinical effects of CTLA-4 antibody blockade in previously vaccinated patients and raise the possibility that selective targeting of antitumor Tregs may constitute a complementary strategy for combination therapy. C1 [Hodi, F. Stephen; Butler, Marcus; Kruse, Andrea; MacRae, Suzanne; Nelson, Marybeth; Canning, Christine; Dranoff, Glenn] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Hodi, F. Stephen; Butler, Marcus; Kruse, Andrea; MacRae, Suzanne; Nelson, Marybeth; Canning, Christine; Dranoff, Glenn] Harvard Univ, Sch Med, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hodi, F. Stephen; Butler, Marcus; Kruse, Andrea; MacRae, Suzanne; Nelson, Marybeth; Canning, Christine; Dranoff, Glenn] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Oble, Darryl A.; Mihm, Martin C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seiden, Michael V.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haluska, Frank G.] Tufts Univ, New England Med Ctr, Ctr Canc, Boston, MA 02111 USA. [Haluska, Frank G.] Tufts Univ, New England Med Ctr, Div Hematol Oncol, Boston, MA 02111 USA. [Lowy, Israel; Korman, Alan] Medarex Inc, Annandale, NJ 08801 USA. [Lautz, David; Russell, Sara; Jaklitsch, Michael T.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Lautz, David; Russell, Sara; Jaklitsch, Michael T.; Ramaiya, Nikhil; Chen, Teresa C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ramaiya, Nikhil] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Chen, Teresa C.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Allison, James P.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA. [Allison, James P.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. RP Hodi, FS (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu; allisonj@mskcc.org FU NCI NIH HHS [CA105776, CA111506, R01 CA111506, R21 CA105776] NR 38 TC 339 Z9 349 U1 1 U2 16 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 FEB 26 PY 2008 VL 105 IS 8 BP 3005 EP 3010 DI 10.1073/pnas.0712237105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 268GQ UT WOS:000253567900047 PM 18287062 ER PT J AU Harvey, KF Mattila, J Sofer, A Bennett, FC Ramsey, MR Ellisen, LW Puig, O Hariharan, IK AF Harvey, Kieran F. Mattila, Jaakko Sofer, Avi Bennett, F. Christian Ramsey, Matthew R. Ellisen, Leif W. Puig, Oscar Hariharan, Iswar K. TI FOXO-regulated transcription restricts overgrowth of Tsc mutant organs SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-GROWTH; TUMOR SUPPRESSORS; SIGNALING PATHWAY; DROSOPHILA; MTOR; HYPOXIA; REDD1; PROLIFERATION; HOMOLOGS; COMPLEX AB FOXO is thought to function as a repressor of growth that is, in turn, inhibited by insulin signaling. However, inactivating mutations in Drosophila melanogaster FOXO result in viable flies of normal size, which raises a question over the involvement of FOXO in growth regulation. Previously, a growth-suppressive role for FOXO under conditions of increased target of rapamycin (TOR) pathway activity was described. Here, we further characterize this phenomenon. We show that tuberous sclerosis complex 1 mutations cause increased FOXO levels, resulting in elevated expression of FOXO-regulated genes, some of which are known to antagonize growth-promoting pathways. Analogous transcriptional changes are observed in mammalian cells, which implies that FOXO attenuates TOR-driven growth in diverse species. C1 [Harvey, Kieran F.; Bennett, F. Christian] Peter MacCallum Canc Ctr, Cell Growth & Proliferat Lab, Melbourne, Vic 3002, Australia. [Harvey, Kieran F.; Bennett, F. Christian] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia. [Mattila, Jaakko; Puig, Oscar] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland. [Sofer, Avi; Ramsey, Matthew R.; Ellisen, Leif W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Harvey, Kieran F.; Hariharan, Iswar K.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Harvey, KF (reprint author), Peter MacCallum Canc Ctr, Cell Growth & Proliferat Lab, Melbourne, Vic 3002, Australia. EM kieran.harvey@petermac.org OI Harvey, Kieran/0000-0001-7845-369X; Ramsey, Matthew/0000-0003-2402-8502 FU NCI NIH HHS [R01 CA122589]; NIGMS NIH HHS [GM61672, R01 GM061672] NR 29 TC 33 Z9 33 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB 25 PY 2008 VL 180 IS 4 BP 691 EP 696 DI 10.1083/jcb.200710100 PG 6 WC Cell Biology SC Cell Biology GA 267FD UT WOS:000253494000018 PM 18299344 ER PT J AU Wu, SM Chien, KR Mummery, C AF Wu, Sean M. Chien, Kenneth R. Mummery, Christine TI Origins and fates of cardiovascular progenitor cells SO CELL LA English DT Article ID EMBRYONIC STEM-CELLS; ACUTE MYOCARDIAL-INFARCTION; BONE-MARROW; SMOOTH-MUSCLE; RAT HEARTS; MAMMALIAN HEART; CARDIAC REPAIR; DIFFERENTIATION; CARDIOMYOCYTES; REGENERATION AB Multipotent cardiac progenitor cells are found in the fetal and adult heart of many mammalian species including humans and form as intermediates during the differentiation of embryonic stem cells. Despite similar biological properties, the molecular identities of these different cardiac progenitor cell populations appear to be distinct. Elucidating the origins and lineage relationships of these cell populations will accelerate clinical applications such as drug screening and cell therapy as well as shedding light on the pathogenic mechanisms underlying cardiac diseases. C1 [Mummery, Christine] Utrecht & Interuniv Cardiol Inst, Hubrecht Inst, Univ Med Ctr, NL-3584 CT Utrecht, Netherlands. [Wu, Sean M.; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Chien, Kenneth R.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Wu, Sean M.; Chien, Kenneth R.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. RP Mummery, C (reprint author), Utrecht & Interuniv Cardiol Inst, Hubrecht Inst, Univ Med Ctr, NL-3584 CT Utrecht, Netherlands. EM c.mummery@niob.knaw.nl FU NHLBI NIH HHS [K08 HL081086, K08 HL081086-02] NR 63 TC 105 Z9 108 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 22 PY 2008 VL 132 IS 4 BP 537 EP 543 DI 10.1016/j.cell.2008.02.002 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271VX UT WOS:000253817900012 PM 18295570 ER PT J AU Daley, GQ Scadden, DT AF Daley, George Q. Scadden, David T. TI Prospects for stem cell-based therapy SO CELL LA English DT Article ID HUMAN SOMATIC-CELLS; HEMATOPOIETIC STEM; DEFINED FACTORS; PROGENITOR CELLS; NUCLEAR TRANSFER; FIBROBLASTS; REJECTION; NICHE; LINES; POPULATION AB Resident pools of somatic stem cells in many organs are responsible for tissue maintenance and repair. The goal of regenerative medicine is to exploit these cells either by transplanting them from an exogenous source or by activating endogenous stem cells pharmacologically. For diseases caused by mutations in a single gene, the therapeutic goal is tissue replacement using stem cells engineered to correct the genetic defect. However, a number of technical hurdles must be overcome before therapies based on pluripotent human stem cells can enter the clinic. C1 [Daley, George Q.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.; Scadden, David T.] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02115 USA. [Scadden, David T.] Harvard Univ, Dept Stem Cell & regenerat Biol, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu; scadden.david@mgh.harvard.edu NR 42 TC 163 Z9 166 U1 2 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 22 PY 2008 VL 132 IS 4 BP 544 EP 548 DI 10.1016/j.cell.2008.02.009 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271VX UT WOS:000253817900013 PM 18295571 ER PT J AU Laird, DJ von Andrian, UH Wagers, AJ AF Laird, Diana J. von Andrian, Ulrich H. Wagers, Amy J. TI Stem cell trafficking in tissue development, growth, and disease SO CELL LA English DT Review ID PRIMORDIAL GERM-CELLS; SKELETAL-MUSCLE DEVELOPMENT; COLONY-STIMULATING FACTOR; C-MET RECEPTOR; HEMATOPOIETIC PROGENITOR CELLS; PROTEIN-KINASE-C; BONE-MARROW; SATELLITE CELLS; IN-VIVO; MOUSE EMBRYO AB Regulated movement of stem cells is critical for organogenesis during development and for homeostasis and repair in adulthood. Here we analyze the biological significance and molecular mechanisms underlying stem cell trafficking in the generation of the germline, and the generation and regeneration of blood and muscle. Comparison across organisms and lineages reveals remarkable conservation as well as specialization in homing and migration mechanisms used by mature leukocytes, adult and fetal stem cells, and cancer stem cells. In vivo trafficking underpins the successful therapeutic application of hematopoietic stem cells for bone-marrow transplant, and further elucidation of homing and migration pathways in other systems will enable broader application of stem cells for targeted cell therapy and drug delivery. C1 [Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Laird, Diana J.] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10058 USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Wagers, Amy J.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. RP Wagers, AJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM amy.wagers@joslin.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL56949]; NIAID NIH HHS [R01 AI069259-01] NR 143 TC 188 Z9 193 U1 0 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 22 PY 2008 VL 132 IS 4 BP 612 EP 630 DI 10.1016/j.cell.2008.01.041 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271VX UT WOS:000253817900021 PM 18295579 ER PT J AU Orkin, SH Zon, LI AF Orkin, Stuart H. Zon, Leonard I. TI Hematopoiesis: An evolving paradigm for stem cell biology SO CELL LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; MOUSE EMBRYO; TRANSCRIPTION FACTORS; DEFINITIVE HEMATOPOIESIS; LINEAGE COMMITMENT; ZEBRAFISH EMBRYOS; YOLK-SAC; ADULT HEMATOPOIESIS; ENDOTHELIAL-CELLS AB Establishment and maintenance of the blood system relies on self-renewing hematopoietic stem cells (HSCs) that normally reside in small numbers in the bone marrow niche of adult mammals. This Review describes the developmental origins of HSCs and the molecular mechanisms that regulate lineage-specific differentiation. Studies of hematopoiesis provide critical insights of general relevance to other areas of stem cell biology including the role of cellular interactions in development and tissue homeostasis, lineage programming and reprogramming by transcription factors, and stage- and age-specific differences in cellular phenotypes. C1 [Orkin, Stuart H.; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Stem Cell Inst, Boston, MA 02115 USA. [Orkin, Stuart H.; Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU Howard Hughes Medical Institute; NHLBI NIH HHS [P01 HL032262, P01 HL032262-27, R01 HL032259, R01 HL032259-27, R01 HL075735, R01 HL075735-06]; NIDDK NIH HHS [P30 DK049216, P30 DK049216-15] NR 113 TC 907 Z9 933 U1 16 U2 150 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 22 PY 2008 VL 132 IS 4 BP 631 EP 644 DI 10.1016/j.cell.2008.01.025 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271VX UT WOS:000253817900022 PM 18295580 ER PT J AU Rossi, DJ Jamieson, CHM Weissman, IL AF Rossi, Derrick J. Jamieson, Catriona H. M. Weissman, Irving L. TI Stems cells and the pathways to aging and cancer SO CELL LA English DT Review ID MURINE HEMATOPOIETIC STEM; ACUTE MYELOID-LEUKEMIA; AGE-RELATED-CHANGES; BONE-MARROW MICROENVIRONMENT; DNA-DAMAGE RESPONSE; LIFE-SPAN; SELF-RENEWAL; OXIDATIVE STRESS; DEPENDENCE DISTINGUISHES; TELOMERE DYSFUNCTION AB The aging of tissue-specific stem cell and progenitor cell compartments is believed to be central to the decline of tissue and organ integrity and function in the elderly. Here, we examine evidence linking stem cell dysfunction to the pathophysiological conditions accompanying aging, focusing on the mechanisms underlying stem cell decline and their contribution to disease pathogenesis. C1 [Rossi, Derrick J.] Harvard Univ, Stem Cell Inst, Immune Dis Inst, Boston, MA 02115 USA. [Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Jamieson, Catriona H. M.] Univ Calif San Diego, Moores Canc Ctr, Div Hematol Oncol, La Jolla, CA 92093 USA. [Jamieson, Catriona H. M.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Weissman, Irving L.] Stanford Univ, Ctr Canc, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Weissman, Irving L.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. RP Rossi, DJ (reprint author), Harvard Univ, Stem Cell Inst, Immune Dis Inst, Boston, MA 02115 USA. EM rossi@idi.harvard.edu NR 157 TC 443 Z9 457 U1 9 U2 62 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 22 PY 2008 VL 132 IS 4 BP 681 EP 696 DI 10.1016/j.cell.2008.01.036 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271VX UT WOS:000253817900025 PM 18295583 ER PT J AU Gerszten, RE Wang, TJ AF Gerszten, Robert E. Wang, Thomas J. TI The search for new cardiovascular biomarkers SO NATURE LA English DT Article ID CORONARY-ARTERY-DISEASE; PLASMA-PROTEOME; IDENTIFICATION; CHEMOKINE; RECEPTOR; ASSOCIATION; DATABASE; EVENTS; RISK AB Despite considerable advances in the treatment of cardiovascular disease, it remains the leading cause of death in developed countries. Assessment of classic cardiovascular risk factors-including high blood pressure, diabetes and smoking-has a central role in disease prevention. However, many individuals with coronary heart disease (a narrowing of the blood vessels that supply the heart) have only one, or none, of the classic risk factors. Thus, new biomarkers are needed to augment the information obtained from traditional indicators and to illuminate disease mechanisms. C1 [Gerszten, Robert E.; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM rgerszten@partners.org NR 26 TC 160 Z9 163 U1 3 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 21 PY 2008 VL 451 IS 7181 BP 949 EP 952 DI 10.1038/nature06802 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264TK UT WOS:000253313100036 PM 18288185 ER PT J AU Yang, XY Ongusaha, PP Miles, PD Havstad, JC Zhang, FX So, WV Kudlow, JE Michell, RH Olefsky, JM Field, SJ Evans, RM AF Yang, Xiaoyong Ongusaha, Pat P. Miles, Philip D. Havstad, Joyce C. Zhang, Fengxue So, W. Venus Kudlow, Jeffrey E. Michell, Robert H. Olefsky, Jerrold M. Field, Seth J. Evans, Ronald M. TI Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance SO NATURE LA English DT Article ID PANCREATIC BETA-CELLS; N-ACETYLGLUCOSAMINE; NUCLEOCYTOPLASMIC GLYCOSYLATION; CYTOSOLIC PROTEINS; SKELETAL-MUSCLE; ACTIVATION; NUCLEAR; GLUCOSE; DOMAIN; SP1 AB Glucose flux through the hexosamine biosynthetic pathway leads to the post-translational modification of cytoplasmic and nuclear proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc). This tandem system serves as a nutrient sensor to couple systemic metabolic status to cellular regulation of signal transduction, transcription, and protein degradation. Here we show that O-GlcNAc transferase (OGT) harbours a previously unrecognized type of phosphoinositide-binding domain. After induction with insulin, phosphatidylinositol 3,4,5-trisphosphate recruits OGT from the nucleus to the plasma membrane, where the enzyme catalyses dynamic modification of the insulin signalling pathway by O-GlcNAc. This results in the alteration in phosphorylation of key signalling molecules and the attenuation of insulin signal transduction. Hepatic overexpression of OGT impairs the expression of insulin-responsive genes and causes insulin resistance and dyslipidaemia. These findings identify a molecular mechanism by which nutritional cues regulate insulin signalling through O-GlcNAc, and underscore the contribution of this modification to the aetiology of insulin resistance and type 2 diabetes. C1 [Yang, Xiaoyong; Havstad, Joyce C.; Evans, Ronald M.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. [Yang, Xiaoyong; Havstad, Joyce C.; Evans, Ronald M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. [Ongusaha, Pat P.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Ongusaha, Pat P.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Miles, Philip D.; Olefsky, Jerrold M.; Field, Seth J.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Zhang, Fengxue; Kudlow, Jeffrey E.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [So, W. Venus] Hoffmann La Roche Inc, Roche Grp Res Informat, Nutley, NJ 07110 USA. [Michell, Robert H.] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England. RP Evans, RM (reprint author), Salk Inst Biol Studies, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM evans@salk.edu FU Howard Hughes Medical Institute; NCI NIH HHS [P30 CA014195] NR 50 TC 253 Z9 264 U1 4 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 21 PY 2008 VL 451 IS 7181 BP 964 EP U1 DI 10.1038/nature06668 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264TK UT WOS:000253313100042 PM 18288188 ER PT J AU Arany, Z Foo, SY Ma, YH Ruas, JL Bommi-Reddy, A Girnun, G Cooper, M Laznik, D Chinsomboon, J Rangwala, SM Baek, KH Rosenzweig, A Spiegelman, BM AF Arany, Zoltan Foo, Shi-Yin Ma, Yanhong Ruas, Jorge L. Bommi-Reddy, Archana Girnun, Geoffrey Cooper, Marcus Laznik, Dina Chinsomboon, Jessica Rangwala, Shamina M. Baek, Kwan Hyuck Rosenzweig, Anthony Spiegelman, Bruce M. TI HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1 alpha SO NATURE LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; CONTROLLING MITOCHONDRIAL BIOGENESIS; SKELETAL-MUSCLE; GENE-EXPRESSION; ERR-ALPHA; PGC-1; METABOLISM; FIBERS; DRIVES; CELLS AB Ischaemia of the heart, brain and limbs is a leading cause of morbidity and mortality worldwide. Hypoxia stimulates the secretion of vascular endothelial growth factor ( VEGF) and other angiogenic factors, leading to neovascularization and protection against ischaemic injury(1). Here we show that the transcriptional coactivator PGC-1 alpha ( peroxisome- proliferator- activated receptor-gamma coactivator-1 alpha), a potent metabolic sensor and regulator(2), is induced by a lack of nutrients and oxygen, and PGC-1 alpha powerfully regulates VEGF expression and angiogenesis in cultured muscle cells and skeletal muscle in vivo. PGC-1 alpha(-/-) mice show a striking failure to reconstitute blood flow in a normal manner to the limb after an ischaemic insult, whereas transgenic expression of PGC-1 alpha in skeletal muscle is protective. Surprisingly, the induction of VEGF by PGC-1 alpha does not involve the canonical hypoxia response pathway and hypoxia inducible factor ( HIF). Instead, PGC-1 alpha coactivates the orphan nuclear receptor ERR-alpha ( oestrogen- related receptor- alpha) on conserved binding sites found in the promoter and in a cluster within the first intron of the VEGF gene. Thus, PGC-1 alpha and ERR-alpha, major regulators of mitochondrial function in response to exercise and other stimuli, also control a novel angiogenic pathway that delivers needed oxygen and substrates. PGC-1 alpha may provide a novel therapeutic target for treating ischaemic diseases. C1 [Arany, Zoltan; Ma, Yanhong; Ruas, Jorge L.; Bommi-Reddy, Archana; Girnun, Geoffrey; Cooper, Marcus; Laznik, Dina; Chinsomboon, Jessica; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Arany, Zoltan; Ma, Yanhong; Ruas, Jorge L.; Bommi-Reddy, Archana; Girnun, Geoffrey; Cooper, Marcus; Laznik, Dina; Chinsomboon, Jessica; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Arany, Zoltan; Foo, Shi-Yin; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Arany, Zoltan; Foo, Shi-Yin; Rosenzweig, Anthony] Harvard Stem Cell Inst, Boston, MA 02215 USA. [Rangwala, Shamina M.] Novartis Inst Biomed Res Diabet & Metab, Cambridge, MA 02139 USA. [Baek, Kwan Hyuck] Harvard Univ, Sch Med, Vasc Biol Program, Dept Surg,Childrens Hosp, Boston, MA 02115 USA. RP Arany, Z (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM zarany1@partners.org; bruce_spiegelman@dfci.harvard.edu OI Ruas, Jorge/0000-0002-1110-2606 FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-12, R01 DK054477] NR 23 TC 486 Z9 516 U1 8 U2 57 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 21 PY 2008 VL 451 IS 7181 BP 1008 EP U8 DI 10.1038/nature06613 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264TK UT WOS:000253313100052 PM 18288196 ER PT J AU Kay, J Bazari, H Avery, LL Koreishi, AF Cibotti-Granof, N Harris, NL Colvin, RB AF Kay, Jonathan Bazari, Hasan Avery, Laura L. Koreishi, Aashiyana F. Cibotti-Granof, Nancy Harris, Nancy Lee Colvin, Robert B. TI A woman with renal failure and stiffness of the joints and skin - Nephrogenic systemic fibrosis, involving the skin, heart, lungs, diaphragm and psoas muscles, dura, and possibly the kidney. End-stage renal disease with nephrocalcinosis. Acute and organizing bronchopneumonia. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MEDICAL PROGRESS; DERMOPATHY; GADOLINIUM; INVOLVEMENT; SARCOIDOSIS; NEUROPATHY; COMPLICATIONS; PHOTOPHERESIS; INSIGHTS; TISSUE C1 [Kay, Jonathan] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Bazari, Hasan] Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. [Avery, Laura L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Koreishi, Aashiyana F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kay, Jonathan; Bazari, Hasan] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Avery, Laura L.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Koreishi, Aashiyana F.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Kay, J (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. NR 40 TC 37 Z9 39 U1 0 U2 1 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 FEB 21 PY 2008 VL 358 IS 8 BP 827 EP 838 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 264AN UT WOS:000253257700010 PM 18287606 ER PT J AU Dudzinski, DM Kesselheim, AS AF Dudzinski, David M. Kesselheim, Aaron S. TI Scientific and legal viability of follow-on protein drugs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EXPENDITURES; BIOPHARMACEUTICALS; BIOLOGICS; MARKET C1 [Dudzinski, David M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kesselheim, Aaron S.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Dudzinski, DM (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 48 TC 28 Z9 28 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 21 PY 2008 VL 358 IS 8 BP 843 EP 849 DI 10.1056/NEJMhle0706973 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 264AN UT WOS:000253257700012 PM 18287608 ER PT J AU Monz, M Kufer, KH Bortfeld, TR Thieke, C AF Monz, M. Kuefer, K. H. Bortfeld, T. R. Thieke, C. TI Pareto navigation-algorithmic foundation of interactive multi-criteria IMRT planning SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; EFFICIENT SET; RADIATION-THERAPY; OPTIMIZATION; VALUES AB Inherently, IMRT treatment planning involves compromising between different planning goals. Multi- criteria IMRT planning directly addresses this compromising and thus makes it more systematic. Usually, several plans are computed from which the planner selects the most promising following a certain procedure. Applying Pareto navigation for this selection step simultaneously increases the variety of planning options and eases the identification of the most promising plan. Pareto navigation is an interactive multi- criteria optimizationmethod that consists of the two navigationmechanisms 'selection' and 'restriction'. The former allows the formulation of wishes whereas the latter allows the exclusion of unwanted plans. They are realized as optimization problems on the so- called plan bundle - a set constructed from pre- computed plans. They can be approximately reformulated so that their solution time is a small fraction of a second. Thus, the user can be provided with immediate feedback regarding his or her decisions. Pareto navigation was implemented in the MIRA navigator software and allows real- time manipulation of the current plan and the set of considered plans. The changes are triggered by simple mouse operations on the so- called navigation star and lead to real- time updates of the navigation star and the dose visualizations. Since any Pareto- optimal plan in the plan bundle can be found with just a few navigation operations the MIRA navigator allows a fast and directed plan determination. Besides, the concept allows for a refinement of the plan bundle, thus offering a middle course between single plan computation and multi- criteria optimization. Pareto navigation offers so far unmatched real- time interactions, ease of use and plan variety, setting it apart from the multi- criteria IMRT planning methods proposed so far. C1 [Monz, M.; Kuefer, K. H.] Fraunhofer Inst Ind Math, Dept Optimizat, D-67663 Kaiserslautern, Germany. [Bortfeld, T. R.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bortfeld, T. R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Thieke, C.] German Canc Res Ctr, Dept Radiat Oncol, D-69120 Heidelberg, Germany. [Thieke, C.] Univ Clin Heidelberg, D-69120 Heidelberg, Germany. RP Monz, M (reprint author), Fraunhofer Inst Ind Math, Dept Optimizat, Fraunhofer Pl 1, D-67663 Kaiserslautern, Germany. EM monz@itwm.fhg.de FU NCI NIH HHS [CA 103904-01A1] NR 33 TC 60 Z9 61 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 21 PY 2008 VL 53 IS 4 BP 985 EP 998 DI 10.1088/0031-9155/53/4/011 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 276WW UT WOS:000254175400012 PM 18263953 ER PT J AU Brugge, WR AF Brugge, William R. TI Diagnosis and management of relapsing pancreatitis associated with cystic neoplasms of the pancreas SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE pancreatitis; relapsing pancreatitis; endoscopic ultrasound; cystic neoplasms; intraductal papillary mucinous neoplasms; fine needle aspiration ID PAPILLARY-MUCINOUS NEOPLASMS; IDIOPATHIC ACUTE-PANCREATITIS; RECURRENT PANCREATITIS; ENDOSCOPIC ULTRASOUND; MICROCYSTIC ADENOMAS; LESIONS; EUS; MALIGNANCY; FEATURES; TUMOR AB One of the most important causes of relapsing pancreatitis is a cystic neoplasm of the pancreas. These low grade malignancies may cause pancreatitis by obstructing or communicating with a pancreatic duct. Patients with relapsing pancreatitis and a focal fluid fluid collection should be investigated for the possibility of a mucinous cystic neoplasm. Cross sectional imaging can provide a diagnosis with the imaging findings of a low attenuation cystic lesion containing mural calcification (CT scanning) or a lobular T2 enhancing lesion (MRCP). Endoscopic ultrasound can provide more detailed imaging with the ability to guide fine needle aspiration of the cyst fluid. Cyst fluid analysis can provide a diagnosis of a mucinous cystic lesion with the combination of cytology (mucinous epithelium), elevated carcinoembryonic antigen (CEA), and the presence of DNA mutations. Management of these patients consists of surgical resection and monitoring in patients not able to withstand surgery. (c) 2008 WJG. All rights reserved. C1 [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, Blake 452C,55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org NR 41 TC 6 Z9 7 U1 0 U2 2 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD FEB 21 PY 2008 VL 14 IS 7 BP 1038 EP 1043 DI 10.3748/wjg.14.1038 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 265VA UT WOS:000253388500012 PM 18286685 ER PT J AU D'Amico, AV AF D'Amico, Anthony V. TI Prostate-specific antigen (PSA) and PSA velocity: Competitors or collaborators in the prediction of curable and clinically significant prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MEN; BIOPSY; RISK; POPULATION; ROTTERDAM 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. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 5 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2008 VL 26 IS 6 BP 823 EP 824 DI 10.1200/JCO.2007.15.1902 PG 2 WC Oncology SC Oncology GA 276XU UT WOS:000254177800002 PM 18281649 ER PT J AU Ross, RW Oh, WK Xie, WL Pomerantz, M Nakabayashi, M Sartor, O Taplin, ME Regan, MM Kantoff, PW Freedman, M AF Ross, Robert W. Oh, William K. Xie, Wanling Pomerantz, Mark Nakabayashi, Mari Sartor, Oliver Taplin, Mary-Ellen Regan, Meredith M. Kantoff, Philip W. Freedman, Matthew TI Inherited variation in the androgen pathway is associated with the efficacy of androgen-deprivation therapy in men with prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Prostate Cancer Symposium of the American-Society-of-Clinical-Oncology CY FEB 22-24, 2007 CL Orlando, FL SP Amer Soc Clin Oncol, Amer Soc Therapeut Radiol & Oncol, Soc Urol Oncol ID ALLELIC VARIANTS; GENES; SUSCEPTIBILITY; POLYMORPHISMS; METABOLISM; EXPRESSION; CARCINOMA; AROMATASE; ESTROGEN; SYSTEM AB Purpose Androgen-deprivation therapy (ADT) is the most common and effective systemic therapy for advanced prostate cancer. We hypothesized that germline genetic variation in the androgen axis would improve the efficacy of ADT. Patients and Methods A cohort of 529 men with advanced prostate cancer treated with ADT was genotyped for 129 DNA polymorphisms distributed across 20 genes involved in androgen metabolism. Results Three polymorphisms in separate genes (CYP19A1, HSD3B1, and HSD17B4) were significantly (P < .01) associated with time to progression (TTP) during ADT, remaining so in multivariate analyses and after correcting for the number of hypotheses tested. Individuals carrying more than one of the polymorphisms associated with improved TTP demonstrated a better response to therapy than individuals carrying zero or one (P < .0001). Conclusion This report is the first to examine the influence of inherited variation in the androgen metabolic pathway on the efficacy of ADT, establishing the importance of pharmacogenomics on individual's response to this therapy. At least two potential clinical benefits may be realized from this study. The first is prognostic - genotyping patients at these loci may yield important information that could improve efficacy prediction. The second is therapeutic - these results shed light on the pathways that govern response to ADT. Drugs could be developed (or may already exist) to inhibit or augment these targets to improve ADT efficacy. C1 [Ross, Robert W.; Oh, William K.; Xie, Wanling; Pomerantz, Mark; Nakabayashi, Mari; Sartor, Oliver; Taplin, Mary-Ellen; Regan, Meredith M.; Kantoff, Philip W.; Freedman, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Freedman, M (reprint author), Dana Farber Canc Inst, Dana 710 C,44 Binney St, Boston, MA 02115 USA. EM freedman@broad.mit.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [5P50CA90381]; NCRR NIH HHS [U54 RR020278-01] NR 17 TC 79 Z9 79 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2008 VL 26 IS 6 BP 842 EP 847 DI 10.1200/JCO.2007.13.6804 PG 6 WC Oncology SC Oncology GA 276XU UT WOS:000254177800008 PM 18281655 ER PT J AU Heist, RS Zhai, RH Liu, G Zhou, W Lin, XH Su, L Asomaning, K Lynch, TJ Wain, JC Christiani, DC AF Heist, Rebecca Suk Zhai, Rihong Liu, Geoffrey Zhou, Wei Lin, Xihong Su, Li Asomaning, Kofi Lynch, Thomas J. Wain, John C. Christiani, David C. TI VEGF polymorphisms and survival in early-stage non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER; FACTOR GENE; TUMOR ANGIOGENESIS; MESSENGER-RNA; PLASMA-LEVELS; EXPRESSION; PROGNOSIS; RISK; ASSOCIATION AB Purpose Polymorphisms in the VEGF gene have been identified that are believed to have functional activity. We hypothesized that such polymorphisms may affect survival outcomes among early-stage non-small-cell lung cancer (NSCLC) patients. Patients and Methods We evaluated the relationship between VEGF polymorphisms and overall survival (OS) among patients with early-stage NSCLC treated with surgical resection at Massachusetts General Hospital from 1992 to 2001. We specifically investigated the VEGF polymorphisms +936C>T (rs3025039), -460T>C (rs833061), and +405G>C (rs2010963). Analyses of genotype associations with survival outcomes were performed using Cox proportional hazards models, Kaplan-Meier methods, and the log-rank test. Results There were 462 patients and 237 deaths. Patients carrying the variant C allele of the VEGF +405G>C polymorphism had significantly improved survival (crude hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.90; P=.006; adjusted HR = 0.70; 95% CI, 0.54 to 0.91; P=.008). Five-year OS for patients carrying the variant C allele of the VEGF +405G>C polymorphism was 61% (95% CI, 54% to 67%) versus 51% (95% CI, 43% to 59%) for those who had the wild-type variant. There was a trend toward improved survival among patients carrying the variant T allele of the VEGF +936C>T polymorphism (crude HR = 0.74; 95% CI, 0.53 to 1.03; P=.07; adjusted HR = 0.73; 95% CI, 0.52 to 1.03; P=.07). Moreover, patients with higher number of variant alleles of the +405G>C and +936C>T polymorphisms had better survival. There was no association found with the -460T>C polymorphism. Conclusion Polymorphisms in VEGF may affect survival in early-stage lung cancer. C1 [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA074386, CA090578, CA092824, K12CA087723] NR 29 TC 84 Z9 85 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2008 VL 26 IS 6 BP 856 EP 862 DI 10.1200/JCO.2007.13.5947 PG 7 WC Oncology SC Oncology GA 276XU UT WOS:000254177800010 PM 18281657 ER PT J AU Guix, M Granja, ND Meszoely, I Adkins, TB Wieman, BM Frierson, KE Sanchez, V Sanders, ME Grau, AM Mayer, IA Pestano, G Shyr, Y Muthuswamy, S Calvo, B Krontiras, H Krop, IE Kelley, MC Arteaga, CL AF Guix, Marta Granja, Nara de Matos Meszoely, Ingrid Adkins, Theresa B. Wieman, Bobbye M. Frierson, Kerek E. Sanchez, Violeta Sanders, Melinda E. Grau, Ana M. Mayer, Ingrid A. Pestano, Gary Shyr, Yu Muthuswamy, Senthil Calvo, Benjamin Krontiras, Helen Krop, Ian E. Kelley, Mark C. Arteaga, Carlos L. TI Short Preoperative treatment with erlotinib inhibits tumor cell proliferation in hormone receptor-positive breast cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas, Hlth Sci Ctr ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITOR; LUNG-CANCER; PHASE-II; POSTMENOPAUSAL PATIENTS; DOUBLE-BLIND; IN-VITRO; GEFITINIB; TRIAL; COMBINATION AB Purpose To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ER alpha. Results In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade <= 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) -positive but not in human epidermal growth factor receptor 2 (HER-2) -positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ER alpha in hormone receptor -positive cancers. Conclusion A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2 -positive or triple-negative breast cancers. C1 Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Breast Canc Res Program,Dept Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Breast Canc Res Program,Dept Pathol, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Breast Canc Res Program,Dept Biostat, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Breast Canc Res Program,Dept Surg, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Breast Canc Res Program,Dept Canc Biol, Nashville, TN 37212 USA. Ventana Med Syst Inc, Tucson, AZ USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ Alabama, Birmingham Canc Ctr, Birmingham, AL USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Arteaga, CL (reprint author), Vanderbilt Univ, Med Ctr, Div Oncol, 2220 Pierce Ave,777 PRB, Nashville, TN 37232 USA. EM carlos.arteaga@vanderbilt.edu FU NCI NIH HHS [CA098131-03S1, P30 CA68485, P50 CA98131, R01 CA80195] NR 34 TC 67 Z9 71 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2008 VL 26 IS 6 BP 897 EP 906 DI 10.1200/JCO.2007.13.5939 PG 10 WC Oncology SC Oncology GA 276XU UT WOS:000254177800016 PM 18180460 ER PT J AU Ligibel, JA Campbell, N Partridge, A Chen, WY Salinardi, T Chen, H Adloff, K Keshaviah, A Winer, EP AF Ligibel, Jennifer A. Campbell, Nancy Partridge, Ann Chen, Wendy Y. Salinardi, Taylor Chen, Haiyan Adloff, Kristie Keshaviah, Aparna Winer, Eric P. TI Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID QUALITY-OF-LIFE; RECREATIONAL PHYSICAL-ACTIVITY; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; FASTING INSULIN; RESISTANCE; RISK; GLUCOSE; PREVENTION; OBESITY AB Purpose Accumulating data suggest that exercise may affect breast cancer risk and outcomes. Studies have demonstrated that high levels of insulin, often seen in sedentary individuals, are associated with increased risk of breast cancer recurrence and death. We sought to analyze whether exercise lowered insulin concentrations in breast cancer survivors. Methods One hundred one sedentary, overweight breast cancer survivors were randomly assigned either to a 16-week cardiovascular and strength training exercise intervention or to a usual care control group. Fasting insulin and glucose levels, weight, body composition, and circumference at the waist and hip were collected at baseline and 16 weeks. Results Baseline and 16-week measurements were available for 82 patients. Fasting insulin concentrations decreased by an average of 2.86 mu U/mL in the exercise group (P=.03), with no significant change in the control group (decrease of 0.27 mu U/mL, P=.65). The change in insulin levels in the exercise group seemed greater than the change in controls, but the comparison did not reach statistical significance (P=.07). There was a trend toward improvement in insulin resistance in the exercise group (P=.09) but no change in fasting glucose levels. The exercise group also experienced a significant decrease in hip measurements, with no change in weight or body composition. Conclusion Participation in an exercise intervention was associated with a significant decrease in insulin levels and hip circumference in breast cancer survivors. The relationship between physical activity and breast cancer prognosis may be mediated, in part, through changes in insulin levels and/or changes in body fat or fat deposition. C1 [Ligibel, Jennifer A.; Campbell, Nancy; Partridge, Ann; Chen, Wendy Y.; Salinardi, Taylor; Chen, Haiyan; Adloff, Kristie; Keshaviah, Aparna; Winer, Eric P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Channing Lab, Boston, MA 02115 USA. RP Ligibel, JA (reprint author), 44 Binney St, Boston, MA 02115 USA. EM jligibel@partners.org NR 30 TC 123 Z9 129 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2008 VL 26 IS 6 BP 907 EP 912 DI 10.1200/JCO.2007.12.7357 PG 6 WC Oncology SC Oncology GA 276XU UT WOS:000254177800017 PM 18281663 ER PT J AU Schneiderman, J London, WB Brodeur, GM Castleberry, RP Look, AT Cohn, SL AF Schneiderman, Jennifer London, Wendy B. Brodeur, Garrett M. Castleberry, Robert P. Look, A. Thomas Cohn, Susan L. TI Clinical significance of MYCN amplification and ploidy in favorable-stage neuroblastoma: A report from the children's oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Advances in Neuroblastoma Research Meeting CY MAY 17-20, 2006 CL Los Angeles, CA ID TUMOR-CELL PLOIDY; N-MYC; GENE AMPLIFICATION; LOCALIZED NEUROBLASTOMA; ONCOGENE AMPLIFICATION; RISK NEUROBLASTOMA; PROGNOSTIC FACTORS; NEURO-BLASTOMA; EXPERIENCE; GANGLIONEUROBLASTOMA AB Purpose MYCN amplification is rarely detected in patients with favorable-stage neuroblastoma (NB). To determine the clinical significance of MYCN amplification in children with favorable-stage NB, we performed a retrospective review of data from the Pediatric Oncology Group (POG) biology study 9047. Patients and Methods MYCN status, tumor cell ploidy, treatment, and outcome of patients with stage A, B, or Ds NB, enrolled on POG 9047 between 1990 and 1999 were analyzed. Event-free survival (EFS) and overall (OS) survival rates were analyzed using the Kaplan-Meier method. Results Of the 1,667 patients enrolled on POG 9047, 643 had favorable-stage disease. Of these, follow-up data were available on 568 (34%) with stage A, B, or Ds disease and normal MYCN copy number, and 32 (1.9%) patients with MYCN-amplified, stage A, B, or Ds tumors. Within the cohort lacking MYCN amplification, the 7-year EFS and OS rates (+/- SE) were 91% +/- 1% and 96% +/- 1%, respectively. Patients with MYCN amplification had significantly worse EFS and OS (50% +/- 9% and 59% +/- 9%, respectively, P<.0001). Within the cohort of children with MYCN amplification, the 7-year EFS and OS rates were 80% +/- 10% and 87% +/- 9%, respectively for patients with hyperdiploid tumors and 25% +/- 11% and 38% +/- 12% for patients with diploid/hypodiploid NBs (P=.0063 and P=.0074, respectively). Conclusion Tumor cell ploidy may be a clinically useful factor for prognostication and treatment stratification in children with MYCN-amplified, favorable-stage NB tumors. C1 [Cohn, Susan L.] Univ Chicago, Sect Pediat Hematol Oncol, Dept Pediat, Chicago, IL 60637 USA. Corner Childrens Hosp, Chicago, IL USA. Northwestern Univ, Feinberg Sch Med, Childrens Mem Hosp, Evanston, IL 60208 USA. Northwestern Univ, Feinberg Sch Med, Dept Pediat, Evanston, IL 60208 USA. Univ Florida, Childrens Oncol Grp Stat & Data Ctr, Gainesville, FL USA. Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Cohn, SL (reprint author), Univ Chicago, Sect Pediat Hematol Oncol, Dept Pediat, 5841 Maryland Ave,MC 4060,Rm N114, Chicago, IL 60637 USA. EM scohn@peds.bsd.uchicago.edu OI Cohn, Susan/0000-0001-5749-7650 FU NCI NIH HHS [CA 98543, CA 30969, CA25408, R01 CA039771, U10CA29139]; NINDS NIH HHS [R01 NS049814] NR 24 TC 32 Z9 37 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2008 VL 26 IS 6 BP 913 EP 918 DI 10.1200/JCO.2007.13.9493 PG 6 WC Oncology SC Oncology GA 276XU UT WOS:000254177800018 PM 18281664 ER PT J AU MacDonald, TJ Stewart, CF Kocak, M Goldman, S Ellenbogen, RG Phillips, P Lafond, D Poussaint, TY Kieran, MW Boyett, JM Kun, LE AF MacDonald, Tobey J. Stewart, Clinton F. Kocak, Mehmet Goldman, Stewart Ellenbogen, Richard G. Phillips, Peter Lafond, Deborah Poussaint, Tina Young Kieran, Mark W. Boyett, James M. Kun, Larry E. TI Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric brain tumor consortium study PBTC-012 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CYCLIC RGD PEPTIDES; ARG-GLY-ASP; VITRONECTIN RECEPTOR; INTEGRIN ANTAGONIST; ALPHA-V-BETA-3; ANGIOGENESIS; APOPTOSIS; METASTASIS; EMD-121974; INHIBITION AB Purpose A phase I trial of the antiangiogenesis agent cilengitide (EMD 121974), an alpha v beta 3,5 integrin antagonist, was performed to estimate the maximum-tolerated dose (MTD) and describe dose-limiting toxicities (DLTs) and the incidence and severity of other toxicities when administered to children with refractory brain tumors. Patients and Methods Thirty-one assessable patients received intravenous cilengitide over 1 hour twice a week for up to 52 weeks at dosages from 120 to 2,400 mg/m(2). Serial blood and urine samples for clinical pharmacology studies were obtained in a subset of consenting patients. Results No DLTs were observed, and thus, the MTD was not estimated. Three of 13 patients at the dosage level of 2,400 mg/m(2) experienced grade 3 or 4 intratumoral hemorrhage (ITH) possibly related to the study drug; however, two of the ITH events were asymptomatic and, by the current toxicity criteria, would be classified as grade 1. For patients treated at cilengitide 2,400 mg/m(2), the 6-month cumulative incidence estimate of ITH is 23% (SE=13%). No ITH was observed at 1,800 mg/m(2). Three patients completed 1 year of protocol therapy; one patient with glioblastoma multiforme demonstrated complete response, and two patients had stable disease (SD). An additional patient had SD for more than 5 months. Conclusion The phase II dosage of intravenous cilengitide in children with refractory brain tumors is 1,800 mg/m(2). A phase II trial to assess the efficacy of cilengitide therapy for children with refractory brain tumors is being developed by the Children's Oncology Group. C1 [MacDonald, Tobey J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Boston, Boston, MA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Pediat Brain Tumor Consortium, Memphis, TN USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. RP MacDonald, TJ (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave,NW, Washington, DC 20010 USA. EM tmacdona@cnmc.org RI MacDonald, Tobey/D-4554-2013; OI Kieran, Mark/0000-0003-2184-7692; Kocak, Mehmet/0000-0002-3386-1734 FU NCI NIH HHS [U01 CA81457] NR 29 TC 91 Z9 96 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2008 VL 26 IS 6 BP 919 EP 924 DI 10.1200/JCO.2007.14.1812 PG 6 WC Oncology SC Oncology GA 276XU UT WOS:000254177800019 PM 18281665 ER PT J AU Eberhard, DA Giaccone, G Johnson, BE AF Eberhard, David A. Giaccone, Giuseppe Johnson, Bruce E. TI Biomarkers of response to epidermal growth factor receptor inhibitors in non-small-cell lung cancer working group: Standardization for use in the clinical trial setting SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IN-SITU-HYBRIDIZATION; HER-2/NEU GENE AMPLIFICATION; SOUTHWEST-ONCOLOGY-GROUP; PHASE-II TRIAL; BREAST-CANCER; COPY NUMBER; EGFR MUTATIONS; BRONCHIOLOALVEOLAR-CARCINOMA; PROTEIN OVEREXPRESSION; INCREASED SENSITIVITY AB The body of literature on the correlations between molecular assessments and patient outcomes after treatment with epidermal growth factor receptor (EGFR) inhibitors continues to grow. It will be important in the future to determine how to most effectively integrate molecular assays that assess the likelihood of therapeutic benefit into clinical practice. Although EGFR-targeted therapies such as erlotinib have been approved for use without molecular testing, immunohistochemistry, fluorescence in situ hybridization, and mutational analyses of the EGFR gene have all been proposed as candidates to help predict response or survival benefit from EGFR-targeted therapy in patients with non-small-cell lung cancer (NSCLC). Further prospective validation from ongoing randomized studies will be needed to fully determine which assays are best to help predict patient outcome. In addition, it will be critical for these assays to undergo standardization before widespread clinical use. The Molecular Assays in NSCLC Working Group, under the sponsorship of Genentech Inc, Roche Pharmaceuticals, and OSI Pharmaceuticals, Inc, was convened to evaluate the available molecular assays for use in the clinical trial setting and provide recommendations for application and interpretation of these tests for future clinical trials. Recommendations of the Molecular Assays in NSCLC Working Group for the use of EGFR molecular assays are presented and include guidelines for tissue storage, handling, and processing. Recommendations for the standardization of molecular assays are also discussed. C1 [Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 1234, Boston, MA 02115 USA. EM bejohnson@partners.org RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 74 TC 209 Z9 221 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2008 VL 26 IS 6 BP 983 EP 994 DI 10.1200/JCO.2007.12.9858 PG 12 WC Oncology SC Oncology GA 276XU UT WOS:000254177800027 PM 18281673 ER PT J AU Partridge, A Adloff, K Blood, E Dees, C Kaelin, C Golshan, M Ligibel, J De Moor, JS Weeks, J Emmons, K Winer, E AF Partridge, Ann Adloff, Kristie Blood, Emily Dees, Claire Kaelin, Carolyn Golshan, Mehra Ligibel, Jennifer De Moor, Janet S. Weeks, Jane Emmons, Karen Winer, Eric TI Risk perceptions and psychosocial outcomes of women with ductal carcinoma in situ: Longitudinal results from a cohort study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER SURVIVORS; QUALITY-OF-LIFE; SURGICAL ADJUVANT BREAST; HEALTH SURVEY SF-36; RADIATION-THERAPY; LOCAL RECURRENCE; PERCEIVED RISK; STATISTICS; ADJUSTMENT; MANAGEMENT AB Background Ductal carcinoma in situ (DCIS) has a generally favorable overall prognosis, with a systemic recurrence rate of approximately 1%, a local recurrence rate after mastectomy of 1%, and a local recurrence rate after breast-conserving treatment of less than 10%. Preliminary studies have suggested that women with DCIS may overestimate their risk of disease recurrence. Few data exist regarding psychosocial outcomes for women with DCIS. Methods Women in Eastern Massachusetts with newly diagnosed DCIS were asked to participate in a longitudinal study of risk perceptions, psychosocial concerns, and health behaviors. Psychosocial outcomes after DCIS diagnosis and risk perceptions were evaluated at enrollment and at 9 and 18 months. All statistical tests were two-sided. Results Four hundred eighty-seven women with DCIS (64% of eligible participants) completed the enrollment survey. Overall quality of life was good among the women surveyed, and the substantial anxiety at enrollment decreased with time (P < .001). At enrollment, 54% perceived at least a moderate risk for DCIS recurrence in the next 5 years, 68% in their lifetime; 39% perceived at least a moderate risk for invasive cancer in the next 5 years, 53% in their lifetime; and 28% perceived at least a moderate likelihood of DCIS spreading to other places in their body. At 18 months after enrollment, perceived risks had not statistically significantly changed from those at enrollment (P = .38). Anxiety at enrollment was the factor that was most consistently and strongly associated with overestimation of future breast cancer-related risks (perceived moderate or greater risk vs less than moderate risk of DCIS recurring within 5 years: odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.6 to 9.9, P = .003; of invasive breast cancer within 5 years: OR = 4.3, 95% CI = 1.9 to 9.9, P < .001; and of invasive breast cancer during lifetime: OR = 5.3, 95% CI = 2.0 to 14.3, P < .001). Conclusions Many women with newly diagnosed DCIS have inaccurate perceptions of the breast cancer risks that they face, and anxiety is particularly associated with these inaccurate perceptions. C1 [Partridge, Ann; Adloff, Kristie; Blood, Emily; Dees, Claire; Kaelin, Carolyn; Golshan, Mehra; Ligibel, Jennifer; De Moor, Janet S.; Weeks, Jane; Emmons, Karen; Winer, Eric] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dees, Claire] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Partridge, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ahpartridge@partners.org FU NCI NIH HHS [5 P50 CA89393-03] NR 53 TC 80 Z9 83 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 20 PY 2008 VL 100 IS 4 BP 243 EP 251 DI 10.1093/jnci/djn010 PG 9 WC Oncology SC Oncology GA 271OB UT WOS:000253796600007 PM 18270338 ER PT J AU Chapman, JAW Meng, D Shepherd, L Parulekar, W Ingle, JN Muss, HB Palmer, M Yu, C Goss, PE AF Chapman, Judith-Anne W. Meng, Daniel Shepherd, Lois Parulekar, Wendy Ingle, James N. Muss, Hyman B. Palmer, Michael Yu, Changhong Goss, Paul E. TI Competing causes of death from a randomized trial of extended adjuvant endocrine therapy for breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FAILURE PROBABILITIES; PREDICTIVE FACTORS; 15-YEAR SURVIVAL; RISKS; RECURRENCE; MODEL AB Background Older women with early-stage breast cancer experience higher rates of non-breast cancer-related death. We examined factors associated with cause-specific death in a large cohort of breast cancer patients treated with extended adjuvant endocrine therapy. Methods In the MA. 17 trial, conducted by the National Cancer Institute of Canada Clinical Trials Group, 5170 breast cancer patients (median age = 62 years; range = 32-94 years) who were disease free after approximately 5 years of adjuvant tamoxifen treatment were randomly assigned to treatment with letrozole (2583 women) or placebo (2587 women). The median follow-up was 3.9 years (range = 0-7 years). We investigated the association of 11 baseline factors with the competing risks of death from breast cancer, other malignancies, and other causes. All statistical tests were two-sided likelihood ratio criterion tests. Results During follow-up, 256 deaths were reported (102 from breast cancer, 50 from other malignancies, 100 from other causes, and four from an unknown cause). Non-breast cancer deaths accounted for 60% of the 252 known deaths (72% for those = 70 years and 48% for those < 70 years). Two baseline factors were differentially associated with type of death: cardiovascular disease was associated with a statistically significant increased risk of death from other causes (P = .002), and osteoporosis was associated with a statistically significant increased risk of death from other malignancies (P = .05). An increased risk of breast cancer-specific death was associated with lymph node involvement (P < .001). Increased risk of death from all three causes was associated with older age (P < .001). Conclusions Non-breast cancer-related deaths were more common than breast cancer-specific deaths in this cohort of 5-year breast cancer survivors, especially among older women. C1 [Chapman, Judith-Anne W.; Meng, Daniel; Shepherd, Lois; Parulekar, Wendy; Palmer, Michael; Yu, Changhong] Queens Univ, Natl Canc Inst Clin Trials Grp, Kingston, ON, Canada. [Ingle, James N.] Mayo Clin, Dept Oncol, Rochester, MN USA. [Muss, Hyman B.] Univ Vermont, Dept Med, Burlington, VT USA. [Goss, Paul E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02115 USA. RP Chapman, JAW (reprint author), Queens Univ, Natl Canc Inst Clin Trials Grp, 10 Stuart St, Kingston, ON, Canada. EM jchapman@ctg.queensu.ca FU NCI NIH HHS [N01 CA038926, CA21115, CA25224, CA31946, N01 CA032102, U10 CA021115, U10 CA025224, U10 CA025224-26, U10 CA031946, U10 CA032102, U10 CA038926] NR 26 TC 71 Z9 71 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 20 PY 2008 VL 100 IS 4 BP 252 EP 260 DI 10.1093/jnci/djn014 PG 9 WC Oncology SC Oncology GA 271OB UT WOS:000253796600008 PM 18270335 ER PT J AU Fakhry, C Westra, WH Cmelak, SLA Ridge, JA Pinto, H Forastiere, A Gillison, ML AF Fakhry, Carole Westra, William H. Cmelak, Sigui Li Anthony Ridge, John A. Pinto, Harlan Forastiere, Arlene Gillison, Maura L. TI Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ORAL-CANCER; MULTICENTER; EXPRESSION; ENTITY AB Background The improved prognosis for patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. Methods We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Results Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P = .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [ 95% CI = 87% to 100%] vs 62% [ 95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P = .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors. Conclusion For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival. C1 [Fakhry, Carole; Westra, William H.; Forastiere, Arlene; Gillison, Maura L.] John Hopkins Kimmel Canc Ctr, Baltimore, MD 21231 USA. [Cmelak, Sigui Li Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cmelak, Sigui Li Anthony] Vanderbilt Univ, Nashville, TN USA. [Pinto, Harlan] Stanford Univ, Palo Alto, CA 94304 USA. [Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Gillison, ML (reprint author), John Hopkins Kimmel Canc Ctr, Res Bldg 1,Rm 3M 54A,1650 Orleans St, Baltimore, MD 21231 USA. EM gillima@jhmi.edu NR 22 TC 1100 Z9 1119 U1 5 U2 58 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 20 PY 2008 VL 100 IS 4 BP 261 EP 269 DI 10.1093/jnci/djn011 PG 9 WC Oncology SC Oncology GA 271OB UT WOS:000253796600009 PM 18270337 ER PT J AU Frahm, N Nickle, DC Linde, CH Roach, T Walker, BD Allen, TM Korber, BT Mullins, JI Brander, C AF Frahm, Nicole Nickle, David C. Linde, Caitlyn H. Roach, Timothy Walker, Bruce D. Allen, Todd M. Korber, Bette T. Mullins, James I. Brander, Christian TI Increased detection of HIV-specific T cell responses by combination of central sequences with comparable immunogenicity SO AIDS LA English DT Article DE amino acid sequence; cell-mediated immunity; HIV sequence diversity; HIV vaccine design; immunogenicity ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONSENSUS ENVELOPE GLYCOPROTEIN; SUBTYPE-B; PEPTIDES; VACCINE; LYMPHOCYTES; ANTIBODIES; SELECTION; VARIANTS; COVERAGE AB Objective: To evaluate the recognition of computationally designed, centralized HIV-1 antigens derived from clade B, C and group M sequences by individuals infected with HIV-1 -M clades B and C. Methods: Three centralized sequences have been described - consensus, ancestor and center-of-tree - each of which attempts to minimize the genetic distance to circulating viruses. It is unclear whether any of these sequences affords an advantage for T cell recognition. The ability of centralized clade B and C and group M peptides to be targeted in ELISpot assays was assessed using samples from the United States, Peru, Barbados and South Africa. Results: Each of the clade-specific centralized peptide sets was equally powerful in detecting cytotoxic T cell (CTL) responses. Importantly, combination of these sets detected significantly broader responses. Although broad responses were observed in populations from which few sequences informed the design of these centralized sequences, the genetic distance between local sequences and the respective test set was inversely associated with response rates. Furthermore, the CTL reactivity in clade C-infected subjects using clade B peptides was reduced relative to within-clade peptide responses, while responses to group M peptides were comparable to within-clade peptide responses in these individuals. Conclusions: All tested centralized antigens provided a similarly potent set of antigenic peptides. However, the significantly broader responses detected using the combination of sets highlight the importance of maximizing coverage of HIV-1 sequence diversity in vaccine preparations, as well as in the evaluation of CTL responses in HIV-1-infected individuals and those vaccinated. (c) 2008 Wolters Kluwer Health I Lippincott Williams & Wilkins C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Frahm, N (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM nfrahm@partners.org RI Allen, Todd/F-5473-2011; OI Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [P01-AI-57005, P30-AI-27757]; PHS HHS [N01-AL-15422, N01-AL-30024, R01-A1-067077] NR 33 TC 24 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD FEB 19 PY 2008 VL 22 IS 4 BP 447 EP 456 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 277XE UT WOS:000254247200002 PM 18301057 ER PT J AU Fruh, M Zhou, W Zhai, R Su, L Heist, RS Wain, JC Nishioka, NS Lynch, TJ Shepherd, FA Christiani, DC Liu, G AF Fruh, M. Zhou, W. Zhai, R. Su, L. Heist, R. S. Wain, J. C. Nishioka, N. S. Lynch, T. J. Shepherd, F. A. Christiani, D. C. Liu, G. TI Polymorphisms of inflammatory and metalloproteinase genes, Helicobacter pylori infection and the risk of oesophageal adenocarcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE polymorphism; metalloproteinases; oesophageal cancer; Helicobacter pylori ID GASTROESOPHAGEAL-REFLUX; PROMOTER; CANCER; CARCINOMA; DISEASE; ASSOCIATION; METAPLASIA; GASTRITIS; GENDER; XRCC1 AB Helicobacter pylori (HP) infection appears protective against oesophageal adenocarcinoma (EA) risk. Matrix metalloproteinases (MMPs) are released in the presence of HP infection. In MMP2 wild-type individuals, HP was significantly protective of EA risk (adjusted odds ratio: 0.29; 95% confidence interval = 0.1 - 0.7). Matrix metalloproteinases may modulate the EA - HP relationship. C1 [Fruh, M.; Shepherd, F. A.; Liu, G.] Princess Margaret Hosp, Ontario Canc Inst, Dept Med, Toronto, ON M5G 2M9, Canada. [Zhou, W.; Zhai, R.; Su, L.; Heist, R. S.; Christiani, D. C.; Liu, G.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Heist, R. S.; Lynch, T. J.; Liu, G.] Harvard Univ, Massachusetts Gen Hosp Canc Ctr, Sch Med, Dept Med, Boston, MA 02115 USA. [Wain, J. C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Nishioka, N. S.] Massachusetts Gen Hosp, Dept Med, Endoscopy Unit, Boston, MA 02114 USA. [Christiani, D. C.] Massachusetts Gen Hosp, Dept Med, Pulm Unit, Boston, MA 02114 USA. [Liu, G.] Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. RP Liu, G (reprint author), Princess Margaret Hosp, Ontario Canc Inst, Suite 7-124,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM Geoffrey.Liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [R01 CA109193, R03 CA110822] NR 24 TC 7 Z9 8 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB 19 PY 2008 VL 98 IS 4 BP 689 EP 692 DI 10.1038/sj.bjc.6604234 PG 4 WC Oncology SC Oncology GA 263LX UT WOS:000253219700003 PM 18253117 ER PT J AU Hassel, D Scholz, EP Trano, N Friedrich, O Just, S Meder, B Weiss, DL Zitron, E Marquart, S Vogel, B Karle, CA Seemann, G Fishman, MC Katus, HA Rottbauer, W AF Hassel, David Scholz, Eberhard P. Trano, Nicole Friedrich, Oliver Just, Steffen Meder, Benjamin Weiss, Daniel L. Zitron, Edgar Marquart, Sabine Vogel, Britta Karle, Christoph A. Seemann, Gunnar Fishman, Mark C. Katus, Hugo A. Rottbauer, Wolfgang TI Deficient zebrafish ether-a-go-go-related gene channel gating causes Short-QT syndrome in zebrafish reggae mutants SO CIRCULATION LA English DT Article DE arrhythmia; fibrillation; genetics; ion channels ID HERG; MODEL; FIBRILLATION; MECHANISM; MUTATION; INTERVAL; EMBRYOS; MUSCLE; TISSUE AB Background-Genetic predisposition is believed to be responsible for most clinically significant arrhythmias; however, suitable genetic animal models to study disease mechanisms and evaluate new treatment strategies are largely lacking. Methods and Results-In search of suitable arrhythmia models, we isolated the zebrafish mutation reggae (reg), which displays clinical features of the malignant human short-QT syndrome such as accelerated cardiac repolarization accompanied by cardiac fibrillation. By positional cloning, we identified the reg mutation that resides within the voltage sensor of the zebrafish ether-a-go-go-related gene (zERG) potassium channel. The mutation causes premature zERG channel activation and defective inactivation, which results in shortened action potential duration and accelerated cardiac repolarization. Genetic and pharmacological inhibition of zERG rescues recessive reg mutant embryos, which confirms the gain-of-function effect of the reg mutation on zERG channel function in vivo. Accordingly, QT intervals in ECGs from heterozygous and homozygous reg mutant adult zebrafish are considerably shorter than in wild-type zebrafish. Conclusions-With its molecular and pathophysiological concordance to the human arrhythmia syndrome, zebrafish reg represents the first animal model for human short-QT syndrome. C1 [Hassel, David; Scholz, Eberhard P.; Trano, Nicole; Just, Steffen; Meder, Benjamin; Weiss, Daniel L.; Zitron, Edgar; Marquart, Sabine; Karle, Christoph A.; Katus, Hugo A.; Rottbauer, Wolfgang] Univ Heidelberg Hosp, Dept Internal Med 3, D-69120 Heidelberg, Germany. [Friedrich, Oliver; Fishman, Mark C.] Univ Heidelberg Hosp, Dept Physiol & Pathophysiol, D-69120 Heidelberg, Germany. [Weiss, Daniel L.; Seemann, Gunnar] Univ Karlsruhe, Inst Biomed Engn, Karlsruhe, Germany. [Fishman, Mark C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Rottbauer, W (reprint author), Univ Heidelberg Hosp, Dept Internal Med 3, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. EM wolfgang.rottbauer@med.uni-heidelberg.de RI Seemann, Gunnar/D-3091-2011; Katus, Hugo/P-1712-2016 OI Seemann, Gunnar/0000-0001-7111-7992; NR 25 TC 55 Z9 55 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD FEB 19 PY 2008 VL 117 IS 7 BP 866 EP 875 DI 10.1161/CIRCULATIONAHA.107.752220 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 266IQ UT WOS:000253428100003 PM 18250272 ER PT J AU Ko, DT Wang, Y Alter, DA Curtis, JP Rathore, SS Stukel, TA Masoudi, FA Ross, JS Foody, JM Krumholz, HM AF Ko, Dennis T. Wang, Yongfei Alter, David A. Curtis, Jeptha P. Rathore, Salf S. Stukel, Therese A. Masoudi, Fredrick A. Ross, Joseph S. Foody, JoAnne M. Krumholz, Harlan M. TI Regional variation in cardiac catheterization appropriateness and baseline risk after acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES COMMITTEE; ACUTE CORONARY EVENTS; BYPASS GRAFT-SURGERY; NEW-YORK-STATE; AMERICAN-COLLEGE; ELDERLY-PATIENTS; GLOBAL REGISTRY; UNITED-STATES; OUTCOMES AB Objectives We evaluated whether appropriateness and baseline risk of cardiac catheterization varied according to regional intensity of invasive therapy after acute myocardial infarction (AMI), and whether AMI mortality varied according to invasive intensity regions. Background Marked regional variations exist in cardiac invasive procedure use after AMI within the U.S. Methods We performed an analysis of 44,639 Medicare fee-for-service beneficiaries hospitalized with AMI between 1998 and 2001. Invasive procedure intensity was determined based on overall cardiac catheterization rates for Medicare enrollees. Cardiac catheterization appropriateness was determined by the American College of Cardiology/American Heart Association classification and baseline risk was estimated using the GRACE (Global Registry of Acute Coronary Events) risk score. The primary outcomes of the study were cardiac catheterization use within 60 days and 3-year mortality after hospital admission. Results Higher invasive intensity regions were more likely to perform cardiac catheterizations on class I patients (appropriate) (RR 1.38, 95% confidence interval [CI] 1.27 to 1.48), class II patients (equivocal) (RR 1.42, 95% CI 1.31 to 1.53), and class III patients (inappropriate) (RR 1.29, 95% 0.97 to 1.67) compared with low-intensity regions after adjusting for patient and physician characteristics. The overall cardiac catheterization use was 5.2% lower for each increase in GRACE risk decile, and this relationship was observed similarly in all regions. Risk-standardized mortality rates of AMI patients at 3 years were not substantially different between regions. Conclusions Although higher-risk patients and those with more appropriate indications may have the most to benefit from an invasive strategy after AMI, we found that higher-invasive regions do not differentiate procedure selection based on the patients' appropriateness or their baseline risks. C1 [Ko, Dennis T.; Alter, David A.; Stukel, Therese A.] Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. [Ko, Dennis T.] Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Div Cardiol, Toronto, ON M4N 3M5, Canada. [Wang, Yongfei; Curtis, Jeptha P.; Rathore, Salf S.; Foody, JoAnne M.; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Masoudi, Fredrick A.] Univ Colorado, Hlth Sci Ctr, Denver Hlth Med Ctr, Dept Med, Denver, CO USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, Dept Epidemiol & Publ Hlth,Sect Hlth Policy & Adm, New Haven, CT USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Ko, DT (reprint author), Inst Clin Evaluat Sci G1 06, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM dennis.ko@ices.on.ca OI Ko, Dennis/0000-0001-6840-8051 NR 31 TC 42 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 19 PY 2008 VL 51 IS 7 BP 716 EP 723 DI 10.1016/j.jacc.2007.10.039 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 265JE UT WOS:000253354100006 PM 18279735 ER PT J AU Miller, M Cannon, CP Murphy, SA Qin, J Ray, KK Braunwald, E AF Miller, Michael Cannon, Christopher P. Murphy, Sabina A. Qin, Jie Ray, Kausik K. Braunwald, Eugene CA PROVE IT-TIMI Investigators TI Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID REACTIVE PROTEIN-LEVELS; HEART-DISEASE RISK; ARTERY-DISEASE; STATIN THERAPY; HYPERCHOLESTEROLEMIC PATIENTS; ADHESION MOLECULES; HDL-CHOLESTEROL; ATORVASTATIN; MANAGEMENT; LDL AB Objectives The purpose of this study was to assess the impact of on-treatment triglycerides (TG) on coronary heart disease (CHD) risk after an acute coronary syndrome (ACS). Background The PROVE IT-TIMI (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) 22 trial demonstrated that low-density lipoprotein cholesterol (LDL-C) <70 mg/dl was associated with greater CHD event reduction than LDL-C <100 mg/dl after ACS. However, the impact of low on-treatment TG on CHD risk beyond LDL-C <70 mg/dl has not been explored. Methods The PROVE IT-TIMI 22 trial evaluated 4,162 patients hospitalized for ACS and randomized to atorvastatin 80 mg or pravastatin 40 mg daily. The relationship between on-treatment levels of TG and LDL-C and the composite end point of death, myocardial infarction (MI), and recurrent ACS were assessed 30 days after initial presentation. Results Low on-treatment TG (<150 mg/dl) was associated with reduced CHD risk compared with higher TG in univariate analysis (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.62 to 0.87; p < 0.001) and in adjusted analysis (HR 0.80, 95% CI 0.66 to 0.97; p = 0.025). For each 10-mg/dl decrement in on-treatment TG, the incidence of death, MI, and recurrent ACS was lower by 1.6% or 1.4% after adjustment for LDL-C or non-high-density lipoprotein cholesterol and other covariates (p < 0.001 and p = 0.01, respectively). Lower CHD risk was also observed with TG <150 mg./dl and LDL-C <70 mg//dl (HR 0.72, 95% CI 0.54 to 0.94; p 0.017) or low on-treatment TG, LDL-C, and C-reactive protein (<2 mg/l) (HR 0.59, 95% CI 0.41 to 0.83; p 0.002) compared with higher levels of each variable in adjusted analysis. Conclusions On-treatment TG <150 mg/dl was independently associated with a lower risk of recurrent CHD events, lending support to the concept that achieving low TG may be an additional consideration beyond low LDL-C in patients after ACS. C1 [Miller, Michael] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Cannon, Christopher P.; Murphy, Sabina A.; Qin, Jie; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Ray, Kausik K.] Univ Cambridge, Cambridge, England. RP Miller, M (reprint author), Univ Maryland Hosp, Div Cardiol, Room S3B06,22 S Greene St, Baltimore, MD 21201 USA. EM mmiller@heart.umaryland.edu FU NHLBI NIH HHS [HL-61369] NR 47 TC 240 Z9 270 U1 0 U2 4 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 FEB 19 PY 2008 VL 51 IS 7 BP 724 EP 730 DI 10.1016/j.jacc.2007.10.038 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 265JE UT WOS:000253354100007 PM 18279736 ER PT J AU Lederer, JA Brownstein, BH Lopez, MC MacMillan, S Delisle, AJ MacConmara, MP Choudhry, MA Xiao, WZ Lekousi, S Cobb, JP Baker, HV Mannick, JA Chaudry, IH AF Lederer, James A. Brownstein, Bernard H. Lopez, M. Cecilia MacMillan, Sandra Delisle, Adam J. MacConmara, Malcolm P. Choudhry, Mashkoor A. Xiao, Wenzhong Lekousi, Steven Cobb, J. Perren Baker, Henry V. Mannick, John A. Chaudry, Irshad H. CA Inflammat TI Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice SO PHYSIOLOGICAL GENOMICS LA English DT Article DE inflammation; gene microarray; immune response; gene microarray analysis; pathway analysis ID MULTIPLE ORGAN FAILURE; THERMAL-INJURY; INFLAMMATORY RESPONSE; SYSTEMIC INFLAMMATION; DYSFUNCTION SYNDROME; IMMUNE SUPPRESSION; MURINE MODEL; SEPSIS; PATHOGENESIS; INFECTION AB A primary objective of the large collaborative project entitled "Inflammation and the Host Response to Injury" was to identify leukocyte genes that are differentially expressed after two different types of injury in mouse models and to test the hypothesis that both forms of injury would induce similar changes in gene expression. We report here the genes that are expressed in white blood cells (WBCs) and in splenocytes at 2 h, 1 day, 3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Affymetrix Mouse Genome 430 2.0 GeneChips were used to profile gene expression, and the results were analyzed by dCHIP, BRB Array Tools, and Ingenuity Pathway Analysis (IPA) software. We found that the highest number of genes differentially expressed following burn injury were at day 1 for both WBCs (4,989) and for splenocytes (4,715) and at day 1 for WBCs (1,167) and at day 3 for splenocytes (1,117) following T-H. The maximum overlap of genes that were expressed after both forms of injury were at day 1 in WBCs (136 genes) and at day 7 in splenocytes (433 genes). IPA revealed that the cell-to-cell signaling, cell death, immune response, antiapoptosis, and cell cycle control pathways were affected most significantly. In summary, this report provides a database of genes that are modulated in WBCs and splenocytes at sequential time points after burn or T-H in mice and reveals that relatively few leukocyte genes are expressed in common after these two forms of injury. C1 [Lederer, James A.; Delisle, Adam J.; MacConmara, Malcolm P.; Mannick, John A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Brownstein, Bernard H.; MacMillan, Sandra; Cobb, J. Perren] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Lopez, M. Cecilia; Baker, Henry V.] Dept Mol Genet & Microbiol, Gainesville, FL USA. [Choudhry, Mashkoor A.; Chaudry, Irshad H.] Univ Alabama, Surg Res Ctr, Birmingham, AL USA. [Xiao, Wenzhong] Stanford Univ, Stanford, CA 94305 USA. [Lekousi, Steven] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Lederer, JA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM jlederer@rics.bwh.harvard.edu OI xiao, wenzhong/0000-0003-4944-6380; Baker, Henry/0000-0002-8273-5320 FU NIGMS NIH HHS [1U54-GM-62119-03, U54 GM062119] NR 37 TC 13 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD FEB 19 PY 2008 VL 32 IS 3 BP 299 EP 310 DI 10.1152/physiolgenomics.00086.2007 PG 12 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 314NO UT WOS:000256816300003 PM 17986522 ER PT J AU Mahdavi, A Ferreira, L Sundback, C Nichol, JW Chan, EP Carter, DJD Bettinger, CJ Patanavanich, S Chignozha, L Ben-Joseph, E Galakatos, A Pryor, H Pomerantseva, I Masiakos, PT Faquin, W Zumbuehl, A Hong, S Borenstein, J Vacanti, J Langer, R Karp, JM AF Mahdavi, Alborz Ferreira, Lino Sundback, Cathryn Nichol, Jason W. Chan, Edwin P. Carter, David J. D. Bettinger, Chris J. Patanavanich, Siamrut Chignozha, Loice Ben-Joseph, Eli Galakatos, Alex Pryor, Howard Pomerantseva, Irina Masiakos, Peter T. Faquin, William Zumbuehl, Andreas Hong, Seungpyo Borenstein, Jeffrey Vacanti, Joseph Langer, Robert Karp, Jeffrey M. TI A biodegradable and biocompatible gecko-inspired tissue adhesive SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemical cross-link; medical adhesive; nanotopography; surgical suture ID FOOT-HAIR; HYDROGELS; FORCE; SETAE AB There is a significant medical need for tough biodegradable polymer adhesives that can adapt to or recover from various mechanical deformations while remaining strongly attached to the underlying tissue. We approached this problem by using a polymer poly(glycerol-co-sebacate acrylate) and modifying the surface to mimic the nanotopography of gecko feet, which allows attachment to vertical surfaces. Translation of existing gecko-inspired adhesives for medical applications is complex, as multiple parameters must be optimized, including: biocompatibility, biodegradation, strong adhesive tissue bonding, as well as compliance and conformability to tissue surfaces. Ideally these adhesives would also have the ability to deliver drugs or growth factors to promote healing. As a first demonstration, we have created a gecko-inspired tissue adhesive from a biocompatible and biodegradable elastomer combined with a thin tissue-reactive biocompatible surface coating. Tissue adhesion was optimized by varying dimensions of the nanoscale pillars, including the ratio of tip diameter to pitch and the ratio of tip diameter to base diameter. Coating these nanomolded pillars of biodegradable elastomers with a thin layer of oxidized dextran significantly increased the interfacial adhesion strength on porcine intestine tissue in vitro and in the rat abdominal subfascial in vivo environment. This gecko-inspired medical adhesive may have potential applications for sealing wounds and for replacement or augmentation of sutures or staples. C1 [Mahdavi, Alborz; Ferreira, Lino; Patanavanich, Siamrut; Chignozha, Loice; Ben-Joseph, Eli; Galakatos, Alex; Hong, Seungpyo; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Ferreira, Lino] Univ Coimbra, Ctr Neurosci & Cell Biol, P-3060197 Cantanhede, Portugal. [Ferreira, Lino] Biocant Biotechnol Innovat Ctr, P-3060197 Cantanhede, Portugal. [Sundback, Cathryn; Pryor, Howard; Pomerantseva, Irina; Vacanti, Joseph] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Masiakos, Peter T.; Vacanti, Joseph] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Faquin, William] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sundback, Cathryn; Pryor, Howard; Pomerantseva, Irina; Masiakos, Peter T.; Faquin, William; Vacanti, Joseph] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nichol, Jason W.; Chan, Edwin P.; Bettinger, Chris J.; Langer, Robert; Karp, Jeffrey M.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Carter, David J. D.; Borenstein, Jeffrey] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. [Zumbuehl, Andreas] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. [Karp, Jeffrey M.] Brigham & Womens Hosp, Ctr Biomed Engn, Boston, MA 02115 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM rlanger@mit.edu; jkarp@rics.bwh.harvard.edu RI Bettinger, Christopher/A-3895-2009; Chan, Edwin/G-1904-2011; Zumbuehl, Andreas/C-5324-2008; OI Zumbuehl, Andreas/0000-0002-8003-4432; ferreira, lino/0000-0001-8985-9302 FU NIDCR NIH HHS [DE013023, R01 DE013023] NR 21 TC 190 Z9 192 U1 11 U2 127 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 FEB 19 PY 2008 VL 105 IS 7 BP 2307 EP 2312 DI 10.1073/pnas.0712117105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 266XB UT WOS:000253469900013 PM 18287082 ER PT J AU Kruger, M Kratchmarova, I Blagoev, B Tseng, YH Kahn, CR Mann, M AF Krueger, Marcus Kratchmarova, Irina Blagoev, Blagoy Tseng, Yu-Hua Kahn, C. Ronald Mann, Matthias TI Dissection of the insulin signaling pathway via quantitative phosphoproteomics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-I; KINASE-C-ALPHA; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE-1; PLASMA-MEMBRANE; BINDING PROTEIN; PROTEOMICS; ADIPOCYTES; DYNAMICS AB The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and in cellular processes, such as aging. Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. To understand the full spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC) in differentiated brown adipocytes. Of 40 identified insulin-induced effectors, 7 have not previously been described in insulin signaling, including SDR, PKC delta binding protein, LRP-6, and PISP/PDZK11, a potential calcium ATPase binding protein. A proteomic interaction screen with PISP/PDZK11 identified the calcium transporting ATPase SERCA2, supporting a connection to calcium signaling. The combination of quantitative phosphoproteomics with cell culture models provides a powerful strategy to dissect the insulin signaling pathways in intact cells. C1 [Krueger, Marcus; Mann, Matthias] Max Planck Inst Biochem, Dept Proteom & Signal Transduct, D-82152 Martinsried, Germany. [Kratchmarova, Irina; Blagoev, Blagoy] Univ So Denmark, Ctr Expt Bioinformat, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark. [Tseng, Yu-Hua; Kahn, C. Ronald] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Tseng, Yu-Hua; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu; mmann@biochem.mpg.de RI Mann, Matthias/A-3454-2013; OI Mann, Matthias/0000-0003-1292-4799; Blagoev, Blagoy/0000-0002-3596-0066 FU NIDDK NIH HHS [DK3320, DK60837, P30 DK040561, P30 DK040561-12, R01 DK060837] NR 49 TC 161 Z9 162 U1 2 U2 20 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 FEB 19 PY 2008 VL 105 IS 7 BP 2451 EP 2456 DI 10.1073/pnas.0711713105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 266XB UT WOS:000253469900038 PM 18268350 ER PT J AU Orengo, JP Chambon, P Metzger, D Mosier, DR Snipes, GJ Cooper, TA AF Orengo, James P. Chambon, Pierre Metzger, Daniel Mosier, Dennis R. Snipes, G. Jackson Cooper, Thomas A. TI Expanded CTG repeats within the DMPK 3 ' UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alternative splicing; CUG-binding protein 1; muscleblind-like 1; muscle atrophy; microsatellite expansion ID PRE-MESSENGER-RNA; BINDING PROTEIN; NUCLEAR FOCI; STRIATED-MUSCLE; IN-VIVO; MICE; CUGBP1; TYPE-1; RECEPTOR; OVEREXPRESSION AB Severe skeletal muscle wasting is the most debilitating symptom experienced by individuals with myotonic dystrophy type 1 (DM1). We present a DM1 mouse model with inducible and skeletal muscle-specific expression of large tracts of CTG repeats in the context of DMPK exon 15. These mice recapitulate many findings associated with DM1 skeletal muscle, such as CUG RNA foci with Muscleblind-like 1 (MBNL1) protein colocalization, misregulation of developmentally regulated alternative splicing events, myotonia, characteristic histological abnormalities, and increased CUGBP1 protein levels. Importantly, this DM1 mouse model recapitulates severe muscle wasting, which has not been reported in models in which depletion of MBNL1 is the main feature. Using these mice, we discovered previously undescribed alternative splicing events that are responsive to CUGBP1 and not MBNL, and these events were found to be misregulated in individuals with DM1. Our results indicate that increased CUGBP1 protein levels are associated with DMPK-CUG RNA expression, suggesting a role for CUGBP1-specific splicing or cytoplasmic functions in muscle wasting. C1 [Orengo, James P.; Snipes, G. Jackson; Cooper, Thomas A.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Orengo, James P.; Cooper, Thomas A.] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. [Mosier, Dennis R.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Snipes, G. Jackson] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. [Mosier, Dennis R.] ME Debakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Chambon, Pierre; Metzger, Daniel] Coll France, Unite Mixte Rech,Inst Genet & Biol Mol & Cellulai, Ctr Natl Rech Sci,Dept Physiol Genet,U596, Inst Natl Sante & Rech Med, F-67400 Illkirch Graffenstaden, France. [Chambon, Pierre; Metzger, Daniel] Univ Strasbourg 1, F-67000 Strasbourg, France. RP Cooper, TA (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Pl, Houston, TX 77030 USA. EM tcooper@bcm.edu FU NIAMS NIH HHS [R01 AR045653, R01AR45653] NR 42 TC 103 Z9 106 U1 0 U2 4 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 FEB 19 PY 2008 VL 105 IS 7 BP 2646 EP 2651 DI 10.1073/pnas.0708519105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 266XB UT WOS:000253469900071 PM 18272483 ER PT J AU Lazar-Molnar, E Gacser, A Freeman, GJ Almo, SC Nathenson, SG Nosanchuk, JD AF Lazar-Molnar, Eszter Gacser, Attila Freeman, Gordon J. Almo, Steven C. Nathenson, Stanley G. Nosanchuk, Joshua D. TI The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE costimulation; fungal infection; programmed death-1 ID CHRONIC VIRAL-INFECTION; T-CELLS; B7 FAMILY; IMMUNE-RESPONSE; PD-1; MACROPHAGES; B7-H1; ACTIVATION; EXPRESSION; LIGAND AB The PD-1 costimulatory receptor inhibits T cell receptor signaling upon interacting with its ligands PD-L1 and PD-L2. The PD-1/PD-L pathway is critical in maintaining self-tolerance. In this study, we examined the role of PD-1 in a mouse model of acute infection with Histoplasma capsulatum, a major human pathogenic fungus. In a lethal model of histoplasmosis, all PD-1-deficient mice survived infection, whereas the wild-type mice died with disseminated disease. PD-L expression on macrophages and splenocytes was up-regulated during infection, and macrophages from infected mice inhibited in vitro T cell activation. Of interest, antibody blocking of PD-1 significantly increased survival of lethally infected wild-type mice. Thus, our studies extend the role of the PD-1/PD-L pathway in regulating antimicrobial immunity to fungal pathogens. The results show that the PD-1/PD-L pathway has a key role in the regulation of antifungal immunity, and suggest that manipulation of this pathway represents a strategy of immunotherapy for histoplasmosis. C1 [Lazar-Molnar, Eszter; Nathenson, Stanley G.; Nosanchuk, Joshua D.] Yeshiva Univ, Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Nathenson, Stanley G.] Yeshiva Univ, Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. [Gacser, Attila; Nosanchuk, Joshua D.] Yeshiva Univ, Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Almo, Steven C.] Yeshiva Univ, Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. [Almo, Steven C.] Yeshiva Univ, Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med, Dept Med Oncol, Boston, MA 02115 USA. RP Nathenson, SG (reprint author), Yeshiva Univ, Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM nathenso@aecom.yu.edu; nosanchu@aecom.yu.edu FU NCI NIH HHS [P30CA013330, P30 CA013330]; NIAID NIH HHS [AI-51519, AI056070-01A2, AI07289, P30 AI051519, R01 AI007289, R01 AI056070, R01 AI056070-04, R56 AI007289] NR 35 TC 47 Z9 49 U1 2 U2 4 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 FEB 19 PY 2008 VL 105 IS 7 BP 2658 EP 2663 DI 10.1073/pnas.0711918105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 266XB UT WOS:000253469900073 PM 18268348 ER PT J AU Dougan, M Dranoff, G AF Dougan, Michael Dranoff, Glenn TI Inciting inflammation: the RAGE about tumor promotion SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IL-6 PRODUCTION; CANCER; IMMUNITY; TUMORIGENESIS; CELLS; PROGRESSION; ACTIVATION; COLON; RISK; LUNG AB Mechanisms of innate and adaptive immunity play a pivotal role in the development of cancer. Chronic inflammation can drive tumor development, but antitumor immunity can also restrict or even prevent tumor growth. New data show that feed-forward signals downstream of the receptor for advanced glycation end-products (RAGE) can fuel chronic inflammation, creating a microenvironment that is ideal for tumor formation. C1 [Dougan, Michael; Dranoff, Glenn] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Dougan, Michael; Dranoff, Glenn] Brigham & Womens Hosp, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dougan, Michael; Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dougan, Michael; Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Brigham & Womens Hosp, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu NR 25 TC 29 Z9 34 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 18 PY 2008 VL 205 IS 2 BP 267 EP 270 DI 10.1084/jem.20080136 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 263XR UT WOS:000253250300003 PM 18268042 ER PT J AU Klionsky, DJ Abeliovich, H Agostinis, P Agrawal, DK Aliev, G Askew, DS Baba, M Baehrecke, EH Bahr, BA Ballabio, A Bamber, BA Bassham, DC Bergamini, E Bi, XN Biard-Piechaczyk, M Blum, JS Breclesen, DE Brodsky, JL Brumell, JH Brunk, UT Bursch, W Camougrand, N Cebollero, E Cecconi, F Chen, YY Chin, LS Choi, A Chu, CT Chung, JK Clarke, PGH Clark, RSB Clarke, SG Clave, C Cleveland, JL Codogno, P Colombo, MI Coto-Montes, A Cregg, JM Cuervo, AM Debnath, J Demarchi, F Dennis, PB Dennis, PA Deretic, V Devenish, RJ Di Sano, F Dice, JF DiFiglia, M Dinesh-Kumar, S Distelhorst, CW Djavaheri-Mergny, M Dorsey, FC Droge, W Dron, M Dunn, WA Duszenko, M Eissa, NT Elazar, Z Esclatine, A Eskelinen, EL Fesues, L Finley, KD Fuentes, JM Fueyo, J Fujisaki, K Galliot, B Gao, FB Gewirtz, DA Gibson, SB Gohla, A Goldberg, AL Gonzalez, R Gonzalez-Estevez, C Gorski, S Gottlieb, RA Haussinger, D He, YW Heidenreich, K Hill, JA Hoyer-Hansen, M Hu, X Huang, WP Iwasaki, A Jaattela, M Jackson, WT Jiang, X Jin, SK Johansen, T Jung, JU Kadowaki, M Kang, C Kelekar, A Kessel, DH Kiel, JAKW Kim, HP Kimchi, A Kinsella, TJ Kiselyov, K Kitamoto, K Knecht, E Komatsu, M Kominami, E Konclo, S Kovacs, AL Kroemer, G Kuan, CY Kumar, R Kundu, M Landry, J Laporte, M Le, WD Lei, HY Lenardo, MJ Levine, B Lieberman, A Lim, KL Lin, FC Liou, W Liu, LF Lopez-Berestein, G Lopez-Otin, C Lu, B Macleod, KF Malorni, W Martinet, W Matsuoka, K Mautner, J Meijer, AJ Melendez, A Michels, P Miotto, G Mistiaen, WP Mizushima, N Mograbi, B Monastyrska, I Moore, MN Moreira, PI Moriyasu, Y Motyl, T Munz, C Murphy, LO Naqvi, NI Neufeld, TP Nishino, I Nixon, RA Noda, T Nurnberg, B Ogawa, M Oleinick, NL Olsen, LJ Ozpolat, B Paglin, S Palmer, GE Papassideri, I Parkes, M Perlmutter, DH Perry, G Piacentini, M Pinkas-Kramarski, R Prescott, M Proikas-Cezanne, T Raben, N Rami, A Reggiori, F Rohrer, B Rubinsztein, DC Ryan, KM Sadoshima, J Sakagami, H Sakai, Y Sandri, M Sasakawa, C Sass, M Schneider, C Seglen, PO Seleverstov, O Settleman, J Shacka, JJ Shapiro, IM Sibirny, A Silva-Zacarin, ECM Simon, HU Simone, C Simonsen, A Smith, MA Spanel-Borowski, K Srinivas, V Steeves, M Stenmark, H Stromhaug, PE Subauste, CS Sugimoto, S Sulzer, D Suzuki, T Swanson, MS Takeshita, F Talbot, NJ Talloczy, Z Tanaka, K Tanaka, K Tanida, I Taylor, GS Taylor, JP Terman, A Tettamanti, G Thompson, CB Thumm, M Tolkovsky, AM Tooze, SA Truant, R Tumanovska, LV Uchiyama, Y Ueno, T Uzcategui, NL van der Klei, I Vaquero, EC Vellai, T Vogel, MW Wang, HG Webster, P Wiley, JW Xi, ZJ Xiao, G Yahalom, J Yang, JM Yap, G Yin, XM Yoshimori, T Yu, L Yue, ZY Yuzaki, M Zabirnyk, O Zheng, XX Zhu, X Deter, RL Tabas, I AF Klionsky, Daniel J. Abeliovich, Hagai Agostinis, Patrizia Agrawal, Devendra K. Aliev, Giumrakch Askew, David S. Baba, Misuzu Baehrecke, Eric H. Bahr, Ben A. Ballabio, Andrea Bamber, Bruce A. Bassham, Diane C. Bergamini, Ettore Bi, Xiaoning Biard-Piechaczyk, Martine Blum, Janice S. Breclesen, Dale E. Brodsky, Jeffrey L. Brumell, John H. Brunk, Ulf T. Bursch, Wilfried Camougrand, Nadine Cebollero, Eduardo Cecconi, Francesco Chen, Yingyu Chin, Lih-Shen Choi, Augustine Chu, Charleen T. Chung, Jongkyeong Clarke, Peter G. H. Clark, Robert S. B. Clarke, Steven G. Clave, Corinne Cleveland, John L. Codogno, Patrice Colombo, Maria I. Coto-Montes, Ana Cregg, James M. Cuervo, Ana Maria Debnath, Jayanta Demarchi, Francesca Dennis, Patrick B. Dennis, Phillip A. Deretic, Vojo Devenish, Rodney J. Di Sano, Federica Dice, J. Fred DiFiglia, Marian Dinesh-Kumar, Savithramma Distelhorst, Clark W. Djavaheri-Mergny, Mojgan Dorsey, Frank C. Droege, Wulf Dron, Michel Dunn, William A., Jr. Duszenko, Michael Eissa, N. Tony Elazar, Zvulun Esclatine, Audrey Eskelinen, Eeva-Liisa Fesues, Laszlo Finley, Kim D. Fuentes, Jose M. Fueyo, Juan Fujisaki, Kozo Galliot, Brigitte Gao, Fen-Biao Gewirtz, David A. Gibson, Spencer B. Gohla, Antje Goldberg, Alfred L. Gonzalez, Ramon Gonzalez-Estevez, Cristina Gorski, Sharon Gottlieb, Roberta A. Haussinger, Dieter He, You-Wen Heidenreich, Kim Hill, Joseph A. Hoyer-Hansen, Maria Hu, Xun Huang, Wei-Pang Iwasaki, Akiko Jaattela, Marja Jackson, William T. Jiang, Xuejun Jin, Shengkan Johansen, Terje Jung, Jae U. Kadowaki, Motoni Kang, Chanhee Kelekar, Ameeta Kessel, David H. Kiel, Jan A. K. W. Kim, Hong Pyo Kimchi, Adi Kinsella, Timothy J. Kiselyov, Kirill Kitamoto, Katsuhiko Knecht, Erwin Komatsu, Masaaki Kominami, Eiki Konclo, Seiji Kovacs, Attila L. Kroemer, Guido Kuan, Chia-Yi Kumar, Rakesh Kundu, Mondira Landry, Jacques Laporte, Marianne Le, Weidong Lei, Huan-Yao Lenardo, Michael J. Levine, Beth Lieberman, Andrew Lim, Kah-Leong Lin, Fu-Cheng Liou, Willisa Liu, Leroy F. Lopez-Berestein, Gabriel Lopez-Otin, Carlos Lu, Bo Macleod, Kay F. Malorni, Walter Martinet, Wim Matsuoka, Ken Mautner, Josef Meijer, Alfred J. Melendez, Alicia Michels, Paul Miotto, Giovanni Mistiaen, Wilhelm P. Mizushima, Noboru Mograbi, Baharia Monastyrska, Iryna Moore, Michael N. Moreira, Paula I. Moriyasu, Yuji Motyl, Tomasz Muenz, Christian Murphy, Leon O. Naqvi, Naweed I. Neufeld, Thomas P. Nishino, Ichizo Nixon, Ralph A. Noda, Takeshi Nuernberg, Bernd Ogawa, Michinaga Oleinick, Nancy L. Olsen, Laura J. Ozpolat, Bulent Paglin, Shoshana Palmer, Glen E. Papassideri, Issidora Parkes, Miles Perlmutter, David H. Perry, George Piacentini, Mauro Pinkas-Kramarski, Ronit Prescott, Mark Proikas-Cezanne, Tassula Raben, Nina Rami, Abdelhaq Reggiori, Fulvio Rohrer, Baerbel Rubinsztein, David C. Ryan, Kevin M. Sadoshima, Junichi Sakagami, Hiroshi Sakai, Yasuyoshi Sandri, Marco Sasakawa, Chihiro Sass, Miklos Schneider, Claudio Seglen, Per O. Seleverstov, Oleksandr Settleman, Jeffre Shacka, John J. Shapiro, Irving M. Sibirny, Andrei Silva-Zacarin, Elaine C. M. Simon, Hans-Uwe Simone, Cristiano Simonsen, Anne Smith, Mark A. Spanel-Borowski, Katharina Srinivas, Vickram Steeves, Meredith Stenmark, Harald Stromhaug, Per E. Subauste, Carlos S. Sugimoto, Seiichiro Sulzer, David Suzuki, Toshihiko Swanson, Michele S. Takeshita, Fumihiko Talbot, Nicholas. J. Talloczy, Zsolt Tanaka, Keiji Tanaka, Kozo Tanida, Isei Taylor, Graham S. Taylor, J. Paul Terman, Alexei Tettamanti, Gianluca Thompson, Craig B. Thumm, Michael Tolkovsky, Aviva M. Tooze, Sharon A. Truant, Ray Tumanovska, Lesya V. Uchiyama, Yasuo Ueno, Takashi Uzcategui, Nestor L. van der Klei, Ida Vaquero, Eva C. Vellai, Tibor Vogel, Michael W. Wang, Hong-Gang Webster, Paul Wiley, John W. Xi, Zhijun Xiao, Gutian Yahalom, Joachim Yang, Jin-Ming Yap, George Yin, Xiao-Min Yoshimori, Tamotsu Yu, Li Yue, Zhenyu Yuzaki, Michisuke Zabirnyk, Olga Zheng, Xiaoxiang Zhu, Xiongwei Deter, Russell L. Tabas, Ira TI Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes SO AUTOPHAGY LA English DT Review DE autolysosome; autophagosome; flux; lysosome; phagophore; stress; vacuole ID GLUCAGON-INDUCED AUTOPHAGY; MURINE PANCREATIC ACINAR; ISOLATED RAT HEPATOCYTES; SEMINAL-VESICLE CELLS; DROSOPHILA FAT-BODY; BETAINE HOMOCYSTEINE METHYLTRANSFERASE; VINBLASTINE-INDUCED AUTOPHAGOCYTOSIS; ELECTRON MICROSCOPIC EXAMINATION; CHAPERONE-MEDIATED AUTOPHAGY; STARVATION-INDUCED AUTOPHAGY AB Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response. C1 [Klionsky, Daniel J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Klionsky, Daniel J.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Klionsky, Daniel J.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA. [Abeliovich, Hagai] Hebrew Univ Jerusalem, Dept Biochem & Food Sci, Rehovot, Israel. [Agostinis, Patrizia] Catholic Univ Louvain, Dept Mol Cell Biol, B-3000 Louvain, Belgium. [Agrawal, Devendra K.] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA. [Aliev, Giumrakch; Perry, George] Univ Texas San Antonio, Coll Sci, Dept Biol, San Antonio, TX USA. [Askew, David S.] Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. [Baba, Misuzu] Japan Womens Univ, Dept Chem & Biol Sci, Tokyo 112, Japan. [Baehrecke, Eric H.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA. [Bahr, Ben A.] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT USA. [Ballabio, Andrea] Telethon Inst Genet & Med, Naples, Italy. [Bamber, Bruce A.] Univ Toledo, Dept Biol Sci, Toledo, OH 43606 USA. [Bassham, Diane C.] Iowa State Univ, Dept Genet, Ames, IA USA. [Bassham, Diane C.] Iowa State Univ, Inst Plant Sci, Ames, IA USA. [Bergamini, Ettore] Univ Pisa, Ctr Res Biol & Pathol Aging, Pisa, Italy. [Bi, Xiaoning] Western Univ Hlth Sci, Pomona, CA USA. [Biard-Piechaczyk, Martine] UM2, CNRS UM1, Ctr Agents Pathogenes & Biotechnol Sante, Inst Biol, Montpellier, France. [Blum, Janice S.] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Breclesen, Dale E.] Bucks Inst Age Res, Novato, CA USA. [Brodsky, Jeffrey L.; Kiselyov, Kirill] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. [Brumell, John H.] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada. [Brunk, Ulf T.] Linkoping Univ, Fac Hlth Sci, Div Pharmacol, Linkoping, Sweden. [Bursch, Wilfried] Med Univ Vienna, Inst Canc Res, Div Oncol, Dept Med 1, Vienna, Austria. [Camougrand, Nadine] Univ Bordeaux 2, CNRS, UMR5095, F-33076 Bordeaux, France. [Cebollero, Eduardo; Gonzalez, Ramon] CSIC, Inst Fermentac Ind, Dept Microbiol, E-28006 Madrid, Spain. [Cecconi, Francesco] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy. [Cecconi, Francesco] Univ Roma Tor Vergata, IRCCS Santa Lucia Fdn, Dulbecco Telethon Inst, Rome, Italy. [Chen, Yingyu] Peking Univ, Ctr Human Dis Genom, Dept Immunol, Beijing 100871, Peoples R China. [Choi, Augustine] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. [Chu, Charleen T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA USA. [Chung, Jongkyeong] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Chu, Charleen T.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA USA. [Chung, Jongkyeong] Korea Adv Inst Sci & Technol, Dept Biol Sci, Natl Creat Res Initiat Ctr Cell Growth Regulat, Taejon, South Korea. [Clarke, Peter G. H.] Univ Lausanne, Dept Biol Cellulaire & Morphol, Lausanne, Switzerland. [Clark, Robert S. B.] Safar Ctr Resuscitat Res, Pittsburgh, PA USA. [Clarke, Steven G.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA. [Clarke, Steven G.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. [Clave, Corinne] Univ Bordeaux 2, Inst Biochim & Genet Cellulaires, Lab Genet Mol Champignons, F-33076 Bordeaux, France. [Codogno, Patrice; Djavaheri-Mergny, Mojgan; Esclatine, Audrey] Univ Paris 11, Chatenay Malabry, France. [Codogno, Patrice; Djavaheri-Mergny, Mojgan; Esclatine, Audrey] INSERM, U756, Chatenay Malabry, France. [Cleveland, John L.; Steeves, Meredith] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. [Colombo, Maria I.] Univ Nacl Cuyo, CONICET, Lab Biol Celular & Mol, Inst Histol & Embryol, RA-5500 Mendoza, Argentina. [Coto-Montes, Ana] Univ Oviedo, Dept Morfol & Biol Celular, E-33006 Oviedo, Spain. [Cregg, James M.] Keck Grad Inst Appl Sci, Claremont, CA USA. [Cuervo, Ana Maria] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Anat & Struct Biol & Dev & Mol Biol, Bronx, NY 10467 USA. [Debnath, Jayanta] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Demarchi, Francesca] Lab Nazl Consorzio Interuniv Biotecnol, Trieste, Italy. [Demarchi, Francesca] Univ Cincinnati, Dept Genome Sci, Cincinnati, OH USA. [Dennis, Phillip A.] USN Med Oncol, NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Deretic, Vojo] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Devenish, Rodney J.] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia. [Devenish, Rodney J.] Monash Univ, ARC Ctr Excellence Struct & Funct Microbial Genom, Melbourne, Vic 3004, Australia. [Di Sano, Federica] Univ Roma Tor Vergata, Dipartimento Biol, I-00173 Rome, Italy. [Dice, J. Fred] Tufts Univ, Dept Physiol, Boston, MA 02111 USA. [DiFiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Dinesh-Kumar, Savithramma] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. [Distelhorst, Clark W.] Case Western Reserve Univ, Ctr Comprehens Canc, Dept Med, Cleveland, OH 44106 USA. [Distelhorst, Clark W.] Case Western Reserve Univ, Ctr Comprehens Canc, Dept Pharmacol, Cleveland, OH 44106 USA. [Distelhorst, Clark W.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Droege, Wulf] Immunotec Res Ltd, Quebec City, PQ, Canada. [Dron, Michel] INRA, UR892, Jouy En Josas, France. [Dunn, William A., Jr.] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL USA. [Duszenko, Michael] Univ Tubingen, Dept Biochem, Tubingen, Germany. [Eissa, N. Tony] Baylor Univ, Coll Med, Houston, TX 77030 USA. [Elazar, Zvulun] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [Eskelinen, Eeva-Liisa] Univ Helsinki, Dept Biol & Environm Sci, Helsinki, Finland. [Fesues, Laszlo; Jaattela, Marja] Univ Debrecen, Res Ctr Mol Med, Hungarian Acad Sci, Apoptosis & Genom Res Grp,Dept Biochem, Debrecen, Hungary. [Fesues, Laszlo; Jaattela, Marja] Univ Debrecen, Res Ctr Mol Med, Hungarian Acad Sci, Apoptosis & Genom Res Grp,Dept Mol Biol, Debrecen, Hungary. [Finley, Kim D.] Salk Inst Biol Studies, Cellular Neurobiol Lab, San Diego, CA USA. [Fuentes, Jose M.] Univ Extremadura, EU Enfermeria, Dept Bioquim & Biol Mol & Genet, CIBERNED, Caceres, Spain. [Fueyo, Juan] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Fujisaki, Kozo] Kagoshima Univ, Dept Frontier Vet Med, Kagoshima 890, Japan. [Galliot, Brigitte] Univ Geneva, Dept Zool & Anim Biol, Geneva, Switzerland. [Gao, Fen-Biao] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94143 USA. [Gao, Fen-Biao] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Gewirtz, David A.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA. [Gewirtz, David A.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Gibson, Spencer B.] Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. [Gohla, Antje] Univ Dusseldorf, Inst Biochem & Mol Biol, Dusseldorf, Germany. [Goldberg, Alfred L.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Gonzalez-Estevez, Cristina] Univ Nottingham, Queens Med Ctr, Inst Genet, Dept Dev Genet & Gene Control, Nottingham NG7 2RD, England. [Gorski, Sharon] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Gottlieb, Roberta A.] San Diego State Univ, BioSci Ctr, San Diego, CA 92182 USA. [Haussinger, Dieter] Univ Dusseldorf, Dept Internal Med, Dusseldorf, Germany. [He, You-Wen] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. [Heidenreich, Kim] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO USA. [Hill, Joseph A.] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Hoyer-Hansen, Maria] Danish Canc Soc, Inst Canc Biol, Apoptosis Dept, Copenhagen, Denmark. [Hoyer-Hansen, Maria] Danish Canc Soc, Inst Canc Biol, Ctr Genotox Stress Res, Copenhagen, Denmark. [Hu, Xun] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Inst Canc, Hangzhou 310027, Zhejiang, Peoples R China. [Huang, Wei-Pang] Natl Taiwan Univ, Dept Life Sci, Taipei 10764, Taiwan. [Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Jackson, William T.] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. [Jiang, Xuejun] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Jin, Shengkan; Liu, Leroy F.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. [Johansen, Terje] Univ Tromso, Inst Med Biol, Dept Biochem, Tromso, Norway. [Jung, Jae U.] Univ So Calif, Keck Med Sch, Dept Mol Microbiol & Immunol, Los Angeles, CA USA. [Kadowaki, Motoni] Niigata Univ, Dept Appl Biol Chem, Niigata, Japan. [Kang, Chanhee] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Kelekar, Ameeta] Univ Minnesota, Ctr Canc, Dept Lab Med & Pathol, Minneapolis, MN USA. [Kessel, David H.] Wayne State Univ, Sch Med, Dept Med & Pharmacol, Detroit, MI USA. [Kiel, Jan A. K. W.; van der Klei, Ida] Univ Groningen, Groningen Biomol Sci Biotechnol Inst GBB, Haren, Netherlands. [Kim, Hong Pyo] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Kinsella, Timothy J.] Univ Hosp Cleveland, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Kimchi, Adi] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. [Kitamoto, Katsuhiko] Univ Tokyo, Dept Biotechnol, Tokyo, Japan. [Knecht, Erwin] Ctr Invest Principe Felipe, Dept Cell Biol, Valencia, Spain. [Komatsu, Masaaki; Tanaka, Keiji] Tokyo Metropolitan Inst Med Sci, Lab Frontier Sci, Tokyo 113, Japan. [Kominami, Eiki; Ueno, Takashi] Juntendo Univ, Sch Med, Dept Biochem, Tokyo 113, Japan. [Kovacs, Attila L.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX USA. [Kroemer, Guido] Eotvos Lorand Univ, Dept Anat Cell & Dev Biol, Budapest, Hungary. [Kroemer, Guido] Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, France. [Kroemer, Guido] Univ Paris 11, F-94805 Villejuif, France. [Kuan, Chia-Yi] Cincinnati Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH USA. [Kumar, Rakesh; Thompson, Craig B.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Kundu, Mondira] Univ Laval, Canc Res Ctr, Quebec City, PQ, Canada. [Landry, Jacques] Eastern Michigan Univ, Dept Biol, Ypsilanti, MI 48197 USA. [Le, Weidong] Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Shanghai, Peoples R China. [Le, Weidong] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. [Lei, Huan-Yao] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Tainan 70101, Taiwan. [Lenardo, Michael J.; Yu, Li] NIAID, Natl Inst Hlth, Immunol Lab, Mol Dev Sect, Bethesda, MD USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Lieberman, Andrew] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Lim, Kah-Leong] Natl Inst Neurosci, Neurodegenerat Res Lab, Singapore, Singapore. [Lin, Fu-Cheng] Zhejiang Univ, Inst Biotechnol, Hangzhou 310027, Peoples R China. [Lopez-Berestein, Gabriel; Ozpolat, Bulent] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX USA. [Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, Oviedo, Spain. [Lu, Bo] Vanderbilt Univ, Dept Radiat Oncol, Nashville, TN USA. [Macleod, Kay F.] Univ Chicago, Gordon Ctr Integrat Sci, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Macleod, Kay F.] Ist Super Sanita, I-00161 Rome, Italy. [Martinet, Wim] Univ Antwerp, Dept Pharmacol, Antwerp, Belgium. [Matsuoka, Ken] Kyushu Univ, Fac Agr, Fukuoka 812, Japan. [Liu, Leroy F.] Natl Res Ctr Environm & Hlth, GSF, Munich, Germany. [Meijer, Alfred J.] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands. [Melendez, Alicia] CUNY, Queens Coll, Dept Biol, Flushing, NY USA. [Michels, Paul] Catholic Univ Louvain, Duve Inst, Trop Dis Res Unit, Brussels, Belgium. [Michels, Paul] Catholic Univ Louvain, Biochem Lab, Brussels, Belgium. [Miotto, Giovanni] Univ Padua, Dept Biol Chem, Padua, Italy. [Mistiaen, Wilhelm P.] Univ Coll Antwerp, Dept Healthcare Sci, Antwerp, Belgium. [Mizushima, Noboru] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Tokyo, Japan. [Mograbi, Baharia] INSERM, ERI 21, Nice, France. [Mograbi, Baharia] IFR 50, Lab Pathol Clin & Expt, Nice, France. [Monastyrska, Iryna; Reggiori, Fulvio] Univ Utrecht, Med Ctr, Dept Cell Biol, Utrecht, Netherlands. [Moore, Michael N.] Plymouth Marine Lab, Plymouth, Devon, England. [Moreira, Paula I.] Ctr Neurosci & Cell Biol, Inst Physiol, Coimbra, Portugal. [Moriyasu, Yuji] Saitama Univ, Grad Sch Sci & Engn, Div Life Sci, Saitama, Japan. [Motyl, Tomasz] Agr Univ Warsaw, Dept Physiol Sci, Warsaw, Poland. [Muenz, Christian] Rockefeller Univ, Lab Viral Immunobiol, New York, NY 10021 USA. [Murphy, Leon O.] Novartis Inst Biomed Res, Cambridge, MA USA. [Naqvi, Naweed I.] Natl Univ Singapore, Temasek Life Sci Lab, Fungal Pathobiol Grp, Singapore 117548, Singapore. [Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Kodaira, Tokyo 187, Japan. [Nixon, Ralph A.] NYU, Sch Med, Nathan Kline Inst, Orangeburg, NY USA. [Noda, Takeshi; Yoshimori, Tamotsu] Osaka Univ, Res Inst Microbial Dis, Dept Cellular Regulat, Osaka, Japan. [Nuernberg, Bernd] Univ Dusseldorf, Inst Biochem & Mol Biol 2, Dusseldorf, Germany. [Ogawa, Michinaga] Univ Tokyo, Dept Microbiol & Immunol, Tokyo, Japan. [Oleinick, Nancy L.] Case Western Reserve Univ, Dept Radiat Oncol, Cleveland, OH USA. [Oleinick, Nancy L.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. [Oleinick, Nancy L.] Case Western Reserve Univ, Dept Environm Hlth Sci, Cleveland, OH 44106 USA. [Oleinick, Nancy L.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Olsen, Laura J.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Paglin, Shoshana] Chaim Sheba Med Ctr, Dept Oncol, Ramat Gan, Israel. [Palmer, Glen E.] Louisiana State Univ, Hlth Sci Ctr, Sch Dent, Dept Oral & Craniofacial Biol, New Orleans, LA USA. [Papassideri, Issidora] Dept Cell Biol & Biophys, Athens, Greece. [Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Inflammatory Bowel Dis Res Grp, Cambridge CB2 2QQ, England. [Perlmutter, David H.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. [Perlmutter, David H.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Piacentini, Mauro] Univ Roma Tor Vergata, Dipartimento Biol, I-00173 Rome, Italy. [Pinkas-Kramarski, Ronit] Tel Aviv Univ, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. [Prescott, Mark] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia. [Proikas-Cezanne, Tassula] Univ Tubingen, Dept Mol Biol, Tubingen, Germany. [Raben, Nina] NIAMSD, Natl Inst Hlth, Arthritis & Rheumatism Branch, Bethesda, MD USA. [Rami, Abdelhaq] Clin JWG Univ, Inst Cellular & Mol Anat, Frankfurt, Germany. [Rohrer, Baerbel] Med Univ S Carolina, Ophthalmol & Neurosci Div, Charleston, SC 29425 USA. [Rubinsztein, David C.] Cambridge Inst Med Res, Dept Med Genet, Cambridge, England. [Ryan, Kevin M.] Beatson Inst Canc Res, Tumor Cell Death Lab, Glasgow G61 1BD, Lanark, Scotland. [Sadoshima, Junichi] Univ Med & Dent New Jersey, Sch Med, Cardiovasc Res Inst, Dept Cell Biol & Mol Med, Newark, NJ 07103 USA. [Sakagami, Hiroshi] Meikai Univ, Sch Dent, Dept Diagnost & Therapeut Sci, Sakado, Saitama 35002, Japan. [Sakai, Yasuyoshi] Kyoto Univ, Div Appl Life Sci, Kyoto, Japan. [Sakai, Yasuyoshi] JST, CREST, Kyoto, Japan. [Sandri, Marco] Univ Padua, Dept Biomed Sci, Padua, Italy. [Sandri, Marco] Venetan Inst Mol Med, Dulbecco Telethon Inst, Padua, Italy. [Sasakawa, Chihiro] Univ Tokyo, Dept Microbiol & Immunol, Tokyo, Japan. [Sass, Miklos] Univ Oslo, Rikshosp, Radiumhosp HF, Inst Canc Res,Dept Cell Biol, N-0027 Oslo, Norway. [Seleverstov, Oleksandr] Univ Oslo, Dept Mol Biosci, N-0027 Oslo, Norway. [Seglen, Per O.] Univ Wyoming, Dept Anim Sci, Laramie, WY 82071 USA. [Brodsky, Jeffrey L.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Shapiro, Irving M.; Srinivas, Vickram] Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. [Sibirny, Andrei] Natl Acad Sci Ukraine, Inst Cell Biol, Lvov, Ukraine. [Silva-Zacarin, Elaine C. M.] Univ Fed Sao Carlos, Sorocaba, Brazil. [Simon, Hans-Uwe] Univ Bern, Dept Pharmacol, Bern, Switzerland. [Simone, Cristiano] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Translat Pharmacol, I-66030 Santa Maria Imbaro, Italy. [Simonsen, Anne] Univ Oslo, Ctr Canc Biomed, Oslo, Norway. [Simonsen, Anne; Stenmark, Harald] Norwegian Radium Hosp, Dept Biochem, Oslo, Norway. [Smith, Mark A.; Zhu, Xiongwei] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Spanel-Borowski, Katharina] Univ Leipzig, Inst Anat, Leipzig, Germany. [Stromhaug, Per E.] Univ Missouri, Div Biol, Columbia, MO USA. [Subauste, Carlos S.] Case Western Reserve Univ, Sch Med, Inst Pathol, Dept Ophthalmol, Cleveland, OH USA. [Subauste, Carlos S.] Case Western Reserve Univ, Sch Med, Inst Pathol, Dept Med, Cleveland, OH USA. [Sugimoto, Seiichiro] Natl Hosp Org, Miyazaki Higashi Hosp, Dept Neurol, Miyazaki, Japan. [Sulzer, David; Talloczy, Zsolt] Columbia Univ, Dept Neurol, New York, NY USA. [Sulzer, David; Talloczy, Zsolt] Columbia Univ, Dept Psychiat, New York, NY USA. [Suzuki, Toshihiko] Univ Ryukyus, Dept Microbiol, Okinawa, Japan. [Swanson, Michele S.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Tabas, Ira] Columbia Univ, Dept Med, New York, NY USA. [Takeshita, Fumihiko] Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Yokohama, Kanagawa 232, Japan. [Talbot, Nicholas. J.] Univ Exeter, Sch Biosci, Exeter, Devon, England. [Tanaka, Kozo] Tohoku Univ, Ctr Res Strategy & Support, Inst Dev Aging & Canc, Sendai, Miyagi 980, Japan. [Tanida, Isei] Natl Inst Infect Dis, Dept Biochem & Cell Biol, Tokyo, Japan. [Taylor, Graham S.] Univ Birmingham, CRUK Inst Canc Studies, Birmingham, W Midlands, England. [Taylor, J. Paul] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Terman, Alexei] Linkoping Univ, Fac Hlth Sci, Div Geriatr Med, Linkoping, Sweden. [Tettamanti, Gianluca] Univ Insubria, Dept Struct & Funct Biol, Varese, Italy. [Thumm, Michael] Univ Gottingen, Zentrum Biochem & Mol Zellbiol, Gottingen, Germany. [Tolkovsky, Aviva M.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Tooze, Sharon A.] Canc Res UK London Res Inst, Secretory Pathways Lab, London, England. [Truant, Ray] McMaster Univ, Hamilton, ON, Canada. [Tumanovska, Lesya V.] AA Bogomolets Physiol Inst, Dept Gen & Mol Pathophysiol, UA-252601 Kiev, Ukraine. [Uchiyama, Yasuo] Osaka Univ, Grad Sch Med, Dept Cell Biol & Neurosci, Osaka, Japan. [Uzcategui, Nestor L.] Cent Univ Venezuela, Escuela Bioanal, Caracas, Venezuela. [Vaquero, Eva C.] Hosp Clin Barcelona, Div Gastroenterol, Barcelona, Catalonia, Spain. [Vellai, Tibor] Eotvos Lorand Univ, Dept Genet, Budapest, Hungary. [Vogel, Michael W.] Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Wang, Hong-Gang] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Webster, Paul] House Ear Res Inst, Ahmanson Ctr Adv Elect Microscopy & Imaging, Los Angeles, CA USA. [Wiley, John W.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Xi, Zhijun] Peking Univ, Hosp 1, Dept Urol, Beijing 100871, Peoples R China. [Xiao, Gutian] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [Yang, Jin-Ming] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Yap, George] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. [Yin, Xiao-Min] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Yue, Zhenyu] Mt Sinai Sch Med, Dept Neurol & Neurosci, New York, NY USA. [Yuzaki, Michisuke] Keio Univ, Sch Med, Dept Neurophysiol, Tokyo, Japan. [Zabirnyk, Olga] NCI, Ctr Canc Res, Comparat Carcinogenesis Lab, Metab & Canc Susceptibil Sect, Frederick, MD USA. [Zabirnyk, Olga] Natl Inst Hlth, Frederick, MD USA. [Zheng, Xiaoxiang] Zhejiang Univ, Dept Biomed Engn, Zhejiang, Peoples R China. [Deter, Russell L.] Baylor Univ, Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Distelhorst, Clark W.] Case Western Reserve Univ, Ctr Comprehens Canc, Dept Pathol, Cleveland, OH 44106 USA. RP Klionsky, DJ (reprint author), Univ Michigan, Inst Life Sci, Rm 6036,210 Washtenaw Ave, Ann Arbor, MI 48109 USA. EM klionsky@umich.edu RI Gonzalez, Ramon/G-9281-2011; Gonzalez, Ramon/B-7843-2008; Stenmark, Harald/B-8868-2008; Michels, Paul/A-5637-2009; Smith, Mark/A-9053-2009; Zhu, Xiongwei/A-9629-2009; Moreira, Paula/B-3608-2009; Tanida, Isei/C-8277-2009; Perry, George/A-8611-2009; lu, bo/G-4573-2010; Matsuoka, Ken/E-3215-2010; Kominami, Eiki/D-3802-2009; Noda, Takeshi/B-7240-2008; Dinesh-Kumar, Savithramma/E-1153-2011; van der Klei, Ida/D-1919-2012; Tettamanti, Gianluca/E-5465-2012; Chu, Charleen/B-1601-2008; Gonzalez-Estevez, Cristina/I-9326-2012; Kroemer, Guido/B-4263-2013; Codogno, Patrice/G-1384-2013; Galliot, Brigitte/I-7051-2013; Mizushima, Noboru/C-3635-2009; Knecht, Erwin/A-9366-2014; Tang, Macy/B-9798-2014; Liao, Yung-Feng/A-9761-2011; Gorski, Sharon/E-9375-2012; Fuentes, Jose/H-9490-2014; Talbot, Nicholas/I-9584-2014; Knecht, Erwin/K-2432-2014; Yuzaki, Michisuke/K-5328-2013; Wang, Hong-Gang/A-3018-2015; Thumm, Michael/A-8033-2015; Martinet, Wim/I-7375-2015; Johansen, Terje/N-2971-2015; Malorni, Walter/G-5874-2016; Lopez-Otin, Carlos/C-6657-2013; Mistiaen, Wilhelm/C-3187-2017; Miotto, Giovanni/S-1903-2016; OI Deretic, Vojo/0000-0002-3624-5208; Subauste, Carlos/0000-0002-5602-1439; BALLABIO, Andrea/0000-0003-1381-4604; Nishino, Ichizo/0000-0001-9452-112X; HUANG, WEI-PANG/0000-0001-8410-6555; Mograbi, Baharia/0000-0002-1025-3429; Van der Klei, Ida J./0000-0001-7165-9679; Vogel, Michael/0000-0002-8402-1495; Gibson, Spencer/0000-0003-0119-732X; Simon, Hans-Uwe/0000-0002-9404-7736; Demarchi, Francesca/0000-0003-1565-3162; Gonzalez, Ramon/0000-0001-7388-1660; Moreira, Paula/0000-0001-5177-6747; Perry, George/0000-0002-6547-0172; Noda, Takeshi/0000-0003-3581-7961; Tettamanti, Gianluca/0000-0002-0665-828X; Chu, Charleen/0000-0002-5052-8271; Codogno, Patrice/0000-0002-5492-3180; Mizushima, Noboru/0000-0002-6258-6444; Gorski, Sharon/0000-0002-3821-8289; Fuentes, Jose/0000-0001-6910-2089; Talbot, Nicholas/0000-0001-6434-7757; Knecht, Erwin/0000-0002-7208-3832; Yuzaki, Michisuke/0000-0002-5750-3544; Johansen, Terje/0000-0003-1451-9578; Lopez-Otin, Carlos/0000-0001-6964-1904; Mistiaen, Wilhelm/0000-0001-8583-2524; Miotto, Giovanni/0000-0002-4278-4873; SIMONE, Cristiano/0000-0002-2628-7658 FU Biotechnology and Biological Sciences Research Council [BB/E01030X/1]; Medical Research Council [G0600194, G0600194(77639), G0601133]; NCI NIH HHS [R01 CA023378, R01 CA023378-29]; NIA NIH HHS [R01 AG026389, R01 AG026389-01A2]; NIAID NIH HHS [P01 AI056097, R01 AI079065]; NIAMS NIH HHS [R01 AR055255, R01 AR055255-02]; NIGMS NIH HHS [GM53396, R01 GM053396, R01 GM062509, R01 GM075061, R01 GM075061-03]; Telethon [TCR04004]; Wellcome Trust [064354] NR 207 TC 1507 Z9 1604 U1 66 U2 436 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD FEB 16 PY 2008 VL 4 IS 2 BP 151 EP 175 PG 25 WC Cell Biology SC Cell Biology GA 260KI UT WOS:000253008800003 PM 18188003 ER PT J AU Thadhani, R AF Thadhani, Ravi TI Activated vitamin D sterols in kidney disease SO LANCET LA English DT Editorial Material ID HEMODIALYSIS-PATIENTS; RENAL-FAILURE; MORTALITY; SURVIVAL; DIALYSIS; RECEPTOR C1 [Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. [Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr D Receptor Activat Res, Boston, MA 02114 USA. RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. EM thadhani.ravi@mgh.harvard.edu FU NCRR NIH HHS [M01 RR00088]; NIDDK NIH HHS [DK 071674, DK 76116] NR 19 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD FEB 16 PY 2008 VL 371 IS 9612 BP 542 EP 544 DI 10.1016/S0140-6736(08)60251-2 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 263FI UT WOS:000253202600010 PM 18280316 ER PT J AU Takano, M Jang, IK Inami, S Yamamoto, M Murakami, D Okamatsu, K Seimiya, K Ohba, T Mizuno, K AF Takano, Masamichi Jang, Ik-Kyung Inami, Shigenobu Yamamoto, Masanori Murakami, Daisuke Okamatsu, Kentaro Seimiya, Koji Ohba, Takayoshi Mizuno, Kyoichi TI In vivo comparison of optical coherence tomography and angioscopy for the evaluation of coronary plaque characteristics SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID INTRAVASCULAR ULTRASOUND; DEATH; ANGINA; COLOR AB Atherosclerotic yellow plaques identified by coronary angioscopy are considered as vulnerable plaques. However, characteristics of yellow plaques are not well understood. Optical coherence tomography (OCT) provides accurate tissue characterization in vivo and has the capability to measure fibrous cap thickness covering a lipid plaque. Characteristics of yellow plaques identified by angioscopy were evaluated by OCT. We examined 205 plaques of 41 coronary arteries in 26 patients. In OCT analysis, plaques were classified as fibrous or lipid. Minimal lumen area of the Plaque, arch of the lipid, and fibrous cap thickness on the lipid plaque were measured. Yellow grade of the plaque was defined as 0 (white), 1 (light yellow), 2 (medium yellow), or 3 (dark yellow) based on the angioscopy. A total of 149 plaques were diagnosed as lipid plaques. Neither the minimal lumen area nor the arch of the lipid was related to the yellow grade. There was an inverse relationship between color grade and the fibrous cap thickness (grade 0 [n = 45] 218 +/- 89 mu m, grade 1 [n = 40] 101 +/- 8 mu m, grade 2 in = 46] 72 +/- 10 mu m, and grade 3 [n = 18] 40 +/- 14 mu m; p <0.05). Sensitivity and specificity of the angioscopy-identified yellow plaque for having a thin fibrous cap (thickness <= 110 mu m) were 98% and 96%, respectively. In conclusion, angioscopy-identified yellow plaques frequently, were lipid tissue with an overlying thin fibrous cap. Fibrous caps of the intense yellow plaques were very thin, and these plaques might be structurally. vulnerable. (C) 2008 Elsevier Inc. All rights reserved. C1 [Takano, Masamichi; Inami, Shigenobu; Yamamoto, Masanori; Murakami, Daisuke; Okamatsu, Kentaro; Seimiya, Koji; Ohba, Takayoshi] Nippon Med Coll, Chiba Hokusoh Hosp, Dept Internal Med, Chiba, Japan. [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Mizuno, Kyoichi] Nippon Med Coll, Div Cardiol, Tokyo 113, Japan. RP Takano, M (reprint author), Nippon Med Coll, Chiba Hokusoh Hosp, Dept Internal Med, Chiba, Japan. EM takanom@nms.ac.jp NR 21 TC 49 Z9 51 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 FEB 15 PY 2008 VL 101 IS 4 BP 471 EP 476 DI 10.1016/j.amjcard.2007.09.106 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 262UQ UT WOS:000253173900011 PM 18312760 ER PT J AU White, DL Li, D Nurgalieva, Z El-Serag, HB AF White, Donna L. Li, Donghui Nurgalieva, Zhannat El-Serag, Hashem B. TI Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: A HuGE systematic review and meta-analysis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE carcinoma; hepatocellular; epidemiology; genetics; glutathione S-transferase pi; glutathione transferase; humans; liver neoplasms; meta-analysis ID HEPATITIS-B CARRIERS; ALCOHOLIC LIVER-DISEASE; COMPLEX DISEASES; NULL GENOTYPES; UNITED-STATES; POLYMORPHISMS; SUSCEPTIBILITY; GSTM1; M1; AFLATOXIN AB The authors performed a systematic review and meta-analysis to determine the effect of polymorphisms in genes encoding glutathione S-transferases (GSTs), phase II isoenzymes involved in cellular detoxification, on risk of hepatocellular carcinoma (HCC). Fifteen eligible studies were identified: 14 evaluated GSTM1; 13, GSTT1; three, GSTP1; and one each evaluated GSTM2, GSTM3, GSTA1, GSTA4, GSTO1, and GSTO2, respectively. All were case-control studies performed in populations with high (Asian, African) and medium (European) HCC incidence rates. Random-effects meta-analyses suggested a small excess risk of HCC with GSTT1 null (odds ratio (OR) = 1.19, 95% confidence interval (CI): 0.99, 1.44) and possibly GSTM1 null (OR = 1.16, 95% CI: 0.89, 1.53) genotypes. Cumulative meta-analyses demonstrated that both pooled estimators generally trended toward a small excess risk with publication of more recent studies. Results for GSTP1 A313G suggested no excess risk (OR = 0.75, 95% CI: 0.50, 1.15). A number of potentially interesting gene-gene and gene-environment interactions were reported, but these were too few and inconsistent to allow meta-analysis. The overall results suggest that there may be a small excess risk of HCC in individuals with GSTT1 null and possibly also with GSTM1 null genotypes. However, given the relatively limited total number of subjects examined and observed between-study heterogeneity, chance could not be excluded. C1 [White, Donna L.; Nurgalieva, Zhannat; El-Serag, Hashem B.] Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. [White, Donna L.; Nurgalieva, Zhannat; El-Serag, Hashem B.] Michael E DeBakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. [White, Donna L.; Nurgalieva, Zhannat; El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. [Li, Donghui] MD Anderson Canc Ctr, Houston, TX USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, Room 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 75 TC 74 Z9 77 U1 0 U2 2 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 FEB 15 PY 2008 VL 167 IS 4 BP 377 EP 389 DI 10.1093/aje/kwm315 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 263WC UT WOS:000253246200001 PM 18065725 ER PT J AU Lieberman-Blum, SS Kang, L Kugler, A Khalifa, M Schiller, DS AF Lieberman-Blum, Sharon S. Kang, Lillian Kugler, Anne Khalifa, Marwa Schiller, Daryl S. TI Making the most of your residency SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 [Lieberman-Blum, Sharon S.] James J Peters VA Med Ctr, Bronx, NY USA. [Kang, Lillian] St John Fisher Coll, Wegmans Sch Pharm, Rochester, NY 14618 USA. [Kugler, Anne] Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Brooklyn, NY USA. [Schiller, Daryl S.] St Barnabas Hosp, Livingston, NJ USA. RP Lieberman-Blum, SS (reprint author), James J Peters VA Med Ctr, Bronx, NY USA. EM DSchiller@sbhcs.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD FEB 15 PY 2008 VL 65 IS 4 BP 293 EP 295 DI 10.2146/ajhp070452 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 263JR UT WOS:000253213900007 PM 18238765 ER PT J AU Adegbola, A Gao, HL Sommer, S Browning, M AF Adegbola, Abidemi Gao, Hanlin Sommer, Steve Browning, Marsha TI A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE autistic disorder; JARID1C/SMCX; X-linked gene ID LINKED MENTAL-RETARDATION; GENE; ASSOCIATION; POLYMORPHISMS AB We describe a nondysmorphic patient with developmental delay and autism spectrum disorder who has a missense mutation in the Jumonji AT-rich interactive domain 1C (JARID1C) gene. This child first presented at 30 months of age with stereotyped and repetitive behaviors, impairment in social reciprocity and in the use of multiple nonverbal behaviors, and developmental delay primarily in the language domain. A diagnosis of autism was made and subsequently confirmed at the current age of 47 months. Cytogenetic and fragile X studies were normal. Mutational analysis revealed a novel missense mutation in exon 16 of the JARID1C gene that results in an arginine to tryptophan substitution at amino acid 766 (R766W). Sequence alignment analysis with Multiple available eukaryotic sequences including the homologous proteins of mouse and zebrafish demonstrated that the affected amino acid is conserved. JARID1C has not previously been implicated in autism susceptibility. Recent novel molecular evidence suggests that it is a histone demethylase specific for di- and trimethylated histone 3 lysine 4 (H3K4) and functions as a transcriptional repressor by fostering REST-mediated neuronal gene regulation. The JARID1C-regulated genes SCN2A, CACNA1H, BDNF, and SLC18A1 have previously been associated with autism and cognitive dysfunction. This patient brings the total number of reported JARID1C mutations to 14. This presentation both extends the range of neurocognitive phenotypes attributable to mutations in this gene and illustrates the importance of molecular studies and DNA sequence analysis for accurate diagnosis of monogenic causes of autism. (c) 2008 Wiley-Liss, Inc. C1 [Adegbola, Abidemi; Browning, Marsha] Harvard Univ, Sch Med, Genet Training Program, Boston, MA USA. [Gao, Hanlin; Sommer, Steve] City Hope Natl Med Ctr, Dept Mol Genet & Mol Diag, Duarte, CA 91010 USA. [Sommer, Steve; Browning, Marsha] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Browning, Marsha] Harvard Partners Ctr Genet & Genom, Boston, MA USA. RP Browning, M (reprint author), Massachusetts Gen Hosp, Ctr Human Genet, Simches Res Ctr, Room 2222,185 Cambridge St, Boston, MA 02114 USA. EM mfbrowning@partners.org FU NIGMS NIH HHS [T32-GM077481-25] NR 31 TC 81 Z9 84 U1 3 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD FEB 15 PY 2008 VL 146A IS 4 BP 505 EP 511 DI 10.1002/ajmg.a.32142 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 258CM UT WOS:000252846000018 PM 18203167 ER PT J AU Bassing, CH Ranganath, S Murphy, M Savic, V Gleason, M Alt, FW AF Bassing, Craig H. Ranganath, Sheila Murphy, Mike Savic, Velibor Gleason, Meagan Alt, Frederick W. TI Aberrant V(D)J recombination is not required for rapid development of H2ax/p53-deficient thymic lymphomas with clonal translocations SO BLOOD LA English DT Article ID DOUBLE-STRAND BREAKS; ACUTE LYMPHOBLASTIC-LEUKEMIA; HISTONE H2AX; GENOMIC INSTABILITY; INTRAGENIC DELETIONS; TUMOR SUSCEPTIBILITY; GENE AMPLIFICATION; DNA BREAKS; MICE; REPAIR AB Histone H2AX is required to maintain genomic stability in cells and to suppress malignant transformation of lymphocytes in mice. H2ax(-/-)p53(-/-) mice succumb predominantly to immature up T-cell lymphomas with translocations, deletions, and genomic amplifications that do not involve T-cell receptor (TCR). In addition, H2ax(-/-)p53(-/-) mice also develop at lower frequencies B and T lymphomas with antigen receptor locus translocations. V(D)J recombination is initiated through the programmed induction of DNA double-strand breaks (DSBs) by the RAG1/RAG2 endonuclease. Because promiscuous RAG1/RAG2 cutting outside of antigen receptor loci can promote genomic instability, H2ax(-/-)p53(-/-) T-lineage lymphomas might arise, at least in part, through erroneous V(D)J recombination. Here, we show that H2ax(-/-)p53(-/-)Rag2(-/-) mice exhibit a similar genetic predisposition as do H2ax(-/-)p53(-/-) mice to thymic lymphoma with translocations, deletions, and amplifications. We also found that H2ax(-/-)p53(-/-)Rag2(-/-) mice often develop thymic lymphomas with loss or deletion of the p53(+) locus. Our data show that aberrant V(D)J recombination is not required for rapid onset of H2ax(-/-)p53(-/-) deficient thymic lymphomas with genomic instability and that H2AX deficiency predisposes p53(-/-)Rag2(-/-) thymocytes; to transformation associated with p53 inactivation. Thus, H2AX is essential for suppressing the transformation of developing thymocytes arising from the aberrant repair of spontaneous DSBs. C1 [Bassing, Craig H.; Ranganath, Sheila; Murphy, Mike; Gleason, Meagan; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, CBR, Inst Biomed Res, Boston, MA 02115 USA. [Bassing, Craig H.; Ranganath, Sheila; Murphy, Mike; Gleason, Meagan; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Bassing, Craig H.; Savic, Velibor] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Cell & Mol Biol Grad Grp,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Bassing, Craig H.; Savic, Velibor] Abramson Family Canc Res Inst, Philadelphia, PA USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, CBR, Inst Biomed Res, Karp Res Bldg,Rm 9216,1 Blackfan Circle, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu OI Savic, Velibor/0000-0002-4830-3591 FU Howard Hughes Medical Institute; NCI NIH HHS [CA 125195, P01 CA109901, T32 CA070083, R01 CA125195-01A1, R01 CA125195, CA 109901] NR 40 TC 15 Z9 15 U1 0 U2 1 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 FEB 15 PY 2008 VL 111 IS 4 BP 2163 EP 2169 DI 10.1182/blood-2007-08-104760 PG 7 WC Hematology SC Hematology GA 263XZ UT WOS:000253251100066 PM 17855626 ER PT J AU Chen, LF Monti, S Juszczynski, P Daley, J Chen, W Witzig, TE Habermann, TM Kutok, JL Shipp, MA AF Chen, Linfeng Monti, Stefano Juszczynski, Przemyslaw Daley, John Chen, Wen Witzig, Thomas E. Habermann, Thomas M. Kutok, Jeffery L. Shipp, Margaret A. TI SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma SO BLOOD LA English DT Article ID TYROSINE KINASE SYK; ANTIGEN RECEPTOR; FOLLICULAR LYMPHOMA; ACTIVATION; EXPRESSION; GROWTH; BCR; PROLIFERATION; INFLAMMATION; PHOSPHATASE AB The role of B-cell receptor (BCR)-mediated survival signals in diffuse large B-cell lymphoma (DLBCL) remains undefined. Ligand-induced BCR signaling induces receptor oligomerization, Ig alpha/beta immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation, and activation of the spleen tyrosine kinase (SYK), which initiates downstream events and amplifies the initial BCR signal. BCRs also transmit low-level tonic survival signals in the absence of receptor engagement. Herein, we assess the role of SYK-dependent tonic BCR survival signals in DLBCL cell lines and primary tumors and evaluate the efficacy of an ATP-competitive inhibitor of SYK, R406, in vitro. R406 induced apoptosis of the majority of examined DLBCL cell lines. In R406-sensitive DLBCL cell lines, R406 specifically inhibited both tonic- and ligand-induced BCR signaling (autophosphorylation of SYK525/526 and SYK-dependent phosphorylation of the B-cell linker protein [BLNK]). The majority of examined primary DLBCLs also exhibited tonic- and ligand-induced BCR signaling; in these primary tumors, BCR signaling was also inhibited by R406. Of note, BCR-dependent and R406-sensitive DLBCL cell lines were independently identified as "BCR-type" tumors by transcriptional profiling. Therefore, SYK-dependent tonic BCR signaling is an important and potentially targetable survival pathway in some, but not all, DLBCLs. In addition, R406-sensitive DLBCLs can be identified by their transcriptional profiles. C1 [Chen, Linfeng; Juszczynski, Przemyslaw; Daley, John; Chen, Wen; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Monti, Stefano] Broad Inst, Cambridge, MA USA. [Witzig, Thomas E.; Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. [Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu OI Monti, Stefano/0000-0002-9376-0660 FU NCI NIH HHS [CA92625, CA97274, P01 CA092625, P50 CA097274] NR 25 TC 189 Z9 191 U1 2 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 FEB 15 PY 2008 VL 111 IS 4 BP 2230 EP 2237 DI 10.1182/blood-2007-07-100115 PG 8 WC Hematology SC Hematology GA 263XZ UT WOS:000253251100073 PM 18006696 ER PT J AU Tyner, JW Walters, DK Willis, SG Luttropp, M Oost, J Loriaux, M Erickson, H Corbin, AS O'Hare, T Heinrich, MC Deininger, MW Druker, BJ AF Tyner, Jeffrey W. Walters, Denise K. Willis, Stephanie G. Luttropp, Mary Oost, Jason Loriaux, Marc Erickson, Heidi Corbin, Amie S. O'Hare, Thomas Heinrich, Michael C. Deininger, Michael W. Druker, Brian J. TI RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia SO BLOOD LA English DT Article ID STEM-CELL FACTOR; CHRONIC MYELOMONOCYTIC LEUKEMIA; ACUTE MEGAKARYOBLASTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; JAK2 V617F MUTATION; GENOME-WIDE RNAI; CONSTITUTIVE ACTIVATION; C-KIT; MOLECULAR TARGETS; KINASE INHIBITOR AB Despite vast improvements in our understanding of cancer genetics, a large percentage of cancer cases present without knowledge of the causative genetic events. Tyrosine kinases are frequently implicated in the pathogenesis of numerous types of cancer, but identification and validation of tyrosine kinase targets in cancer can be a time-consuming process. We report the establishment of an efficient, functional screening assay using RNA! technology to directly assess and compare the effect of individually targeting each member of the tyrosine kinase family. We demonstrate that siRNA screening can identify tyrosine kinase targets containing activating mutations in Janus kinase (JAK) 3 (A572V) in CMK cells and c-KIT (V560G) in HMC1.1 cells. In addition, this assay identifies targets that do not contain mutations, such as JAM and the focal adhesion kinases (FAK), that are crucial to the survival of the cancer cells. This technique, with additional development, might eventually offer the potential to match specific therapies with individual patients based on a functional assay. C1 [Tyner, Jeffrey W.; Walters, Denise K.; Willis, Stephanie G.; Luttropp, Mary; Oost, Jason; Loriaux, Marc; Erickson, Heidi; Corbin, Amie S.; O'Hare, Thomas; Heinrich, Michael C.; Deininger, Michael W.; Druker, Brian J.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Walters, Denise K.; O'Hare, Thomas; Druker, Brian J.] Howard Hughes Med Inst, Portland, OR USA. [Loriaux, Marc] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. RP Druker, BJ (reprint author), Basic Sci 5390,Mailcode L592,3181 SW Sam Jackson, Portland, OR 97239 USA. EM drukerb@ohsu.edu OI Tyner, Jeffrey/0000-0002-2133-0960 FU Howard Hughes Medical Institute; NCATS NIH HHS [UL1 TR000128] NR 57 TC 45 Z9 45 U1 0 U2 1 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 FEB 15 PY 2008 VL 111 IS 4 BP 2238 EP 2245 DI 10.1182/blood-2007-06-097253 PG 8 WC Hematology SC Hematology GA 263XZ UT WOS:000253251100074 PM 18025156 ER PT J AU Moore, VD Schlis, KD Sallan, SE Armstrong, SA Letai, A AF Moore, Victoria Del Gaizo Schlis, Krysta D. Sallan, Stephen E. Armstrong, Scott A. Letai, Anthony TI BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia SO BLOOD LA English DT Article ID SURVIVAL-PROMOTING PROTEINS; BH3 MIMETIC ABT-737; B-CELL LEUKEMIA; LUNG-CANCER; LYMPHOCYTIC-LEUKEMIA; ANTIAPOPTOTIC BCL-2; MULTIPLE-MYELOMA; FAMILY PROTEINS; EGFR MUTATIONS; X-L AB Cancer cells acquire disruptions in normal signal transduction pathways and homeostatic mechanisms that would trigger apoptosis in normal cells. These abnormalities include genomic instability, oncogene activation, and growth factor independent proliferation. Therefore, cancer cells likely require a block in apoptosis in order to survive. Overexpression of the antiapoptotic protein BCL-2 provides a block in apoptosis that is frequently observed in cancer cells. We have developed methods for the detection and ana-lysis of BCL-2 dependence and here apply them to acute lymphoblastic leukemia (ALL). BH3 profiling, a mitochondrial assay that classifies blocks in the intrinsic apoptotic pathway, indicated a dependence on BCL-2 of both ALL cell lines and primary samples. This dependence predicted that BCL-2 would be complexed with select pro-death BH3 family proteins, a prediction confirmed by the isolation of BCL-2 complexes with BIM. Furthermore, the BH3 profiling and protein analysis predicted that ALL cell lines and primary cells would be sensitive to ABT-737 as a single agent. Finally, BH3 profiling and protein studies accurately predicted a relative degree of sensitivity to BCL-2 antagonism in cell lines. The ALL cells studied exhibit BCL-2 dependence, supporting clinical trials of BCL-2 antagonists in ALL as single agents or combination therapies. C1 [Moore, Victoria Del Gaizo; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Schlis, Krysta D.; Sallan, Stephen E.; Armstrong, Scott A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Schlis, Krysta D.; Sallan, Stephen E.; Armstrong, Scott A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu NR 54 TC 81 Z9 81 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2008 VL 111 IS 4 BP 2300 EP 2309 DI 10.1182/blood-2007-06-098012 PG 10 WC Hematology SC Hematology GA 263XZ UT WOS:000253251100081 ER PT J AU Al-Noori, S Sanders, NM Taborsky, GJ Wilkinson, CW Fiylewicz, DP AF Al-Noori, Salwa Sanders, Nicole M. Taborsky, Gerald J., Jr. Wilkinson, Charles W. Fiylewicz, Dianne P. TI Acute THPVP inactivation decreases the glucagon and sympathoadrenal responses to recurrent hypoglycemia SO BRAIN RESEARCH LA English DT Article DE rat; posterior paraventricular nucleus of the thalamus (THPVP); hypoglycernia; catecholamine; stress; glucagon ID PARAVENTRICULAR THALAMIC NUCLEUS; CHRONICALLY STRESSED RATS; PREFRONTAL CORTEX; MIDLINE THALAMUS; EFFECTIVE SPREAD; CORTICOSTERONE; ACTIVATION; NEURONS; AFFERENTS; LIDOCAINE AB The posterior paraventricular nucleus of the thalamus (THPVP) has been identified as a forebrain region that modulates the central nervous system (CNS) response to recurrent experiences of stressors. The THPVP is activated in response to a single (SH) or recurrent (RH) experience of the metabolic stress of hypoglycemia. In this study, we evaluated whether temporary experimental inactivation of the THPVP would modify the neuroendocrine response to SH or RH. Infusion of lidocaine (LIDO) or vehicle had no effect on the neuroendocrine response to SH, comparable to findings with other stressors. THPVP vehicle infusion concomitant with RH resulted in a prevention of the expected impairment of neuroendocrine responses, relative to SH. LIDO infusion with RH resulted in significantly decreased glucagon and sympathoadrenal responses, relative to SH. These results suggest that the THPVP may contribute to the sympathoadrenal stimulation induced by hypoglycemia; and emphasizes that the THPVP is a forebrain region that may contribute to the coordinated CNS response to metabolic stressors. (c) 2008 Published by Elsevier B.V. C1 [Al-Noori, Salwa; Wilkinson, Charles W.; Fiylewicz, Dianne P.] VA Puget Sound Hlth Care Syst, Div Endocrinol Metab & Geriatr Res, Seattle, WA 98108 USA. [Sanders, Nicole M.; Taborsky, Gerald J., Jr.; Fiylewicz, Dianne P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Taborsky, Gerald J., Jr.; Fiylewicz, Dianne P.] Univ Washington, Dept Med, Seattle, WA USA. [Wilkinson, Charles W.] VA Puget Sound Hlth Care Syst, Educ & Clin Ctr, Seattle, WA USA. RP Al-Noori, S (reprint author), VA Puget Sound Hlth Care Syst, Div Endocrinol Metab & Geriatr Res, Metab Endocrinol 151,1660 So Columbian Way, Seattle, WA 98108 USA. EM saan@u.washington.edu FU NIDDK NIH HHS [DK40963, R01 DK050154-10, R01 DK050154, R01 DK040963]; PHS HHS [R21-062446] NR 33 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 15 PY 2008 VL 1194 BP 65 EP 72 DI 10.1016/j.brainres.2007.11.040 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 274ML UT WOS:000254005300008 PM 18191818 ER PT J AU Hoffman, KE Hong, TS Zietman, AL Russell, AH AF Hoffman, Karen E. Hong, Theodore S. Zietman, Anthony L. Russell, Anthony H. TI External beam radiation treatment for rectal cancer is associated with a decrease in subsequent prostate cancer diagnosis SO CANCER LA English DT Article DE radiotherapy; second primary cancer; rectal cancer; prostatic cancer ID BREAST-CANCER; 2ND CANCERS; RADIOTHERAPY; THERAPY; IRRADIATION; CARCINOMA; CARE; MALIGNANCIES; SURVIVORS; PATTERNS AB BACKGROUND. External beam radiation therapy (EBRT) for rectal cancer unavoidably delivers significant radiation dose to the prostate gland. The effect of this incidental exposure on subsequent prostate cancer diagnosis was investigated using the Surveillance, Epidemiology, and End Results (SEER) cancer registry. METHODS. Men diagnosed with localized or regional (L/R) rectal cancer from 1988-1997 and treated with EBRT and sphincter-sparing surgery (SSS) were identified. Men treated for L/R rectal cancer with SSS who did not receive EBRT, and men with L/R colon cancer who did not receive EBRT, were studied for comparison. Multiple Primary Standardized Incidence Ratios of observed to expected (O/ E) cases of prostate cancer were calculated using SEER*Stat. RESULTS. In all, 1574 men with L/R rectal cancer treated with EBRT and SSS were identified. The median age at diagnosis was 64 and median survival was 76 months. Twenty were subsequently diagnosed with prostate cancer, a number significantly less than expected compared with the general population of similar age and race. The ratio of O/E cases was 0.28 (95% confidence interval [CI], 0.17, 0.43). In contrast, 3114 men diagnosed with rectal cancer undergoing SSS who were not treated with EBRT and 24,578 men diagnosed with colon cancer who were not treated with EBRT were subsequently diagnosed with prostate cancer at rates similar to the general population (O/E of 0.94 and 1.09). CONCLUSIONS. EBRT for L/R rectal cancer was associated with a 72% decrease in the frequency of subsequent prostate cancer diagnosis when compared with men of similar age and race. Possible mechanisms that may explain this observation are discussed. C1 [Hoffman, Karen E.; Hong, Theodore S.; Zietman, Anthony L.; Russell, Anthony H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hoffman, Karen E.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. RP Hoffman, KE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM khoffmanl@partners.org NR 24 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2008 VL 112 IS 4 BP 943 EP 949 DI 10.1002/cncr.23241 PG 7 WC Oncology SC Oncology GA 260PZ UT WOS:000253023700025 PM 18098220 ER PT J AU Arroyo, JD Lee, GM Hahn, WC AF Arroyo, Jason D. Lee, Grace M. Hahn, William C. TI Liprin alpha 1 interacts with PP2A B56 gamma SO CELL CYCLE LA English DT Article DE PP2A; B56 gamma; liprin alpha 1; cell morphology ID PROTEIN PHOSPHATASE 2A; HUMAN CELL-TRANSFORMATION; SMALL-T-ANTIGEN; LIPRIN-ALPHA; REGULATORY SUBUNIT; CYCLIN-G; SV40; COMPLEXES; RELEASE; FAMILY AB Inhibition of the protein phosphatase 2A (PP2A) family of serine-threonine phosphatases contributes to human cell transformation. Depletion of PP2A complexes containing the PP2A B56 gamma regulatory subunit in immortalized human cells induces cell transformation in vitro. To examine the function of PP2A B56 gamma complexes, we applied tandem affinity purification and mass spectrometry to detect proteins that bind to PP2A B56 gamma. We identified liprin alpha 1 as a novel PP2A B56 gamma interacting protein. B56 gamma-liprin alpha 1 complexes are distinct from PP2A complexes containing B56 gamma. Consistent with this finding, liprin alpha 1 does not directly contribute to cell transformation. However, suppression of liprin alpha 1 by RNA interference alters cell morphology. These findings suggest a novel role for PP2A B56 gamma independent of its regulation of PP2A activity. C1 [Arroyo, Jason D.; Lee, Grace M.; Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Arroyo, Jason D.; Lee, Grace M.; Hahn, William C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Arroyo, Jason D.; Lee, Grace M.; Hahn, William C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Arroyo, Jason D.; Lee, Grace M.; Hahn, William C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Hahn, William C.] MIT, Cambridge, MA 02139 USA. RP Hahn, WC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 1538, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu OI Arroyo, Jason/0000-0002-5674-6739 FU Howard Hughes Medical Institute; NCI NIH HHS [P01 CA50661] NR 33 TC 7 Z9 7 U1 0 U2 1 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 FEB 15 PY 2008 VL 7 IS 4 BP 525 EP 532 PG 8 WC Cell Biology SC Cell Biology GA 279OP UT WOS:000254364800018 PM 18235218 ER PT J AU Gururangan, S Turner, CD Stewart, CF O'Shaughnessy, M Kocak, M Poussaint, T Phillips, PC Goldman, S Packer, R Pollack, IF Blaney, SM Karsten, V Gerson, SL Boyett, JM Friedman, HS Kun, LE AF Gururangan, Sridharan Turner, Christopher D. Stewart, Clinton F. O'Shaughnessy, Melinda Kocak, Mehmet Poussaint, TinaYoung Phillips, Peter C. Goldman, Stewart Packer, Roger Pollack, Ian F. Blaney, Susan M. Karsten, Verena Gerson, Stanton L. Boyett, James M. Friedman, Henry S. Kun, Larry E. TI Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: A pediatric brain tumor consortium study SO CLINICAL CANCER RESEARCH LA English DT Article ID SULFONYLHYDRAZINE ALKYLATING AGENT; ACUTE MYELOID-LEUKEMIA; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; REFRACTORY LEUKEMIA; PRODRUG AB Purpose: VNP40101M (Cloretazine), a novel DNA alkylating agent, was evaluated in a phase I study in children with recurrent brain tumors. Experimental Design: VNP40101M was given i.v. daily for 5 consecutive days every 6 weeks for up to eight cycles. Dose escalation was done independently in patients stratified based on intensity of prior therapy (moderately pretreated, stratum I; heavily pretreated, stratum II). Correlative studies included pharmacokinetics and measurement of O-6-alkylguanine-DNA alkyl transferase levels in peripheral blood mononuclear cells before and after treatment. Results: Forty-one eligible patients (stratum 1, 19; stratum 11, 22) were enrolled on this study. The dose-limiting toxicity in 35 evaluable patients was myelosuppression, which occurred in 4 of 16 patients in stratum I and 3 of 19 patients in stratum II. Pharmacokinetic studies showed a median terminal half-life of 30 min (range, 14-39.5).The maximum tolerated dose in stratum I and II were 45 and 30 mg/m(2)/d daily for 5 days every 6 weeks, respectively. Peripheral blood mononuclear cells alkylguanine alkyl transferase levels did not decrease significantly after VNP40101M treatment. Central imaging review confirmed that three patients had stable disease for a median of 45 weeks (range, 37-61 +) after therapy. Conclusions: The recommended dose of VNP40101M for phase II studies in children with brain tumors is 45 mg/m(2)/d in moderately pretreated and 30 mg/m(2)/d in heavily pretreated patients when administered for 5 consecutive days every 6 weeks. C1 [Gururangan, Sridharan; Friedman, Henry S.] Duke Univ, Preston Robert Tisch Brain Tumor Ctr, Med Ctr, Durham, NC 27710 USA. [Turner, Christopher D.] Dana Farber Canc Inst, Boston, MA USA. [Turner, Christopher D.; Poussaint, TinaYoung] Childrens Hosp, Boston, MA 02115 USA. [Stewart, Clinton F.; O'Shaughnessy, Melinda] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Kocak, Mehmet; Boyett, James M.; Kun, Larry E.] Pediat Brain Tumor Consortium, Operat & Biostat Ctr, Memphis, TN USA. [Phillips, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Goldman, Stewart] Childrens Mem Hosp, Chicago, IL 60614 USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pollack, Ian F.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Karsten, Verena] Vion Pharmaceut, New Haven, CT USA. [Gerson, Stanton L.] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA. RP Gururangan, S (reprint author), Duke Univ, Preston Robert Tisch Brain Tumor Ctr, Med Ctr, Box 3624, Durham, NC 27710 USA. EM gurur002@mc.duke.edu OI Kocak, Mehmet/0000-0002-3386-1734 FU NCI NIH HHS [U01 CA81457]; NCRR NIH HHS [M01 RR00188] NR 22 TC 15 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2008 VL 14 IS 4 BP 1124 EP 1130 DI 10.1158/1078-0432.CCR-07-4242 PG 7 WC Oncology SC Oncology GA 266PX UT WOS:000253449700023 PM 18281546 ER PT J AU Jasti, H Mortensen, EM Obrosky, DS Kapoor, WN Fine, MJ AF Jasti, Harish Mortensen, Eric M. Obrosky, David Scott Kapoor, Wishwa N. Fine, Michael J. TI Causes and risk factors for rehospitalization of patients hospitalized with community-acquired pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SOCIOECONOMIC-STATUS; MEDICARE POPULATION; EARLY READMISSION; HEART-FAILURE; CARE; DISCHARGE; QUALITY; OUTCOMES; SERVICE; TRIAL AB Background. Rehospitalization after inpatient treatment of community-acquired pneumonia occurs in one-tenth of all hospitalizations, but the clinical circumstances surrounding readmission to the hospital have not been well studied. The objective of this study was to identify the causes and risk factors for rehospitalization of inpatients with community-acquired pneumonia. Methods. This project was performed as part of a randomized, multicenter, controlled trial of the implementation of practice guidelines to reduce the duration of intravenous antibiotic therapy and duration of hospitalization for patients who have received a clinical and radiographic diagnosis of pneumonia. The trial was conducted at 7 hospitals in Pittsburgh, Pennsylvania, from February 1998 through March 1999. The primary outcome for these analyses was rehospitalization within 30 days after the index hospitalization. Two physicians independently assigned the cause of rehospitalization as pneumonia related, comorbidity related, or both; consensus was reached for all assignments. Patient demographic characteristics and clinical factors independently associated with rehospitalization were identified using multiple logistic regression analysis. Results. Of the 577 patients discharged after hospitalization for community-acquired pneumonia, 70 (12%) were rehospitalized within 30 days. The median time to rehospitalization was 8 days (interquartile range, 4-13 days). Overall, 52 rehospitalizations (74%) were comorbidity related, and 14 (20%) were pneumonia related. The most frequent comorbid conditions responsible for rehospitalization were cardiovascular (n=19), pulmonary (n=6), and neurological () in origin. Less than a high school education (odds ratio, 2.0; 95% confidence interval, 1.1-3.4), unemployment (odds ratio, 3.7; 95% confidence interval, 1.1-12.3), coronary artery disease (odds ratio, 2.7; 95% confidence interval, 1.5-4.7), and chronic obstructive pulmonary disease (odds ratio, 2.3; 95% confidence interval, 1.3-4.1) were independently associated with rehospitalization. Conclusions. The majority of rehospitalizations following pneumonia are comorbidity related and are the result of underlying cardiopulmonary and/or neurologic diseases. Careful attention to the clinical stability of patients with these coexisting conditions at and following hospital discharge may decrease the frequency of rehospitalization of patients with community-acquired pneumonia. C1 [Obrosky, David Scott; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promat, Pittsburgh, PA 15240 USA. [Jasti, Harish; Obrosky, David Scott; Kapoor, Wishwa N.; Fine, Michael J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. [Mortensen, Eric M.] Audie L Murphy Vet Affairs Hosp, Vet Evidencebased Res Disseminat & Implementat Ct, San Antonio, TX USA. [Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Div Gen Internal Med, San Antonio, TX USA. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promat, 151 C-U,Univ Dr C MB 28,1A102, Pittsburgh, PA 15240 USA. EM finemj@upmc.edu OI Mortensen, Eric/0000-0002-3880-5563 FU AHRQ HHS [F32 HS00135, R01 HS08282]; NIAID NIH HHS [5K24 AI01769] NR 26 TC 62 Z9 63 U1 0 U2 4 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 FEB 15 PY 2008 VL 46 IS 4 BP 550 EP 556 DI 10.1086/526526 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 254WB UT WOS:000252617600011 PM 18194099 ER PT J AU Nishimura, W Rowan, S Salameh, T Maas, RL Bonner-Weir, S Sell, SM Sharma, A AF Nishimura, Wataru Rowan, Sheldon Salameh, Therese Maas, Richard L. Bonner-Weir, Susan Sell, Susan M. Sharma, Arun TI Preferential reduction of cells derived from Pax6-MafB pathway in MafB deficient mice SO DEVELOPMENTAL BIOLOGY LA English DT Article DE MafB; MafA; Pax6; Sey; Kreisler; insulin gene transcription factor; pancreatic development; endocrine differentiation; pancreatic islets ID INSULIN GENE-TRANSCRIPTION; BETA-CELLS; PANCREATIC ORGANOGENESIS; ENDOCRINE PANCREAS; SEGMENTATION GENE; KEY REGULATOR; ALPHA-CELL; EXPRESSION; ISLET; DIFFERENTIATION AB During pancreatic development insulin(+) cells co-express the transcription factors MafB and Pax6, and transition from a MafA(-) to MafA(+) state. To examine the role of Pax6 and MafB in the development of beta-cells, we analyzed embryonic pancreata from Pax6- and MqfB-deficient mice. Pax6 deficiency, as manifest in the Pax6(Sey - Neu) allele, reduced not only the number of cells expressing insulin or glucagon, but also the number of MafB, PDX-1 and MafA expressing cells. We show that MafB can directly activate expression of insulin and glucagon, and a MafB protein engineered to contain N248S mutation in the MafB (kr(ENU)) results in significantly reduced activation. Furthermore, pancreata from MafB deficient (kr(ENU)/kr(ENU)) mice exhibited reduced number of cells expressing insulin, glucagon, PDX-1 and MafA, with only a minor reduction in MafB expressing cells. MafB deficiency does not affect endocrine specification but does affect the lineage commitment of the endocrine cells and their maturation. Similar to Pax6 deficient mice, MafB deficient mice showed reductions both in insulin and glucagon expressing cells and in the ability of MafB and PDX-1 expressing cells to activate expression of these hormones. However, MafB deficient mice exhibited no effect on Pax6 expression. These results suggest that MafB may function as a downstream mediator of Pax6 in regulating the specification of insulin and glucagon expressing cells. Interestingly, the remaining insulin+ cells in these knockouts preferentially express Hb9, suggesting the existence of an alternate pathway for the generation of insulin expressing cells, even in the absence of Pax6 and MafB function. Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation. (c) 2007 Elsevier Inc. All rights reserved. C1 [Nishimura, Wataru; Salameh, Therese; Bonner-Weir, Susan; Sharma, Arun] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Nishimura, Wataru; Rowan, Sheldon; Maas, Richard L.; Bonner-Weir, Susan; Sharma, Arun] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Rowan, Sheldon; Maas, Richard L.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA. [Sell, Susan M.] Univ N Carolina, Bioinformat Res Ctr, Charlotte, NC 28223 USA. [Sell, Susan M.] Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. RP Sharma, A (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM arun.sharma@joslin.harvard.edu FU NCI NIH HHS [3R01 CA95021-04S1, R01 CA095021]; NIDDK NIH HHS [R01 DK060127-02, R01 DK060127-01A2, R01 DK060127-04, DK-36836, P30 DK036836, R01 DK060127, R01 DK060127-05, R01 DK065791] NR 47 TC 36 Z9 38 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD FEB 15 PY 2008 VL 314 IS 2 BP 443 EP 456 DI 10.1016/j.ydbio.2007.12.009 PG 14 WC Developmental Biology SC Developmental Biology GA 265BL UT WOS:000253334000016 PM 18199433 ER PT J AU de la Iglesia, N Konopka, G Puram, SV Chan, JA Bachoo, RM You, MJ Levy, DE DePinho, RA Bonni, A AF de la Iglesia, Nuria Konopka, Genevieve Puram, Sidharth V. Chan, Jennifer A. Bachoo, Robert M. You, Mingjian J. Levy, David E. DePinho, Ronald A. Bonni, Azad TI Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway SO GENES & DEVELOPMENT LA English DT Article DE STAT3; astrocyte; glioblastoma; PTEN; EGFRvIII ID EPIDERMAL-GROWTH-FACTOR; FACTOR-RECEPTOR GENE; GLIOBLASTOMA-MULTIFORME CELLS; DNA-BINDING ACTIVITY; EGF RECEPTOR; NUCLEAR-LOCALIZATION; MALIGNANT GLIOMAS; SIGNALING PATHWAY; PROSTATE-CANCER; BREAST-CANCER AB Activation of the transcription factor STAT3 is thought to potently promote oncogenesis in a variety of tissues, leading to intense efforts to develop STAT3 inhibitors for many tumors, including the highly malignant brain tumor glioblastoma. However, the function of STAT3 in glioblastoma pathogenesis has remained unknown. Here, we report that STAT3 plays a pro-oncogenic or tumor-suppressive role depending on the mutational profile of the tumor. Deficiency of the tumor suppressor PTEN triggers a cascade that inhibits STAT3 signaling in murine astrocytes and human glioblastoma tumors. Specifically, we forge a direct link between the PTEN-Akt-FOXO axis and the leukemia inhibitory factor receptor beta (LIFR beta)-STAT3 signaling pathway. Accordingly, PTEN knockdown induces efficient malignant transformation of astrocytes upon knockout of the STAT3 gene. Remarkably, in contrast to the tumor-suppressive function of STAT3 in the PTEN pathway, STAT3 forms a complex with the oncoprotein epidermal growth factor receptor type III variant (EGFRvIII) in the nucleus and thereby mediates EGFRvIII-induced glial transformation. These findings indicate that STAT3 plays opposing roles in glial transformation depending on the genetic background of the tumor, providing the rationale for tailored therapeutic intervention in glioblastoma. C1 [de la Iglesia, Nuria; Konopka, Genevieve; Puram, Sidharth V.; Bonni, Azad] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Konopka, Genevieve; Bonni, Azad] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Puram, Sidharth V.; Bonni, Azad] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Chan, Jennifer A.] Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA. [Bachoo, Robert M.; You, Mingjian J.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. [Bachoo, Robert M.; You, Mingjian J.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Bachoo, Robert M.; You, Mingjian J.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Levy, David E.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Levy, David E.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. RP Bonni, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM azad_bonni@hms.harvard.edu RI de la Iglesia, Nuria/E-1420-2015; OI de la Iglesia, Nuria/0000-0002-1083-7715; Levy, David/0000-0002-7320-7788 FU NIGMS NIH HHS [T32 GM007753]; NINDS NIH HHS [NS047188, NS051255, NS41021, R01 NS041021, R01 NS047188, R01 NS051255] NR 74 TC 158 Z9 159 U1 0 U2 9 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 FEB 15 PY 2008 VL 22 IS 4 BP 449 EP 462 DI 10.1101/gad.1606508 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 266SW UT WOS:000253458300005 PM 18258752 ER PT J AU Sankaran, VG Orkin, SH Walkley, CR AF Sankaran, Vijay G. Orkin, Stuart H. Walkley, Carl R. TI Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis SO GENES & DEVELOPMENT LA English DT Article DE Rb; cell cycle; cell differentiation; crythropoiesis; hematopoiesis; mitochondrial biogenesis ID HEMATOPOIETIC STEM-CELLS; RETINOBLASTOMA TUMOR-SUPPRESSOR; PHASE-II MULTICENTER; ERYTHROID-DIFFERENTIATION; MYELODYSPLASTIC SYNDROMES; DEFINITIVE ERYTHROPOIESIS; ARSENIC TRIOXIDE; GENE-EXPRESSION; CHIMERIC MICE; MOUSE AB Regulation of the cell cycle is intimately linked to erythroid differentiation, yet how these processes are coupled is not well understood. To gain insight into this coordinate regulation, we examined the role that the retinoblastoma protein (Rb), a central regulator of the cell cycle, plays in erythropoiesis. We found that Rb serves a cell-intrinsic role and its absence causes ineffective erythropoiesis, with a differentiation block at the transition from early to late erythroblasts. Unexpectedly, in addition to a failure to properly exit the cell cycle, mitochondrial biogenesis fails to be up-regulated concomitantly, contributing to this differentiation block. The link between erythropoiesis and mitochondrial function was validated by inhibition of mitochondrial biogenesis. Erythropoiesis in the absence of Rb resembles the human myelodysplastic syndromes, where defects in cell cycle regulation and mitochondrial function frequently occur. Our work demonstrates how these seemingly disparate pathways play a role in coordinately regulating cellular differentiation. C1 [Sankaran, Vijay G.; Orkin, Stuart H.; Walkley, Carl R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.; Orkin, Stuart H.; Walkley, Carl R.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Walkley, Carl/0000-0002-4784-9031 FU Howard Hughes Medical Institute NR 68 TC 79 Z9 83 U1 0 U2 0 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 FEB 15 PY 2008 VL 22 IS 4 BP 463 EP 475 DI 10.1101/gad.1627208 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 266SW UT WOS:000253458300006 PM 18258751 ER PT J AU Brown, AH Cohen, AN Chinman, MJ Kessler, C Young, AS AF Brown, Alison H. Cohen, Amy N. Chinman, Matthew J. Kessler, Christopher Young, Alexander S. TI EQUIP: Implementing chronic care principles and applying formative evaluation methods to improve care for schizophrenia: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID RESEARCH-TEAM PORT; CONCEPTUAL-FRAMEWORK; TREATMENT RECOMMENDATIONS; CHRONIC ILLNESS; QUALITY; OUTCOMES; HEALTH; TECHNOLOGY; GUIDELINE; PROGRAM AB Background: This paper presents a case study that demonstrates the evolution of a project entitled "Enhancing Quality of care In Psychosis" (EQUIP) that began approximately when the U. S. Department of Veterans Affairs' Quality Enhancement Research Initiative (QUERI), and implementation science were emerging. EQUIP developed methods and tools to implement chronic illness care principles in the treatment of schizophrenia, and evaluated this implementation using a small-scale controlled trial. The next iteration of the project, EQUIP-2, was further informed by implementation science and the use of QUERI tools. Methods: This paper reports the background, development, results and implications of EQUIP, and also describes ongoing work in the second phase of the project (EQUIP-2). The EQUIP intervention uses implementation strategies and tools to increase the adoption and implementation of chronic illness care principles. In EQUIP-2, these strategies and tools are conceptually grounded in a stages-of-change model, and include clinical and delivery system interventions and adoption/ implementation tools. Formative evaluation occurs in conjunction with the intervention, and includes developmental, progress-focused, implementation-focused, and interpretive evaluation. Results: Evaluation of EQUIP provided an understanding of quality gaps and how to address related problems in schizophrenia. EQUIP showed that solutions to quality problems in schizophrenia differ by treatment domain and are exacerbated by a lack of awareness of evidence-based practices. EQUIP also showed that improving care requires creating resources for physicians to help them easily implement practice changes, plus intensive education as well as product champions who help physicians use these resources. Organizational changes, such as the addition of care managers and informatics systems, were shown to help physicians with identifying problems, making referrals, and monitoring follow-up. In EQUIP-2, which is currently in progress, these initial findings were used to develop a more comprehensive approach to implementing and evaluating the chronic illness care model. Discussion: In QUERI, small-scale projects contribute to the development and enhancement of hands-on, action-oriented service-directed projects that are grounded in current implementation science. This project supports the concept that QUERI tools can be useful in implementing complex care models oriented toward evidence-based improvement of clinical care. C1 [Brown, Alison H.; Cohen, Amy N.; Chinman, Matthew J.; Young, Alexander S.] VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA. [Kessler, Christopher] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Brown, Alison H.; Cohen, Amy N.; Young, Alexander S.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Chinman, Matthew J.] RAND Corp, Santa Monica, CA USA. RP Brown, AH (reprint author), VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA. EM alisonh@ucla.edu; amy.cohen@va.gov; chinman@rand.org; Christopher.Kessler@va.gov; ayoung@ucla.edu RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU Department of Veterans Affairs through the Health Services Research & Development Service [RCD 00-033, CPI 99-383]; Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC); National Institute of Mental Health (NIMH) UCLA- RAND Center for Research on Quality in Managed Care [MH 068639] FX This project was supported by the Department of Veterans Affairs through the Health Services Research & Development Service (RCD 00-033 and CPI 99-383) and the Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC); and by the National Institute of Mental Health (NIMH) UCLA- RAND Center for Research on Quality in Managed Care (MH 068639). NR 41 TC 15 Z9 15 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD FEB 15 PY 2008 VL 3 AR 9 DI 10.1186/1748-5908-3-9 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QO UT WOS:000265149400002 PM 18279505 ER PT J AU Chaney, E Rabuck, LG Uman, J Mittman, DC Simons, C Simon, BF Ritchie, M Cody, M Rubenstein, LV AF Chaney, Edmund Rabuck, Laura G. Uman, Jane Mittman, Deborah C. Simons, Carol Simon, Barbara F. Ritchie, Mona Cody, Marisue Rubenstein, Lisa V. TI Human subjects protection issues in QUERI implementation research: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID HEALTH-SERVICES RESEARCH; RE-AIM FRAMEWORK; QUALITY IMPROVEMENT; MULTICENTER; BOARD; IMPACT; INTERVENTIONS; OVERSIGHT; BENEFITS; TRIALS AB Background: Human Subjects protections approaches, specifically those relating to research review board oversight, vary throughout the world. While all are designed to protect participants involved in research, the structure and specifics of these institutional review boards (IRBs) can and do differ. This variation affects all types of research, particularly implementation research. Methods: In 2001, we began a series of inter-related studies on implementing evidence-based collaborative care for depression in Veterans Health Administration primary care. We have submitted more than 100 IRB applications, amendments, and renewals, and in doing so, we have interacted with 13 VA and University IRBs across the United States (U. S.). We present four overarching IRB-related themes encountered throughout the implementation of our projects, and within each theme, identify key challenges and suggest approaches that have proved useful. Where applicable, we showcase process aids developed to assist in resolving a particular IRB challenge. Results: There are issues unique to implementation research, as this type of research may not fit within the traditional Human Subjects paradigm used to assess clinical trials. Risks in implementation research are generally related to breaches of confidentiality, rather than health risks associated with traditional clinical trials. The implementation-specific challenges discussed are: external validity considerations, Plan-Do-Study-Act cycles, risk-benefit issues, the multiple roles of researchers and subjects, and system-level unit of analysis. Discussion: Specific aspects of implementation research interact with variations in knowledge, procedures, and regulatory interpretations across IRBs to affect the implementation and study of best methods to increase evidence-based practice. Through lack of unambiguous guidelines and local liability concerns, IRBs are often at risk of applying both variable and inappropriate or unnecessary standards to implementation research that are not consistent with the spirit of the Belmont Report (a summary of basic ethical principles identified by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research), and which impede the conduct of evidence-based quality improvement research. While there are promising developments in the IRB community, it is incumbent upon implementation researchers to interact with IRBs in a manner that assists appropriate risk-benefit determinations and helps prevent the process from having a negative impact on efforts to reduce the lag in implementing best practices. C1 [Chaney, Edmund; Rabuck, Laura G.; Uman, Jane; Simons, Carol] VA Puget Sound Hlth Care Syst, HSR&D NW Ctr Excellence Outcomes Res Older Adults, Seattle, WA USA. [Chaney, Edmund] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Mittman, Deborah C.; Simon, Barbara F.; Rubenstein, Lisa V.] VA Greater Angeles Healthcare Syst, VA Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Ritchie, Mona] Cent Arkansas Vet Healthcare Syst, HSR&D Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. [Cody, Marisue] VA Off Res & Dev, COACH, Washington, DC USA. [Rubenstein, Lisa V.] RAND Hlth Program, Santa Monica, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Chaney, E (reprint author), VA Puget Sound Hlth Care Syst, HSR&D NW Ctr Excellence Outcomes Res Older Adults, Metropolitan Pk W,1100 Olive Way 1400, Seattle, WA USA. EM chaney@u.washington.edu; Laura.Rabuck@va.gov; Jane.Uman@va.gov; Debbie.Mittman@va.gov; Carol.Simons@va.gov; Barbara.Simon@va.gov; RitchieMonaJ@uams.edu; Marisue.Cody@va.gov; lisar@rand.org FU U. S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [MNT 03-215] FX The research reported here and the production of this manuscript was supported by U. S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, MNT 03-215. All authors are ( or were) VA employees at the time this paper was written. In order to receive VA funding, all VA studies must undergo scientific review internal to the VA ( which includes a general review of the study design, plan for data collection, etc). Data analysis, the decision to publish, etc are left to the discretion of the study's Investigators. However, it should be noted that the findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily, represent the views of the U. S. Department of Veterans Affairs. NR 33 TC 9 Z9 10 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD FEB 15 PY 2008 VL 3 AR 10 DI 10.1186/1748-5908-3-10 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QO UT WOS:000265149400003 PM 18279507 ER PT J AU Liu, G Wheatley-Price, P Zhou, W Park, S Heist, RS Asomaning, K Wain, JC Lynch, TJ Su, L Christiani, DC AF Liu, Geoffrey Wheatley-Price, Paul Zhou, Wei Park, Sohee Heist, Rebecca S. Asomaning, Kofi Wain, John C. Lynch, Thomas J. Su, Li Christiani, David C. TI Genetic polymorphisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE MDM2; genetic polymorphism; lung cancer risk ID MICROSOMAL EPOXIDE HYDROLASE; PROMOTER; P53; SUSCEPTIBILITY; POPULATION AB Abnormalities of the tumor suppressor TP53 pathway are critical in the development of many cancers since it regulates cell cycle components and apoptosis. Murine double minute-2 (MDM2) protein is a central node in the p53 pathway and a direct negative regulator of p53. The MDM2 SNP309 (rs2279744) polymorphism increases MDM2 RNA and protein levels, attenuating the p53 pathway. The MDM2 SNP309 polymorphism was investigated in 1,787 Caucasian nonsmall cell lung cancer (NSCLC) patients and 1,360 healthy controls. Cases and controls were analyzed for associations with genotype and adjusted for age, gender, histology and smoking history. There were no overall associations between the MDM2 genotypes and risk of lung cancer (adjusted odds ratios [AORs] = 0.82 [95% confidence interval [CI] = 0.6-1.1] for the T/G genotype and AOR = 1.32 [95% CI = 0.9-2.0] for the GIG genotype). A statistically significant interaction (P = 0.01) was found between smoking and MDM2 genotypes. Consistent with this interaction, stratified analysis by pack-years of smoking demonstrated that the AORs of G/G vs. T/T were 1.56 (1.0-2.7), 1.46 (1.0-2.2), 0.80 (0.5-1.3) and 0.63 (0.4-1.1), respectively, for never, mild (<30 pack-years), moderate (30-57 packyears) and heavy smokers (>= 58 pack-years). In conclusion, a strong gene-smoking interaction was observed between the MDM2 SNP309 and NSCLC risk. (c) 2007 Wiley-Liss, Inc. C1 [Liu, Geoffrey; Wheatley-Price, Paul] Univ Toronto, Princess Margaret Hosp, Ontario Canc Inst, Dept Med, Toronto, ON M5G 2M9, Canada. [Liu, Geoffrey; Zhou, Wei; Heist, Rebecca S.; Asomaning, Kofi; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Liu, Geoffrey; Heist, Rebecca S.; Lynch, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol Oncol, Boston, MA USA. [Park, Sohee] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wain, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Liu, G (reprint author), Univ Toronto, Princess Margaret Hosp, Ontario Canc Inst, Dept Med, 610 Univ Ave,Rm 7-124, Toronto, ON M5G 2M9, Canada. EM geoffrey.liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016; OI Wheatley-Price, Paul/0000-0002-3725-9767 FU NCI NIH HHS [ES/CA 06409, CA090578, CA074386] NR 21 TC 22 Z9 24 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD FEB 15 PY 2008 VL 122 IS 4 BP 915 EP 918 DI 10.1002/ijc.23178 PG 4 WC Oncology SC Oncology GA 253MQ UT WOS:000252522700028 PM 17957785 ER PT J AU Yu, PB Deng, DY Beppu, H Hong, CC Lai, C Hoyng, SA Kawai, N Bloch, KD AF Yu, Paul B. Deng, Donna Y. Beppu, Hideyuki Hong, Charles C. Lai, Carol Hoyng, Stefan A. Kawai, Noriko Bloch, Kenneth D. TI Bone morphogenetic protein (BMP) type II receptor is required for BMP-mediated growth arrest and differentiation in pulmonary artery smooth muscle cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA RECEPTOR; VASCULAR CALCIFICATION; SIGNALING PATHWAYS; INHIBITS PROLIFERATION; GERMLINE MUTATIONS; ENDOTHELIAL-CELLS; CROSS-TALK; IN-VITRO; HYPERTENSION; EXPRESSION AB Bone morphogenetic protein (BMP) signals regulate the growth and differentiation of diverse lineages. The association of mutations in the BMP type II receptor (BMPRII) with idiopathic pulmonary arterial hypertension suggests an important role of this receptor in vascular remodeling. Pulmonary artery smooth muscle cells lacking BMPRII can transduce BMP signals using ActRIIa (Activin type II receptor). We investigated whether or not BMP signaling via the two receptors leads to differential effects on vascular smooth muscle cells. BMP4, but not BMP7, inhibited platelet-derived growth factor-activated proliferation in wild-type pulmonary artery smooth muscle cells, whereas neither ligand inhibited the growth of BMPRII-deficient cells. Adenoviral gene transfer of BMPRII enabled BMP4, as well as BMP7, to inhibit proliferation in BMPRII-deficient cells. BMP-mediated growth inhibition was also reconstituted by the BMPRII short isoform, lacking the C-terminal domain present in the long form. BMP4, but not BMP7, induced the expression of osteoblast markers in wild-type cells, whereas neither ligand induced these markers in BMPRII-deficient cells. Overexpression of short or long forms of BMPRII in BMPRII-deficient cells enabled BMP4 and BMP7 to induce osteogenic differentiation. Although signaling via BMPRII or ActRIIa transiently activated SMAD1/5/8, only BMPRII signaling led to persistent SMAD1/5/8 activation and sustained increases in Id1 mRNA and protein expression. Pharmacologic blockade of BMPtype I receptor function within 24 h after BMP stimulation abrogated differentiation. These data suggest that sustained BMP pathway activation, such as that mediated by BMPRII, is necessary for growth and differentiation control in vascular smooth muscle. C1 [Yu, Paul B.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Anesthesia Ctr Crit Care Res, Harvard Med Sch, Boston, MA 02114 USA. RP Yu, PB (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Anesthesia Ctr Crit Care Res, Harvard Med Sch, Boston, MA 02114 USA. EM pbyu@partners.org RI Hong, Charles/C-9989-2010; OI Hoyng, Stefan/0000-0001-8371-3871; Yu, Paul/0000-0003-2145-4944 FU NHLBI NIH HHS [R01 HL074352, 1K08HL079943, K08 HL079943-02, K08 HL079943, 5R01HL074352] NR 79 TC 54 Z9 54 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 15 PY 2008 VL 283 IS 7 BP 3877 EP 3888 DI 10.1074/jbc.M706797200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261MO UT WOS:000253083500022 PM 18042551 ER PT J AU Tan, K Duquette, M Liu, JH Shanmugasundaram, K Joachimiak, A Gallagher, JT Rigby, AC Wang, JH Lawler, J AF Tan, Kemin Duquette, Mark Liu, Jin-huan Shanmugasundaram, Kumaran Joachimiak, Andrzej Gallagher, John T. Rigby, Alan C. Wang, Jia-huai Lawler, Jack TI Heparin-induced cis- and trans-dimerization modes of the thrombospondin-1 N-terminal domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; PROMOTES ANGIOGENESIS; CRYSTAL-STRUCTURE; MOLECULAR DIPOLE; COMPLEX REVEALS; TERNARY COMPLEX; BINDING; RECOGNITION; PROTEINS; INTEGRIN AB Through its interactions with proteins and proteoglycans, thrombospondin-1 (TSP-1) functions at the interface of the cell membrane and the extracellular matrix to regulate matrix structure and cellular phenotype. We have previously determined the structure of the high affinity heparin-binding domain of TSP-1, designated TSPN-1, in association with the synthetic heparin, Arixtra. To establish that the binding of TSPN-1 to Arixtra is representative of the association with naturally occurring heparins, we have determined the structures of TSPN-1 in complex with heparin oligosaccharides containing eight (dp8) and ten (dp10) subunits, by x-ray crystallography. We have found that dp8 and dp10 bind to TSPN-1 in a manner similar to Arixtra and that dp8 and dp10 induce the formation of trans and cis TSPN-1 dimers, respectively. In silico docking calculations partnered with our crystal structures support the importance of arginine residues in positions 29, 42, and 77 in binding sulfate groups of the dp8 and dp10 forms of heparin. The ability of several TSPN-1 domains to bind to glycosaminoglycans simultaneously probably increases the affinity of binding through multivalent interactions. The formation of cis and trans dimers of the TSPN-1 domain with relatively short segments of heparin further enhances the ability of TSP-1 to participate in high affinity binding to glycosaminoglycans. Dimer formation may also involve TSPN-1 domains from two separate TSP-1 molecules. This association would enable glycosaminoglycans to cluster TSP-1. C1 [Wang, Jia-huai] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Vasc Biol Res Ctr,Dept Med,Div Mol & Vasc Med, Boston, MA 02215 USA. [Tan, Kemin; Liu, Jin-huan; Wang, Jia-huai] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Duquette, Mark; Lawler, Jack] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, Boston, MA 02215 USA. [Tan, Kemin; Liu, Jin-huan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lawler, Jack] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tan, Kemin; Joachimiak, Andrzej] Argonne Natl Lab, Midwest Ctr Struct Gem & Struct Biol Ctr, Biosci Div, Argonne, IL 60439 USA. [Gallagher, John T.] Univ Manchester, Christie Hosp NHS Trust, Dept Med Oncol, Manchester M20 4BX, Lancs, England. RP Rigby, AC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Vasc Biol Res Ctr,Dept Med,Div Mol & Vasc Med, 330 Brookline Ave, Boston, MA 02215 USA. EM arigby@bidmc.harvard.edu; jwang@red.dfci.harvard.edu; jlawler@bidmc.harvard.edu FU NHLBI NIH HHS [P01 HL048675, HL48675, R01 HL068003, HL68003, R01 HL049081-10, R01 HL049081, HL49081] NR 51 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 15 PY 2008 VL 283 IS 7 BP 3932 EP 3941 DI 10.1074/jbc.M705203200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261MO UT WOS:000253083500027 PM 18065761 ER PT J AU Chandrasekar, B Patel, DN Mummidi, S Kim, JW Clark, RA Valente, AJ AF Chandrasekar, Bysani Patel, Devang N. Mummidi, Srinivas Kim, Jae-Woo Clark, Robert A. Valente, Anthony J. TI Interleukin-18 suppresses adiponectin expression in 3T3-L1 adipocytes via a novel signal transduction pathway involving ERK1/2-dependent NFATc4 phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; CCAAT/ENHANCER BINDING-PROTEIN; VASCULAR INFLAMMATORY MARKERS; ADIPOSE-SPECIFIC PROTEIN; CORONARY-ARTERY-DISEASE; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; WEIGHT-LOSS AB An inverse correlation between the pro-inflammatory cytokine interleukin-18 and the anti-atherogenic adipokine adiponectin has been reported in the chronic pathological conditions obesity, insulin resistance, coronary artery disease, and metabolic syndrome. We investigated whether this relationship is coincidental or has a causal basis. Here we show that interleukin-18 (IL-18) suppresses adiponectin transcription, mRNA expression, and secretion by 3T3-L1 adipocytes. IL-18 suppresses adiponectin promoter-reporter activity, an effect reversed by deletion or mutation of the NFATc4 core DNA-binding site. IL-18 induces NFATc4 phosphorylation (Ser(676)), nuclear translocation, and in vivo DNA binding. IL-18 induces ERK1/2 phosphorylation and enzyme activity, and pretreatment with the MEK inhibitor U0126, ERK1/2 inhibitor PD98059, or small interference RNA targeted to ERK1/2 attenuates ERK1/2 activation and NFATc4 phosphorylation. Finally, inhibition of ERK1/2 or NFATc4 knockdown reverses IL-18-mediated adiponectin suppression. In contrast to its inhibitory effects on adiponectin expression, IL-18 potently stimulates PAI-1 secretion. These data demonstrate for the first time that IL-18 selectively suppresses adiponectin expression via ERK1/2-dependent NFATc4 activation and suggest that the inverse relationship observed between IL-18 and adiponectin in various chronic pathological conditions is causally related. Thus, targeting IL-18 expression may enhance adiponectin expression and mitigate disease progression. C1 [Chandrasekar, Bysani; Patel, Devang N.; Mummidi, Srinivas; Clark, Robert A.; Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Chandrasekar, Bysani; Mummidi, Srinivas; Clark, Robert A.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. [Kim, Jae-Woo] Yonsei Univ, Coll Med, Med Res Ctr Chron Metab Dis, Dept Biochem & Mol Biol, Seoul 120752, South Korea. RP Chandrasekar, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chandraseka@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 NR 56 TC 24 Z9 26 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 15 PY 2008 VL 283 IS 7 BP 4200 EP 4209 DI 10.1074/jbc.M708142200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261MO UT WOS:000253083500055 PM 18086672 ER PT J AU Hellman, NE SpectorO, J Robinson, J Zuo, XF Saunier, S Antignac, C Tobias, JW Lipschutz, JH AF Hellman, Nathan E. SpectorO, June Robinson, Jonathan Zuo, Xiaofeng Saunier, Sophie Antignac, Corinne Tobias, John W. Lipschutz, Joshua H. TI Matrix metalloproteinase 13 (MMP13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1), regulated by the MAPK pathway, are both necessary for Madin-Darby canine kidney tubulogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; POLARIZED EPITHELIAL-CELLS; MATRIX METALLOPROTEINASES; IN-VITRO; BRANCHING MORPHOGENESIS; COLLAGEN ACCUMULATION; RNA INTERFERENCE; MOUSE KIDNEY; MDCK CELLS; LINE MDCK AB A classic model of tubulogenesis utilizes Madin-Darby canine kidney (MDCK) cells. MDCK cells form monoclonal cysts in three-dimensional collagen and tubulate in response to hepatocyte growth factor, which activates multiple signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway. It was shown previously that MAPK activation is necessary and sufficient to induce the first stage of tubulogenesis, the partial epithelial to mesenchymal transition (p-EMT), whereas matrix metalloproteinases (MMPs) are necessary for the second redifferentiation stage. To identify specific MMP genes, their regulators, tissue inhibitors of matrix metalloproteinases (TIMPs), and the molecular pathways by which they are activated, we used two distinct MAPK inhibitors and a technique we have termed subtraction pathway microarray analysis. Of the 19 MMPs and 3 TIMPs present on the Canine Genome 2.0 Array, MMP13 and TIMP1 were up-regulated 198- and 169-fold, respectively, via the MAPK pathway. This was confirmed by two-dimensional and three-dimensional real time PCR, as well as in MDCK cells inducible for the MAPK gene Raf. Knockdown of MMP13 using short hairpin RNA prevented progression past the initial phase of p-EMT. Knockdown of TIMP1 prevented normal cystogenesis, although the initial phase of p-EMT did occasionally occur. The MMP13 knockdown phenotype is likely because of decreased collagenase activity, whereas the TIMP1 knockdown phenotype appears due to increased apoptosis. These data suggest a model, which may also be important for development of other branched organs, whereby the MAPK pathway controls both MDCK p-EMT and redifferentiation, in part by activating MMP13 and TIMP1. C1 [Hellman, Nathan E.; SpectorO, June; Robinson, Jonathan; Zuo, Xiaofeng; Lipschutz, Joshua H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Lipschutz, Joshua H.] Univ Penn, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA. [Lipschutz, Joshua H.] Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Saunier, Sophie; Antignac, Corinne] Univ Paris 05, Hop Necker Enfants Malades, INSERM, U 574, F-75015 Paris, France. [Tobias, John W.] Univ Penn, Genom Inst Bioinformat Core, Philadelphia, PA 19104 USA. RP Lipschutz, JH (reprint author), 431 Hill Pavil,380 S Univ Ave, Philadelphia, PA 19104 USA. EM jhlipsch@mail.med.upenn.edu FU NIDDK NIH HHS [DK070980, DK069909] NR 58 TC 34 Z9 34 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 15 PY 2008 VL 283 IS 7 BP 4272 EP 4282 DI 10.1074/jbc.M708027200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261MO UT WOS:000253083500062 PM 18039671 ER PT J AU Bischoff, DS Zhu, JH Makhijani, NS Kumar, A Yamaguchi, DT AF Bischoff, D. S. Zhu, J. H. Makhijani, N. S. Kumar, A. Yamaguchi, D. T. TI Angiogenic CXC chemokione expression during differentiation of human mesenchymal stem cells towards the osteoblastic lineage SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ELR+ CXC chemokines; human mesenchymal stem cells; osteoblastic differentiation; dexamethasone; HMEC-1 angiogenesis ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; MARROW STROMAL CELLS; GROWTH-FACTOR; GENE-EXPRESSION; OSTEOGENIC DIFFERENTIATION; RHEUMATOID-ARTHRITIS; SIGNALING PATHWAYS; INTERLEUKIN-8 GENE; ENDOTHELIAL-CELLS AB The potential role of ELR+ CXC chemokines in early events in bone repair was studied using human mesenchymal stem cells(hMSCs). Inflammation, which occurs in the initial phase of tissue healing in general, is critical to bone repair. Release of cytokines from infiltrating immune cells and injured bone can lead to recruitment of MSCs to the region of repair. CXC chemokines bearing the Glu-Leu-Arg (ELR) motif are also released by inflammatory cells and serve as angiogenic factors stimulating chemotaxis and proliferation of endothelial cells. hMSCs, induced to differentiate with osteogenic medium (OGM) containing ascorbate, P-glycerophosphate (beta-GP), and dexamethasone (DEX), showed an increase in mRNA and protein secretion of the ELR+ CXC chemokines CXCL8 and CXCL1. CXCL8 mRNA half-life studies reveal an increase in mRNA stability upon OGM stimulation. Increased expression and secretion is a result of DEX in OGM and is dose-dependent. Inhibition of the glucocorticoid receptor with mifepristone only partially inhibits DEX-stimulated CXCL8 expression indicating both glucocorticoid receptor dependent and independent pathways. Treatment with signal transduction inhibitors demonstrate that this expression is due to activation of the ERK and p38 mitogen-activated protein kinase (MAPR) pathways and is mediated through the G(alpha i)-coupled receptors. Angiogenesis assays demonstrate that OGM-stimulated conditioned media containing secreted CXCL8 and CXCL1 can induce angiogenesis of human microvascular endothelial cells in an in vitro Matrigel assay. C1 [Bischoff, D. S.; Zhu, J. H.; Makhijani, N. S.; Kumar, A.; Yamaguchi, D. T.] Vet Adm Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Bischoff, D. S.; Yamaguchi, D. T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Yamaguchi, DT (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dean.yamaguchi@med.va.gov NR 47 TC 12 Z9 13 U1 0 U2 7 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 FEB 15 PY 2008 VL 103 IS 3 BP 812 EP 824 DI 10.1002/jcb.21450 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 262EW UT WOS:000253132800011 PM 17583554 ER PT J AU Ranganath, S Carpenter, AC Gleason, M Shaw, AC Bassing, CH Alt, FW AF Ranganath, Sheila Carpenter, Andrea C. Gleason, Megan Shaw, Albert C. Bassing, Craig H. Alt, Frederick W. TI Productive coupling of accessible V beta 14 segments and DJ beta complexes determines the frequency of V beta 14 rearrangement SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; RECOMBINATION SIGNAL SEQUENCE; REGION GENE SEGMENTS; V(D)J RECOMBINATION; ALLELIC EXCLUSION; GERMLINE TRANSCRIPTION; SYNAPTIC COMPLEX; IN-VIVO; LOCUS; EXPRESSION AB To elucidate mechanisms that regulate V beta rearrangement, we generated and analyzed mice with a V(D)J recombination reporter cassette of germline D beta-J beta segments inserted into the endogenous V beta 14 locus (V beta 14(Rep)). As a control, we first generated and analyzed mice with the same D beta-J beta cassette targeted into the generally expressed c-myc locus (c-myc(Rep)). Substantial c-myc(Rep) recombination occurred in both T and B cells and initiated concurrently with endogenous D beta to J beta rearrangements in thymocytes. In contrast, V beta 14(Rep) recombination was restricted to T cells and initiated after endogenous D beta to J beta rearrangements, but concurrently with endogenous V beta 14 rearrangements. Thus, the local chromatin environment imparts lineage and developmental stage-specific accessibility upon the inserted reporter. Although V beta 14 rearrangements occur on only 5% of endogenous TCR beta alleles, the V beta 14(Rep) cassette underwent rearrangement on 80-90% of alleles, supporting the suggestion that productive coupling of accessible V beta 14 segments and DJ beta complexes influence the frequency of V beta 14 rearrangements. Strikingly, V beta 14(Rep) recombination also occurs on TCR beta alleles lacking endogenous V beta to DJ beta rearrangements, indicating that V beta 14 accessibility per se is not subject to allelic exclusion. C1 [Carpenter, Andrea C.; Bassing, Craig H.] Univ Penn, Childrens Hosp Philadelphia, Sch Med,Dept Pathol, Abramson Family Canc Res Inst,Immunol Grad Grp, Philadelphia, PA 19104 USA. [Carpenter, Andrea C.; Bassing, Craig H.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst,Lab Med, Philadelphia, PA 19104 USA. [Ranganath, Sheila; Gleason, Megan; Shaw, Albert C.; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,CBR Inst Biomed Res, Boston, MA 02115 USA. [Ranganath, Sheila; Gleason, Megan; Shaw, Albert C.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Bassing, CH (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med,Dept Pathol, Abramson Family Canc Res Inst,Immunol Grad Grp, Room 807A,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bassing@email.chop.edu; alt@enders.tch.harvard.edu FU Howard Hughes Medical Institute; NCI NIH HHS [R01 CA125195, R01 CA136470]; NIAID NIH HHS [R01 AI020047-27, AI 20047, R01 AI020047] NR 45 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2008 VL 180 IS 4 BP 2339 EP 2346 PG 8 WC Immunology SC Immunology GA 260JC UT WOS:000253005600047 PM 18250443 ER PT J AU Maung, AA Fujimi, S MacConmara, MP Tajima, G McKenna, AM Delisle, AJ Stallwood, C Onderdonk, AB Mannick, JA Lederer, JA AF Maung, Adrian A. Fujimi, Satoshi MacConmara, Malcolm P. Tajima, Goro McKenna, Ann M. Delisle, Adam J. Stallwood, Christopher Onderdonk, Andrew B. Mannick, John A. Lederer, James A. TI Injury enhances resistance to Escherichia coli infection by boosting innate immune system function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MULTIPLE ORGAN FAILURE; THERMAL-INJURY; INFLAMMATORY RESPONSE; INTERLEUKIN-12 PRODUCTION; INTRAABDOMINAL SEPSIS; BACTERIAL CLEARANCE; TLR4 REACTIVITY; EXPRESSION; BURN; SUPPRESSION AB Major injury is widely thought to predispose the injured host to opportunistic infections. This idea is supported by animal studies showing that major injury causes reduced resistance to polymicrobial sepsis induced by cecal ligation and puncture. Although cecal ligation and puncture represents a clinically relevant sepsis model, we wanted to test whether injury might also lead to greater susceptibility to peritoneal infection caused by a single common pathogen, Escherichia coli. Contrary to our expectation, we show herein that the LD50 for sham-injured mice was 10(3) CFU of E. coli, whereas the LD50 for burn-injured mice was 50 x 10(3) CFU at 7 days postinjury. This injury-associated enhanced resistance was apparent as early as 1 day after injury, and maximal resistance was observed at days 7 and 14. We found that burn-injured mice had higher numbers of circulating neutrophils and monocytes than did sham mice before infection and that injured mice were able to recruit greater numbers of neutrophils to the site of infection. Moreover, the peritoneal neutrophils in burn-injured mice were more highly activated than neutrophils from sham mice as determined by Mac-1 expression, superoxide generation, and bactericidal activity. Our findings suggest that the enhanced innate immune response that develops following injury, although it is commonly accepted as the mediator of the detrimental systemic inflammatory response syndrome, may also, in some cases, benefit the injured host by boosting innate immune antimicrobial defenses. C1 [Maung, Adrian A.; Fujimi, Satoshi; MacConmara, Malcolm P.; Tajima, Goro; McKenna, Ann M.; Delisle, Adam J.; Stallwood, Christopher; Mannick, John A.; Lederer, James A.] Brigham & Womens Hosp, Dept Surg Immunol, Boston, MA 02115 USA. [Onderdonk, Andrew B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Onderdonk, Andrew B.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Maung, Adrian A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Lederer, JA (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM jlederer@rics.bwh.harvard.edu FU NIGMS NIH HHS [GM 57664, GM 35633] NR 45 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2008 VL 180 IS 4 BP 2450 EP 2458 PG 9 WC Immunology SC Immunology GA 260JC UT WOS:000253005600058 PM 18250454 ER PT J AU Pereyra, F Addo, MM Kaufmann, DE Liu, Y Miura, T Rathod, A Baker, B Trocha, A Rosenberg, R Mackey, E Ueda, P Lu, ZG Cohen, D Wrin, T Petropoulos, CJ Rosenberg, ES Walker, BD AF Pereyra, Florencia Addo, Marylyn M. Kaufmann, Daniel E. Liu, Yang Miura, Toshiyuki Rathod, Almas Baker, Brett Trocha, Alicja Rosenberg, Rachel Mackey, Elizabeth Ueda, Peggy Lu, Zhigang Cohen, Daniel Wrin, Terri Petropoulos, Christos J. Rosenberg, Eric S. Walker, Bruce D. TI Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODY-RESPONSES; T-CELL RESPONSES; LONG-TERM NONPROGRESSORS; TYPE-1 INFECTION; VIRAL LOAD; IMMUNODOMINANT REGIONS; ANTIRETROVIRAL THERAPY; ELITE SUPPRESSORS; ESCAPE MUTATIONS AB Background. Spontaneous control of human immunodeficiency virus (HIV) infection has been documented in a minority of HIV-infected individuals. The mechanisms behind this outcome remain largely unknown, and a better understanding of them will likely influence future vaccine strategies. Methods. HIV-specific T cell and antibody responses as well as host genetics were examined in untreated HIV-infected patients who maintain comparatively low plasma HIV RNA levels (hereafter, controllers), including those with levels of < 50 RNA copies/mL (elite controllers, n = 64), those with levels of 50-2000 copies/mL (viremic controllers, n = 60); we also examined HIV-specific T cell and antibody responses as well as host genetics for patients with levels of > 10,000 copies/mL (chronic progressors, n = 30). Results. CD8 + T cells from both controller groups preferentially target Gag over other proteins in the context of diverse HLA class I alleles, whereas responses are more broadly distributed in persons with progressive infection. Elite controllers represent a distinct group of individuals who have significantly more CD4 and CD8 T cells that secrete interferon-gamma and interleukin-2 and lower levels of HIV-neutralizing antibodies. Individual responses were quite heterogeneous, and none of the parameters evaluated was uniquely associated with the ability to control viremia. Conclusions. Elite controllers are a distinct group, even when compared to persons with low level viremia, but they exhibit marked genetic and immunologic heterogeneity. Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies. C1 [Pereyra, Florencia; Addo, Marylyn M.; Kaufmann, Daniel E.; Miura, Toshiyuki; Rathod, Almas; Baker, Brett; Trocha, Alicja; Rosenberg, Rachel; Mackey, Elizabeth; Ueda, Peggy; Lu, Zhigang; Rosenberg, Eric S.; Walker, Bruce D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. [Pereyra, Florencia; Addo, Marylyn M.; Kaufmann, Daniel E.; Miura, Toshiyuki; Rathod, Almas; Baker, Brett; Trocha, Alicja; Rosenberg, Rachel; Mackey, Elizabeth; Ueda, Peggy; Lu, Zhigang; Rosenberg, Eric S.; Walker, Bruce D.] Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA. [Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Cohen, Daniel] Fenway Community Hlth Care Ctr, Boston, MA USA. [Trocha, Alicja; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Liu, Yang; Wrin, Terri; Petropoulos, Christos J.] Monogram Biosci, San Francisco, CA USA. RP Walker, BD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. EM bwalker@partners.org FU Howard Hughes Medical Institute; NHLBI NIH HHS [R01 HL092565] NR 44 TC 313 Z9 317 U1 5 U2 27 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 FEB 15 PY 2008 VL 197 IS 4 BP 563 EP 571 DI 10.1086/526786 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263BC UT WOS:000253191600011 PM 18275276 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 Calbindin-D28k is a more reliable marker of human Purkinje cells than standard Nissl stains: A stereological experiment SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE cerebellum; Purkinje cell; Nissl; calcium binding protein; calbindin ID HUMAN CEREBELLUM; BRAIN; FRACTIONATOR; NUMBER; EXCITOTOXICITY; HYPOXIA AB In a study of human Purkinje cell (PC) number, a striking mismatch between the number of PCs observed with the Nissl stain and the number of PCs immunopositive for calbindin-D28k (CB) was identified in 2 of the 10 brains examined. In the remaining eight brains this mismatch was not observed. Further, in these eight brains, analysis of CB immunostained sections counterstained with the Nissl stain revealed that more than 99% Nissl stained PCs were also immunopositive for CB. In contrast, in the two discordant brains, only 10-20% of CB immunopositive PCs were also identified with the Nissl stain. Although this finding was unexpected, a historical survey of the literature revealed that Spielmeyer [Spielmeyer W. Histopathologie des nervensystems. Julius Springer: Berlin; 1922. p. 56-79] described human cases with PCs that lacked the expected Nissl staining intensity, an important historical finding and critical issue when studying postmortem human brains. The reason for this failure in Nissl staining is not entirely clear, but it may result from premortern circumstances since it is not accounted for by postmortem delay or processing variables. Regardless of the exact cause, these observations suggest that Nissl staining may not be a reliable marker for PCs and that CB is an excellent alternative marker. (c) 2007 Elsevier B.V. All rights reserved. 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 02118 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-1004,715 Albany St, Boston, MA 02118 USA. EM ewhitney@bu.edu RI Rosene, Douglas/G-1973-2015; OI Rosene, Douglas/0000-0001-8719-1441 FU NICHD NIH HHS [HD39459] NR 21 TC 27 Z9 27 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD FEB 15 PY 2008 VL 168 IS 1 BP 42 EP 47 DI 10.1016/j.jneumeth.2007.09.009 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 261EQ UT WOS:000253062300006 PM 17961663 ER PT J AU Hothi, SS Killeen, MJ AF Hothi, Sandeep S. Killeen, Matthew J. TI The role of I-Ks in atrial arrhythmogenesis SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID FIBRILLATION; MODEL C1 [Hothi, Sandeep S.] Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. [Killeen, Matthew J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Hothi, SS (reprint author), Univ Cambridge, Physiol Lab, Downing St, Cambridge CB2 3EG, England. EM ssh26@cam.ac.uk; matthew.killeen@gmail.com NR 5 TC 0 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 15 PY 2008 VL 586 IS 4 BP 927 EP 928 DI 10.1113/jphysiol.2007.149534 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 267CE UT WOS:000253485300006 PM 18096595 ER PT J AU Yoon, SO Shin, S Liu, Y Ballif, BA Woo, MS Gygi, SP Blenis, J AF Yoon, Sang-Oh Shin, Sejeong Liu, Yuzhen Ballif, Bryan A. Woo, Michele S. Gygi, Steven P. Blenis, John TI Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport SO MOLECULAR CELL LA English DT Article ID NUCLEAR IMPORT; KINASE; SIGNAL; GTPASE; CELLS; RCC1; LOCALIZATION; CHROMOSOMES; REQUIREMENT; MITOSIS AB The major participants of the Ras/ERK and PI3-kinase (PI3K) pathways are well characterized. The cellular response to activation of these pathways, however, can vary dramatically. How differences in signal strength, timing, spatial location, and cellular context promote specific cell-fate decisions remains unclear. Nuclear transport processes can have a major impact on the determination of cell fate; however, little is known regarding how nuclear transport is regulated by or regulates these pathways. Here we show that RSK and Akt, which are activated downstream of Ras/ERK and PI3K, respectively, modulate the Ran gradient and nuclear transport by interacting with, phosphorylating, and regulating Ran-binding protein 3 (RanBP3) function. Our findings highlight an important link between two major cell-fate determinants: nuclear transport and the Ras/ERK/RSK and PI3K/Akt signaling pathways. C1 [Yoon, Sang-Oh; Shin, Sejeong; Liu, Yuzhen; Gygi, Steven P.; Blenis, John] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Ballif, Bryan A.] Univ Vermont, Dept Biol, Burlington, VT 05405 USA. [Woo, Michele S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Blenis, J (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM john_blenis@hms.harvard.edu FU NCI NIH HHS [R37 CA46595, R37 CA046595-21, R37 CA046595]; NHGRI NIH HHS [HG3456, R01 HG003456]; NIGMS NIH HHS [R01 GM051405-12, R01 GM5105, R01 GM051405] NR 36 TC 48 Z9 47 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD FEB 15 PY 2008 VL 29 IS 3 BP 362 EP 375 DI 10.1016/j.molcel.2007.12.024 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 265AG UT WOS:000253330900008 PM 18280241 ER PT J AU Brass, AL Dykxhoorn, DM Benita, Y Yan, N Engelman, A Xavier, RJ Lieberman, J Elledge, SJ AF Brass, Abraham L. Dykxhoorn, Derek M. Benita, Yair Yan, Nan Engelman, Alan Xavier, Ramnik J. Lieberman, Judy Elledge, Stephen J. TI Identification of host proteins required for HIV infection through a functional genomic screen SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; N-LINKED GLYCOSYLATION; ENDOPLASMIC-RETICULUM; NUCLEAR IMPORT; SNARE TLG1P; LATE GOLGI; COMPLEX; GLYCOPROTEINS; TRANSPORT; CXCR4 AB HIV- 1 exploits multiple host proteins during infection. We performed a large- scale small interfering RNA screen to identify host factors required by HIV- 1 and identified more than 250 HIV- dependency factors ( HDFs). These proteins participate in a broad array of cellular functions and implicate new pathways in the viral life cycle. Further analysis revealed previously unknown roles for retrograde Golgi transport proteins ( Rab6 and Vps53) in viral entry, a karyopherin ( TNPO3) in viral integration, and the Mediator complex ( Med28) in viral transcription. Transcriptional analysis revealed that HDF genes were enriched for high expression in immune cells, suggesting that viruses evolve in host cells that optimally perform the functions required for their life cycle. This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy. C1 [Brass, Abraham L.; Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp,Dept Genet,Ctr Genet & Geno, Boston, MA 02115 USA. [Brass, Abraham L.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Dykxhoorn, Derek M.; Yan, Nan; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Dykxhoorn, Derek M.; Yan, Nan; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Benita, Yair; Xavier, Ramnik J.] Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Aids, Boston, MA 02115 USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp,Dept Genet,Ctr Genet & Geno, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu RI Benita, Yair/E-3094-2012; Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU Howard Hughes Medical Institute; NIAID NIH HHS [AI062773, AI052014, P30 AI060354, U19-AI056900]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-13] NR 35 TC 857 Z9 888 U1 9 U2 72 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 FEB 15 PY 2008 VL 319 IS 5865 BP 921 EP 926 DI 10.1126/science.1152725 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 262RM UT WOS:000253165700037 PM 18187620 ER PT J AU Duran-Struuck, R Reddy, P AF Duran-Struuck, Raimon Reddy, Pavan TI Biological advances in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation SO TRANSPLANTATION LA English DT Review DE T cells; dendritic cells; bone marrow transplantation ID BONE-MARROW-TRANSPLANTATION; ANTIGEN-PRESENTING CELLS; G-CSF ANALOGS; T-CELLS; DENDRITIC CELLS; B-CELLS; GVHD; CD4(+); ALLOREACTIVITY; MOBILIZATION AB Allogeneic hematopoietic stem cell transplantation is a potentially curative therapy for many malignant and nonmalignant hematological diseases. Unfortunately, naive donor T cells that are critical for the success of this effective therapy also cause its most severe toxicity - graft-versus-host disease (GVHD). Recent experimental observations have brought into focus a critical role for additional cell populations in the pathogenesis and modulation of GVHD. A better understanding of the complex interactions involving these cellular subsets and the inflammatory cascades is likely to be critical in the pathophysiology of GVHD. This review will primarily focus on the immunobiology of experimental acute GVHD with an emphasis on the recent observations on the novel role of innate and adaptive cellular subsets in the activation, effector phases, and target organ specificity of acute GVHD. C1 [Duran-Struuck, Raimon; Reddy, Pavan] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. [Reddy, Pavan] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Reddy, P (reprint author), Univ Michigan, Ctr Canc, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM reddypr@umich.edu NR 31 TC 18 Z9 18 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 FEB 15 PY 2008 VL 85 IS 3 BP 303 EP 308 DI 10.1097/TP.0b013e318162d357 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 264HT UT WOS:000253279100001 PM 18301323 ER PT J AU Hoerbelt, R Benjamin, CL Shoji, T Houser, SL Muniappan, A Hasse, RS Ledgerwood, LG Allan, JS Sachs, DH Madsen, JC AF Hoerbelt, Ruediger Benjamin, Christopher L. Shoji, Tsuyoshi Houser, Stuart L. Muniappan, Ashok Hasse, Rebecca S. Ledgerwood, Levi G. Allan, James S. Sachs, David H. Madsen, Joren C. TI The effects of tolerance on allograft damage caused by the innate immune system SO TRANSPLANTATION LA English DT Article DE tolerance; inflammation; cytokines; heart; swine ID MAJOR HISTOCOMPATIBILITY COMPLEX; REGULATORY T-CELLS; CLASS-II ANTIGENS; COLD ISCHEMIA/REPERFUSION INJURY; DISPARATE SKIN ALLOGRAFTS; IFN-GAMMA; INTERFERON-GAMMA; MINIATURE SWINE; IN-VIVO; ACUTE REJECTION AB Background. It is not known whether tolerance can be induced in a strong proinflammatory milieu or whether the induction of tolerance can prevent interferon (IFN)-gamma-associated graft injury. To address these questions, we studied the effects of rIFN-gamma infusion on porcine cardiac allograft survival. Methods. Recombinant interferon (rIFN)-gamma was continuously infused into the left anterior descending artery of hearts transplanted into major histocompatibility complex-inbred miniature swine treated with a 12-day course of cyclosporine A. Group 1 recipients received a nearly syngeneic heart, group 2 recipients received a class I disparate heart, and group 3 recipients were cotransplanted with a class I-disparate heart and kidney, a procedure demonstrated to induce tolerance to both grafts. A fourth group of animals were not transplanted but received intracoronary rIFN-gamma infusion into the native heart. Results. rIFN-gamma perfusion not only accelerated the acute rejection of class I-disparate hearts (mean survival time, 19 +/- 7.21 vs. 38 +/- 8.19; P=0.025) but caused near-syngeneic heart transplants, which otherwise survived indefinitely, to reject within 35 days. In contrast, rIFN-gamma perfusion had no demonstrable effects on hearts grafts in tolerant recipients or on autologous hearts. Conclusions. These results suggest that tolerance induction can occur in the presence of IFN-gamma-mediated inflammation, and that tolerance induction can prevent the tissue injury caused by the overproduction of IFN-gamma. This suggests that the beneficial effects of tolerance may include protection from nonspecific inflammatory responses, such as those produced by ischemia-reperfusion injury and brain death. C1 [Hoerbelt, Ruediger; Benjamin, Christopher L.; Shoji, Tsuyoshi; Houser, Stuart L.; Muniappan, Ashok; Hasse, Rebecca S.; Ledgerwood, Levi G.; Allan, James S.; Sachs, David H.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Allan, James S.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Curg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jcmadsen@partners.org FU NHLBI NIH HHS [R01 HL054211-11, R01 HL054211, R01HL54211] NR 74 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 2008 VL 85 IS 3 BP 314 EP 322 DI 10.1097/TP.0b013e3181629b05 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 264HT UT WOS:000253279100004 PM 18301326 ER PT J AU Yoo, SD Cho, YH Tena, G Xiong, Y Sheen, J AF Yoo, Sang-Dong Cho, Young-Hee Tena, Guillaume Xiong, Yan Sheen, Jen TI Dual control of nuclear EIN3 by bifurcate MAPK cascades in C2H4 signalling SO NATURE LA English DT Article ID ACTIVATED PROTEIN-KINASE; ETHYLENE-RESPONSE PATHWAY; F-BOX PROTEINS; ARABIDOPSIS-THALIANA; FUNCTIONAL-ANALYSIS; PLANTS; STRESS; TRANSDUCTION; UBIQUITIN; CTR1 AB A principal question in MAP kinase ( MAPK/ MPK) cascade signalling is how similar components dictate different specificity in the information- processing machineries from yeast to humans and plants. In Arabidopsis, how MPK3/ 6modulates distinct outputs in diverse signal transduction pathways remains elusive. By combining systematic cellular and genetic screens, here we uncover a previously unexpected MKK9 - MPK3/ MPK6 cascade promoting ethylene- insensitive 3 ( EIN3)- mediated transcription in ethylene signalling. The mkk9 mutant exhibits a broad spectrum of moderate ethylene- insensitive phenotypes, and translocated MKK9 governs nuclear signalling downstream of receptors. Breaking a linear model and conventional MAPK signalling, ethylene inactivates the negative regulator constitutive triple response 1 ( CTR1, a Raf- like MAPK kinase kinase ( MAPKKK)) to activate the positive MKK9 - MPK3/ 6 cascade. The bifurcate and antagonistic CTR1 and MKK9 pathways are both critical in determining ethylene- signalling specificity through two MAPK phosphorylation sites with opposite effects on EIN3 stability. The results suggest a new paradigm for linking intertwined MAPK cascades to control quantitative responses and specificity in signalling networks. C1 [Yoo, Sang-Dong; Cho, Young-Hee; Tena, Guillaume; Xiong, Yan; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yoo, Sang-Dong; Cho, Young-Hee; Tena, Guillaume; Xiong, Yan; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM yoo@molbio.mgh.harvard.edu; sheen@molbio.mgh.harvard.edu OI Tena, Guillaume/0000-0001-8652-905X FU NIGMS NIH HHS [R01 GM060493, R01 GM070567] NR 50 TC 238 Z9 268 U1 4 U2 47 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 14 PY 2008 VL 451 IS 7180 BP 789 EP U1 DI 10.1038/nature06543 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 263BA UT WOS:000253191400034 PM 18273012 ER PT J AU Weiss, LA Shen, YP Korn, JM Arking, DE Miller, DT Fossdal, R Saemundsen, E Stefansson, H Ferreira, MAR Green, T Platt, OS Ruderfer, DM Walsh, CA Altshuler, D Chakravarti, A Tanzi, RE Stefansson, K Santangelo, SL Gusella, JF Sklar, P Wu, B Daly, MJ AF Weiss, Lauren A. Shen, Yiping Korn, Joshua M. Arking, Dan E. Miller, David T. Fossdal, Ragnheidur Saemundsen, Evald Stefansson, Hreinn Ferreira, Manuel A. R. Green, Todd Platt, Orah S. Ruderfer, Douglas M. Walsh, Christopher A. Altshuler, David Chakravarti, Aravinda Tanzi, Rudolph E. Stefansson, Kari Santangelo, Susan L. Gusella, James F. Sklar, Pamela Wu, Bai-Lin Daly, Mark J. CA Autism Consortium TI Association between microdeletion and microduplication at 16p11.2 and autism SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID REARRANGEMENTS; DISORDERS; DUPLICATION; GENOME AB Background: Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role. Methods: As a first component of a genomewide association study of families from the Autism Genetic Resource Exchange (AGRE), we used two novel algorithms to search for recurrent copy-number variations in genotype data from 751 multiplex families with autism. Specific recurrent de novo events were further evaluated in clinical-testing data from Children's Hospital Boston and in a large population study in Iceland. Results: Among the AGRE families, we observed five instances of a de novo deletion of 593 kb on chromosome 16p11.2. Using comparative genomic hybridization, we observed the identical deletion in 5 of 512 children referred to Children's Hospital Boston for developmental delay, mental retardation, or suspected autism spectrum disorder, as well as in 3 of 299 persons with autism in an Icelandic population; the deletion was also carried by 2 of 18,834 unscreened Icelandic control subjects. The reciprocal duplication of this region occurred in 7 affected persons in AGRE families and 4 of the 512 children from Children's Hospital Boston. The duplication also appeared to be a high-penetrance risk factor. Conclusions: We have identified a novel, recurrent microdeletion and a reciprocal microduplication that carry substantial susceptibility to autism and appear to account for approximately 1% of cases. We did not identify other regions with similar aggregations of large de novo mutations. ` C1 [Weiss, Lauren A.; Shen, Yiping; Korn, Joshua M.; Ferreira, Manuel A. R.; Green, Todd; Ruderfer, Douglas M.; Altshuler, David; Santangelo, Susan L.; Gusella, James F.; Sklar, Pamela; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Weiss, Lauren A.; Shen, Yiping; Korn, Joshua M.; Miller, David T.; Green, Todd; Platt, Orah S.; Ruderfer, Douglas M.; Walsh, Christopher A.; Altshuler, David; Tanzi, Rudolph E.; Santangelo, Susan L.; Gusella, James F.; Sklar, Pamela; Wu, Bai-Lin; Daly, Mark J.] Harvard Univ, Sch Med, Autism Consortium, Boston, MA 02115 USA. [Weiss, Lauren A.; Platt, Orah S.; Walsh, Christopher A.; Altshuler, David; Tanzi, Rudolph E.; Santangelo, Susan L.; Gusella, James F.; Sklar, Pamela; Wu, Bai-Lin; Daly, Mark J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Weiss, Lauren A.; Platt, Orah S.; Walsh, Christopher A.; Altshuler, David; Tanzi, Rudolph E.; Santangelo, Susan L.; Gusella, James F.; Sklar, Pamela; Wu, Bai-Lin; Daly, Mark J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Weiss, Lauren A.; Platt, Orah S.; Walsh, Christopher A.; Altshuler, David; Tanzi, Rudolph E.; Santangelo, Susan L.; Gusella, James F.; Sklar, Pamela; Wu, Bai-Lin; Daly, Mark J.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Weiss, Lauren A.; Platt, Orah S.; Walsh, Christopher A.; Altshuler, David; Tanzi, Rudolph E.; Santangelo, Susan L.; Gusella, James F.; Sklar, Pamela; Wu, Bai-Lin; Daly, Mark J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Weiss, Lauren A.; Platt, Orah S.; Walsh, Christopher A.; Altshuler, David; Tanzi, Rudolph E.; Santangelo, Susan L.; Gusella, James F.; Sklar, Pamela; Wu, Bai-Lin; Daly, Mark J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Shen, Yiping; Miller, David T.; Platt, Orah S.; Walsh, Christopher A.; Wu, Bai-Lin] Harvard Univ, Sch Publ Hlth, Dept Lab Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Shen, Yiping; Miller, David T.; Platt, Orah S.; Walsh, Christopher A.; Wu, Bai-Lin] Harvard Univ, Sch Publ Hlth, Div Genet, Childrens Hosp Boston, Boston, MA 02115 USA. [Santangelo, Susan L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Weiss, Lauren A.; Korn, Joshua M.; Ferreira, Manuel A. R.; Green, Todd; Ruderfer, Douglas M.; Walsh, Christopher A.; Altshuler, David; Gusella, James F.; Sklar, Pamela; Daly, Mark J.] Harvard Univ, Broad Inst Harvard, Cambridge, MA 02138 USA. [Weiss, Lauren A.; Korn, Joshua M.; Ferreira, Manuel A. R.; Green, Todd; Ruderfer, Douglas M.; Walsh, Christopher A.; Altshuler, David; Gusella, James F.; Sklar, Pamela; Daly, Mark J.] Harvard Univ, MIT, Cambridge, MA 02139 USA. [Korn, Joshua M.] Harvard Univ, MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Korn, Joshua M.] Harvard Univ, Grad Program Biophys, Cambridge, MA 02139 USA. [Arking, Dan E.; Chakravarti, Aravinda] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Fossdal, Ragnheidur; Stefansson, Hreinn; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Saemundsen, Evald] State Diagnost & Counseling Ctr, Kopavogur, Iceland. [Ferreira, Manuel A. R.] Univ Queensland, Royal Brisbane Hosp, Queensland Inst Med Res, Herston, Qld, Australia. RP Daly, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu RI Altshuler, David/A-4476-2009; Ferreira, Manuel/D-3609-2013; Ruderfer, Douglas/M-5795-2016 OI Altshuler, David/0000-0002-7250-4107; Ruderfer, Douglas/0000-0002-2365-386X FU OMHHE CDC HHS [R01-MN071425-01A1] NR 17 TC 850 Z9 879 U1 6 U2 73 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 FEB 14 PY 2008 VL 358 IS 7 BP 667 EP 675 DI 10.1056/NEJMoa075974 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 262CX UT WOS:000253127700003 PM 18184952 ER PT J AU Teles, MG Bianco, SDC Brito, VN Trarbach, EB Kuohung, W Xu, SY Seminara, SB Mendonca, BB Kaiser, UB Latronico, AC AF Teles, Milena Gurgel Bianco, Suzy D. C. Brito, Vinicius Nahime Trarbach, Ericka B. Kuohung, Wendy Xu, Shuyun Seminara, Stephanie B. Mendonca, Berenice B. Kaiser, Ursula B. Latronico, Ana Claudia TI A GPR54-activating mutation in a patient with central precocious puberty SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MONKEY MACACA-MULATTA; HYPOGONADOTROPIC HYPOGONADISM; RECEPTOR GPR54; KISS-1 PEPTIDE; HORMONE; ACTIVATION; ONSET; G-PROTEIN-COUPLED-RECEPTOR-54; KISSPEPTIN; EXPRESSION AB Gonadotropin-dependent, or central, precocious puberty is caused by early maturation of the hypothalamic-pituitary-gonadal axis. In girls, this condition is most often idiopathic. Recently, a G protein-coupled receptor, GPR54, and its ligand, kisspeptin, were described as an excitatory neuroregulator system for the secretion of gonadotropin-releasing hormone (GnRH). In this study, we have identified an autosomal dominant GPR54 mutation - the substitution of proline for arginine at codon 386 (Arg386Pro) - in an adopted girl with idiopathic central precocious puberty (whose biologic family was not available for genetic studies). In vitro studies have shown that this mutation leads to prolonged activation of intracellular signaling pathways in response to kisspeptin. The Arg386Pro mutant appears to be associated with central precocious puberty. C1 [Teles, Milena Gurgel; Brito, Vinicius Nahime; Trarbach, Ericka B.; Mendonca, Berenice B.; Latronico, Ana Claudia] Univ Sao Paulo, Hosp Clin, Disciplina Endocrinol & Metabol, Fac Med,Med Sch,Med Invest Lab, BR-05403900 Sao Paulo, Brazil. [Teles, Milena Gurgel; Brito, Vinicius Nahime; Trarbach, Ericka B.; Mendonca, Berenice B.; Latronico, Ana Claudia] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Teles, Milena Gurgel; Bianco, Suzy D. C.; Kuohung, Wendy; Xu, Shuyun; Seminara, Stephanie B.; Kaiser, Ursula B.] Harvard Reprod Endocrine Sci Ctr, Boston, MA USA. [Kuohung, Wendy] Boston Univ, Sch Med, Boston, MA 02118 USA. [Seminara, Stephanie B.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Latronico, AC (reprint author), Univ Sao Paulo, Hosp Clin, Disciplina Endocrinol & Metabol, Fac Med,Med Sch,Med Invest Lab, Av Dr Eneas Carvalho Aguiar 155-2 Andar Bloco 6, BR-05403900 Sao Paulo, Brazil. EM anacl@usp.br RI Bianco, Suzy/E-8892-2010; Mendonca, Berenice/C-2827-2012; BRITO, VINICIUS/C-1938-2012; Latronico, Ana Claudia/E-1198-2012; Teles, Milena/H-7026-2012; Trarbach, Ericka/I-5395-2012; BRITO, VINICIUS/B-3776-2013 OI Bianco, Suzy/0000-0003-3794-9853; BRITO, VINICIUS/0000-0003-4140-6296 FU NICHD NIH HHS [U54 HD028138, U54 HD028138-140002, U54 HD28138]; NIDDK NIH HHS [T32 DK007529] NR 26 TC 222 Z9 235 U1 5 U2 10 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 FEB 14 PY 2008 VL 358 IS 7 BP 709 EP 715 DI 10.1056/NEJMoa073443 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 262CX UT WOS:000253127700007 PM 18272894 ER PT J AU Sheridan, RL Ryan, DP Fuzaylov, G Nimkin, K Martyn, JAJ AF Sheridan, Robert L. Ryan, Daniel P. Fuzaylov, Gennadiy Nimkin, Katherine Martyn, J. A. Jeevendra TI A girl with an advanced neck contracture after a burn - Dermal scarring with severe contractures of the neck and face after a burn injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EXTRACORPOREAL MEMBRANE-OXYGENATION; TRACHEAL RECONSTRUCTION; MANAGEMENT; ANESTHESIA; AIRWAY C1 [Sheridan, Robert L.] Massachusetts Gen Hosp, Dept Burn Surg, Boston, MA 02114 USA. [Ryan, Daniel P.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Fuzaylov, Gennadiy; Martyn, J. A. Jeevendra] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Nimkin, Katherine] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sheridan, Robert L.] Shriners Hosp Children, Dept Surg, Boston, MA USA. [Fuzaylov, Gennadiy; Martyn, J. A. Jeevendra] Shriners Hosp Children, Dept Anesthesia, Boston, MA USA. [Sheridan, Robert L.; Ryan, Daniel P.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Fuzaylov, Gennadiy; Martyn, J. A. Jeevendra] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Nimkin, Katherine] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Dept Burn Surg, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM055082] NR 11 TC 6 Z9 7 U1 1 U2 1 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 FEB 14 PY 2008 VL 358 IS 7 BP 729 EP 735 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 262CX UT WOS:000253127700011 PM 18272897 ER PT J AU Beppu, H Mwizerwa, ON Beppu, Y Dattwyler, MP Lauwers, GY Bloch, KD Goldstein, AM AF Beppu, H. Mwizerwa, O. N. Beppu, Y. Dattwyler, M. P. Lauwers, G. Y. Bloch, K. D. Goldstein, A. M. TI Stromal inactivation of BMPRII leads to colorectal epithelial overgrowth and polyp formation SO ONCOGENE LA English DT Article DE bone morphogenetic proteins; BMPRII; nestin hamartomatous polyps; colorectal polyps; stromal-epithelial interactions ID JUVENILE POLYPOSIS; INTESTINAL EPITHELIUM; CANCER; CELLS; MYOFIBROBLASTS; GENE; FIBROBLASTS; SUPPRESSION; MUTATIONS; SIGNALS AB Stromal - epithelial interactions play a central role in development and tumorigenesis. Bone morphogenetic protein ( BMP) signaling in the intestine is involved in both of these processes. Inactivation of BMP pathway genes in the epithelium is known to cause intestinal polyposis. However, the role of the intestinal stroma in polyp initiation is incompletely understood. We observed that conditional inactivation of the BMP type II receptor ( BMPRII) in the stroma leads to epithelial hyperplasia throughout the colon with increased epithelial cell proliferation. Mutant mice developed rectal bleeding and hamartomatous polyps in the colorectum. The polyps demonstrated increased proliferation of epithelial and mesenchymal cells in the mucosa with an expansion of the myofibroblast cell population. These results demonstrate that genetic mutations altering the BMP signaling pathway in the stromal microenvironment can lead to epithelial tumors in the colon. C1 [Mwizerwa, O. N.; Goldstein, A. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Beppu, H.; Beppu, Y.; Dattwyler, M. P.; Bloch, K. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lauwers, G. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, 55 Fruit St,Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org FU NHLBI NIH HHS [R01 HL074352] NR 26 TC 49 Z9 51 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 14 PY 2008 VL 27 IS 8 BP 1063 EP 1070 DI 10.1038/sj.onc.1210720 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 262GJ UT WOS:000253136700005 PM 17700526 ER PT J AU Ehringhaus, SH Weissman, JS Sears, JL Goold, SD Feibelmann, S Campbell, EG AF Ehringhaus, Susan H. Weissman, Joel S. Sears, Jacqueline L. Goold, Susan Dorr Feibelmann, Sandra Campbell, Eric G. TI Responses of medical schools to institutional conflicts of interest SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INDUSTRY AB Context Institutional financial conflicts of interest may affect research results. No national data exist on the extent to which US medical schools have formally responded to challenges associated with institutional conflicts of interest ( ICOI). Objective To assess the current state of ICOI policies and practices in US medical schools using the recommendations issued by 2 national higher education and research organizations as the standard. Design, Setting, and Participants National survey of deans of all 125 accredited allopathic medical schools in the United States, administered between February 2006 and December 2006. Main Outcome Measures The extent to which medical schools have adopted ICOI policies applicable to their institution and to their institutional officials; the scope of these policies in terms of those covered entities, offices, and financial relationships; the existence of recommended organizational structures as means to address ICOI; and the institutions' linkages between ICOI and their institutional review boards ( IRBs). Results Responses were received from a total of 86 ( 69%) of 125 US medical schools. Although only 30 ( 38%) respondents ( not all overall respondents answered all questions) have adopted an ICOI policy applicable to financial interests held by the institutions, a much higher number have adopted ICOI policies applicable to the financial interests of the officials: 55 ( 71%) for senior officials, 55 ( 69%) for midlevel officials, 62 ( 81%) for IRB members, and 51 ( 66%) for governing board members. Most institutions treat as potential ICOI the financial interests held by an institutional research official for a research sponsor ( 43 [ 78%]) or for a product that is the subject of research ( 43 [ 78%]). The majority of institutions have adopted organizational structures that separate research responsibility from investment management and from technology transfer responsibility. Gaps exist in institutions informing their IRBs of potential ICOI in research projects under review. Conclusions This study provides the first national data on the existence and nature of policies and practices of US medical schools for addressing potential ICOI. The gaps identified suggest the need for continuing attention by the academic medical community to address the challenges presented by ICOI more consistently and comprehensively. C1 [Ehringhaus, Susan H.; Sears, Jacqueline L.] Assoc Amer Med Coll, Washington, DC 20037 USA. [Weissman, Joel S.; Feibelmann, Sandra; Campbell, Eric G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goold, Susan Dorr] Univ Michigan, Ann Arbor, MI 48109 USA. RP Ehringhaus, SH (reprint author), Assoc Amer Med Coll, 2450 N St NW, Washington, DC 20037 USA. EM sehringhaus@aamc.org OI Goold, Susan Dorr/0000-0002-0258-9774 NR 16 TC 38 Z9 39 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 13 PY 2008 VL 299 IS 6 BP 665 EP 671 DI 10.1001/jama.299.6.665 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 261QN UT WOS:000253095200024 PM 18270355 ER PT J AU Hung, AY Futai, K Sala, C Valtschanoff, JG Ryu, J Woodworth, MA Kidd, FL Sung, CC Miyakawa, T Bear, MF Weinberg, RJ Sheng, M AF Hung, Albert Y. Futai, Kensuke Sala, Carlo Valtschanoff, Juli G. Ryu, Jubin Woodworth, Mollie A. Kidd, Fleur L. Sung, Clifford C. Miyakawa, Tsuyoshi Bear, Mark F. Weinberg, Richard J. Sheng, Morgan TI Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE postsynaptic density; gene knock-out; learning and memory; dendritic spine; autism; scaffolding proteins ID POSTSYNAPTIC DENSITY PROTEINS; LONG-TERM POTENTIATION; IN-VIVO; DIFFERENTIAL EXPRESSION; HIPPOCAMPAL-NEURONS; BINDING-PROTEIN; AMPA RECEPTORS; ADULT CORTEX; MUTANT MICE; FAMILY AB Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, the Shank family of postsynaptic scaffold proteins are abundant and enriched in the postsynaptic density (PSD) of central excitatory synapses. When expressed in cultured hippocampal neurons, Shank promotes the maturation and enlargement of dendritic spines. Recently, Shank3 has been genetically implicated in human autism, suggesting an important role for Shank proteins in normal cognitive development. Here, we report the phenotype of Shank1 knock-out mice. Shank1 mutants showed altered PSD protein composition; reduced size of dendritic spines; smaller, thinner PSDs; and weaker basal synaptic transmission. Standard measures of synaptic plasticity were normal. Behaviorally, they had increased anxiety-related behavior and impaired contextual fear memory. Remarkably, Shank1-deficient mice displayed enhanced performance in a spatial learning task; however, their long-term memory retention in this task was impaired. These results affirm the importance of Shank1 for synapse structure and function in vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders. C1 [Hung, Albert Y.; Futai, Kensuke; Ryu, Jubin; Woodworth, Mollie A.; Kidd, Fleur L.; Sung, Clifford C.; Bear, Mark F.; Sheng, Morgan] MIT, Picower Inst Learning & Memory, RIKEN, Howard Hughes Med Inst,Neurosci Res Ctr, Cambridge, MA 02139 USA. [Hung, Albert Y.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sala, Carlo] Univ Milan, Dept Pharmacol, CNR, Inst Neurosci Cellular & Mol Pharmacol, I-20129 Milan, Italy. [Valtschanoff, Juli G.; Weinberg, Richard J.] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. [Valtschanoff, Juli G.; Weinberg, Richard J.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. [Miyakawa, Tsuyoshi] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Syst Med Sci, Aichi 4701192, Japan. RP Sheng, M (reprint author), MIT, Picower Inst Learning & Memory, RIKEN, Howard Hughes Med Inst,Neurosci Res Ctr, 77 Massachusetts Ave,46-4303, Cambridge, MA 02139 USA. EM msheng@mit.edu RI Sala, Carlo/A-2493-2009; Miyakawa, Tsuyoshi/A-7741-2008; OI Sala, Carlo/0000-0003-0662-9523; Miyakawa, Tsuyoshi/0000-0003-0137-8200; Weinberg, Richard/0000-0001-9689-7278 FU NINDS NIH HHS [K08 NS041411, K08 NS41411, R01 NS039444, R01 NS039444-07] NR 59 TC 164 Z9 167 U1 1 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 13 PY 2008 VL 28 IS 7 BP 1697 EP 1708 DI 10.1523/JNEUROSCI.3032-07.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 262LM UT WOS:000253150000017 PM 18272690 ER PT J AU Grodstein, F van Oijen, M Irizarry, MC Rosas, HD Hyman, BT Growdon, JH De Vivo, I AF Grodstein, Francine van Oijen, Marieke Irizarry, Michael C. Rosas, H. Diana Hyman, Bradley T. Growdon, John H. De Vivo, Immaculata TI Shorter Telomeres May Mark Early Risk of Dementia: Preliminary Analysis of 62 Participants from the Nurses' Health Study SO PLOS ONE LA English DT Article AB Background: Dementia takes decades to develop, and effective prevention will likely require early intervention. Thus, it is critical to identify biomarkers of preclinical disease, allowing targeting of high-risk subjects for preventive efforts. Since telomeres shorten with age and oxidative stress, both of which are important contributors to the onset of dementia, telomere length might be a valuable biomarker. Methodology/Principal Findings: Among 62 participants of the Nurses' Health Study, we conducted neurologic evaluations, including patient and caregiver interviews, physical exam, neurologic exam, and neuropsychologic testing. We also conducted magnetic resonance imaging (MRI) in a sample of 29 of these women. In these preliminary data, after adjustment for numerous health and lifestyle factors, we found that truncated telomeres in peripheral blood leukocytes segregate with preclinical dementia states, including mild cognitive impairment (MCI); the odds of MCI were 12-fold higher (odds ratio = 12.00, 95% confidence interval 1.24-116.5) for those with shorter telomere length compared to longer telomere length. In addition, decreasing telomere length was strongly related to decreasing hippocampal volume (p = 0.038). Conclusions: These preliminary data suggest that telomere length may be a possible early marker of dementia risk, and merits further study in large, prospective investigations. C1 [Grodstein, Francine; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Grodstein, Francine; De Vivo, Immaculata] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [van Oijen, Marieke] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [van Oijen, Marieke] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Irizarry, Michael C.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Rosas, H. Diana; Hyman, Bradley T.; Growdon, John H.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Massachusetts Alzheimer Dis Res Ctr, Boston, MA USA. RP Grodstein, F (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 75 Francis St, Boston, MA 02115 USA. EM fgrodstein@partners.org FU National Institutes of Health [AG15424, AG05134, CA87969] FX The study was supported by grants AG15424, AG05134, and CA87969 from the National Institutes of Health. The funders had no part in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript NR 12 TC 43 Z9 43 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 13 PY 2008 VL 3 IS 2 AR e1590 DI 10.1371/journal.pone.0001590 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367ES UT WOS:000260535900024 PM 18795148 ER PT J AU Yan, M Roehrl, MH Basar, E Wang, JY AF Yan, Ming Roehrl, Michael H. Basar, Emre Wang, Julia Y. TI Selection and evaluation of the immunogenicity of protective antigen mutants as anthrax vaccine candidates SO VACCINE LA English DT Article DE anthrax; protective antigen; vaccine ID NEUTRALIZING MONOCLONAL-ANTIBODIES; T-LYMPHOCYTE ACTIVATION; LETHAL FACTOR; CELLULAR RECEPTOR; CRYSTAL-STRUCTURE; IN-VIVO; TOXIN; CELLS; INTERNALIZATION; INHIBITION AB Protective antigen (PA) is a central component of anthrax toxin and a major antigen in anthrax vaccines. However, the use of native PA as a vaccine is not optimal. If administered to people who have been freshly exposed to anthrax, PA may actually aid in anthrax toxin formation and thus may pose a serious safety concern for postexposure vaccination applications. A non-functional PA mutant may be a much safer alternative. To identify an improved anthrax vaccine antigen, we examined four non-functional mutants of PA, each being impaired in a critical step of the cellular intoxication pathway of PA. These mutants were Rec(-) (unable to bind PA-receptors), SSSR (resistant to activation by furin), Oligo(-) (unable to form oligomers), and DNI (Dominant Negative Inhibitory, unable to form endosomal transmembrane pores). When tested in mice and after three doses of immunization, all four mutants were highly potent in eliciting PA-specific, toxin -neutralizing antibodies, with immunogenicity increasing in the order of PA < Rec(-) < SSSR < Oligo(-) < DNI. White the differences between Rec(-) or SSSR and PA were small and not statistically significant, DNI and Oligo(-) were significantly more immunogenic than wildtype PA. One year after immunization and compared with PA-immunized mice, DNI-immunized mice maintained significantly higher levels of anti-PA IgG with correspondingly higher titers of toxin - neutralizing activity. In contrast, Oligo(-)-immunized mice had high levels of anti-PA IgG but lower titers of toxin-neutralizing activity, suggesting that Oligo(-) mutation sites may overlap with critical protective epitopes of PA. Our study demonstrates that PA-based vaccines could be improved both in terms of safety and efficacy by strategic mutations that not only render PA non-functional but also simultaneously enhance its immunogenic potency. Recombinant PA mutants, particularly DNI, hold great promise as better and safer antigens than wild-type PA for use in postexposure vaccination. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Yan, Ming; Basar, Emre; Wang, Julia Y.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. [Roehrl, Michael H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Roehrl, Michael H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Med, Boston, MA 02114 USA. RP Wang, JY (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM jutia_wang@rics.bwh.harvard.edu FU NIAID NIH HHS [R01 AI057926, R01 AI057926-01A1, R01 AI057926-02, R01 AI057926-03, R01 AI057926-04, R01 AI068826, R01 AI068826-01A2] NR 34 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 13 PY 2008 VL 26 IS 7 BP 947 EP 955 DI 10.1016/j.vaccine.2007.11.087 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 268LG UT WOS:000253580700011 PM 18192092 ER PT J AU Conrad, MF Cambria, RP AF Conrad, Mark F. Cambria, Richard P. TI Contemporary management of descending thoracic and thoracoabdominal aortic aneurysms: Endovascular versus open SO CIRCULATION LA English DT Article DE aneurysm; grafting; stents; surgery ID CEREBROSPINAL-FLUID DRAINAGE; OPEN-SURGICAL REPAIR; LEFT-HEART BYPASS; SPINAL-CORD PROTECTION; NATURAL-HISTORY; STENT-GRAFT; RISK-FACTOR; CARDIOPULMONARY BYPASS; RESPIRATORY-FAILURE; CIRCULATORY ARREST C1 [Conrad, Mark F.; Cambria, Richard P.] Harvard Univ, Sch Med, Dept Surg,Div Vasc & Endovasc Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Conrad, MF (reprint author), Massachusetts Gen Hosp, WACC 4,15 Parkman St, Boston, MA 02114 USA. EM mconrad@partners.org NR 84 TC 40 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 12 PY 2008 VL 117 IS 6 BP 841 EP 852 DI 10.1161/CIRCULATIONAHA.107.690958 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 261OU UT WOS:000253090700016 PM 18268161 ER PT J AU Muehlschlegel, S Goddeau, RP Sims, JR AF Muehlschlegel, Susanne Goddeau, Richard P., Jr. Sims, John R., Jr. TI Teaching NeuroImage: Cerebral T-waves from an aneurysmal cardunculus compression SO NEUROLOGY LA English DT Editorial Material C1 [Muehlschlegel, Susanne; Sims, John R., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Div Neurocrit Care & Stroke, Boston, MA 02129 USA. [Sims, John R., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. [Goddeau, Richard P., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. RP Sims, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Div Neurocrit Care & Stroke, CNY 149 Room 6403,13th St, Boston, MA 02129 USA. EM jsims@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2008 VL 70 IS 7 BP E28 EP E29 DI 10.1212/01.wnl.0000297555.60074.48 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 260XJ UT WOS:000253043400020 PM 18268239 ER EF