FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sonnenberg, A AF Sonnenberg, A TI Personal view: cost and benefit of medical rituals in gastroenterology SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MANAGEMENT; SCIENCE AB Background: Unable to resolve a medical problem, gastroenterologists occasionally choose an ineffectual intervention instead. The elusive path to effectual management becomes substituted with an ineffectual but readily available medical ritual. The term 'ritual' refers to the utilization of an ineffectual intervention with little chances of achieving a medically relevant goal. Aim: The aim of the article is to analyse the cost-benefit relationship of rituals in gastroenterology and the reasons why gastroenterologists utilize them. Methods: Ritualistic disease management is described in terms of medical decision and threshold analysis. Results: If the perceived benefit of a ritual exceeds its cost, the ineffectual path becomes more attractive than expectant management or doing nothing. To engage in an ineffectual intervention, the threshold probability for success needs to exceed its cost-benefit difference divided by the benefit associated with success. In choosing an ineffectual intervention, doctors tend to underestimate the true costs of a ritual and overestimate its probability of success. The availability of an effectual path leads to more stringent conditions for the benefit associated with an ineffectual path. Conclusions: A better understanding of their economical underpinnings should lead to more restricted utilization of rituals in gastroenterology, especially, in situations where they drain scarce resources disproportionately to their perceived benefit. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 18 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD NOV 1 PY 2004 VL 20 IS 9 BP 939 EP 942 DI 10.1111/j.1365-2036.2004.02252.x PG 4 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 867QE UT WOS:000224856300003 PM 15521840 ER PT J AU Morrow, DA AF Morrow, DA TI Evidence-based decision limits for cardiac troponin: Low-level elevation and prognosis SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; DIAGNOSTIC-CRITERIA; AMERICAN-COLLEGE; EUROPEAN-SOCIETY; UNSTABLE ANGINA; CHEST-PAIN; I LEVELS; RECOMMENDATIONS; MANAGEMENT C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 18 TC 10 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2004 VL 148 IS 5 BP 739 EP 742 DI 10.1016/j.ahj.2004.05.024 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 870GH UT WOS:000225045100001 PM 15523301 ER PT J AU Au, DH Udris, EM Curtis, JR McDonnell, MB Fihn, SD AF Au, DH Udris, EM Curtis, JR McDonnell, MB Fihn, SD CA ACQUIP Investigators TI Association between chronic heart failure and inhaled beta-2-adrenoceptor agonists SO AMERICAN HEART JOURNAL LA English DT Article ID IDIOPATHIC DILATED CARDIOMYOPATHY; LEFT-VENTRICULAR FUNCTION; PHARMACY RECORDS; MERIT-HF; DISEASE; POLYMORPHISMS; TERBUTALINE; MANAGEMENT; METOPROLOL; DENSITY AB Background Recent reports suggest an association between beta-agonists and the risk of incident chronic heart failure (CHF). We sought to examine the association between inhaled beta-agonists and risk,of incident and nonincident heart failure. Methods We performed a nested case-control study within the Ambulatory Care Quality Improvement Project (ACQUIP). Case subjects were defined as having had a hospitalization with a primary discharge diagnosis of CHF. Controls were randomly selected from the ACQUIP cohort. The exposure was the number of beta-agonist canisters filled in the 90 days before an index date. Results After adjusting for potentially confounding factors, there appeared to be no association between the use of inhaled beta-agonists and the risk of heart failure (1-2 canisters per month, OR 1.3 [95% Cl 0.9, 1.8], greater than or equal to3 canisters per month, 1.1 [95% Cl 0.8, 1.6]). However, among the cohort that had a history of CHF, there appeared to be a close-response association between the number of inhaled beta-agonists and the risk of hospitalization for chronic heart failure (1-2 canisters per month, adjusted OR 1.8 [95% Cl 1.1, 3.0], greater than or equal to3 canisters per month, adjusted OR 2.1 [95% Cl 1.2, 3.8]). Conclusion beta-Agonists did not appear to be associated with incident heart failure but were associated with risk of CHIF hospitalization among those subjects with a previous CHIF diagnosis. Although a causal relationship cannot be inferred from these findings, further research is warranted to determine the safety and effectiveness of inhaled beta-agonists for patients with CHF. C1 VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Au, DH (reprint author), VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM dau@u.washington.edu NR 28 TC 30 Z9 32 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2004 VL 148 IS 5 BP 915 EP 920 DI 10.1016/j.ahj.2004.03.048 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 870GH UT WOS:000225045100027 PM 15523327 ER PT J AU Gibson, CM AF Gibson, CM TI NRMI and current treatment patterns for ST-elevation myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 1st International Quality Improvement Summit on Acute Coronary Syndromes CY NOV 10, 2003 CL Duke Univ Sch Med, Orlando, FL HO Duke Univ Sch Med ID FIBRINOLYTIC THERAPY; PRIMARY ANGIOPLASTY; NATIONAL REGISTRY; MORTALITY; THROMBOLYSIS; REPERFUSION; TIME AB The National Registry of Myocardial Infarction (NRMI) is one of the oldest and largest registries of acute myocardial infarction (AMI). Since 1990, 4 NRMI studies have been launched, one of which is ongoing (Table 1). In all, 1600 hospitals have participated and >2.2 million patients have been followed. This paper highlights some of our discoveries pertaining to ST-segment elevation and subsequent contributions to patient care. C1 Harvard Univ, Sch Med, Boston, MA USA. RP Gibson, CM (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM mgibson@perfuse.org NR 10 TC 28 Z9 31 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2004 VL 148 IS 5 SU S BP S29 EP S33 DI 10.1016/j.ahj.2004.09.012 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 871UV UT WOS:000225160900002 PM 15514631 ER PT J AU Pasternak, RC McKenney, JM Brown, WV Cahill, E Cohen, JD AF Pasternak, RC McKenney, JM Brown, WV Cahill, E Cohen, JD TI Understanding physician and consumer attitudes concerning cholesterol management: Results from the National Lipid Association Surveys SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID AWARENESS; PREVENTION; TRIALS; RISK AB Two online surveys commissioned by the National Lipid Association (NLA) were conducted to determine the current attitudes of physicians and consumers regarding cholesterol and heart disease. Physicians and consumers from preexisting independent panels were randomly invited to participate in the online surveys that were open from January 26 to 30, 2004. Both physicians (n = 200) and consumers (n = 600) agreed that high cholesterol and coronary artery disease (CAD) are significant health risks. Physicians reported the primary barriers for patients being prescribed cholesterol-lowering medication as patient fear of side effects (61%) and reluctance to take prescription medications (52%). While most physicians were aware of and felt they adhered to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, considerably fewer thought the same of other physicians. The con-sumer survey focused on untreated moderate-risk patients (an approximate 10% to 20% 10-year risk of myocardial infarction and cardiac death) because this group is often undertreated. Untreated moderate-risk patients reported that their physicians did not advise them to take prescription cholesterol-lowering drugs (51%) and that they were trying to control their cholesterol with diet and exercise (58%). Consumers believe they are taking an increased role in their own health management and decision making. Current attitudes of physicians and consumers are similar with regard to their recognition of the significance of cholesterol and CAD. for health, but differ with regard to why patients do not take prescription medications. (C) 2004 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Clin Res Inc, Richmond, VA USA. Emory Univ, Sch Med, Atlanta, GA USA. Appl Res & Consulting LLC, New York, NY USA. St Louis Univ, Sch Med, St Louis, MO USA. RP Pasternak, RC (reprint author), Massachusetts Gen Hosp, 55 Fruit St,CLN-BA 060, Boston, MA 02114 USA. EM rpasternak@partners.org NR 14 TC 4 Z9 4 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV PY 2004 VL 94 IS 9 SU S BP 9F EP 15F DI 10.1016/j.amjcard.2004.07.047 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 868LG UT WOS:000224914500003 PM 15519286 ER PT J AU Karmpaliotis, D Turakhia, MP Kirtane, A Murphy, SA Kosmidou, I Morrow, DA Giugliano, RP Cannon, CP Antman, EM Braunwald, E Gibson, CM AF Karmpaliotis, D Turakhia, MP Kirtane, A Murphy, SA Kosmidou, I Morrow, DA Giugliano, RP Cannon, CP Antman, EM Braunwald, E Gibson, CM CA TIMI Study Grp TI Sequential risk stratification using TIMI risk score and TIMI flow grade among patients treated with fibrinolytic therapy for ST-segment elevation acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; FRAME COUNT; TRIAL; THROMBOLYSIS; REPERFUSION; ANGIOPLASTY; PREDICTION; MORTALITY; BLUSH AB In the setting of ST-segment elevation myocardial infarction (STEMI), the Thrombolysis In Myocardial Infarction (TIMI) risk score (TRS) and indexes of epicardial and myocardial perfusion are associated with mortality. The association between TRS at presentation and angio-graphic indexes of epicardial and myocardial perfusion after reperfusion therapy has not been investigated. We hypothesized that TRS, TIMI flow grade (TFG), and TIMI myocardial perfusion grade (TMPG) would provide independent prognostic information and that angiographic indexes of poor flow and perfusion would be associated with a higher TRS. TRS and angiographic data were evaluated in 3,801 patients from the TIMI 4, 10A, 10B, 14, 20, 23, and 24 trials. Within each TRS stratum (TRS 0 to 2, 3 to 4, greater than or equal to5), 30-day mortality increased stepwise among-patients with impaired TFG at 60 minutes after fibrinolytic administration. In a multivariate model adjusting for the IRS strata, impaired TMPG (0/1) was independently associated with higher mortality (odds ratio 2.28, p = 0.018). In a multivariate model adjusting for the TFG and infarct location, the likelihood of impaired TMPG (0/1) was greater among intermediate-risk (TRS 3 to 4) and high-risk (TRS 5) patients than among low-risk (TRS 0 to 2) patients (odds ratio 1.43, p = 0.019 and 1.50, p = 0.055, respectively). Thus, impaired epicardial flow and myocardial perfusion are independently associated with increased 30-day mortality among patients identified by TRS as high risk, although there is no synergism between either TFG or TMPG and TRS. High TRS at presentation is associated with abnormal myocardial perfusion, even after adjusting for possible confounders. (C)2004 by Excerpta Medica, Inc. C1 Beth Israel Deaconess Med Ctr, TIMI Study Grp, Dept Med, Brigham & Womens Hosp, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Gibson, CM (reprint author), 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org NR 20 TC 5 Z9 8 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2004 VL 94 IS 9 BP 1113 EP 1117 DI 10.1016/j.amjcard.2004.07.075 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 867IY UT WOS:000224837500002 PM 15518603 ER PT J AU Pierpont, GL Moritz, TE Goldman, S Krupski, WC Littooy, F Ward, HB McFalls, E AF Pierpont, GL Moritz, TE Goldman, S Krupski, WC Littooy, F Ward, HB McFalls, E CA Revascularization Study Grp TI Disparate opinions regarding indications for coronary artery revascularization before elective vascular surgery SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC RISK; NONCARDIAC SURGERY; CLINICAL-TRIALS; DISEASE; BYPASS; MANAGEMENT; MORTALITY; INDEX AB Despite consensus guidelines, the optimal strategy for preoperative cardiac risk management among patients scheduled for major noncardiac surgery remains controversial. This study assesses current opinion about the role of preoperative coronary revascularization for patients with coronary artery disease scheduled for elective vascular surgery. Thirty-one practicing cardiologists recruited from 4 different regions reviewed case records, imaging tests, and coronary angiograms of 12 patients with coronary artery disease participating in the Coronary Artery Revascularization Prophylaxis (CARP) trial. The need for preoperative coronary revascularization was determined and results summarized using 3 categories: favoring conservative management, neutral, or recommending revascularization (either by percutaneous intervention or bypass surgery). We found recommendations were frequently disparate and often deviated from published guidelines (40% of the time). The likelihood of discordance between 2 cardiologists was 54%, with a 26% chance that recommendations for revascularization would be directly contradictory. Opinions were more often conservative (43%) or aggressive (40%) than neutral (17%). Similar inconsistency was found as to the preferred method of revascularization, with only 1 patient having complete agreement. Thus, this study reveals substantial differences of opinion among cardiologists across the country about the role of preoperative coronary artery. revascularization for patients scheduled for elective vascular operations. Deviations from published guidelines are common, suggesting that current consensus statements need additional data to support their recommendations. (C)2004 by Excerptal Medica, Inc. C1 Minneapolis VA Med Ctr, Minneapolis, MN 55417 USA. Univ Minnesota, Minneapolis, MN USA. Hines VA Hosp, Cooperat Studies Program Coorinating Ctr, Hines, IL USA. So Arizona VA Hlth Care Ctr, Tucson, AZ USA. Denver VA Med Ctr, Denver, CO USA. RP Pierpont, GL (reprint author), Minneapolis VA Med Ctr, 1 Vet Dr,Med Ctr 111-C, Minneapolis, MN 55417 USA. EM pierp002@umn.edu NR 17 TC 20 Z9 21 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2004 VL 94 IS 9 BP 1124 EP 1128 DI 10.1016/j.amjcard.2004.07.077 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 867IY UT WOS:000224837500004 PM 15518605 ER PT J AU Mozaffarian, D Rimm, EB Herrington, DM AF Mozaffarian, D Rimm, EB Herrington, DM TI Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet; saturated fat; carbohydrate; coronary atherosclerosis; women ID AMERICAN-HEART-ASSOCIATION; ARTERY DISEASE; MYOCARDIAL-INFARCTION; ESTROGEN REPLACEMENT; CARDIOVASCULAR RISK; INTERVENTION TRIAL; UNSATURATED FAT; FOLLOW-UP; A-I; CHOLESTEROL AB Background: The influence of diet on atherosclerotic progression is not well established, particularly in postmenopausal women, in whom risk factors for progression may differ from those for men. Objective: The objective was to investigate associations between dietary macronutrients and progression of coronary atherosclerosis among postmenopausal women. Design: Quantitative coronary angiography was performed at baseline and after a mean follow-up of 3.1 y in 2243 coronary segments in 235 postmenopausal women with established coronary heart disease. Usual dietary intake was assessed at baseline. Results: The mean (+/-SD) total fat intake was 25+/-6% of energy. In multivariate analyses. a higher saturated fat intake was associated with a smaller decline in mean minimal coronary diameter (P = 0.001) and less progression of coronary stenosis (P = 0.002) during follow-up. Compared with a 0.22-mm decline in the lowest quartile of intake. there was a 0.10-mm decline in the second quartile (P = 0.002), a 0.07-mm decline in the third quartile (P = 0.002), and no decline in the fourth quartile (P < 0.001); P for trend = 0.001. This inverse association was more pronounced among women with lower monounsaturated fat (P for interaction = 0.04) and higher carbohydrate (P for interaction 0.004) intakes and possibly lower total fat intake (P for interaction 0.09). Carbohydrate intake was positively associated with atherosclerotic progression (P = 0.001), particularly when the glycemic index was high. Polyunsaturated fat intake was positively associated with progression when replacing other fats (P = 0.04) but not when replacing carbohydrate or protein. Monounsaturated and total fat intakes were not associated with progression. Conclusions: In postmenopausal women with relatively low total fat intake, a greater saturated fat intake is associated with less progression of coronary atherosclerosis. whereas carbohydrate intake is associated with a greater progression. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epodemiol & Nutr, Boston, MA 02115 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Program, Seattle, WA USA. Tufts Univ, Cardiovasc Nutr Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Wake Forest Univ, Cardiol Sect, Dept Internal Med, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Mozaffarian, D (reprint author), 665 Huntington Ave,Bldg 2,Room 315, Boston, MA 02115 USA. RI Mozaffarian, Dariush/B-2276-2008 FU NCRR NIH HHS [M01 RR007122, M01 RR07122]; NHLBI NIH HHS [K08 HL075628, U01 HL-45488]; NIDDK NIH HHS [DK07703, T32 DK007703] NR 53 TC 80 Z9 83 U1 0 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2004 VL 80 IS 5 BP 1175 EP 1184 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 870EE UT WOS:000225036000011 PM 15531663 ER PT J AU Radeos, MS Camargo, CA AF Radeos, MS Camargo, CA TI Predicted peak expiratory flow: Differences across formulae in the literature SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE practice guidelines; reference values; peak expiratory flow; spirometry ID SPIROMETRIC REFERENCE VALUES; VENTILATORY FUNCTIONS; MEXICAN-AMERICAN; NORMAL STANDARDS; NORMAL-CHILDREN; YOUNG-ADULTS; POPULATION; SAMPLE; WHITE; BLACK AB The study objectives were to examine. the, differences between Peak Expiratory Flow (PEF) formulae in the literature and to assess the potential impact of those differences on the interpretation of clinical guidelines for asthma management. We calculated 100% PEF values for hypothetical patients at the 50(th) percentile for height and weight and classified the percent predicted PEF into severity groups according to national asthma guidelines. Choosing different formulae could give an 18 year old man a 100% predicted PEF as low as 501 L/min and as high as 730 L/min (delta = 229 L/min); and a 35 year old woman a classification of severe (46%) using one, but moderate (57%) using another. Predicted PEF varied widely across formulae and choice of formula may alter guideline-based care. We propose recently published population-based equations as the reference standard for future asthma guidelines. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, EMNet Coordinat Ctr, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, EMNet Coordinat Ctr, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU NHLBI NIH HHS [HL 07427, HL 03533] NR 20 TC 11 Z9 12 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2004 VL 22 IS 7 BP 516 EP 521 DI 10.1016/j.ajem.2004.08.018 PG 6 WC Emergency Medicine SC Emergency Medicine GA 886VN UT WOS:000226261000002 PM 15666252 ER PT J AU Shaib, Y El-Serag, HB AF Shaib, Y El-Serag, HB TI The prevalence and risk factors of functional dyspepsia in a. multiethnic population in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL-REFLUX; NONULCER DYSPEPSIA; HELICOBACTER-PYLORI; PEPTIC-ULCER; SYMPTOMS; ASSOCIATION; SUBGROUPS; IMPACT AB BACKGROUND AND AIMS: The prevalence of functional dyspepsia (FD) in the general population is not known. The aim of this study is to measure the prevalence of FD and its risk factors in a multiethnic volunteer sample of the U.S. population. METHODS: One thousand employees at the Houston VA Medical Center were targeted with a symptom questionnaire asking about upper abdominal symptoms, followed by a request to undergo endsocopy. Dyspepsia was defined by the presence of epigastric pain, fullness, nausea, or vomiting, and FD was defined as dyspepsia in the absence of esophageal erosions, gastric ulcers, or duodenal ulcers or erosions. The presence of dyspepsia and FD was examined in multiple logistic regression analyses. RESULTS: A total of 465 employees completed the relevant questions and of those 203 had endoscopic examination. The age-adjusted prevalence rate of dyspepsia was 31.9 per 100 (95% CI: 26.7-37.1), and 15.8 per 100 (95% CI: 9.6-22.0) if participants with concomitant heartburn or acid regurgitation were excluded. Subjects with dyspepsia were more likely to report smoking, using antacids, aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), and consulting a physician for their symptoms (p < 0.05) than participants without dyspepsia. Most (64.5%) participants with dyspepsia who underwent endoscopy had FD. The age-adjusted prevalence rate of FD was 29.2 per 100 (95% CI: 21.9-36.5), and 15.0 per 100 (6.7-23.3) if subjects with GERD were excluded. Apart from a trend towards association with older age in the multiple regression analysis, there were no significant predictors of FD among participants with dyspepsia. CONCLUSIONS: Most subjects with dyspepsia have FD. The prevalence of FD is high but predictors of FD remain poorly defined. C1 Michael E Debakey Vet Affairs Med Ctr, Sect Hlth Serv Res & Gastroenterol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E Debakey Vet Affairs Med Ctr, Sect Hlth Serv Res & Gastroenterol, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. NR 20 TC 85 Z9 96 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2004 VL 99 IS 11 BP 2210 EP 2216 DI 10.1111/j.1572-0241.2004.40052.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 866IT UT WOS:000224767900023 PM 15555004 ER PT J AU Wong, W Denton, M Rennke, HG Lin, J AF Wong, W Denton, M Rennke, HG Lin, J TI Hepatitis C, proteinuria, and renal insufficiency SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hepatitis C; thrombotic microanglopathy (TMA); antiphospholipid antibodies ID HEMOLYTIC-UREMIC SYNDROME; ANTICARDIOLIPIN ANTIBODIES; THROMBOTIC MICROANGIOPATHY; ANTIPHOSPHOLIPID SYNDROME; FIBRILLARY GLOMERULONEPHRITIS; VIRAL-INFECTION; AUTOANTIBODIES; DISEASE; PURPURA; VIRUS C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Lin, J (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St, Boston, MA 02115 USA. EM jlin11@partners.org NR 19 TC 2 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2004 VL 44 IS 5 BP 924 EP 929 DI 10.1053/j.ajkd.2004.05.047 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 870FX UT WOS:000225044100023 PM 15492962 ER PT J AU Chan, KS Morton, SC Shekelle, PG AF Chan, KS Morton, SC Shekelle, PG TI Systematic reviews for evidence-based management: How to find them and what to do with them SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID MEDICAL LITERATURE; USERS GUIDES; QUALITY; CARE; INTERVENTIONS; METAANALYSIS; PRINCIPLES; GUIDELINES; MEDLINE AB Objective: To identify strategies for retrieval and evaluation of systematic reviews from a management perspective. Study Design: Review of available literature and resources on systematic reviews. Methods: From published literature on evidence-based medicine and systematic review, we identified resources and adapted retrieval and evaluation strategies for healthcare managers. A published systematic review then was assessed for quality and relevance to management decisions. Results: Systematic reviews relevant to the organization and delivery of care are available. Criteria for evaluating the relevance and quality of systematic reviews on clinical topics may be adapted for systematic reviews on organizational topics. However, even a systematic review that focuses on an organizational topic can lack important information on costs and study setting. Conclusions: Greater familiarity with the retrieval and evaluation of systematic reviews can help managers use these sources effectively and encourage the development of evidence-based management. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. RAND Corp, Hlth Program, Santa Monica, CA USA. So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. RP Chan, KS (reprint author), 624 N Broadway,Rm 644, Baltimore, MD 21205 USA. EM kchan@jhsph.edu NR 25 TC 13 Z9 13 U1 0 U2 4 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2004 VL 10 IS 11 BP 806 EP 812 PN 1 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 871DX UT WOS:000225110600009 PM 15623270 ER PT J AU Corson, K Gerrity, MS Dobscha, SK AF Corson, K Gerrity, MS Dobscha, SK TI Screening for depression and suicidality in a VA primary care setting: 2 items are better than 1 item SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CASE-FINDING INSTRUMENTS; DISORDERS; VALIDITY; PHQ-9; VALIDATION; UTILITY; LIFE AB Objective: To evaluate the psychometric properties of a single-item depression screen against validated scoring algorithms for the Patient Health Questionnaire (PHQ) and the utility of these algorithms in screening for depression and suicidality in a Department of Veterans Affairs (VA) primary care setting. Study Design: Recruitment phase of a randomized trial. Methods: A total of 1211 Portland VA patients with upcoming primary care clinic appointments were administered by telephone a single item assessing depressed mood over the past year and the PHQ. The PHQ-9 (9 items) encompasses DSM-IV criteria for major depression, the PHQ-8 (8 items) excludes the thoughts of death or suicide item, and the PHQ-2 (2 items) assesses depressed mood and anhedonia. Patients whose responses suggested potential suicidality were administered 2 additional items assessing suicidal ideation. Patients receiving mental health specialty care were excluded. Results: Using the PHQ-9 algorithm for major depression as the reference standard, the VA single-item screen was specific (88%) but less sensitive (78%). A PHQ-2 score of greater than or equal to3 demonstrated similar specificity (91%) with high sensitivity (97%). For case finding, the PHQ-8 was similar to the PHQ-9. Approximately 20% of patients screened positive for moderate depression, 7% reported thoughts of death or suicide, 2% reported thoughts of harming themselves, and 1% had specific plans. Conclusions: The PHQ-2 offers brevity and better psychometric properties for depression screening than the single-item screen. The PHQ-9 item assessing thoughts of death or suicide does not improve depression case finding; however, one third of patients endorsing this item reported recent active suicidal ideation. C1 Portland VA Med Ctr, Res Serv, Behav Hlth & Clin Neurosci Div, Portland, OR 97207 USA. Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. RP Corson, K (reprint author), Portland VA Med Ctr, Res Serv, Behav Hlth & Clin Neurosci Div, POB 1034,P3 DEP-PC, Portland, OR 97207 USA. EM kathryn.corson@med.va.gov NR 28 TC 102 Z9 103 U1 3 U2 5 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2004 VL 10 IS 11 BP 839 EP 845 PN 2 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 874BE UT WOS:000225325100003 PM 15609737 ER PT J AU Weiner, J Aguirre, A Ravenell, K Kovath, K McDevit, L Murphy, J Asch, DA Shea, JA AF Weiner, J Aguirre, A Ravenell, K Kovath, K McDevit, L Murphy, J Asch, DA Shea, JA TI Designing an illustrated patient satisfaction instrument for low-literacy populations SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID IMPROVE COMPREHENSION; INJURY PREVENTION; READABILITY; INFORMATION; QUALITY; CARE; INSTRUCTIONS; CHILDREN; VERSION AB Up to 25% of adults in the United States have difficulty with everyday reading tasks. As patients, adults with low literacy may not be able to complete many self-administered written questionnaires, which often are used to obtain information from patients and to gauge their satisfaction with care. We developed an illustrated version of a patient satisfaction instrument used by the Veterans Health Administration. This paper describes the extensive design process used to develop, pilot-test, and revise this 63-item illustrated instrument. A total of 438 patients were interviewed over a 1-year period to obtain feedback on illustrations, with at least 15 people viewing and commenting on each picture and revision. All pictures were revised, with the majority revised at least 4 times. We report on this iterative design process as well as on lessons we learned in illustrating questions for low-literacy populations. C1 Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Weiner, J (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3641 Locust Walk, Philadelphia, PA 19104 USA. EM weinerja@mail.med.upenn.edu OI Weiner, Janet/0000-0001-5810-5807 NR 35 TC 9 Z9 9 U1 2 U2 4 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2004 VL 10 IS 11 BP 853 EP 860 PN 2 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 874BE UT WOS:000225325100005 PM 15609739 ER PT J AU Fung, CH Woods, JN Asch, SM Glassman, P Doebbeling, BN AF Fung, CH Woods, JN Asch, SM Glassman, P Doebbeling, BN TI Variation in implementation and use of computerized clinical reminders in an integrated healthcare system SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID INFORMATION TECHNOLOGY; AMBULATORY-CARE; ISSUES AB Objectives: To identify patterns of use of computerized clinical reminders (CCRs) across an integrated healthcare system and describe institutional factors associated with their implementation. Study Design: Cross-sectional study. Methods: At a national electronic health record (EHR) meeting, we surveyed 261 participants from 104 Veterans Health Administration (VHA) healthcare facilities regarding the number and types of CCRs available at each facility. Potential explanatory measures included perceived utility and ease of use of CCRs, training and personnel support for computer use, EHR functionalities, and performance data feedback to providers at each facility. Results: The number of conditions with CCRs in use at a facility ranged from I to 15; most reported implementation of reminders for 10 of the 15 conditions surveyed. The most commonly implemented CCRs, used in more than 85% of facilities, were for conditions with VHA national performance measures (eg, tobacco cessation, immunizations, diabetes mellitus). The least commonly implemented CCRs were for post-deployment health evaluation and management, medically unexplained symptoms, and erectile dysfunction. Facilities that had implemented greater numbers of clinical reminders had providers who reported greater ease of use and utility of the reminders (P=.01). Conclusions: VHA facilities Vary markedly in their implementation of CCRs. This effect may be partly explained by greater incorporation of clinical reminders for conditions with performance measures. Further study is needed to determine how to best implement clinical reminders and the institutional factors important in their use. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. VA Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. Richard L Roudebush Vet Affairs Med Ctr, HSR&D Ctr Excellence Implementing Evidence Based, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Internal Med, Indianapolis, IN 46204 USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. RP Fung, CH (reprint author), 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM cfung@mednet.ucla.edu NR 19 TC 53 Z9 53 U1 0 U2 7 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2004 VL 10 IS 11 BP 878 EP 885 PN 2 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 874BE UT WOS:000225325100008 PM 15609742 ER PT J AU Davila, JA Brooks, JM Pendergast, JF Chrischilles, EA AF Davila, JA Brooks, JM Pendergast, JF Chrischilles, EA TI The effect of physician characteristics and their practice environment on surgical referral patterns for early-stage breast cancer in Iowa SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE breast cancer; physician behavior; physician practice patterns; surveillance; epidemiology and end results program ID CLINICAL-PRACTICE GUIDELINES; UNITED-STATES; FEEDBACK; WOMEN; SURGERY; TRIAL; AUDIT AB The objective of this article was to examine whether characteristics of referring physicians and their practice environment were associated with surgical referral behavior for early-stage breast cancer patients. A total of 2801 women diagnosed with early-stage breast cancer and their referring physicians were identified from the Iowa Surveillance, Epidemiology, and End Results (SEER) database during 1989-1996. The Iowa Physician Inventory was used to collect information on characteristics of referring physicians. Multiple logistic regression analyses were conducted to evaluate characteristics of the referring physicians and their practice environment to explain surgical referral behavior. Affiliation with physicians' networks and professional diversity among area specialists were associated with increased referrals to surgeons more likely to perform breast-conserving surgery. Promoting interaction among physicians, particularly among those with different specialties, may increase the diffusion of new behaviors into clinical practice. C1 Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX USA. Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Davila, JA (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM jdavila@bcm.tmc.edu NR 24 TC 1 Z9 1 U1 0 U2 3 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD NOV-DEC PY 2004 VL 19 IS 6 BP 266 EP 273 DI 10.1177/106286060401900606 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 872UN UT WOS:000225234300005 PM 15620078 ER PT J AU Mullins, ME Grant, PE Wang, B Gonzalez, RG Schaefer, PW AF Mullins, ME Grant, PE Wang, B Gonzalez, RG Schaefer, PW TI Parenchymal abnormalities associated with cerebral venous sinus thrombosis: Assessment with diffusion-weighted MR imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID MAGNETIC-RESONANCE; BRAIN-DAMAGE; STATUS EPILEPTICUS; HYPERACUTE STROKE; BLOOD-FLOW; COEFFICIENT; EPILEPSY; ADULTS; EDEMA AB BACKGROUND AND PURPOSE: The common entity cerebral venous sinus thrombosis is associated with the poorly characterized imaging finding of parenchymal abnormalities; diffusion-weighted imaging has offered some insight into these manifestations. We assessed the relationship between the diffusion constant from apparent diffusion coefficient (ADC) maps in patients with cerebral venous thrombosis (CVT) with follow-up imaging findings and clinical outcome. METHODS: We evaluated the medical records and T2-weighted MR images of 13 patients with CVT complicated by intraparenchymal abnormality. Diffusion-weighted (DW) images and ADC maps were evaluated for increased, decreased, or unchanged signal intensity and were compared with signal intensity of contralateral, normal-appearing brain. In addition, ADCs were obtained in nine pixel regions of interest in abnormal regions in eight of the 13 patients. RESULTS: Eight patients had superficial CVT, and five had superficial and deep CVT. CVT of deep veins was associated with deep gray nucleus and deep white matter abnormalities, whereas superficial CVT was associated with cortical and subcortical abnormalities. Twenty-four nonhemorrhagic lesions were identified in 10 of 13 patients on the basis of follow-up imaging findings. Four patients without seizures had lesions with decreased diffusion that appeared hyperintense on follow-up T2-weighted images, three patients with seizures had lesions with decreased diffusion that resolved, and seven patients had lesions with increased diffusion that resolved. Three of 10 patients had more than one lesion type. No difference was noted in mean ADCs for lesions with decreased diffusion that resolved compared with lesions with decreased diffusion that persisted. CONCLUSION: DW imaging in these patients disclosed three lesion types: lesions with elevated diffusion that resolved, consistent with vasogenic edema; lesions with low diffusion that persisted, consistent with cytotoxic edema in patients without seizure activity; and lesions with low diffusion that resolved in patients with seizure activity. This information may be important in prospectively determining severity of irreversible injury and in patient treatment. C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mullins, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. NR 42 TC 60 Z9 65 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2004 VL 25 IS 10 BP 1666 EP 1675 PG 10 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 874IN UT WOS:000225344200009 PM 15569728 ER PT J AU Paulsen, JS Zimbelman, JL Hinton, SC Langbehn, DR Leveroni, CL Benjamin, ML Reynolds, NC Rao, SM AF Paulsen, JS Zimbelman, JL Hinton, SC Langbehn, DR Leveroni, CL Benjamin, ML Reynolds, NC Rao, SM TI fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's disease SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID BASAL GANGLIA VOLUME; PARKINSONS-DISEASE; PROJECTION NEURONS; TIME-ESTIMATION; AT-RISK; ONSET; GENE; CORTEX; MOUSE; DISCRIMINATION AB BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) has been used to probe basal ganglia function in people with presymptomatic Huntington's disease (pre-HD). A previous fMRI study in healthy individuals demonstrated activation of the basal ganglia during a time-discrimination task. The current study was designed to examine the relative sensitivity of fMRI compared with that of behavioral testing and morphometric measurements in detecting early neurodegenerative changes related to Huntington's disease (HD). METHODS: Pre-HD participants were assigned to two groups based on estimated years to diagnosis of manifest disease: close < 12 years and far greater than or equal to 12 years. Age at disease onset was estimated using a regression equation based on the number of trinucleotide CAG repeats. The time-discrimination task required participants to determine whether a specified interval was shorter or longer than a standard interval of 1200 milliseconds. RESULTS: Participants in the close group performed more poorly on the time-task discrimination than did control subjects; however, no differences were observed between far participants and control subjects. Similarly, close participants had reduced bilateral caudate volume relative to that of control subjects, whereas far participants did not. On functional imaging, close participants had significantly less activation in subcortical regions (caudate, thalamus) than control subjects; far participants had an intermediate degree of activation. In contrast, far participants had hyperactivation in medial hemispheric structures (anterior cingulate, pre-supplementary motor area) relative to close and control subjects. CONCLUSION: Hyperactivation of medial prefrontal regions compensated for reduced subcortical participation during time discrimination in pre-HD. This pattern of brain activation may represent an early neurobiologic marker of neuronal dysfunction. C1 Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. Carroll Coll, Dept Hlth Sci, Waukesha, WI USA. Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Psychol Assessment Ctr, Boston, MA USA. RP Paulsen, JS (reprint author), Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. RI Rao, Stephen/A-2460-2010 OI Rao, Stephen/0000-0002-6463-7460 FU NCRR NIH HHS [RR00058]; NIMH NIH HHS [MH01579, MH51358]; NINDS NIH HHS [NS40068] NR 42 TC 137 Z9 142 U1 0 U2 7 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2004 VL 25 IS 10 BP 1715 EP 1721 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 874IN UT WOS:000225344200017 PM 15569736 ER PT J AU Hatton, MP Loewenstein, J AF Hatton, MP Loewenstein, J TI Attrition from ophthalmology residency programs SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SURGERY AB PURPOSE: To investigate the incidence of and reasons for voluntary resident attrition from ophthalmology training programs. DESIGN: Retrospective survey. METHODS: A survey was mailed to residency program directors of the 121 Accreditation Council for Graduate Medical Education-accredited ophthalmology residency programs asking them to report the number of residents who withdrew from training during 2001 to 2002 and the reasons for withdrawal. RESULTS: Of 102 responding programs, 13 (12.7%) had one resident withdraw from training in the academic year 2001 to 2002. These 13 residents represented 1.1% of all ophthalmology residents in training at the responding institutions during that academic year. The most frequent reason for withdrawing was to enter another medical specialty. CONCLUSIONS: Voluntary resident attrition from ophthalmology training programs is uncommon. The 1.1% attrition rate in this study is the lowest among published reports of attrition from other specialties. (C) 2004 by Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Hatton, MP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Mark_Hatton@meei.harvard.edu NR 5 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2004 VL 138 IS 5 BP 863 EP 864 DI 10.1016/j.ajo.2004.06.063 PG 2 WC Ophthalmology SC Ophthalmology GA 870UF UT WOS:000225083100023 PM 15531325 ER PT J AU Busaba, NY Siegel, NS Salman, SD AF Busaba, NY Siegel, NS Salman, SD TI Microbiology of chronic ethmoid sinusitis: Is this a bacterial disease? SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID CHRONIC MAXILLARY SINUSITIS; SINUSES; CHILDREN; ADULTS AB Purpose: Review the microbiology of chronic rhinosinusitis and test the hypothesis that bacterial infections are not the predominant etiology for chronic rhinosinusitis. Materials and Methods: Tissue cultures were prospectively collected from the ethmoid mucosa of 179 patients (94 had chronic rhinosinusitis and 85 had chronic rhinosinusitis with polyposis) at the time of endoscopic sinus surgery. All patients were off antibiotics for at least 1 week at the time of surgery. Both aerobic and anaerobic cultures were obtained for each specimen. Results: A total of 263 isolates were identified (average: 1.5 isolates per specimen). Coagulase-negative Staphylococcus, a likely contaminant, was the most common isolate and was identified in 51% of patients. Forty percent of patients (72/179) grew pathogenic aerobic bacteria, the most common was Staphylococcus aureus (18%). Six percent of patients (10/179) grew pathogenic anaerobic bacteria. The microbiology of patients with and without nasal polyposis was not significantly different. Conclusion: These findings suggest that factors other than bacterial infection may play an integral role in the pathogenesis of chronic rhinosinusitis. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM nicolas_busaba@meei.harvard.edu NR 16 TC 19 Z9 23 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 2004 VL 25 IS 6 BP 379 EP 384 DI 10.1016/j.amjoto.2004.04.001 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 877WQ UT WOS:000225606100001 PM 15547805 ER PT J AU Plummer, NW Gallione, CJ Srinivasan, S Zawistowski, JS Louis, DN Marchuk, DA AF Plummer, NW Gallione, CJ Srinivasan, S Zawistowski, JS Louis, DN Marchuk, DA TI Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of cerebral vascular malformations SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CAVERNOUS MALFORMATIONS; EXPRESSION ANALYSIS; BINDING-PROTEIN; ENCODING KRIT1; POLYOMA-VIRUS; CHROMOSOME 7Q; SPECTRUM; CELLS; PATHOGENESIS; APOPTOSIS AB Cerebral cavernous malformations (CCM) consist of clusters of abnormally dilated blood vessels. Hemorrhaging of these lesions can cause seizures and lethal stroke. Three loci are associated with autosomal dominant CCM, and the causative genes have been identified for CCM1 and CCM2. We have generated mice with a targeted mutation of the Ccm1 gene, but an initial survey of 20 heterozygous mice failed to detect any cavernous malformations. To test the hypothesis that growth of cavernous malformations depends on somatic loss of heterozygosity at the Ccm1 locus, we bred animals that were heterozygous for the Ccm1 mutation and homozygous for loss of the rumor suppressor Trp53 (P53), which has been shown to increase the rate of somatic mutation. We observed vascular lesions in the brains of 55% of the double-mutant animals but none in littermates with other genotypes. Although the genetic evidence suggested somatic mutation of the wild-type Ccm1 allele, we were unable to demonstrate loss of heterozygosity by molecular methods. An alternative explanation is that p53 plays a direct role in formation of the vascular malformations. The striking similarity of the human and mouse lesions indicates that the Ccm1(+/-)Trp53(-/-) mice are an appropriate animal model of CCM. C1 Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Marchuk, DA (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Box 3175, Durham, NC 27710 USA. EM march004@mc.duke.edu FU NINDS NIH HHS [F32 NS011133, 5F32NS011133] NR 32 TC 64 Z9 64 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2004 VL 165 IS 5 BP 1509 EP 1518 DI 10.1016/S0002-9440(10)63409-8 PG 10 WC Pathology SC Pathology GA 865XF UT WOS:000224736800007 PM 15509522 ER PT J AU Gooch, JL Toro, JJ Guler, RL Barnes, JL AF Gooch, JL Toro, JJ Guler, RL Barnes, JL TI Calcineurin A-alpha but not A-beta is required for normal kidney development and function SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DEFICIENT MICE; HYPERTROPHY; PHOSPHORYLATION; EXPRESSION; P27(KIP1); PROTEIN; CYCLOSPORINE; HYPERPLASIA; ACTIVATION; REDUCTION AB Calcineurin is an important signaling molecule in the kidney and may be involved in a variety of processes. The phosphatase subunit of calcineurin (CnA) has three isoforms, alpha, beta, and gamma. In this study, we investigated the effect of loss of calcineurin A-alpha (CnA-alpha) or calcineurin A-beta (CnA-beta) on the development and function of the kidney. Total calcineurin expression and activity was significantly reduced in whole kidney homogenates from both CnA-alpha -/- and CnA-beta -/- mice. Kidneys of CnA-beta -/- mice appear normal and the mice develop with no phenotypic abnormalities. in contrast, kidneys of CnA-alpha -/- animals fail to fully develop. in particular, postnatal maturation of the nephrogenic zone (NZ) is defective. Within the NZ, glomeruli also fail to mature and lack mesangial cells. In addition to alterations in development, there is an absence of proliferation and an increase of cell death in the NZ with loss of CnA-alpha. Finally, increased collagen deposition is observed and serum creatinine levels are significantly increased in CnA-alpha -/- animals compared to wild-type littermates, indicating that kidney function is impaired. In summary, absence of CnA-alpha but not CnA-beta leads to a defect in normal maturation of the NZ and glomeruli, alterations in the cell cycle, and impaired kidney function. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RP Gooch, JL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Gooch@uthscsa.edu NR 35 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2004 VL 165 IS 5 BP 1755 EP 1765 DI 10.1016/S0002-9440(10)63430-X PG 11 WC Pathology SC Pathology GA 865XF UT WOS:000224736800028 PM 15509543 ER PT J AU Oliveira, AM Perez-Atayde, AR Inwards, CY Medeiros, F Derr, V Hsi, BL Gebhardt, MC Rosenberg, AE Fletcher, JA AF Oliveira, AM Perez-Atayde, AR Inwards, CY Medeiros, F Derr, V Hsi, BL Gebhardt, MC Rosenberg, AE Fletcher, JA TI USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID REPARATIVE GRANULOMA; FUSION ONCOGENES; SOLID VARIANT; LESIONS; 17P13; PATHOGENESIS; TISSUE; TUMOR; 16Q22 AB Aneurysmal bone cyst (ABC) is a locally recurrent bone lesion that has been regarded as a reactive process. Recently, a neoplastic basis in primary ABC was evidenced by demonstration of clonal chromosome band 17p13 translocations that place the USP6 (TRE2 or TRE17) oncogene under the regulatory influence of the highly active CDH11 promoter. Herein, we report CDH11 and/or USP6 rearrangements in 36 of 52 primary ABCs (69%), of which 10 had CDH11-USP6 fusion, 23 had variant USP6 rearrangements without CDH11 rearrangement, and three had variant CDH11 rearrangements without USP6 rearrangement. USP6 and CDH11 rearrangements were restricted to spindle cells in the ABC and were not found in multinucleated giant cells, inflammatory cells, endothelial cells, or osteoblasts. CDH11 and USP6 rearrangements did not correlate with recurrence-free survival, or with other clinicopathological features. CDH11 and USP6 rearrangements were not found in any of 17 secondary ABC associated with giant cell tumor, chondroblastoma, osteoblastoma, and fibrous dysplasia. These findings demonstrate that primary ABC are mesenchymal neoplasms exhibiting USP6 and/or CDH11 oncogenic rearrangements. By contrast, secondary ABC lack CDH11 and USP6 rearrangements, and although morphological mimics of primary ABC, appear to represent a non-specific morphological pattern of a diverse group of non-ABC neoplasms. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Childrens Hosp, Med Ctr, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Dept Orthoped Surg, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Oliveira, AM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM oliveira.andre@mayo.edu; jfletcher@partners.org NR 29 TC 117 Z9 120 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2004 VL 165 IS 5 BP 1773 EP 1780 DI 10.1016/S0002-9440(10)63432-3 PG 8 WC Pathology SC Pathology GA 865XF UT WOS:000224736800030 PM 15509545 ER PT J AU Badizadegan, K Wheeler, HE Fujinaga, Y Lencer, WI AF Badizadegan, K Wheeler, HE Fujinaga, Y Lencer, WI TI Trafficking of cholera toxin-ganglioside G(M1) complex into Golgi and induction of toxicity depend on actin cytoskeleton SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE membrane microdomains; membrane lipids; bacterial toxins; endocytosis; intestinal mucosa ID CYCLIC-AMP ACCUMULATION; GPI-ANCHORED PROTEINS; LOW-BUOYANT DENSITY; LIPID RAFTS; MEMBRANE DOMAINS; SIGNAL-TRANSDUCTION; POLARIZED EPITHELIA; PLASMA-MEMBRANE; LABILE TOXIN; CELL LINE AB Intestinal epithelial lipid rafts contain ganglioside G(M1) that is the receptor for cholera toxin (CT). The ganglioside binds CT at the plasma membrane ( PM) and carries the toxin through the trans-Golgi network (TGN) to the endoplasmic reticulum (ER). In the ER, a portion of the toxin unfolds and translocates to the cytosol to activate adenylyl cyclase. Activation of the cyclase leads to an increase in intracellular cAMP, which results in apical chloride secretion. Here, we find that an intact actin cytoskeleton is necessary for the efficient transport of CT to the Golgi and for subsequent activation of adenylyl cyclase. CT bound to G(M1) on the cell membrane fractionates with a heterogeneous population of lipid rafts, a portion of which is enriched in actin and other cytoskeletal proteins. In this actin-rich fraction of lipid rafts, CT and actin colocalize on the same membrane microdomains, suggesting a possible functional association. Depolymerization or stabilization of actin filaments interferes with transport of CT from the PM to the Golgi and reduces the levels of cAMP generated in the cytosol. Depletion of membrane cholesterol, which also inhibits CT trafficking to the TGN, causes displacement of actin from the lipid rafts while CT remains stably raft associated. On the basis of these observations, we propose that the CT-G(M1) complex is associated with the actin cytoskeleton via the lipid rafts and that the actin cytoskeleton plays a role in trafficking of CT from the PM to the Golgi/ER and the subsequent activation of adenylyl cyclase. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Okayama Univ, Grad Sch Med & Dent, Dept Bacteriol, Okayama 7008530, Japan. Harvard Univ, Ctr Digest Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Badizadegan, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN219, Boston, MA 02114 USA. EM kbadizadegan@partners.org FU NIDDK NIH HHS [DK-48106, DK-34854, DK/AI-53056, DK-02907] NR 65 TC 21 Z9 22 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 2004 VL 287 IS 5 BP C1453 EP C1462 DI 10.1152/ajpcell.00189.2004 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 860RS UT WOS:000224361300036 PM 15294854 ER PT J AU Pacher, P Mabley, JG Liaudet, L Evgenov, OV Marton, A Hasko, G Kollai, M Szabo, C AF Pacher, P Mabley, JG Liaudet, L Evgenov, OV Marton, A Hasko, G Kollai, M Szabo, C TI Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE systolic dysfunction; diastolic dysfunction ID POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; ENDOTHELIAL DYSFUNCTION; STRUCTURAL-PROPERTIES; AORTIC CONSTRICTION; FISCHER-344 RATS; AGE; MYOCARDIUM; COLLAGEN; CONTRACTILITY; RELAXATION AB Aging is associated with profound changes in the structure and function of the heart. A fundamental understanding of these processes, using relevant animal models, is required for effective prevention and treatment of cardiovascular disease in the elderly. Here, we studied cardiac performance in 4- to 5-mo-old ( young) and 24- to 26-mo-old ( old) Fischer 344 male rats using the Millar pressure-volume (P-V) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (+dP/dt), and its relation to end-diastolic volume (+dP/dt-EDV) as well as the time constant of left ventricular pressure decay, as an index of relaxation. The slope of the end-diastolic P-V relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/dt, maximal slope of the diastolic pressure decrement, +dP/dt-EDV, PRSW, ejection fraction, stroke volume, cardiac and stroke work indexes, and efficiency. In contrast, total peripheral resistance, left ventricular end-diastolic volume, left ventricular end-diastolic pressure, and EDPVR were greater in aging than in young animals. Taken together, these data suggest that advanced aging is characterized by decreased systolic performance accompanied by delayed relaxation and increased diastolic stiffness of the heart in male Fischer 344 rats. P-V analysis is a sensitive method to determine cardiac function in rats. C1 Inotek Pharmaceut Corp, Beverly, MA 01915 USA. Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1082 Budapest, Hungary. Univ Hosp, Dept Internal Med, Crit Care Div, CH-1005 Lausanne, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, H-1083 Budapest, Hungary. Inst Human Physiol & Clin Expt Res, H-1082 Budapest, Hungary. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, 12420 Parklawn Dr,MSC-8115, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z99 AA999999]; NIA NIH HHS [R01AG59266, 1R03-AG-21206-01] NR 40 TC 78 Z9 79 U1 2 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2004 VL 287 IS 5 BP H2132 EP H2137 DI 10.1152/ajpheart.00405.2004 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 860TO UT WOS:000224366400037 PM 15231502 ER PT J AU Roose, SP Sackeim, HA Krishnan, KRR Pollock, BG Alexopoulos, G Lavretsky, H Katz, IR Hakkarainen, H AF Roose, SP Sackeim, HA Krishnan, KRR Pollock, BG Alexopoulos, G Lavretsky, H Katz, IR Hakkarainen, H CA Old Old Depression Study Grp TI Antidepressant pharmacotherapy in the treatment of depression in the very old: A randomized, placebo-controlled trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RECURRENT MAJOR DEPRESSION; NURSING-HOME RESIDENTS; DOUBLE-BLIND; SUBCORTICAL HYPERINTENSITIES; ELECTROCONVULSIVE-THERAPY; HEART-DISEASE; NORTRIPTYLINE; SERTRALINE; PAROXETINE; DISORDER AB Objective: This study determined the efficacy of antidepressant medication for the treatment of depression in the "old-old." Method: This randomized 8-week medication trial compared citalopram, 10-40 mg/day, to placebo in the treatment of patients 75 and older with unipolar depression. Results: A total of 174 patients who were 58% women with a mean age of 79.6 years (SD=4.4) and a mean baseline Hamilton Depression Rating Scale score of 24.3 (SD=4.1) were randomly assigned to treatment at 15 sites. There was a main effect for site but not for treatment condition. The remission rate, defined as a final Hamilton depression scale score <10, was 35% for the citalopram and 33% for the placebo groups. However, patients with severe depression (baseline Hamilton depression scale score >24) tended to have a higher remission rate with medication than with placebo (35% versus 19%). Conclusions: In the oldest group of community-dwelling patients to be studied to date, medication was not more effective than placebo for the treatment of depression. However, given the considerable psychosocial support received by all patients, the placebo condition represents more than the ingestion of an inactive pill. Across sites, there was considerable range in response to medication, 18% to 82%, and to placebo, 16% to 80%. C1 Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Radiol, New York, NY 10032 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Univ Pittsburgh, Acad Div Geriatr Psychiat, Pittsburgh, PA 15260 USA. Cornell Univ, Weill Med Coll, Cornell Inst Geriatr Psychiat, White Plains, NY USA. Univ Calif Los Angeles, David Geffen Sch Med, Neuropsychiat Inst & Hosp, Los Angeles, CA USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Forest Res Inst, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Roose, SP (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM spr2@columbia.edu RI Lavretsky, Helen/M-5711-2015 OI Lavretsky, Helen/0000-0001-9990-5085 FU NIMH NIH HHS [K23 MH001948, K23 MH001948-01A1] NR 40 TC 114 Z9 120 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2004 VL 161 IS 11 BP 2050 EP 2059 DI 10.1176/appi.ajp.161.11.2050 PG 10 WC Psychiatry SC Psychiatry GA 866IY UT WOS:000224768400017 PM 15514406 ER PT J AU Albers, AB Siegel, M Cheng, DM Rigotti, NA Biener, L AF Albers, AB Siegel, M Cheng, DM Rigotti, NA Biener, L TI Effects of restaurant and bar smoking regulations on exposure to environmental tobacco smoke among Massachusetts adults SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID WORKPLACE; HEALTH AB Objectives. We examined the association of local restaurant and bar regulations with self-reported exposure to environmental tobacco smoke among adults. Methods. Data were derived from a telephone survey involving a random sample of Massachusetts households. Results. Compared with adults from towns with no restaurant smoking restrictions, those from towns with strong regulations had more than twice the odds of reporting nonexposure to environmental tobacco smoke (odds ratio [OR] = 2.74; 95% confidence interval [CI] = 1.97, 3.80), and those from towns with some restrictions had 1.62 times the odds of reporting nonexposure (OR = 1.62; 95% CI = 1.29, 2.02). Bar smoking bans had even greater effects on exposure. Conclusions. Strong local clean indoor air regulations were associated with lower levels of reported exposure to environmental tobacco smoke in restaurants and bars. C1 Boston Univ, Sch Publ Hlth, Social & Behav Sci Dept, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Albers, AB (reprint author), Boston Univ, Sch Publ Hlth, Social & Behav Sci Dept, 715 Albany St,TW2, Boston, MA 02118 USA. EM aalbers@bu.edu OI Biener, Lois/0000-0002-4130-8138 FU NCI NIH HHS [5R01 CA 86257-03, R01 CA086257] NR 14 TC 21 Z9 23 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2004 VL 94 IS 11 BP 1959 EP 1964 DI 10.2105/AJPH.94.11.1959 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 866NS UT WOS:000224780800030 PM 15514237 ER PT J AU Busaba, NY Hossain, M AF Busaba, NY Hossain, M TI Clinical outcomes of septoplasty and inferior turbinate reduction in the geriatric veterans' population SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article ID PHYSIOLOGY AB Background: Patients older than 65 years constitute an increasingly large percentage of the patient population that presents to an adult otolaryngology practice due to the increase in life expectancy. The objective of this study is to assess the clinical outcomes of septoplasty with or without inferior turbinate reduction in patients who are 65 years or older. Methods: This is a prospective nonrandomized longitudinal study of 40 patients aged 65 years or more and who underwent septoplasty with or without inferior turbinate reduction. Patients received Nasal Health Survey (NHS) and General Health Status Short Form (SF-12) questionnaires before and 6 months after surgery. Statistical analysis was performed using the paired t-test. Results: The preoperative NHS score was 52.3, while the postoperative score was 76.6 (p < 0.001). The reported benefit reflected improvement in symptoms (p < 0.001) and reduction in medication usage (p < 0.001). In addition, the SF-12 score improved after the surgery but the difference did not reach statistical significance (p = 0.055). Conclusion and Significance: Septoplasty and inferior turbinate reduction is beneficial in the veterans' population for patients 65 years or older who present with nasal obstruction and are noted on physical examination to have septal deviation and inferior turbinate hypertrophy. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Div Otolaryngol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Dept Res & Dev, Boston, MA USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD NOV-DEC PY 2004 VL 18 IS 6 BP 343 EP 347 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 893FY UT WOS:000226705900001 PM 15706979 ER PT J AU Singh, AK Gervais, DA Hahn, PF Rhea, J Mueller, PR AF Singh, AK Gervais, DA Hahn, PF Rhea, J Mueller, PR TI CT appearance of acute appendagitis. SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PRIMARY EPIPLOIC APPENDAGITIS; DIAGNOSIS; US; MANIFESTATIONS; APPENDICITIS AB OBJECTIVE. Our aim was to describe the spectrum of CT findings in patients with acute epiploic appendagitis and also to evaluate the changes seen with this condition. MATERIALS AND METHODS. Fifty patients diagnosed with acute epiploic appendagitis seen on contrast-enhanced CT were included in this study. The CT scans of the epiploic appendagitis were evaluated for the presence of colon wall thickening, a focal fatty center, inflammatory changes, location in relationship to the colon, size, and presence or absence of central high density within the fat. In 10 patients, the initial findings were compared with findings of follow-up CT performed between 3 days-21 months after the first CT. RESULTS. The most common part of colon involved by acute epiploic appendagitis was the sigmoid colon (31/50), and the most common position was anterior to the colonic lumen (41/50). All 50 patients with acute epiploic appendagitis had a central fatty core surrounded by inflammation. Colon wall thickening was present in only two, and a central high-density focus was noted only in 27 of 50 patients. In 86% (43/50) of patients, the fatty central core was between 1.5 and 3.5 cm in length. The changes seen on follow-up CT varied, including increased density with a decrease in the size of the fatty central core, no change, complete resolution of findings, and minimal residual density. CONCLUSION. On CT, acute epiploic appendagitis has a predictable appearance in terms of location, size, and density. The most common finding on CT is a fat-density oval lesion with surrounding inflammation on the anterior aspect of the sigmoid colon. The changes on CT are not predictable in the 2-week to 6-month window. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 19 TC 60 Z9 64 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2004 VL 183 IS 5 BP 1303 EP 1307 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 865EQ UT WOS:000224685700020 PM 15505294 ER PT J AU Shankar, S vanSonnenberg, E Morrison, PR Tuncali, K Silverman, SG AF Shankar, S vanSonnenberg, E Morrison, PR Tuncali, K Silverman, SG TI Combined radiofrequency and alcohol injection for percutaneous hepatic tumor ablation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ETHANOL INJECTION; HEPATOCELLULAR-CARCINOMA; TISSUE ABLATION; COAGULATION NECROSIS; LIVER-TUMORS; THERAPY; SIZE; METASTASES; CIRRHOSIS; MODEL AB OBJECTIVE. We sought to determine if alcohol potentiates radiofrequency energy by obtaining larger ablative volumes in 30 liver tumors in human patients. SUBJECTS AND METHODS. We compared two groups of patients: one group treated with radiofrequency ablation alone (radiofrequency-alone group), and a second group treated with radiofrequency ablation and immediate prior injection of alcohol (combined group). The. radiofrequency-alone group comprised 20 ablations (mean diameter, 8.4 cm; colorectal cancer metastases [n = 15]; other metastases [n = 5]). The combined group consisted of 30 radiofrequency ablations (mean diameter, 8.8 cm; metastatic colorectal cancer [n = 17]; other metastases [n = 8]; and hepatocellular carcinoma [n = 5]) treated with alcohol injection immediately before radiofrequency ablation. The amount of alcohol injected was determined by the size and location of tumors. Preprocedural laboratory tests (complete blood cell count with differential, liver function tests, and coagulation parameters) were performed in all patients, along with pre- and postprocedural CT, MRI, and PET. Measurements of tissue necrosis were obtained on the postprocedural CT scans and MR images. Volumes of necrosis calculated in each group were corrected for the number of radiofrequency applications and were statistically compared using the Student's t test. In addition, tissue impedances obtained during the radiofrequency ablation procedure were compared between the two groups. RESULTS. The mean ablation volumes for the radiofrequency-alone group were 32.3 cm(2) (median, 28.6 cm(2); range, 14.4-61.8 cm(2)) and for the combined group, 84.6 cm(2) (median, 78.3 cm(2); range, 34.6-149 cm(2)). The difference in the necrosis volumes was significantly larger (p < 0.0001) in the combined group. Overall, the combined treatment group underwent fewer radiofrequency applications per session. Tissue impedance during radiofrequency ablation was higher in the combined group (mean, 62.7 vs 57.3 Omega in the radiofrequency alone group; p = 0.0005) at comparable times during the ablations. No major complications were seen in either group. CONCLUSION. Percutaneous radiofrequency ablation appears to be potentiated by immediate prior alcohol injection into the tumor. Consistently larger lesions are obtainable in fewer sessions, without any increase of complications, using the combined method. C1 Univ Massachusetts, Dept Radiol, Worcester, MA 01655 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Shankar, S (reprint author), Univ Massachusetts, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM shankars@ummhc.org NR 26 TC 30 Z9 34 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2004 VL 183 IS 5 BP 1425 EP 1429 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 865EQ UT WOS:000224685700041 PM 15505315 ER PT J AU Nguyen, L Fagan, SP Lee, TC Aoki, N Itani, KMF Berger, DH Awad, SS AF Nguyen, L Fagan, SP Lee, TC Aoki, N Itani, KMF Berger, DH Awad, SS TI Use of a predictive equation for diagnosis of acute gangrenous cholecystitis SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Surgical Symposium of the Association-of-VA-Surgeons CY APR 25-27, 2004 CL Richmond, VA SP Assoc VA Surg DE gangrenous cholecystitis; cholecystectomy; predictive equation ID LAPAROSCOPIC CHOLECYSTECTOMY AB Background: Factors previously identified by multivariate logistic regression that were predictive for gangrenous cholecystitis (GC) were used to develop a predictive equation. Our objective was to evaluate the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of this equation for detecting GC in patients with acute cholecystitis (AC). Methods: Medical records of patients who presented to a tertiary care hospital with AC were reviewed. Twenty-one patient and clinical variables were recorded. We prospectively tested the results of the following equation against pathologic diagnosis: P = e ((0.7116+0.9944.DM+1.7157-WBC-1.0319-ALT-2.0518.ALP+2.7078-PCF))/(1 +e([-0.7116+0.9944-DM+1.7157-WBC-1.0319-ALT-2.0518-ALP+2.7078-PCF])), where P = predicted value: DM = diabetes mellitus; WBC = white blood cell count; ALT = alanine aminotransferase; AST = aspartate aminotransferase; and PCF = pericholecystic fluid. Results: Ninety-eight patients presented with AC and 18% had GC (18 of 98). Using a cutoff of P = 0.724, our equation had a specificity of 93%, sensitivity of 83%. PPV of 71%, and NPV of 96%, P <0.001 for the detection of GC. Conclusions: Our study demonstrates the equation may be useful in detecting the subset of AC patients who have GC. (C) 2004 Excerpta Medica, Inc. All rights reserved. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Michael E DeBakey VAMC, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX USA. RP Awad, SS (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Michael E DeBakey VAMC, OCL 112,2002 Holcombe Blvd, Houston, TX 77030 USA. EM sawad@bcm.tmc.edu NR 14 TC 15 Z9 17 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2004 VL 188 IS 5 BP 463 EP 466 DI 10.1016/j.amjsurg.2004.07.013 PG 4 WC Surgery SC Surgery GA 872LL UT WOS:000225208600003 PM 15546551 ER PT J AU Awad, SS Hayley, B Fagan, SP Berger, DH Brunicardi, FC AF Awad, SS Hayley, B Fagan, SP Berger, DH Brunicardi, FC TI The impact of a novel resident leadership training curriculum SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Surgical Symposium of the Association-of-VA-Surgeons CY APR 25-27, 2004 CL Richmond, VA SP Assoc VA Surg DE alignment; communication; curriculum; integrity; leadership AB Background: Today's complex health care environment Coupled with the 80-hour workweek mandate has required that surgical resident team interactions evolve from a military command-and-control style to a collaborative leadership style. Methods: A novel educational Curriculum was implemented with objectives of training the residents to have the capacity/ability to create and manage powerful teams through alignment, communication, and integrity integral tools to practicing a collaborative leadership style while working 80 hours per week. Specific strategies were as follows: (1) to focus on quality of patient care and service while receiving a high education-to-service ratio, and (2) to maximize efficiency through time management. Results: This article shows that leadership training as part of a resident Curriculum can significantly increase a resident's view of leadership in the areas of alignment. communication, and integrity; tools previously shown in business models to be vital for effective and efficient teams. Conclusion: This curriculum, over the course of the surgical residency, can provide residents with the necessary tools to deliver efficient quality of care while working within the 80-hour workweek mandate in a more collaborative style environment. (C) 2004 Excerpta Medica, Inc. All rights reserved. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Surg Serv 112, Houston, TX 77030 USA. RP Awad, SS (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Surg Serv 112, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM sawad@bcm.tmc.edu NR 11 TC 13 Z9 14 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2004 VL 188 IS 5 BP 481 EP 484 DI 10.1016/j.amjsurg.2004.07.024 PG 4 WC Surgery SC Surgery GA 872LL UT WOS:000225208600006 PM 15546554 ER PT J AU Kaafarani, HMA Itani, KMF Thornby, J Berger, DH AF Kaafarani, HMA Itani, KMF Thornby, J Berger, DH TI Thirty-day and one-year predictors of death in noncardiac major surgical procedures SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Surgical Symposium of the Association-of-VA-Surgeons CY APR 25-27, 2004 CL Richmond, VA SP Assoc VA Surg DE operative surgical procedure; risk factors; death; mortality; mortality determinant; cardiac risk classifications; obesity; smoking; hyperlipidemia; renal insufficiency ID PERIOPERATIVE CARDIOVASCULAR EVALUATION; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; CARDIAC-ASSESSMENT; AMERICAN-COLLEGE; SURGERY; RISK; HEART; MORTALITY; INDEX AB Background: We evaluated the predictive value of the American College of Cardiology/Ainerican Heart Association (ACC/AHA) cardiac risk classification, as well as other potential risk factors (procedure risk, smoking, obesity, hyperlipidemia, and renal insufficiency), on all-cause mortality at 30 days and at 1 year postoperatively. Methods: In the year 2000, 1238 consecutive patients undergoing general anesthesia for various noncardiac surgical procedures at the Houston veterans Affairs Medical Center were screened preoperatively and classified according to the ACC/AHA guidelines. Patients' charts were reviewed for the above-mentioned risk factors. Results: A logistic regression analysis demonstrated that older age and higher procedure risk were associated with higher 30-day mortalities (P = 0.0012 and 0.0441, respectively). The ACC/AHA classification was positively correlated with mortality at 1 year (P = 0.0071). Conclusions: The ACC/AHA classification predicts mortality at 1 year but not at 30 days for major noncardiac surgeries; procedure-related risk is a better predictor of 30-day postoperative mortality in our patient population. Published by Excerpta Medica, Inc. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. VA Boston Hlth Care Syst 112, Dept Surg, Boston, MA 02132 USA. RP Itani, KMF (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM kitani@med.va.gov NR 14 TC 7 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2004 VL 188 IS 5 BP 495 EP 499 DI 10.1016/j.amjsurg.2004.07.018 PG 5 WC Surgery SC Surgery GA 872LL UT WOS:000225208600009 PM 15546557 ER PT J AU Farnsworth, N Fagan, SP Berger, DH Awad, SS AF Farnsworth, N Fagan, SP Berger, DH Awad, SS TI Child-Turcotte-Pugh versus MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Surgical Symposium of the Association-of-VA-Surgeons CY APR 25-27, 2004 CL Richmond, VA SP Assoc VA Surg DE Child-Turcotte-Pugh; cirrhosis; MELD; surgery ID STAGE LIVER-DISEASE; SURVIVAL; MODEL; PROGNOSIS AB Background: Cirrhotic patients who present for elective and emergent surgery pose a formidable challenge for the surgeon because of the high reported morbidity and mortality. The Child-Turcotte-Pugh (CTP) score previously has been used to evaluate preoperative severity of liver dysfunction and to predict postoperative outcome. Recently, a more objective scoring classification, the model for end-stage liver disease (MELD), has been shown to predict accurately the 3-month mortality for cirrhotic patients awaiting transplantation. We sought to compare the CTP and MELD scores in predicting outcomes in Cirrhotic patients undergoing surgical procedures requiring general anesthesia. Methods: During the study period, 40 patients with a history of cirrhosis who required elective (E) or emergent (EM) surgical procedures under general anesthesia were reviewed (E = 24, EM = 16). The preoperative CTP and MELD scores were calculated and patient short(30-day) and long-term (3-month) outcomes were recorded. Results: There was a significant difference in the 1-month and 3-month mortality rates between the emergent and elective groups (EM group: 1 mo = 19%, 3 mo = 44%; E group: 1 mo = 17%, 3 mo = 21 %, P < 0.05). There was good correlation between the CP and MELD scores, which was greater in the emergent groups as compared with the elective group (EM: r = 0.81; E: r = 0.65). Conclusions: Our study shows that cirrhotic patients who undergo surgery under general anesthesia have an extremely high 1 - and 3-month mortality rate that progressively increases with severity of preoperative liver dysfunction. Additionally, the MELD score correlates well with the CTP score, providing a more objective predictor of postoperative mortality in cirrhotic patients undergoing surgery. (C) 2004 Excerpta Medica, Inc. All rights reserved. C1 Baylor Coll Med, Surg Serv 112, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Awad, SS (reprint author), Baylor Coll Med, Surg Serv 112, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM sawad@bcm.tmc.edu NR 17 TC 119 Z9 124 U1 0 U2 8 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2004 VL 188 IS 5 BP 580 EP 583 DI 10.1016/j.amjsurg.2004.07.034 PG 4 WC Surgery SC Surgery GA 872LL UT WOS:000225208600026 PM 15546574 ER PT J AU Lerwill, MF Sung, RY Oliva, E Prat, J Young, RH AF Lerwill, MF Sung, RY Oliva, E Prat, J Young, RH TI Smooth muscle tumors of the ovary - A clinicopathologic study of 54 cases emphasizing prognostic criteria, histologic variants, and differential diagnosis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GA SP US & Canadian Acad Pathol DE ovary; smooth muscle tumor; leiomyoma; leiomyosarcoma; leiomyomatosis ID LEIOMYOMATOSIS PERITONEALIS DISSEMINATA; CELL CARCINOMA SYNDROME; OF-THE-LITERATURE; C-KIT EXPRESSION; IMMUNOHISTOCHEMICAL ANALYSIS; PRIMARY LEIOMYOSARCOMA; INTRAVENOUS LEIOMYOMATOSIS; MUCINOUS CYSTADENOMA; MESENCHYMAL TUMORS; ESTROGEN-RECEPTOR AB We studied 54 ovarian smooth Muscle tumors with an emphasis on histologic criteria for malignancy. Twenty-two leiomyomas were identified, including 7 typical, 11 cellular, 2 mitotically active, I with bizarre nuclei, and 1 myxoid. Follow-up ranging from 12 to 240 months (mean, 77.6 months) was available for 14 patients; all were alive with no evidence of disease. Of 26 leiomyosarcomas, including 2 myxoid leiomyosarcomas, most were readily diagnosed by the presence of at least two of the following: moderate or severe cytologic atypia, mitotic rate greater than or equal to10 mitotic figures per 10 high power fields, and tumor cell necrosis. Some cytologically atypical tumors demonstrated lesser mitotic activity of 5 to 9 mitotic figures per 10 high power fields, in the absence of tumor cell necrosis. Sixty percent of these were clinically malignant, supporting a diagnosis of leiomyosarcoma in such tumors. Follow-up was available for 21 patients. Seventy-one percent developed recurrent disease at a mean of 19 months, and 62% died of their disease at a mean of 24 months. Four tumors were deemed of uncertain malignant potential, and two that were stage 11 both recurred in the pelvis. One case of ovarian intravenous leiomyomatosis had a benign outcome at 42 months, as did one case of ovarian leiomyoma with leiomyomatosis peritonealis disseminata at 180 months. Overall, ovarian smooth muscle tumors encompass the same varied histologic spectrum as their uterine counterparts. The main tumors in the differential diagnosis are those in the fibroma/thecoma category, spindle cell carcinomas, and metastatic gastrointestinal stromal tumors. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. Univ Autonoma Barcelona, Hosp Santa Cruz & San Pablo, Dept Pathol, E-08193 Barcelona, Spain. RP Lerwill, MF (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. EM mlerwill@partners.org RI Prat, Jaime/G-4679-2011 NR 118 TC 38 Z9 47 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2004 VL 28 IS 11 BP 1436 EP 1451 DI 10.1097/01.pas.0000141393.99300.d0 PG 16 WC Pathology; Surgery SC Pathology; Surgery GA 865NI UT WOS:000224709400004 PM 15489647 ER PT J AU Ban, S Mino, M Nishioka, NS Puricelli, W Zukerberg, LR Shimizu, M Lauwers, GY AF Ban, S Mino, M Nishioka, NS Puricelli, W Zukerberg, LR Shimizu, M Lauwers, GY TI Histopathobgic aspects of photodynamic therapy for dysplasia asia and early adenocarcinoma arising in Barrett's esophagus SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Barrett's esophagus; dysplasia; carcinoma; photodynamic therapy; histopathology ID HIGH-GRADE DYSPLASIA; ACID SUPPRESSION; SQUAMOUS REEPITHILIALIZATION; COLUMNAR METAPLASIA; INVASIVE-CARCINOMA; EARLY CANCER; FOLLOW-UP; ABLATION; SURVEILLANCE; ERADICATION AB The efficacy of photodynamic therapy (PDT) is currently evaluated for the treatment of superficial neoplasms arising in Barrett's esophagus (BE). An accurate assessment of this technique requires the evaluation of biopsies before and after treatment. However, despite the importance of pathology, only a limited number of studies have systematically assessed the mucosal changes after PDT. To evaluate mucosal changes after PDT, and pathologic variables that may impact on the success of this therapy, we analyzed the pre- and post-PDT biopsies of a cohort of patients treated by this modality. Thirty-three patients (mean age, 71 years) with high-grade dysplasia (HGD) and/or intramucosal carcinoma (IMC) arising in BE and followed up after PDT using Porfimer sodium form the basis of this study. In all patients, a review of all pre- and post-PDT biopsies was performed. The variables recorded included the histologic grade and architecture of neoplasms, the distribution of neoplasms, and squamous re-epithelialization. IMC and HGD coexisted in the pre-PDT biopsies of 18 patients (54.5%). IMC and HGD showed a prominent tubular proliferation in 14 patients and displayed a papillary pattern (at least partially) in 19 patients. In post-PDT, patches of specialized columnar epithelium were buried under squamous epithelium in 17 patients (51.5%), and foci of dysplasia/carcinoma covered by squamous epithelium were found in 9 patients (27.3%). HGD and/or IMC were eradicated in 17 patients (eradicated group) and persisted in 16 patients (persistent group). In the persistent group, grade and architecture were unchanged after PDT in 62.5% and 87.5% of patients, respectively. The persistent group was characterized by: 1) a more frequent papillary architecture (P < 0.05), and 2) a diffuse distribution of the neoplasms on pre-PDT biopsies (P = 0.05). Singularly, the persistent neoplastic lesions were observed in the distal esophagus (P < 0.05). A systematic histopathologic evaluation allowed us to draw attention to the fact that distally located and papillary-type neoplasia seem resistant to PDT. The higher than expected incidence of buried residual neoplastic epithelium should also be emphasized since it represents a risk for undetected growth of malignancy. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Saitama Med Sch, Dept Pathol, Saitama, Saitama, Japan. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, 55 Fruit St, Boston, MA 02114 USA. EM glauwers@partners.org NR 46 TC 49 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2004 VL 28 IS 11 BP 1466 EP 1473 DI 10.1097/01.pas.0000141392.91677.7f PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 865NI UT WOS:000224709400007 PM 15489650 ER PT J AU Forman, JP Lin, J Pascual, M Denton, MD Tolkoff-Rubin, N AF Forman, JP Lin, J Pascual, M Denton, MD Tolkoff-Rubin, N TI Significance of anticardiolipin antibodies on short and long term allograft survival and function following kidney transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE kidney transplantation; anticardiolipin antibodies; outcomes ID ANTIPHOSPHOLIPID ANTIBODIES; RENAL-TRANSPLANTATION; LUPUS-ERYTHEMATOSUS; RISK; CLASSIFICATION; THROMBOSIS; HEMODIALYSIS; PREVALENCE; CRITERIA; FAILURE AB The significance of anticardiolipin antibodies (ACAs) prior to renal transplantation is unclear. We studied a cohort of 337 patients who underwent renal transplantation from 1996 to 2001. Follow-up continued until allograft loss, patient death or 31 December 2002. The primary outcome was a composite endpoint of death-censored allograft loss or a 25% reduction in estimated glomerular filtration rate (GFR) from 1-month post-transplant. Secondary outcomes were allograft loss, a 25% reduction in GFR, acute rejection and creatinine at 1 year. IgG and IgM ACA titers were positive (greater than or equal to15) in 18.1% of recipients. There were no significant differences at baseline between recipients, except coumadin therapy in those with positive ACA titers (20% vs. 7.4%). Post-transplant, there was no increase in the primary outcome in ACA-positive patients, even after adjustment for anticoagulation with coumadin (HR = 1.42 [0.68, 2.96]). There was no difference in secondary outcomes between those with or without positive titers. Two of five patients with very high titers (>50) who were not anticoagulated had early graft loss. A positive ACA titer prior to kidney transplantation was not associated with inferior renal outcomes after transplantation, although more research is required to address the prognostic significance of very high ACA titers. C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tolkoff-Rubin, N (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. EM ntolkoffrubin@partners.org NR 24 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2004 VL 4 IS 11 BP 1786 EP 1791 DI 10.1111/j.1600-6143.2004.00602.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 861RD UT WOS:000224435000013 PM 15476477 ER PT J AU Sethu, P Anahtar, M Moldawer, LL Tompkins, RG Toner, M AF Sethu, P Anahtar, M Moldawer, LL Tompkins, RG Toner, M TI Continuous flow microfluidic device for rapid erythrocyte lysis SO ANALYTICAL CHEMISTRY LA English DT Article ID CELLS; LEUKOCYTES; ASSAY AB Leukocyte isolation from whole blood to study inflammation requires the removal of contaminating erythrocytes. Leukocytes, however, are sensitive to prolonged exposure to hyper/hypoosmotic solutions, temperature changes, mechanical manipulation, and gradient centrifugation. Even though care is taken to minimize leukocyte activation and cell loss during erythrocyte lysis, it is often not possible to completely avoid it. Most procedures for removal of contaminating erythrocytes from leukocyte preparations are designed for bulk processing of blood, where the sample is manipulated for longer periods of time than necessary at the single-cell level. Ammonium chloride-mediated lysis is the most commonly used method to obtain enriched leukocyte populations but has been shown to cause some activation and selective loss of certain cell types. The leukocyte yield and subsequent activation status of residual leukocytes after NH(4)Cl-mediated lysis have been shown to depend on the time of exposure to the lysis buffer. We have developed a microfluidic lysis device that deals with erythrocyte removal at nearly the single-cell level. We can achieve complete lysis of erythrocytes and similar to100% recovery of leukocytes where the cells are exposed to an isotonic lysis buffer for less than 40 s, after which the leukocytes are immediately returned to physiological conditions. Theoretically, this process can be made massively parallel to process several milliliterss of whole blood to obtain a pure leukocyte population in less than 15 min. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. EM mtoner@sbi.org FU NIBIB NIH HHS [P41 EB002503]; NIGMS NIH HHS [U54 GM062119] NR 11 TC 79 Z9 80 U1 3 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 2004 VL 76 IS 21 BP 6247 EP 6253 DI 10.1021/ac049429p PG 7 WC Chemistry, Analytical SC Chemistry GA 867KK UT WOS:000224841300018 PM 15516115 ER PT J AU Chau, AH Chan, RC Shishkov, M MacNeill, B Iftimiia, N Tearney, GJ Kamm, RD Bouma, BE Kaazempur-Mofrad, MR AF Chau, AH Chan, RC Shishkov, M MacNeill, B Iftimiia, N Tearney, GJ Kamm, RD Bouma, BE Kaazempur-Mofrad, MR TI Mechanical analysis of atherosclerotic plaques based on optical coherence tomography SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE optical coherence tomography (OCT); FEM; atherosclerotic plaques ID HUMAN CAROTID BIFURCATION; INTRAVASCULAR ULTRASOUND; CIRCUMFERENTIAL STRESS; STRUCTURAL-ANALYSIS; WALL; ELASTOGRAPHY; STRAIN; MODEL; STABILITY; RUPTURE AB Finite element analysis is a powerful tool for investigating the biomechanics of atherosclerosis and has thereby provided an improved understanding of acute myocardial infarction. Structural analysis of arterial walls is traditionally performed using geometry contours derived from histology. In this paper we demonstrate the first use of a new imaging technique, optical coherence tomography (OCT), as a basis for finite element analysis. There are two primary benefits of OCT relative to histology: 1) imaging is performed without excessive tissue handling, providing a more realistic geometry than histology and avoiding structural artifacts common to histologic processing, and 2) OCT imaging can be performed in vivo, making it possible to study disease progression and the effect of therapeutic treatments in animal models and living patients. Patterns of mechanical stress and strain distributions computed from finite element analysis based on OCT were compared with those from modeling based on "gold standard" histology. Our results indicate that vascular structure and composition determined by OCT provides an adequate basis for investigating the biomechanical factors relevant to atherosclerosis and acute myocardial infarction. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Kaazempur-Mofrad, MR (reprint author), 77 Massachusetts Ave,Room NE47-317, Cambridge, MA 02139 USA. EM mrk@mit.edu OI /0000-0002-7232-304X FU NHLBI NIH HHS [5-R01-HL70039] NR 37 TC 44 Z9 48 U1 0 U2 19 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV PY 2004 VL 32 IS 11 BP 1494 EP 1503 DI 10.1114/B:ABME.0000049034.75368.4a PG 10 WC Engineering, Biomedical SC Engineering GA 873RL UT WOS:000225298500004 PM 15636110 ER PT J AU Magid, DJ Rurnsfeld, JS Masoudi, FA AF Magid, DJ Rurnsfeld, JS Masoudi, FA TI Chest pain in the emergency department in search of the holy grail SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID ACUTE CARDIAC ISCHEMIA; MYOCARDIAL-INFARCTION; DIAGNOSIS; PROTOCOL; CARE; NEED C1 Kaiser Permanente Clin Res Unit, Denver, CO 80237 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Div Emergency Med, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80202 USA. Denver VA Med Ctr, Denver, CO USA. Denver Hlth Med Ctr, Denver, CO USA. RP Magid, DJ (reprint author), Kaiser Permanente Clin Res Unit, POB 378066, Denver, CO 80237 USA. EM David.J.Magid@kp.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2004 VL 44 IS 6 BP 575 EP 576 DI 10.1016/j.annemergmed.2004.06.001 PG 2 WC Emergency Medicine SC Emergency Medicine GA 876NN UT WOS:000225503900002 PM 15573031 ER PT J AU Noel, PH Williams, JW Unutzer, J Worchel, J Lee, S Cornell, J Katon, W Harpole, LH AF Noel, PH Williams, JW Unutzer, J Worchel, J Lee, S Cornell, J Katon, W Harpole, LH TI Depression and comorbid illness in elderly primary care patients: Impact on multiple domains of health status and well-being SO ANNALS OF FAMILY MEDICINE LA English DT Article DE depression; primary health care; quality of life; health status ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; OLDER-ADULTS; COLLABORATIVE CARE; MAJOR DEPRESSION; SYMPTOMS; DISORDERS; OUTCOMES; RELIABILITY; DISABILITY AB PURPOSE Our objective was to examine the relative association of depression severity and chronicity, other comorbid psychiatric conditions, and coexisting medical illnesses with multiple domains of health status among primary care patients with clinical depression. METHODS We collected cross-sectional data as part of a treatment effectiveness trial that was conducted in 8 diverse health care organizations. Patients aged 60 years and older (N = 1,801) who met diagnostic criteria for major depression or dysthymia participated in a baseline survey. A survey instrument included questions on sociodemographic characteristics, depression severity and chronicity, neuroticism, and the presence of 11 common chronic medical illnesses, as well as questions screening for panic disorder and posttraumatic stress disorder. Measures of 4 general health indicators (physical and mental component scales of the SF-12, Sheehan Disability Index, and global quality of life) were included. We conducted separate mixed-effect regression linear models predicting each of the 4 general health indicators. RESULTS Depression severity was significantly associated with all 4 indicators of general health after controlling for sociodemographic differences, other psychological dysfunction, and the presence of 11 chronic medical conditions. Although study participants had an average of 3.8 chronic medical illnesses, depression severity made larger independent contributions to 3 of the 4 general health indicators (mental functional status, disability, and quality of life) than the medical comorbidities. CONCLUSIONS Recognition and treatment of depression has the potential to improve functioning and quality of life in spite of the presence of other medical comorbidities. C1 S Texas Vet Hlth Care Syst, VERDICT, HSR&D Ctr Excellence, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Duke Univ, Med Ctr, Durham, NC USA. Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Univ Calif Los Angeles, Los Angeles, CA USA. Cent Texas Vet Hlth Care Syst, Austin, TX USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. Kaiser Permanente, Oakland, CA USA. RP Noel, PH (reprint author), S Texas Vet Hlth Care Syst, VERDICT, HSR&D Ctr Excellence, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM pollyh@verdict.uthscsa.edu RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 40 TC 85 Z9 89 U1 5 U2 10 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672, UNITED STATES SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD NOV-DEC PY 2004 VL 2 IS 6 BP 555 EP 562 DI 10.1370/afm.143 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 892TE UT WOS:000226672100007 PM 15576541 ER PT J AU Margolis, RL Holmes, SE Rosenblatt, A Gourley, L O'Hearn, E Ross, CA Seltzer, WK Walker, RH Ashizawa, T Rasmussen, A Hayden, M Almqvist, EW Harris, J Fahn, S MacDonald, ME Mysore, J Shimohata, T Tsuji, S Potter, N Nakaso, K Adachi, Y Nakashima, K Bird, T Krause, A Greenstein, P AF Margolis, RL Holmes, SE Rosenblatt, A Gourley, L O'Hearn, E Ross, CA Seltzer, WK Walker, RH Ashizawa, T Rasmussen, A Hayden, M Almqvist, EW Harris, J Fahn, S MacDonald, ME Mysore, J Shimohata, T Tsuji, S Potter, N Nakaso, K Adachi, Y Nakashima, K Bird, T Krause, A Greenstein, P TI Huntington's disease-like 2 (HDL2) in North America and Japan SO ANNALS OF NEUROLOGY LA English DT Article ID DISEASE-LIKE 2; CAG/CTG REPEAT EXPANSIONS; HUNTINGTONS-DISEASE; CHOREA-ACANTHOCYTOSIS; JUNCTOPHILIN-3; FEATURES; LOCUS; GENE AB Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of 33 triplets. A younger age of onset is correlated with a longer repeat length (r(2) = 0.29, p = 0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype. C1 Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Dept Psychiat, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA. Athena Diagnost Inc, Worcester, MA USA. Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Texas, Dept Neurol, Galveston, TX 77555 USA. Inst Nacl Neurol & Neurocirug, Dept Neurogenet & Mol Biol, Mexico City, DF, Mexico. Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. Columbia Univ, Dept Neurol, New York, NY 10027 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Niigata Univ, Brain Res Inst, Dept Neurol, Niigata 951, Japan. Univ Tokyo, Dept Neurol, Tokyo, Japan. RP Margolis, RL (reprint author), Meyer 2-181,600 N Wolfe St, Baltimore, MD 21287 USA. EM rmargoli@jhmi.edu RI Ross, Christopher/H-8395-2013; Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 FU NINDS NIH HHS [NS16375, NS16367, NS38054, NS41547] NR 19 TC 53 Z9 55 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2004 VL 56 IS 5 BP 670 EP 674 DI 10.1002/ana.20248 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 869FR UT WOS:000224969300009 PM 15468075 ER PT J AU Grobmyer, SR Maki, RG Demetri, GD Mazumdar, M Riedel, E Brennan, MF Singer, S AF Grobmyer, SR Maki, RG Demetri, GD Mazumdar, M Riedel, E Brennan, MF Singer, S TI Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol DE chemotherapy; doxorubicin; ifosfamide; neo-adjuvant; sarcoma ID ADJUVANT CHEMOTHERAPY; INTERGROUP RHABDOMYOSARCOMA; IFOSFAMIDE; RECURRENCE; PREDICTOR; SURVIVAL; THERAPY; TRIAL AB Background: The purpose of this study was to retrospectively analyze the relationship between neo-adjuvant chemotherapy (NAC) and outcome in patients with high-grade extremity sarcomas. Patients and methods: Inclusion criteria were high-grade, deep, >5 cm extremity soft tissue sarcomas. Patients diagnosed between 1990 and 2001 were treated with surgery only (n=282) or NAC containing doxorubicin/ifosfamide/mesna (AIM) (n=74). The stratified Cox proportional hazards model was used to test the effect of NAC on disease-specific survival and recurrence while adjusting for known prognostic factors. Results: NAC was associated with improved disease-specific survival for this cohort of patients (P=0.02). This overall improvement appears to be driven by the benefit of NAC on disease-specific survival for patient with tumors >10 cm. The 3-year disease-specific survival for tumors >10 cm was 0.62 (95% CI: 0.53-0.71) for patients not receiving NAC and 0.83 (95% CI: 0.72-0.95) for patients receiving NAC. Conclusion: NAC with AIM was associated with a significant improvement in disease-specific survival in patients with high-grade extremity soft tissue sarcomas >10 cm. These data emphasize the need for further prospective clinical studies of neo-adjuvant or adjuvant chemotherapy for patients with large high-grade extremity sarcomas. C1 Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Singer, S (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA. EM singers@mskcc.org OI Brennan, Murray/0000-0003-2358-4371 FU NCI NIH HHS [P01CA47179] NR 22 TC 92 Z9 98 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2004 VL 15 IS 11 BP 1667 EP 1672 DI 10.1093/annonc/mdh431 PG 6 WC Oncology SC Oncology GA 871XQ UT WOS:000225170300014 PM 15520069 ER PT J AU Grikscheit, TC Siddique, A Ochoa, ER Srinivasan, A Alsberg, E Hodin, RA Vacanti, JP AF Grikscheit, TC Siddique, A Ochoa, ER Srinivasan, A Alsberg, E Hodin, RA Vacanti, JP TI Tissue-engineered small intestine improves recovery after massive small bowel resection SO ANNALS OF SURGERY LA English DT Article ID CELL-LINE; IN-VIVO; MANAGEMENT; SEQUENCES; ADULTS; COLON AB Objective: Rescue with tissue-engineered small intestine (TEST) after massive small bowel resection (MSBR). Summary Background Data: Short bowel syndrome is a morbid product of massive small bowel resection. We report the first replacement of a vital organ by tissue engineering with TESI after MSBR. Methods: Ten male Lewis rats underwent TESI implantation with green fluorescent protein (GFP)-marked cells (TESI+, n = 5) or sham laparotomy (TESI, n = 5) followed by MSBR. Side-to-side anastomosis of TEST to proximal small intestine was performed or omitted. TESIcircle divide animals underwent implantation of engineered intestine with no further surgery. Weights were measured QOD until day 40. Transit times were measured. DNA assay was performed with computer morphometry. Northern blots of RNA were probed for intestinal alkaline phosphatase (TAP) and villin. Hematoxylin and eosin, 5100, and smooth muscle actin immunohistochemistry were performed. Blood was collected at sacrifice. Results: All 10 rats initially lost then regained weight. The initial rate of weight loss was higher in TESI+ versus TESI-, but the nadir was reached a week earlier with more rapid weight gain subsequently to 98% preoperative weight on day 40 in animals with engineered intestine versus 76% (P < 0.03). Serum B12 was higher at 439 pg/mL versus 195.4 pg/mL. IAP mRNA appeared greater in TESI+ than TESIcircle divide, with constant villin levels. Histology revealed appropriate architecture including nerve. GFP labeling persisted. Conclusions: Anastomosis of TEST significantly improved postoperative weight and B12 absorption after MSBR. TAP, a marker of differentiation in intestinal epithelium, is present in TEST, and GFP labeling was accomplished. C1 Massachusetts Gen Hosp, Dept Pediat Surg, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Integrat Med & Innovat Technol, Boston, MA 02115 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Cardiovasc Res Ctr, Warren 1157,55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org NR 21 TC 113 Z9 118 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD NOV PY 2004 VL 240 IS 5 BP 748 EP 754 DI 10.1097/01.sla.0000143246.07277.73 PG 7 WC Surgery SC Surgery GA 865YD UT WOS:000224739200003 PM 15492554 ER PT J AU O'Connell, JB Maggard, MA Ko, CY AF O'Connell, JB Maggard, MA Ko, CY TI Cancer-directed surgery for localized disease: Decreased use in the elderly SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE elderly; cancer; surgery; cancer registry; SEER; quality ID TREATMENT TRIALS; RECTAL-CANCER; COLON-CANCER; AGE; CHEMOTHERAPY; OLDER; POPULATION AB Background: Previous studies report underuse of radiation and chemotherapy in the elderly, yet few have examined the rates of use (or underuse) of surgery. Using national data, we examined rates of surgical resection for patients with local-stage cancers. Methods: By using the Surveillance, Epidemiology, and End Results database (1988-1997), patients (greater than or equal to40 years) were identified with localized adenocarcinoma of the breast, esophagus, stomach, pancreas, colon, or rectum; non-small-cell lung carcinoma; and sarcoma (n = 200,360). Rates of cancer-directed surgery (CDS) were compared across age groups (at 5-year intervals). Multivariate regression was used to identify predictors of receipt of CDS in each tumor group. Results: Rates of CDS declined steadily with increasing age for all nine localized tumors. Most striking were the low rates of CDs for patients >70 years with esophagus, stomach, pancreas, and lung cancers (range, 0%-83%). However, CDS rates were >90% for breast and colon and >84% for rectal cancer in all age groups. Multivariate regression found lower odds of CDS for elderly patients for all cancers except colon. For example, age significantly decreased the odds of receiving CDS beginning at 60 years for lung cancer (odds ratio [OR], .550; P = .03), at 70 years for liver cancer (OR, .109; P = .003), and at 80 years for pancreatic cancer (OR, .120; P < .05). Conclusions: Although CDS for localized disease is being performed regularly in the elderly for some cancers (e.g. breast, colon, and rectum), this analysis shows that elderly patients are not receiving surgery for many potentially curable cancers. Whether these rates are appropriate or too low requires further evaluation. This is particularly essential because our population is aging. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Hosp, Dept Surg, Los Angeles, CA USA. RP O'Connell, JB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,Room 72-215, Los Angeles, CA 90095 USA. EM jbocjboc@hotmail.com NR 11 TC 52 Z9 54 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 2004 VL 11 IS 11 BP 962 EP 969 DI 10.1245/ASO.2004.03.052 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 866NX UT WOS:000224781300005 PM 15525824 ER PT J AU Hossain, A Ferraro, MJ Pino, RM Dew, RB Moland, ES Lockhart, TJ Thomson, KS Goering, RV Hanson, ND AF Hossain, A Ferraro, MJ Pino, RM Dew, RB Moland, ES Lockhart, TJ Thomson, KS Goering, RV Hanson, ND TI Plasmid-mediated carbapenem-hydrolyzing enzyme KPC-2 in an Enterobacter sp. SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BETA-LACTAMASE; KLEBSIELLA-PNEUMONIAE; RESISTANT STRAIN AB A strain of an Enterobacter sp. with reduced susceptibility to imipenem, which produced a plasmid-mediated class A carbapenem-hydrolyzing enzyme, KPC-2 beta-lactamase, was isolated from a patient with sepsis at a Boston hospital. This is the first report of the production of a plasmid-encoded KPC-2 beta-lactamase by an Enterobacter sp. C1 Creighton Univ, Sch Med, Dept Med Microbiol & Immunol, Omaha, NE 68178 USA. Creighton Univ, Sch Med, Ctr Res Anti Infect & Biotechnol, Omaha, NE 68178 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hanson, ND (reprint author), Creighton Univ, Sch Med, Dept Med Microbiol & Immunol, 2500 Calif Plaza, Omaha, NE 68178 USA. EM ndhanson@creighton.edu NR 12 TC 71 Z9 86 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2004 VL 48 IS 11 BP 4438 EP 4440 DI 10.1128/AAC-.48.11.4438-4440.2004 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 869XM UT WOS:000225017900053 PM 15504876 ER PT J AU Borucki, MJ Spritzler, J Asmuth, DM Gnann, J Hirsch, MS Nokta, M Aweeka, F Nadler, PI Sattler, F Alston, B Nevin, TT Owens, S Waterman, K Hubbard, L Caliendo, A Pollard, RB AF Borucki, MJ Spritzler, J Asmuth, DM Gnann, J Hirsch, MS Nokta, M Aweeka, F Nadler, PI Sattler, F Alston, B Nevin, TT Owens, S Waterman, K Hubbard, L Caliendo, A Pollard, RB CA AACTG 266 Team TI A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitis SO ANTIVIRAL RESEARCH LA English DT Article DE MSL-109; AIDS; cytomegalovirus retinitis; cytomegalovirus; monoclonal antibody ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; MARROW-TRANSPLANT RECIPIENTS; STEM-CELL TRANSPLANTATION; HUMORAL IMMUNE-RESPONSE; ACQUIRED-IMMUNODEFICIENCY; GANCICLOVIR THERAPY; INFECTION; DISEASE; TRIAL AB ACTG 266 was designed as a randomized study to evaluate two doses of the human monoclonal antibody directed against CMV gH (MSL-109) versus placebo, each in combination with standard antiviral therapy for the treatment of newly diagnosed Cytomegalovirus (CMV) retinitis in AIDS patients. A total of 82 subjects were enrolled and received either placebo (n = 28), or MSL-109 at 15 mg (n = 26) or 60 mg (n = 28) every 2 weeks until disease progression was diagnosed. The primary endpoint, disease progression, was determined by masked reading of retinal photographs taken every 4 weeks read by a single investigator. The median time to progression was 8.0, 8.3, and 12.1 weeks in the placebo, MSL-109 15 mg, and MSL-109 60 mg cohorts, respectively (P = 0.087, placebo versus 60 mg cohort). There were 22 deaths during the study period (9, 9, and 4 in the placebo. MSL-109 15 mg and MSL-109 60 mg cohorts, respectively (P = 0.0058, placebo versus 60 mg cohort)). MSL-109 was well tolerated with no significant adverse events attributable to study medication. The unexplained survival advantage in the higher dose cohort was discordant with the findings of the parallel Studies of ocular Complications of AIDS Research Group (SOCA)-Monoclonal Anti-CMV Retinitis Trial (MACRT), which was prematurely halted because of increased mortality in subjects treated with high-dose MSL-109, recognizing that A266 enrolled subjects with newly diagnosed, whereas the MACRT enrolled subjects with relapsed, CMV retinitis. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif Davis, Med Ctr, Div Infect Dis, Sacramento, CA 95817 USA. Univ Texas, Ctr Hlth, Tyler, TX USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Alabama, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Prot Design Labs, Mountain View, CA USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. NIH, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Silver Spring, MD USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Wisconsin, Madison, WI USA. Emory Univ Hosp, Atlanta, GA 30322 USA. RP Asmuth, DM (reprint author), Univ Calif Davis, Med Ctr, Div Infect Dis, 4150 V St,PSSB Suite G500, Sacramento, CA 95817 USA. EM david.asmuth@ucdmc.ucdavis.edu FU NCRR NIH HHS [RR00044]; NEI NIH HHS [U01 EY08057]; NIAID NIH HHS [AI-27658, U01 AI 32783]; PHS HHS [U01A127673-14] NR 44 TC 14 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD NOV PY 2004 VL 64 IS 2 BP 103 EP 111 DI 10.1016/j.antivirial.2004.06.012 PG 9 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 868XR UT WOS:000224946900004 PM 15498605 ER PT J AU Wambaugh, J Cameron, R Kalinyak-Fliszar, M Nessler, C Wright, S AF Wambaugh, J Cameron, R Kalinyak-Fliszar, M Nessler, C Wright, S TI Retrieval of action names in aphasia: Effects of two cueing treatments SO APHASIOLOGY LA English DT Article ID BRAIN-DAMAGED SUBJECTS; VERB RETRIEVAL; LEXICAL RETRIEVAL; DEFICITS; AGRAMMATISM; ANOMIA; NOUNS AB Background: The treatment of word-retrieval deficits in aphasia has most frequently focused oil the retrieval of object names. The retrieval of action names has received relatively little attention in terms of rehabilitation despite the important role played by verbs in communication. Treatments that have been successful in promoting improved object name retrieval cannot be assumed to also facilitate improved action name retrieval. Aims: The Purpose Of this investigation was to examine the effects Of two cueing treatments oil the retrieval of action names with speakers with chronic aphasia. Methods & Procedures: The effects Of two Cueing treatments, Phonological Cueing Treatment (PCT) and Semantic Cueing Treatment (SCT), were examined with five speakers with aphasia. Treatment effects oil action naming were measured using single subject, multiple baseline, and alternating treatments designs. Outcomes & Results: Results varied across participants. For two speakers, both treatments produced strong positive increases in naming, with effects being similar across treatments. For two other speakers, modest increases in correct naming were observed and for the remaining speaker, no increases were found. Conclusions: These findings indicate that PCT and SCT may have utility in facilitating action naming for some speakers with aphasia, but that the effects may vary across speakers. C1 VA Salt Lake City Healthcare Syst, Res Serv 151A, Salt Lake City, UT 84148 USA. Univ Utah, Salt Lake City, UT 84112 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. VA Philadelphia Healthcare Syst, Philadelphia, PA USA. RP Wambaugh, J (reprint author), VA Salt Lake City Healthcare Syst, Res Serv 151A, 500 Foothill Blvd, Salt Lake City, UT 84148 USA. EM julie.wambaugh@health.utah.edu NR 36 TC 32 Z9 32 U1 1 U2 6 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD NOV PY 2004 VL 18 IS 11 BP 979 EP 1004 DI 10.1080/02687030444000471 PG 26 WC Clinical Neurology SC Neurosciences & Neurology GA 877LN UT WOS:000225572200001 ER PT J AU Corless, IB Nicholas, PK McGibbon, CA Wilson, C AF Corless, IB Nicholas, PK McGibbon, CA Wilson, C TI Weight change, body image, and quality of life in HIV disease: A pilot study SO APPLIED NURSING RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; PALLIATIVE CARE; AIDS; INFECTION; MEN; HIV/AIDS; IMPACT AB Fat distribution alterations and lipodystrophy occur as part of a broad spectrum of body alterations in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Recent advances in HIV therapies, including highly active antiretroviral therapy, contribute to these fat distribution alterations. The purpose of this pilot study was to investigate the relationships of weight change, body image, length of time with HIV/AIDS diagnosis, and quality of fife in HIV disease. The sample consisted of 23 men with mean age of 42.2 years (SD = 8.2) and 17 women with mean age of 36.8 years (SD = 5.2). Participants reported a net increase in weight from 3 months prior (M = 2.4 lb, SD = 12.9 lb) and 12 months prior (M = 10.9 lb, SD = 19.1 lb). They also reported that their weight was greater than their ideal weight (M = 9.2 lb, SD = 22.9 lb). Body image scores (0-100 scale) were found to be significantly (F-(1,F- 37) = 5.41, p = .03) higher for women (73.1 +/- 17.0) compared with men (60.2 +/- 17.0). Although HIV-positive participants had slightly higher body image scores (M = 68.0, SD = 17.0) compared with participants with AIDS (M = 60.5, SD = 18.8), there was no significant difference (F-(1,F-37) = 1.56, p = .22) in body image scores between those with HIV and those with AIDS. Finally, weight change was related to three scales of the Medical Outcomes Study-HIV. mental health (r = .42, p = .03), vitality (r = .53, p = .006), and quality of fife (r = .45, p = .02) for men. There were no significant correlations between weight change and quality of life domains for women. Education of clinicians and individuals living with HIV/AIDS should focus on the assessment, management, and evaluation of weight change during the course of HIV disease. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Nursing, Boston, MA 02129 USA. RP Corless, IB (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Nursing, 31 1st Ave, Boston, MA 02129 USA. OI Corless, Inge/0000-0003-0438-2037 NR 21 TC 6 Z9 6 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD NOV PY 2004 VL 17 IS 4 BP 292 EP 296 DI 10.1016/j.apnr.2004.09.006 PG 5 WC Nursing SC Nursing GA 880PI UT WOS:000225801300010 PM 15573338 ER PT J AU Delsanto, PP Guiot, C Degiorgis, PG Condat, CA Mansury, Y Deisboeck, TS AF Delsanto, PP Guiot, C Degiorgis, PG Condat, CA Mansury, Y Deisboeck, TS TI Growth model for multicellular tumor spheroids SO APPLIED PHYSICS LETTERS LA English DT Article ID MATHEMATICAL-MODELS; UNIVERSAL LAW; METABOLISM; CELLS AB Most organisms grow according to simple laws, which in principle can be derived from energy conservation and scaling arguments, critically dependent on the relation between the metabolic rate B of energy flow and the organism mass m. Although this relation is generally recognized to be of the form B(m)=m(p), the specific value of the exponent p is the object of an ongoing debate, with many mechanisms being postulated to support different predictions. We propose that multicellular tumor spheroids provide an ideal experimental model system for testing these allometric growth theories, especially under controlled conditions of malnourishment and applied mechanical stress. (C) 2004 American Institute of Physics. C1 Univ Turin, INFM, Dipartimento Neurosci, I-10125 Turin, Italy. Colleretto Giacosa, Turin, Italy. Politecn Torino, INFM, Dipartimento Fis, Turin, Italy. Univ Puerto Rico, Dept Phys, Mayaguez, PR 00681 USA. Univ Nacl Cordoba, CONICET, RA-5000 Cordoba, Argentina. Univ Nacl Cordoba, FaMAF, RA-5000 Cordoba, Argentina. MIT, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, HST Biomed Engn Ctr, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Charlestown, MA 02129 USA. RP Guiot, C (reprint author), Univ Turin, INFM, Dipartimento Neurosci, I-10125 Turin, Italy. EM caterina.guiot@unito.it RI guiot, caterina/C-6708-2009; OI guiot, caterina/0000-0001-8529-1625 NR 15 TC 38 Z9 39 U1 1 U2 4 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD NOV 1 PY 2004 VL 85 IS 18 BP 4225 EP 4227 DI 10.1063/1.1812842 PG 3 WC Physics, Applied SC Physics GA 868DS UT WOS:000224894900090 ER PT J AU Strasswimmer, J AF Strasswimmer, J TI Beyond the biopsy in laser surgery SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID ERBIUM-YAG; SKIN C1 Massachusetts Gen Hosp, Wellman Ctr BAR 722, Boston, MA 02114 USA. RP Strasswimmer, J (reprint author), Massachusetts Gen Hosp, Wellman Ctr BAR 722, 55 Fruit St, Boston, MA 02114 USA. EM jstrasswimmer@partners.org OI strasswimmer, john/0000-0002-5790-2633 NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 2004 VL 140 IS 11 BP 1391 EP 1392 DI 10.1001/archderm.140.11.1391 PG 2 WC Dermatology SC Dermatology GA 870RQ UT WOS:000225076000012 PM 15545550 ER PT J AU Lang, K Menzin, J Earle, CC Jacobson, J Hsu, MA AF Lang, K Menzin, J Earle, CC Jacobson, J Hsu, MA TI The economic cost of squamous cell cancer of the head and neck - Findings from linked SEER-Medicare data SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID UPPER AERODIGESTIVE TRACT; BREAST-CANCER; GEOGRAPHIC-VARIATION; UNITED-STATES; HOSPICE USE; CLAIMS DATA; CARCINOMA; MANAGEMENT; CARE; STAGE AB Objective: To evaluate the excess mortality, resource use, and costs associated with squamous cell carcinoma of the head and neck (SCCHN) among elderly Medicare beneficiaries. Design: Retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and Medicare claims. Subjects: Study cohorts included patients aged 65 years and older who were newly diagnosed as having SCCHN in a SEER registry between 1991 and 1993 (N = 4536) and controls matched 1:1 by age and sex. Patients were followed up for 5 years or until death, whichever occurred first. Results: Initial treatment was primarily surgery and/or radiation among patients with early-stage SCCHN, with only modest use of chemotherapy. Patients with SCCHN had significantly (P<.001) higher 5-year mortality (64% vs; 25%) and health care costs than controls. Average Medicare payments (1998 US dollars) among patients with SCCHN were $25 542 higher than those of matched comparison patients (P<.001), with monthly payments 3 times as high ($1428 vs $446). Patients diagnosed as having advanced SCCHN had shorter survival times (5-year mortality, 85%, 75%, 47%, and 35% among patients diagnosed as having distant, regional, local, and in situ cancer, respectively) and higher costs (average total Medicare payments, $53 741, $58 387, $42 698, and $37 434, respectively). Conclusion: These results suggest that the health economic burden of SCCHN is substantial, with costs that are comparable with or higher than those of other solid tumors. C1 Boston Hlth Econ Inc, Waltham, MA 02451 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wyeth Pharmaceut, Cambridge, MA USA. Pfizer Inc, Groton, CT USA. RP Menzin, J (reprint author), Boston Hlth Econ Inc, 20 Fox Rd, Waltham, MA 02451 USA. EM jmenzin@bhei.com NR 45 TC 32 Z9 32 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2004 VL 130 IS 11 BP 1269 EP 1275 DI 10.1001/archotol.130.11.1269 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 868TK UT WOS:000224935700004 PM 15545580 ER PT J AU Choi, S Schwartz, DL Farwell, DG Austin-Seymour, M Futran, N AF Choi, S Schwartz, DL Farwell, DG Austin-Seymour, M Futran, N TI Radiation therapy does not impact local complication rates after free flap reconstruction for head and neck cancer SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 19-23, 2003 CL SALT LAKE CITY, UT SP Amer Soc Therapeut Radiol & Oncol ID FREE-TISSUE TRANSFER; MANDIBULAR RECONSTRUCTION; RADIOTHERAPY; TRANSFERS; VESSELS; REGION AB Objective(m: To determine whether external beam radiation therapy (XRT), administered either before or after surgery, increases the rate and/or severity of local postoperative complications in patients with head and neck cancer who undergo microvascular free flap reconstruction. Design: Retrospective cohort study. Setting: University of Washington Medical Center, Seattle, a tertiary care hospital. Patients: A total of 100 consecutive patients underwent fibular free flap reconstruction of the mandible. The study cohort was divided according to radiation treatment status: (1) no XRT (28 patients), (2) preoperative XRT (37 patients), and (3) postoperative XRT (35 patients). The median follow-up after surgery was 11 months (range, 1-89 months). Main Outcome Measures. Rate and severity of local postoperative complications. Results: Fifty-four patients (54%) had at least I postoperative complication. There were no differences among the 3 XRT subgroups in the overall proportion of patients with complications of any severity (15 [54%] of 28 patients in the no XRT group, 24 [65%] of 37 patients in the preoperative XRT group, and 16 [46%] of 35 patients in the postoperative XRT group; P=.26, X2 analysis). There were also no differences seen when mild and severe complication rates were specifically examined (P=.58 and P=.10, respectively). No case of complete flap loss was observed. We noted no significant correlations between the rate of postoperative complications and the following covariates: total radiation dose, size of radiation field, disease stage, exposure to chemotherapy, presence of serious medical comorbidities, patient age, or history of tobacco use. Conclusions: Our experience suggests that XRT can be safety administered before or after surgery to patients undergoing head and neck free flap reconstruction at an experienced surgical referral center. Postoperative complication rates were not significantly affected by administration, timing, dose, or extent of XRT. C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Radiat Oncol, Seattle, WA USA. RP Schwartz, DL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 97, Houston, TX 77030 USA. EM docdls@mdanderson.org NR 12 TC 53 Z9 54 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2004 VL 130 IS 11 BP 1308 EP 1312 DI 10.1001/archotol.130.11.1308 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 868TK UT WOS:000224935700011 PM 15545587 ER PT J AU Davey, DD Neal, MH Wilbur, DC Colgan, TJ Styer, PE Mody, DR AF Davey, DD Neal, MH Wilbur, DC Colgan, TJ Styer, PE Mody, DR TI Bethesda 2001 implementation and reporting rates - 2003 practices of participants in the College of American Pathologists Interlabolatory Comparison Program in Cervicovaginal Cytology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ATYPICAL SQUAMOUS-CELLS; INTERLABORATORY COMPARISON PROGRAM; CURRENT LABORATORY PRACTICES; UNDETERMINED SIGNIFICANCE; SPECIMEN ADEQUACY; PAPANICOLAOU TESTS; QUALITY-ASSURANCE; TERMINOLOGY; MANAGEMENT; POPULATION AB Context.-The 2001 Bethesda System for the reporting of cervical cytology specimens and the use of new liquid-based and human papillomavirus testing technologies have led to changes in cervical cytology reporting practices. Objectives.-To analyze current laboratory reporting practices using Bethesda 2001 terminology and to compare results with previous survey data from 1996. Design.-Questionnaire survey mailed to 1751 laboratories in mid-2003. Participants.-Laboratories enrolled in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. Results.-Of the 759 responding laboratories, most (85.5%) had implemented Bethesda 2001 terminology, and the majority had adopted major changes, such as elimination of the benign cellular changes category and the satisfactory but limited category. The median reporting rate for low-grade squamous intraepithelial lesion was 2.1%, compared to a 1996 median rate of 1.6%, but the increase was confined to liquid-based preparations. Reporting rates for high-grade squamous intraepithelial lesion (median, 0.5%) and atypical squamous cells (ASC) had changed little. Most ASC cases were subclassified as "undetermined significance" (median, 3.9%) with ASC, cannot exclude high-grade SIL accounting for a minority (median, 0.2%). The median ratio of ASC to squamous intraepithelial lesions and carcinomas (SIL+) was 1.4 and was lower than the 1996 median ratio of 2.0. Median reporting rates for squamous abnormalities for 2002 were noted to be significantly higher for liquid-based preparations than for conventional smears, while median ASC/SIL+ ratios were lower. Most laboratories offer human papillomavirus testing, but almost half (47%) of laboratories do not know the percentage of positive testing results in patients with ASC. Conclusions.-Most laboratories have implemented Bethesda 2001 terminology. New criteria and liquid-based methods have led to an increase in low-grade squamous intraepithelial lesion reporting rates and a decrease in ASC/ SIL+ ratios when compared with 1996 data. Liquid-based preparations have higher median squamous intraepithelial lesion rates and. lower ASC/SIL+ ratios than conventional smears. C1 Univ Kentucky, Med Ctr, Dept Pathol & Lab Med, Lexington, KY 40526 USA. KWB Pathol Assoc, Tallahassee, FL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. Coll Amer Pathologists, Northfield, IL USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Davey, DD (reprint author), Univ Kentucky, Med Ctr, Dept Pathol & Lab Med, 800 Rose St, Lexington, KY 40526 USA. EM Ddavey@uky.edu RI Colgan, Terence/J-2339-2016 NR 23 TC 121 Z9 134 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 2004 VL 128 IS 11 BP 1224 EP 1229 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 867XC UT WOS:000224875100005 PM 15504056 ER PT J AU Chaves, ES Boninger, ML Cooper, R Fitzgerald, SG Gray, DB Cooper, RA AF Chaves, ES Boninger, ML Cooper, R Fitzgerald, SG Gray, DB Cooper, RA TI Assessing the influence of wheelchair technology on perception of participation in spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE activities of daily living; outcomes research; rehabilitation; spinal cord injuries; wheelchairs ID QUALITY-OF-LIFE; ASSISTIVE TECHNOLOGY; SATISFACTION; USERS AB Objective: To investigate factors related to the wheelchair, impairment, and environment that affect perception of participation of persons with spinal cord injury (SCI) in activities performed in 3 settings: in the home, in the community, and during transportation. Design: Cross-sectional study. Setting: Research centers and a specialized assistive technology (AT) clinic in Pittsburgh (Pitt). Research centers and communitybased rehabilitation technology suppliers in Saint Louis (SL). Participants: Seventy wheelchair users with SCI. Interventions: Subjects from Pitt and SL completed a written survey of AT usage in daily activities. Main Outcome Measures: Subjects were asked 5 questions within each setting (home, community, transportation) related to their perceived reason for functional limitations. Results: The wheelchair was the most commonly cited factor limiting participation, followed by physical impairment and physical environment. Twenty-one percent of subjects with paraplegia reported pain as a limiting factor for their transportation use, significantly more (P=.047) than subjects with tetraplegia (3%). A trend (P=.099) was seen toward a higher percentage of subjects with tetraplegia (tetraplegia, 7%; paraplegia, 3%) reporting lack of equipment as a limiting factor for use of transportation. Differences were also seen across sites. Conclusions: The wheelchair was the most commonly cited limiting factor, followed by physical impairment and physical environmental The wheelchair is the most important mobility device used by persons with SCI and the one that users most associate with barriers. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci, Pittsburgh, PA USA. Univ Pittsburgh, Dept Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Washington Univ, Sch Med, Program Occupat Therapy, St Louis, MO USA. VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs, Pittsburgh, PA USA. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM Boninger@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 26 TC 46 Z9 47 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2004 VL 85 IS 11 BP 1854 EP 1858 DI 10.1016/j.apmr.2004.03.033 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 870WO UT WOS:000225089700015 PM 15520981 ER PT J AU Algood, SD Cooper, RA Fitzgerald, SG Cooper, R Boninger, ML AF Algood, SD Cooper, RA Fitzgerald, SG Cooper, R Boninger, ML TI Impact of a pushrim-activated power-assisted wheelchair on the metabolic demands, stroke frequency, and range of motion among subjects with tetraplegia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT RESNA 2003 Conference CY JUN 21-23, 2003 CL ATLANTA, GA SP RESNA DE kinematics; metabolism; rehabilitation; tetraplegia; wheelchairs ID SHOULDER JOINT KINETICS; BEARING UPPER EXTREMITY; COORDINATE SYSTEM; PHYSICAL STRAIN; 2 SPEEDS; PROPULSION; BIOMECHANICS; EFFICIENCY; PARAPLEGIA; KINEMATICS AB Objectives: To determine differences in metabolic demands, stroke frequency, and upper-extremity joint range of motion (ROM) during pushrim-activated power-assisted wheelchair (PAPAW) propulsion and traditional manual wheelchair propulsion among subjects with tetraplegia. Design: Repeated measures. Setting: A biomechanics laboratory within a Veterans Affairs medical center. Participants: Fifteen full-time manual wheelchair users who had sustained cervical-level spinal cord injuries. Interventions: Participants propelled both their own manual wheelchairs and a PAPAW through 3 different resistances (slight, 10W; moderate, 12W; high, 14W) on a wheelchair dynamometer. Each propulsion trial was 3 minutes long. Main Outcome Measures: Primary variables that were compared between the 2 wheelchairs were participants' mean steady-state oxygen consumption, ventilation, heart rate, mean stroke frequency, and maximum upper-extremity joint ROM. Results: When using the PAPAW, participants showed a significant (P<.05) decrease in mean oxygen consumption and ventilation throughout all trials. Mean heart rate was significantly lower when using the PAPAW for the high resistance trial. Stroke frequency was significantly lower when using the PAPAW for the slight and moderate resistances. Overall joint ROM was significantly lower when using the PAPAW. Conclusions: For subjects with tetraplegia, PAPAWs reduce the energy demands, stroke frequency, and overall joint ROM when compared with traditional manual wheelchair propulsion. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Lab, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Lab, VA Rehabil Res & Dev Ctr, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 31 TC 26 Z9 27 U1 3 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2004 VL 85 IS 11 BP 1865 EP 1871 DI 10.1016/j.apmr.2004.04.043 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 870WO UT WOS:000225089700017 PM 15520983 ER PT J AU Friedman, DM Berger, DL AF Friedman, DM Berger, DL TI Improving team structure and communication - A key to hospital efficiency SO ARCHIVES OF SURGERY LA English DT Article ID PATIENT OUTCOMES; CARE AB Hypothesis: Improving team structure and heightening communication will help provide cost-effective and high-quality patient care for general surgery patients. Design: This study surveys teamwork initiatives and their effects on specific variables related to patient care. Patients: The study population comprised all patients admitted to the hospital's general surgery teams during 5 years 3 months. Setting: Tertiary care hospital. Interventions: A complete restructuring of the patient care team for general surgery patients admitted to the hospital. The intervention occurred midway through the study period. Main Outcome Measures: Mean length of stay for general surgery patients as a marker of team efficiency and a standardized patient satisfaction survey. Results: The mean length of stay after initiation of the restructured care team was significantly shorter than before initiation. The significance was present despite a consistent patient acuity measure and was associated with a high patient satisfaction level. Conclusions: Restructuring the patient care team yielded a decreased mean length of stay while maintaining a high level of patient satisfaction. This analysis helps validate a hospitalwide initiative to maintain a high level of patient care while increasing patient volume. C1 Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Performance Management Team, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr, Suite 465,15 Parkman St, Boston, MA 02114 USA. EM dberger@partners.org NR 5 TC 26 Z9 26 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD NOV PY 2004 VL 139 IS 11 BP 1194 EP 1198 DI 10.1001/archsurg.139.11.1194 PG 5 WC Surgery SC Surgery GA 868SE UT WOS:000224932500009 PM 15545566 ER PT J AU Diaz, A Hu, CB Kastner, DL Schaner, P Reginato, AM Richards, N Gumucio, DL AF Diaz, A Hu, CB Kastner, DL Schaner, P Reginato, AM Richards, N Gumucio, DL TI Lipopolysaccharide-induced expression of multiple alternatively spliced MEFV transcripts in human synovial fibroblasts SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; ENCODING MEVALONATE KINASE; NECROSIS-FACTOR-ALPHA; EXPANDING FAMILY; PAPA SYNDROME; PYRIN DOMAIN; KAPPA-B; MUTATIONS; GENE; PROTEIN AB Objective. To investigate the expression of the familial Mediterranean fever (IMF) gene (MEFP) in human synovial fibroblasts. Methods. MEFV messenger RNA in synovial fibroblasts, chondrocytes, and peripheral blood leukocytes (PBLs) was analyzed by semiquantitative and real-time polymerase chain reaction and ribonuclease protection assay. The subcellular localization of pyrin, the MEFV product, was determined in transfected synovial fibroblasts and HeLa cells with plasmids encoding pyrin isoforms. Native pyrin was detected with an antipyrin antibody. Results. MEFV was expressed in synovial fibroblasts, but not in chondrocytes. Four alternatively spliced transcripts were identified: an extension of exon 8 (exon 8ext) resulting in a frameshift that predicts a truncated protein lacking exons 9 and 10, the addition of an exon (exon 4a) predicting a truncated protein at exon 5, the in-frame substitution of exon 2a for exon 2, and the previously described removal of exon 2 (exon 2Delta). Exon 8ext transcripts represented 27% of the total message population in synovial fibroblasts. All other alternatively spliced transcripts were rare. Consensus and alternatively spliced transcripts were induced by lipopolysaccharide in synovial fibroblasts and PBLs. In transfected cells, the proteins encoded by all highly expressed splice forms were cytoplasmic. In contrast, native pyrin was predominantly nuclear in synovial fibroblasts, neutrophils, and dendritic cells, but was cytoplasmic in monocytes. Conclusion. Several MEFV transcripts are expressed and inducible in synovial fibroblasts. A prominent isoform lacks the C-terminal domain that contains the majority of mutations found in patients with IMF. While recombinant forms of all major pyrin isoforms are cytoplasmic, native pyrin is nuclear in several cell types. Thus, mechanisms in addition to splicing patterns must control pyrin's subcellular distribution. C1 Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gumucio, DL (reprint author), Univ Michigan, Sch Med, Dept Cell & Dev Biol, 1301 Catherine St,5704 MS 2, Ann Arbor, MI 48109 USA. EM dgumucio@umich.edu FU NIAID NIH HHS [R01 AI 053262-01A1, K08 AI 50092-01A1] NR 37 TC 63 Z9 64 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2004 VL 50 IS 11 BP 3679 EP 3689 DI 10.1002/art.20600 PG 11 WC Rheumatology SC Rheumatology GA 870QB UT WOS:000225071700036 PM 15529356 ER PT J AU Koenen, KC AF Koenen, KC TI Sex differences in the relationship between IQ and antisocial behavior in young children SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 34th Annual Meeting of the Behavior-Genetics-Association CY JUN 27-30, 2004 CL Aix en Provence, FRANCE SP Behav Genet Assoc C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02139 USA. EM Karestan.Koenen@bmc.org 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 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2004 VL 34 IS 6 BP 646 EP 646 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 866YB UT WOS:000224808200065 ER PT J AU Pham, W Choi, YD Weissleder, R Tung, CH AF Pham, W Choi, YD Weissleder, R Tung, CH TI Developing a peptide-based near-infrared molecular probe for protease sensing SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MATRIX-METALLOPROTEINASE INHIBITORS; TUMOR PROGRESSION; CANCER; EXPRESSION; CELLS AB Recently near-infrared (NIR) molecular probes have become important reporter molecules for a number of types of in vivo biomedical imaging. A peptide-based NIR fluorescence probe consisting of a NIR fluorescence emitter (Cy5.5), a NIR fluorescence absorber (NIRQ820), and a protease selective peptide sequence was designed to sense protease activity. Using a MMP-7 model, we showed that NIRQ820 efficiently absorbs the emission energy of Cy5.5 resulting in a low initial signal. Upon reacting with its target, MMP-7, the fluorescence signal of the designed probe was increased by 7-fold with a K-cat/ K-m of 100 000 M-1 s(-1). The described synthetic strategy should have wide application for other NIR probe preparations. C1 Harvard Univ, Ctr Mol Imaging Res, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Ctr Mol Imaging Res, Sch Med, Massachusetts Gen Hosp, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R01-CA99385] NR 23 TC 101 Z9 105 U1 3 U2 35 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 2004 VL 15 IS 6 BP 1403 EP 1407 DI 10.1021/bc049924s PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 872XW UT WOS:000225243800031 PM 15546208 ER PT J AU Metelev, V Weissleder, R Bogdanov, A AF Metelev, V Weissleder, R Bogdanov, A TI Synthesis and properties of fluorescent NF-kappa B-recognizing hairpin oligodeoxyribonucleotide decoys SO BIOCONJUGATE CHEMISTRY LA English DT Article ID ANTISENSE OLIGONUCLEOTIDES; IN-VIVO; SUBCELLULAR TRAFFICKING; THERAPEUTIC AGENTS; GENE-EXPRESSION; BINDING; INHIBITION; DELIVERY; CELLS; SIRNA AB Intramolecular fluorescence quenching of cyanine dyes was investigated using a model hairpin oligonucleotide decoy encoding a NF-kappaB p50 subunit binding site. Two types of hairpin oligonucleotides were synthesized: (1) 5'-(6-aminohexyl)- and 3'-(3-aminopropyl)-linked (I); (2) 5'-(6-aminohexyl)- and 3'-[3-(3-hydroxypropyldithio)propyl]-linked (II). Oligonucleotide I was covalently modified using monofunctional either Cy3- or Cy5.5-N-hydroxysuccinimide esters. Using reverse-phase HPLC, mono- and dicyanineamide derivatives of I were isolated. Mono-Cy3-modified derivatives of 1, but not the mono-Cy5.5-modified derivatives, showed a 2-fold higher Cy3 fluorescence intensity compared to the free dye. There was no detectable difference in fluorescence between the di-CY3 derivative of I and the free dye at the same concentration. However, there was a 4-fold quenching of fluorescence in the case of the di-Cy5.5 derivative of the same hairpin oligonucleotide. The quenching of Cy5.5 fluorescence could not be explained by the interaction of Cy5.5 with nucleotide bases as demonstrated by incubating free Cy5.5 dye with oligonuclotides. The quenching effect was further investigated using an oligonucleotide bearing a cleavable X-amino-terminated linker bearing an S-S bond (III). After modification of the 5'- and T-end of oligonucleotide III with a Cy5.5 monofunctional hydroxysuccinimide ester, a 70-75% quenching of fluorescence was observed. Fluorescence was 100% dequenched after the reduction of S-S bond. The obtained result unequivocally demonstrates that the formation of intramolecular Cy5.5 dimers is the dominant mechanism of fluorescence quenching in symmetric dyedye hairpin decoy beacons. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,5420, Charlestown, MA 02129 USA. EM abogdanov@helix.mgh.harvard.edu RI Metelev, Valeri/I-3238-2012 FU PHS HHS [P50] NR 31 TC 15 Z9 16 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 2004 VL 15 IS 6 BP 1481 EP 1487 DI 10.1021/bc049916b PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 872XW UT WOS:000225243800041 PM 15546218 ER PT J AU Oral, E Wannomae, KK Hawkins, N Harris, WH Muratoglu, OK AF Oral, E Wannomae, KK Hawkins, N Harris, WH Muratoglu, OK TI alpha-tocopherol-doped irradiated UHMWPE for high fatigue resistance and low wear SO BIOMATERIALS LA English DT Article DE UHMWPE; arthroplasty; fatigue; antioxidant; lipid ID MOLECULAR-WEIGHT POLYETHYLENE; CROSS-LINKING; IN-VITRO; KNEE; STERILIZATION; ARTHROPLASTY; OSTEOLYSIS; OXIDATION AB Longevity of total joints has been compromised by wear and fatigue of ultrahigh molecular weight polyethylene (UHMWPE) components. Crosslinking reduces UHMWPE wear, but combined with postirradiation melting, also reduces its fatigue strength, therefore limiting its use in high-stress applications. We hypothesized that a lipophilic antioxidant (alpha-tocopherol, alpha-T) can protect UHMWPE against oxidation eliminating the need for postirradiation melting of crosslinked UHMWPE and improve its fatigue strength. To test these hypotheses, 65- and 100-kGy irradiated, alpha-T-doped and subsequently gamma-sterilized UHMWPE were used. (I) alpha-T-doped irradiated UHMWPEs showed significantly lower oxidation levels (0.48+/-0.25 and 0.44+/-0.06) compared to 100-kGy irradiated UHMWPE (3.74+/-0.16) after 5 weeks of accelerated aging at 80degreesC in air. (II) Wear rate of alpha-T-doped irradiated UHMWPE (1.9+/-0.5, and 0.9+/-0.1 mg/million cycles (MC) for 65- and 100-kGy irradiated UHMWPE, respectively) were comparable to that of 100-kGy irradiated/melted UHMWPE (1.1+/-0.7 mg/million cycles). (III) The stress intensity factor at crack inception (DeltaK(i)) of 100-kGy irradiated UHMWPE increased significantly upon doping with alpha-T from 0.74 to 0.87 MPa m(1/2) (p<0.01). The DeltaK(i) for the 100-kGy irradiated and melted UHMWPE, currently in clinical use, was 0.55 MPa m(1/2). Doping with alpha-T eliminated the need for postirradiation melting to protect irradiated UHMWPE against long-term oxidation. The fatigue strength was improved by 58% for alpha-T-doped 100-kGy irradiated UHMWPE compared to irradiated and melted UHMWPE. The increase in oxidative stability of alpha-T-doped UHMWPE is attributed to the ability of alpha-T to react with peroxy free radicals on lipid chains and arrest the oxidation reactions. The improved fatigue strength is attributed to the increase in plasticity of UHMWPE due to the lipophilic nature of alpha-T. (C) 2003 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM orhun@alum.mit.edu NR 21 TC 146 Z9 150 U1 1 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD NOV PY 2004 VL 25 IS 24 BP 5515 EP 5522 DI 10.1016/j.biomaterials.2003.12.048 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 822ST UT WOS:000221561200009 PM 15142733 ER PT J AU Aranyosi, AJ Freeman, DM AF Aranyosi, AJ Freeman, DM TI Sound-induced motions of individual cochlear hair bundles SO BIOPHYSICAL JOURNAL LA English DT Article ID ALLIGATOR LIZARD COCHLEA; GUINEA-PIG COCHLEA; BASILAR-MEMBRANE; FREESTANDING STEREOCILIA; RECEPTOR POTENTIALS; TONOTOPIC ORGANIZATION; FREQUENCY-SELECTIVITY; HYDRODYNAMIC-FORCES; SIGNAL TRANSMISSION; RESPONSE PHASE AB We present motions of individual freestanding hair bundles in an isolated cochlea in response to tonal sound stimulation. Motions were measured from images taken by strobing a light source at the tone frequency. The tips and bases of hair bundles moved a comparable amount, but with a phase difference that increased by 180degrees with frequency, indicating that distributed fluid properties drove hair bundle motion. Hair bundle rotation increased with frequency to a constant value, and underwent >90degrees of phase change. The frequency at which the phase of rotation relative to deflection of the bundle base was 60degrees was comparable to the expected best frequency of each hair cell, and varied inversely with the square of bundle height. The sharpness of tuning of individual hair bundles was comparable to that of hair cell receptor potentials at high sound levels. These results indicate that frequency selectivity at high sound levels in this cochlea is purely mechanical, determined by the interaction of hair bundles with the surrounding fluid. The sharper tuning of receptor potentials at lower sound levels is consistent with the presence of a negative damping, but not a negative stiffness, as an active amplifier in hair bundles. C1 MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Aranyosi, AJ (reprint author), MIT, Elect Res Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM aja@mit.edu OI Aranyosi, Alexander/0000-0002-8133-5026 FU NIDCD NIH HHS [R01-DC00238, R01 DC000238] NR 51 TC 24 Z9 25 U1 0 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2004 VL 87 IS 5 BP 3536 EP 3546 DI 10.1529/biophysj.104.044404 PG 11 WC Biophysics SC Biophysics GA 865VO UT WOS:000224732500054 PM 15315953 ER PT J AU Look, AT AF Look, AT TI Gene expression arrays and the therapist's dilemma SO BLOOD LA English DT Editorial Material ID LEUKEMIA; FLT3 C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 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 NOV 1 PY 2004 VL 104 IS 9 BP 2611 EP 2612 DI 10.1182/blood-2004-08-3163 PG 2 WC Hematology SC Hematology GA 866TI UT WOS:000224795700001 ER PT J AU Lacayo, NJ Meshinchi, S Kinnunen, P Yu, R Wang, Y Stuber, CM Douglas, L Wahab, R Becton, DL Weinstein, H Chang, MN Willman, CL Radich, JP Tibshirani, R Ravindranath, Y Sikic, BI Dahl, GV AF Lacayo, NJ Meshinchi, S Kinnunen, P Yu, R Wang, Y Stuber, CM Douglas, L Wahab, R Becton, DL Weinstein, H Chang, MN Willman, CL Radich, JP Tibshirani, R Ravindranath, Y Sikic, BI Dahl, GV TI Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE PROMYELOCYTIC LEUKEMIA; TYROSINE KINASE INHIBITOR; CELL-LINES; CONSTITUTIVE ACTIVATION; PROGNOSTIC-SIGNIFICANCE; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS AB Fms-like tyrosine kinase 3 (FLT3) mutations are associated with unfavorable outcomes in children with acute myeloid leukemia (AML). We used DNA microarrays to identify gene expression profiles related to FLT3 status and outcome in childhood AML. Among 81 diagnostic specimens, 36 had FLT3 mutations (FLT3-MUs), 24 with internal tandem duplications (ITDs) and 12 with activating loop mutations (ALMs). In addition, 8 of 19 specimens from patients with relapses had FLT3-MUs. Predictive analysis of microarrays (PAM) identified genes that differentiated FLT3-ITD from FLT3-ALM and FLT3 wildtype (FLT3-WT) cases. Among the 42 specimens with FLT3-MUs, PAM identified 128 genes that correlated with clinical outcome. Event-free survival (EFS) in FLT3-MU patients with a favorable signature was 45% versus 5% for those with an unfavorable signature (P = .018). Among FLT3-MU specimens, high expression of the RUNX3 gene and low expression of the ATRX gene were associated with inferior outcome. The ratio of RUNX3 to ATRX expression was used to classify FLT3-MU cases into 3 EFS groups: 70%, 37%, and 0% for low, intermediate, and high ratios, respectively (P < .0001). Thus, gene expression profiling identified AML patients with divergent prognoses within the FLT3-MU group, and the RUNX3 to ATRX expression ratio should be a useful prognostic indicator in these patients. (C) 2004 by The American Society of Hematology. C1 Stanford Univ, Sch Med, Div Pediat Hematol Oncol, Palo Alto, CA USA. Stanford Univ, Sch Med, Div Med Oncol & Stat, Palo Alto, CA USA. Arkansas Childrens Hosp, Little Rock, AR USA. Massachusetts Gen Hosp, Boston, MA USA. Childrens Hosp Michigan, Detroit, MI USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Childrens Oncol Grp, Arcadia, CA USA. RP Dahl, GV (reprint author), POB 60012, Arcadia, CA 91066 USA. EM gary.dahl@stanford.edu FU NCI NIH HHS [R01 CA90916, CA98543, R01 CA 92474]; NCRR NIH HHS [M01 RR 00070] NR 69 TC 67 Z9 71 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 NOV 1 PY 2004 VL 104 IS 9 BP 2646 EP 2654 DI 10.1182/blood-2004-12-4449 PG 9 WC Hematology SC Hematology GA 866TI UT WOS:000224795700014 PM 15251987 ER PT J AU Le Gouill, S Podar, K Amiot, M Hideshima, T Chauhan, D Ishitsuka, K Kumar, S Raje, N Richardson, PG Harousseau, JL Anderson, KC AF Le Gouill, S Podar, K Amiot, M Hideshima, T Chauhan, D Ishitsuka, K Kumar, S Raje, N Richardson, PG Harousseau, JL Anderson, KC TI VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW MICROENVIRONMENT; HEMATOPOIETIC-CELLS; DRUG-RESISTANCE; PAN-INHIBITOR; BCL-2 FAMILY; SURVIVAL; PROLIFERATION; EXPRESSION; MIGRATION AB Interleukin-6 (IL-6) triggers multiple myeloma (MM) cell proliferation and protects against apoptosis by up-regulating myeloid cell leukemia 1 (Mcl-1). Vascular endothelial growth factor (VEGF) induces modest proliferation of MM cells and induces IL-6 secretion in a paracrine loop involving MM cells and bone marrow stromal cells. Using murine embryonic fibroblast cell lines as a model (Mcl-1(wt/wt) and Mcl-1(Delta/null) MEFs), we here demonstrate that deletion of Mcl-1 reduces fetal bovine serum (FBS)-, VEGF-, and IL-6-induced proliferation. We also show that VEGF up-regulates Mcl-1 expression in a time and dose-dependent manner in 3 human MM cell lines and MM patient cells. Importantly, we demonstrate that the pan-VEGF inhibitor, GW654652, inhibits VEGF-induced up-regulation of Mcl-1 and, as with Mcl-1 siRNA, is associated with decreased proliferation and induction of apoptosis. Finally, we show that VEGF protects MM patient cells against FBS starvation-induced apoptosis. Our studies therefore demonstrate that VEGF-induced MM cell proliferation and survival are mediated via Mcl-1, providing the preclinical framework for novel therapeutics targeting Mcl-1 and/or VEGF to improve patient outcome in MM. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. CHU Nantes, Hotel Dieu, Serv Hematol Clin, F-44035 Nantes 01, France. CHU Nantes, Hotel Dieu, Inst Biol, UO601,INSERM, F-44035 Nantes 01, France. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu FU PHS HHS [P0-1 50947, P0-1 78378] NR 45 TC 98 Z9 99 U1 0 U2 6 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 NOV 1 PY 2004 VL 104 IS 9 BP 2886 EP 2892 DI 10.1182/blood-2004-05-1760 PG 7 WC Hematology SC Hematology GA 866TI UT WOS:000224795700047 PM 15217829 ER PT J AU Griswold, IJ Shen, LJ La Rosee, P Demehri, S Heinrich, MC Braziel, RM McGreevey, L Haley, AD Giese, N Druker, BJ Deininger, MWN AF Griswold, IJ Shen, LJ La Rosee, P Demehri, S Heinrich, MC Braziel, RM McGreevey, L Haley, AD Giese, N Druker, BJ Deininger, MWN TI Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; RECEPTOR TYROSINE KINASE; PROGNOSTIC-SIGNIFICANCE; MYELOBLASTIC-LEUKEMIA; PROGENITOR CELLS; MUTATIONS; GROWTH; LIGAND AB Internal tandem duplications (ITDs) of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase are found in approximately 30% of patients with acute myelogenous leukemia (AML) and are associated with a poor prognosis. FLT3 ITD mutations result in constitutive kinase activation and are thought to be pathogenetically relevant, implicating FLT3 as a plausible therapeutic target. MLN518 (formerly CT53518) is a small molecule inhibitor of the FLT3, KIT, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases with significant activity in murine models of FLT3 ITD-positive leukemia. Given the importance of FLT3 and KIT for normal hematopoietic progenitor cells, we analyzed the effect of MLN518 on murine hematopoiesis under steady-state conditions, after chemotherapy-induced myelosuppression, and during bone marrow transplantation. In these assays, we show that MLN518 has mild toxicity toward normal hematopoiesis at concentrations that are effective in treating FLT3 ITD-positive leukemia in mice. We also demonstrate that MLN518 preferentially inhibits the growth of blast colonies from FLT3 ITD-positive compared with ITD-negative patients with AML, at concentrations that do not significantly affect colony formation by normal human progenitor cells. In analogy to imatinib mesylate in BCR-ABL-positive acute leukemia, MLN518-induced remissions may not be durable. Our studies provide the basis for integrating this compound into chemotherapy and transplantation protocols. (C) 2004 by The American Society of Hematology. C1 Oregon Hlth Sci Univ, Howard Hughes Med Inst, BMT Leukemia Ctr, Inst Canc, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Millenium Pharmaceut, San Francisco, CA USA. Univ Heidelberg, Fak Klin Med Mannheim, Med Klin 3, Heidelberg, Germany. RP Deininger, MWN (reprint author), Oregon Hlth Sci Univ, Howard Hughes Med Inst, BMT Leukemia Ctr, Inst Canc, 3181 SW Sam Jackson Pk Rd,L592, Portland, OR 97239 USA. EM deininge@ohsu.edu NR 32 TC 27 Z9 29 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 NOV 1 PY 2004 VL 104 IS 9 BP 2912 EP 2918 DI 10.1182/blood-2003-05-1669 PG 7 WC Hematology SC Hematology GA 866TI UT WOS:000224795700050 PM 15242881 ER PT J AU Guinan, EC AF Guinan, EC TI Costimulatory blockade ex vivo: Results of 2 pilot clinical trials. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th International Workshop on Haploidentical Stem Cell Transplantation CY JUL 08-10, 2004 CL Naples, ITALY SP Leukemia & Lymphoma Soc C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 5 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2004 VL 33 IS 3 BP 204 EP 204 PG 1 WC Hematology SC Hematology GA 871FF UT WOS:000225114500052 ER PT J AU Bourquin, JP Thornley, I Neuberg, D Brennan, L Kung, A Clark, J Lehmann, L Guinan, EC AF Bourquin, JP Thornley, I Neuberg, D Brennan, L Kung, A Clark, J Lehmann, L Guinan, EC TI Favorable outcome of allogeneic hematopoietic stem cell transplantation for relapsed or refractory acute promyelocytic leukemia in childhood SO BONE MARROW TRANSPLANTATION LA English DT Article DE acute promyelocytic leukemia; allogeneic hematopoietic stem cell transplantation; relapse; pediatric ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; TRANS-RETINOIC ACID; VERSUS-HOST DISEASE; ACUTE GRAFT; ARSENIC TRIOXIDE; CHEMOTHERAPY; REMISSION; CYCLOSPORINE; METHOTREXATE AB The optimal therapy for children with relapsed or refractory acute promyelocytic leukemia (APL) is unclear. We therefore reviewed our institutional outcomes for children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for advanced APL. Between 1986 and 2003, 12 allogeneic HSCTs (five related donor, seven unrelated donor) were performed for 11 patients (median age, 13 years) with relapsed (n=8) or refractory (n=3) APL. All patients engrafted, after a median of 18.5 days. Grade B-D acute graft-versus-host disease (GVHD) developed after five transplants (42%; 90% CI, 18-68%), and the cumulative incidence of chronic GVHD was 45%(90% CI, 19-71%). The cumulative incidence of overt relapse post-HSCT was 10% (90% CI, 0-28%). The overall 5-year survival was 73% (90% confidence interval (CI), 51-95%), with a median post-HSCT follow-up of 64 months. The Lansky/Karnofsky performance scores are 100% in six of eight survivors. In view of the low risk of subsequent relapse and favorable survival suggested by other reports and our own experience, we continue to recommend allogeneic HSCT for children with advanced APL for whom a suitably HLA-matched donor is identified. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Eva_Guinan@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X NR 18 TC 12 Z9 14 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2004 VL 34 IS 9 BP 795 EP 798 DI 10.1038/sj.bmt.1704676 PG 4 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 862BU UT WOS:000224465400005 PM 15354207 ER PT J AU Rodacki, M Zajdenverg, L Albernaz, MS Bencke-Goncalves, MR Milech, A Oliveira, JEP AF Rodacki, M Zajdenverg, L Albernaz, MS Bencke-Goncalves, MR Milech, A Oliveira, JEP TI Relationship between the prevalence of anti-glutamic acid decarboxylase autoantibodies and duration of type 1 diabetes mellitus in Brazilian patients SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE anti-GAD65 auto-antibodies; type 1 diabetes mellitus; time from diagnosis ID BETA-CELL FUNCTION; C-PEPTIDE; CLINICAL CHARACTERISTICS; HLA-DR; ANTIBODIES; ONSET; DISEASE; IDDM; GAD; AGE AB The objective of the present study was to determine whether the duration of disease has any influence on the prevalence of glutamic acid decarboxylase autoantibodies (GADA) in Brazilian patients with type 1 diabetes (T1D) and variable disease duration. We evaluated 83 patients with T1D. All participants were interviewed and blood was obtained for GADA measurement by a commercial radioimmunoassay (RSR Limited, Cardiff, UK). Four groups of patients were established according to disease duration: A) 1-5 years of disease (N = 24), B) 6-10 years of disease (N = 19), C) 11-15 years of disease (N = 25), and D) >15 years of disease (N = 15). GADA prevalence and its titers were determined in each group. GADA was positive in 38 patients (45.8%) and its frequency did not differ between the groups. The prevalence was 11/24 (45.8%), 8/19 (42.1%), 13/25 (52%), and 6/15 (40%) in groups A, B, C, and D, respectively (P = 0.874). Mean GADA titer was 12.54 +/- 11.33 U/ml for the sample as a whole and 11.95 +/- 11.8, 12.85 +/- 12.07, 10.57 +/- 8.35, and 17.45 +/- 16.1 U/ml for groups A, B, C, and D, respectively (P = 0.686). Sex, age at diagnosis or ethnic background had no significant effect on GADA (+) frequency. In conclusion, in this transversal study, duration of disease did not affect significantly the prevalence of GADA or its titers in patients with T1D after one year of diagnosis. This was the first study to report this finding in the Brazilian population. C1 Fed Univ Rio De Janeiro, Serv Diabet & Nutrol, Rio De Janeiro, RJ, Brazil. Fed Univ Rio De Janeiro, Serv Med Nucl, Rio De Janeiro, RJ, Brazil. Inst Estadual Diabet & Endocrinol, Rio De Janeiro, RJ, Brazil. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. RP Rodacki, M (reprint author), 109 Queensberry St 12, Boston, MA 02215 USA. EM melanie.rodacki@joslin.harvard.edu NR 30 TC 7 Z9 8 U1 0 U2 1 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD NOV PY 2004 VL 37 IS 11 BP 1645 EP 1650 PG 6 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 871JX UT WOS:000225128700008 PM 15517079 ER PT J AU Pardo, FS Hsu, DW Zeheb, R Efird, JT Okunieff, PG Malkin, DM AF Pardo, FS Hsu, DW Zeheb, R Efird, JT Okunieff, PG Malkin, DM TI Mutant, wild type, or overall p53 expression: freedom from clinical progression in tumours of astrocytic lineage SO BRITISH JOURNAL OF CANCER LA English DT Article DE brain tumour; glioma survival; radiation therapy ID HUMAN-PAPILLOMAVIRUS TYPE-16; GROWTH-FACTOR-RECEPTOR; MALIGNANT GLIOMAS; GLIOBLASTOMA-MULTIFORME; PROLIFERATION MARKERS; MUTATION FREQUENCY; HUMAN FIBROBLASTS; TP53 MUTATION; PROTEIN; CELLS AB Abnormalities of the p53 tumor-suppressor gene are found in a significant proportion of astrocytic brain tumours. We studied tumour specimens from 74 patients evaluated over 20 years at the Massachusetts General Hospital, where clinical outcome could be determined and sufficient pathologic material was available for immunostaining. p53 expression studies employed an affinity-purified p53 monoclonal antibody, whose specificity was verified in absorption studies and, in a minority of cases, a second antibody recognising a different epitope of p53. Significant overexpression of p53 protein was found in 48% of the 74 tumours included in this series and high levels of expression were associated with higher mortality from astrocytic tumours (P<0.001, log rank). Multivariate analyses revealed that immunohistochemically detected p53 was an independent marker of shortened progression-free and overall actuarial survival in patients with astrocytic tumours, suggesting that increased expression of p53 plays an important role in the pathobiology of these tumours. In a subset of 36 cases, coding regions of the p53 gene were completely sequenced via SSCP and direct DNA sequencing, revealing that overexpression of p53 protein is not always associated with point mutations in conserved exons of the p53 gene. Finally, we confirmed p53 protein expression in early-passage human glioma cell lines of known p53 mutational status and immunostaining scores. Although grade continues to be the strongest prognostic variable, the use of p53 staining as a prognostic indicator, in contrast to mutational DNA analyses, may be a useful adjunct in identifying patients at higher risk of treatment failure. C1 Univ Calif San Diego, Dept Radiol, Div Radiat Oncol, Radiat & Cellular Biol Lab, San Diego, CA 92103 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA USA. Oncogene Sci Inc, Uniondale, NY USA. Stanford Univ, Med Ctr, Dept Epidemiol & Biostat, Stanford, CA 94305 USA. Univ Rochester, Dept Radiat Oncol, Rochester, NY USA. Hosp Sick Children, Div Oncol, Toronto, ON M5G 1X8, Canada. RP Pardo, FS (reprint author), Univ Calif San Diego, Dept Radiol, Div Radiat Oncol, Radiat & Cellular Biol Lab, San Diego, CA 92103 USA. EM fpardo@ucsd.edu FU NCI NIH HHS [CA-13311] NR 59 TC 21 Z9 21 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 NOV 1 PY 2004 VL 91 IS 9 BP 1678 EP 1686 DI 10.1038/sj.bjc.6602161 PG 9 WC Oncology SC Oncology GA 867BN UT WOS:000224817200009 PM 15494720 ER PT J AU Haining, WN Evans, JW Seth, NP Callaway, GD Wucherpfennig, KW Nadler, LM Guinan, EC AF Haining, WN Evans, JW Seth, NP Callaway, GD Wucherpfennig, KW Nadler, LM Guinan, EC TI Measuring T cell immunity to influenza vaccination in children after haemopoietic stem cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE malignant lymphomas; molecular pathogenesis; immunodeficiency; somatic mutation; proto-oncogenes ID CD4(+) AB Quantitative assessment of immunogen-specific T cell responses may provide a meaningful surrogate marker of functional immunity in patients following haemopoietic stem cell transplantation (HSCT). We developed a flow-cytometric assay to quantify antigen-specific T cell immunity to influenza-A and studied the T cell response to influenza vaccination in five children, 3 21 months post-HSCT. All patients showed an increase in influenza-A-specific CD4(+) immunity following vaccination while none had a detectable IgG response to the vaccine. This assay proved sufficiently sensitive to evaluate changes in T cell memory in immunocompromised individuals and could be used to better characterize post-HSCT immune reconstitution. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Haining, WN (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu FU NCI NIH HHS [1P01CA100265, P01 CA100265]; NHLBI NIH HHS [K08 HL072750, 5K08HL72750] NR 10 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2004 VL 127 IS 3 BP 322 EP 325 DI 10.1111/j.1365-2141.2004.05204.x PG 4 WC Hematology SC Hematology GA 862IS UT WOS:000224484800010 PM 15491293 ER PT J AU Saslow, D Hannan, J Osuch, J Alciati, MH Baines, C Barton, M Bobo, JK Coleman, C Dolan, M Gaumer, G Kopans, D Kutner, S Lane, DS Lawson, H Meissner, H Moorman, C Pennypacker, H Pierce, P Sciandra, E Smith, R Coates, R AF Saslow, D Hannan, J Osuch, J Alciati, MH Baines, C Barton, M Bobo, JK Coleman, C Dolan, M Gaumer, G Kopans, D Kutner, S Lane, DS Lawson, H Meissner, H Moorman, C Pennypacker, H Pierce, P Sciandra, E Smith, R Coates, R TI Clinical breast examination: Practical recommendations for optimizing performance and reporting SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID EVALUATION SKILLS; AMERICAN-COLLEGE; CANCER; MAMMOGRAPHY; ASSESSMENTS; GUIDELINES; CONCORDANCE; COMPETENCE; PREDICTORS; PHYSICIANS AB Clinical breast examination (CBE) seeks to detect breast abnormalities or evaluate patient reports of symptoms to find palpable breast cancers at an earlier stage of progression. Treatment options for earlier-stage cancers are generally more numerous, include less toxic alternatives, and are usually more effective than treatments for later-stage cancers. For average-risk women aged 40 and younger, earlier detection of palpable tumors identified by CBE can lead to earlier therapy. After age 40, when mammography is recommended, CBE is regarded as an adjunct to mammography. Recent debate, however, has questioned the contributions of CBE to the detection of breast cancer in asymptomatic women and particularly to improved survival and reduced mortality rates. Clinicians remain widely divided about the level of evidence supporting CBE and their confidence in the examination. Yet, CBE is practiced extensively in the United States and continues to be recommended by many leading health organizations. It is in this context that this report provides a brief review of evidence for CBE's role in the earlier detection of breast cancer, highlights current practice issues, and presents recommendations that, when implemented, could contribute to greater standardization of the practice and reporting of CBE. These recommendations may also lead to improved evidence of the nature and extent of CBE's contribution to the earlier detection of breast cancer. C1 Amer Canc Soc, Atlanta, GA 30329 USA. Ctr Dis Control & Prevent, Program Serv Branch, Div Canc Prevent & Control, Atlanta, GA USA. Michigan State Univ, E Lansing, MI 48824 USA. Management Solut Hlth Inc, Reston, VA USA. Univ Toronto, Dept Hlth Sci, Fac Med, Toronto, ON, Canada. Harvard Univ, Sch Med, Dept Ambultory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambultory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Pilgrim Hlth Care, Boston, MA 02115 USA. Batelle Ctr Public Hlth, Seattle, WA USA. Breast Ctr Dev, Tiburon, CA USA. Univ N Carolina, Sch Med, Womens Primary Healthcare, Chapel Hill, NC USA. Univ Georgia, Dept Human Resources, Savannah, GA USA. Massachusetts Gen Hosp, Breast Imaging Div, Boston, MA 02114 USA. RP Saslow, D (reprint author), Amer Canc Soc, Atlanta, GA 30329 USA. OI Alciati, Marianne/0000-0001-6294-1090 NR 45 TC 60 Z9 60 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD NOV-DEC PY 2004 VL 54 IS 6 BP 327 EP 344 PG 18 WC Oncology SC Oncology GA 958YG UT WOS:000231483500008 PM 15537576 ER PT J AU Ceilley, E Jagsi, R Goldberg, S Kachnic, L Powell, S Taghian, A AF Ceilley, E Jagsi, R Goldberg, S Kachnic, L Powell, S Taghian, A TI The management of ductal carcinoma in situ in north America and Europe - Results of a survey SO CANCER LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 06-10, 2002 CL NEW ORLEANS, LA SP Amer Soc Therapeut Radiol & Oncol DE breast carcinoma; radiotherapeutic management; ductal carcinoma in situ; survey ID SURGICAL ADJUVANT BREAST; PHYSICIAN-ASSISTED SUICIDE; TERM FOLLOW-UP; INTRADUCTAL CARCINOMA; RADIATION-THERAPY; CANCER; ONCOLOGISTS; PREVENTION; TAMOXIFEN; TRIAL AB BACKGROUND. The goal of the current study was to understand and document contemporary treatment approaches in the management of ductal carcinoma in situ (DCIS). METHODS. An original questionnaire was designed to assess radiation oncologists' management of breast carcinoma, including 26 questions specifically addressing DCIS. A postal survey was conducted of members of the American and European Societies of Therapeutic Radiology and Oncology. The results of 702 responses from North America were compared with 435 responses from Europe, to determine treatment recommendations and variability by type of institution and geographic region. RESULTS. There were strong correlations between the grade of DCIS and/or the margin status and the use of radiotherapy (RT; P < 0.0001). For Grade 3 DCIS, RT was recommended regardless of the margin status. Opinions were split in the treatment of low-grade DCIS with 10-mm margins. North American respondents were more likely to recommend RT for low-grade DCIS than their European counterparts (P < 0.0001). Within the United States, there were significant regional variations in physician recommendations for tamoxifen (P < 0.001), but not in the tendency to recommend RT. North American academic physicians were less likely to recommend RT for favorable DCIS than nonacademic physicians (P < 0.01). CONCLUSIONS. There were marked differences in physician opinions regarding the management of DCIS, with significant international differences in patterns of care. The survey quantified and highlighted areas of agreement and controversy regarding the use of RT and tamoxifen in the management of DCIS. It provided support for large international trials to evaluate the optimal management of DCIS in the areas identified as most controversial. (C) 2004 American Cancer Society. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org NR 34 TC 32 Z9 33 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2004 VL 101 IS 9 BP 1958 EP 1967 DI 10.1002/cncr.20580 PG 10 WC Oncology SC Oncology GA 864IL UT WOS:000224627100005 PM 15389481 ER PT J AU Alvarez, JV Frank, DA AF Alvarez, JV Frank, DA TI Genome-wide analysis of STAT target genes - Elucidating the mechanism of STAT-mediated oncogenesis SO CANCER BIOLOGY & THERAPY LA English DT Review DE STAT3; STAT5; STAT; transcription factor; cancer; oncogenesis; microarray; expression profiling ID SIGNALING INDUCES APOPTOSIS; CELL-CYCLE PROGRESSION; CONSTITUTIVE ACTIVATION; TRANSCRIPTION FACTORS; TUMOR-CELLS; HEMATOPOIETIC-CELLS; MULTIPLE-MYELOMA; TYROSINE KINASES; SRC ONCOPROTEIN; CARCINOMA CELLS AB Inappropriate activation of transcription factors is a common event in cancer. These transcription factors contribute to a malignant phenotype by regulating genes involved in cellular proliferation, survival, differentiation, angiogenesis, and invasion. An important goal remains identifying the targets of oncogenic transcription factors that execute these changes. STAT proteins are among the best-studied of these transcription factors, and are involved in oncogenesis both in vivo and in vitro. They thus represent an ideal model for understanding how transcription factors cause cancer through coordinated changes in gene expression. Recent studies have employed microarray-based expression analysis to comprehensively identify STAT target genes. Analysis of these targets can provide insight into mechanisms of neoplastic transformation, and may shed light on new strategies for targeted therapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Alvarez, JV (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Mayer 520, Boston, MA 02115 USA. EM james_alvarez@student.hms.harvard.edu NR 55 TC 52 Z9 53 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV PY 2004 VL 3 IS 11 BP 1045 EP 1050 PG 6 WC Oncology SC Oncology GA 913FA UT WOS:000228135800009 PM 15539936 ER PT J AU Wu, K Hu, FB Fuchs, C Rimm, EB Willett, WC Giovannucci, E AF Wu, K Hu, FB Fuchs, C Rimm, EB Willett, WC Giovannucci, E TI Dietary patterns and risk of colon cancer and adenoma in a cohort of men (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE colon adenoma; colon cancer; dietary pattern; men ID FOOD-FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; REPRODUCIBILITY; VALIDITY; DISEASE; FIBER; RECURRENCE; FRUIT; WOMEN AB Background: Examining the effects of dietary patterns on cancer risk may provide insights beyond the assessment of individual foods or nutrients. Design: In the health professionals follow-up cohort, associations between the 'prudent' and the 'western' dietary pattern and risk of colon cancer and adenomas were examined in 561 colon cancer cases and 1207 distal colon adenoma cases. Results: Higher prudent pattern scores were only weakly and non-significantly associated with decreased risk of colon cancer or distal colon adenoma (highest versus lowest quintile: colon cancer: multivariate adjusted relative risk (RR) 0.84 (95% confidence interval (CI) 0.64-1.10); p(trend) 0.37; distal adenoma: multivariate odds ratio (OR) 0.88 (95% CI 0.73-1.08); p(trend)=0.12). Our findings suggest a moderately increased risk of colon cancer and distal adenoma with higher western pattern scores (colon cancer: RR=1.27 (95% CI 0.96-1.69), p(trend)=0.05; distal adenoma: OR 1.28 (95% CI=1.05-1.56), p(trend)=0.01). Adding body mass index, which is positively related to western pattern and thus may be considered an intermediate endpoint between western pattern and colon cancer, attenuated associations somewhat but not substantially. Conclusion: Our data do not provide evidence for an appreciable inverse association between higher prudent pattern scores and risk of colon cancer or distal colon adenomas, but do support a moderate positive association between higher western pattern scores and risk of colon cancer or distal colon adenomas. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Wu, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2, Boston, MA 02115 USA. EM kana.wu@channing.harvard.edu FU NCI NIH HHS [CA95589, CA55075] NR 31 TC 51 Z9 51 U1 0 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2004 VL 15 IS 9 BP 853 EP 862 DI 10.1007/s10552-004-1809-2 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 876AW UT WOS:000225468700001 PM 15577287 ER PT J AU Weir, B Zhao, XJ Meyerson, M AF Weir, B Zhao, XJ Meyerson, M TI Somatic alterations in the human cancer genome SO CANCER CELL LA English DT Review ID NUCLEOTIDE POLYMORPHISM ARRAYS; HIGH-RESOLUTION ANALYSIS; TUMOR-SUPPRESSOR GENE; ABL TYROSINE KINASE; HUMAN LUNG-CANCER; COPY NUMBER; OLIGONUCLEOTIDE MICROARRAY; HETEROZYGOSITY ANALYSIS; MUTATIONAL ANALYSIS; COLORECTAL CANCERS AB Most human malignancies are caused by somatic alterations within the cancer genome, leading to oncogene activation or tumor suppressor gene inactivation. The sequence of the human genome has enabled systematic approaches to identify cancer genome alterations, including point mutations, copy number increases and decreases, loss of allelic heterozygosity, and chromosome translocations. Systematic cancer genome analysis has recently led to the discovery of somatic mutations in the BRAF, PIK3CA, and EGFR genes, among others. With further development of targeted cancer therapies and improvement in genome analysis technology, genome-wide surveys of cancer will likely become tools for diagnosis as well as discovery. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 76 TC 100 Z9 102 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2004 VL 6 IS 5 BP 433 EP 438 DI 10.1016/j.ccr.2004.11.004 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 872YA UT WOS:000225244200004 PM 15542426 ER PT J AU Mitsiades, CS Mitsiades, N Munshi, NC Anderson, KC AF Mitsiades, CS Mitsiades, N Munshi, NC Anderson, KC TI Focus on multiple myeloma SO CANCER CELL LA English DT Review ID NF-KAPPA-B; HISTONE DEACETYLASE INHIBITION; OVERCOMES DRUG-RESISTANCE; BONE-MARROW STROMA; THERAPEUTIC IMPLICATIONS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; CLINICAL-IMPLICATIONS; MOLECULAR SEQUELAE; RECEPTOR ACTIVATOR C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM constantine_mitsiades@dfci.harvard.edu; kenneth-anderson@dfci.harvard.edu NR 64 TC 115 Z9 117 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2004 VL 6 IS 5 BP 439 EP 444 DI 10.1016/j.ccr.2004.10.020 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 872YA UT WOS:000225244200005 PM 15542427 ER PT J AU Wei, EK Giovannucci, E Selhub, J Fuchs, CS Hankinson, S Ma, J AF Wei, EK Giovannucci, E Selhub, J Fuchs, CS Hankinson, S Ma, J TI Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1854S EP 1854S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100102 ER PT J AU Randolph-Steele, W Moser, RP Hesse, BW Viswanath, K AF Randolph-Steele, W Moser, RP Hesse, BW Viswanath, K TI Differences in cancer knowledge by socioeconomic status: A partial explanation for cancer health disparities? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1857S EP 1857S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100112 ER PT J AU Wark, PA Wu, K Van't Veer, P Fuchs, C Willett, WC Giovannucci, EL AF Wark, PA Wu, K Van't Veer, P Fuchs, C Willett, WC Giovannucci, EL TI Diet, lifestyle, and advanced and non-advanced colorectal adenomas in men. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ Wageningen & Res Ctr, Div Human Nutr, Wageningen, Netherlands. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1891S EP 1891S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100229 ER PT J AU Keeton, EK O'Kane, HE Li, XC Brown, MA Garber, JE AF Keeton, EK O'Kane, HE Li, XC Brown, MA Garber, JE TI Assessing the use of ductal lavage specimens to measure biomarkers for a study on the efficacy of the PPAR-gamma agonist rosiglitazone in reducing cyclin D1 expression levels for the prevention of ER-negative breast cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1918S EP 1918S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100325 ER PT J AU Vadaparampil, ST Wideroff, L Freedman, AN Viswanath, KV Olson, L AF Vadaparampil, ST Wideroff, L Freedman, AN Viswanath, KV Olson, L TI Physician exposure to advertisements for genetic tests for inherited cancer susceptibility and clinical care implications SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. NCI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. ABT Associates Inc, Chicago, IL USA. RI Hernandez, Jessica/G-6527-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1936S EP 1936S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100385 ER PT J AU Viswanath, KV AF Viswanath, KV TI Cancer communications and social class. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1951S EP 1951S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100429 ER PT J AU Emmons, K AF Emmons, K TI Smoking cessation among childhood cancer survivors. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Dana Farber Canc Inst, Dept Hlth & Social Behav, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1954S EP 1954S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100439 ER PT J AU Fukuchi, J Hiipakka, RA Kokontis, JM Hsu, S Ko, AL Fitzgerald, ML Liao, ST AF Fukuchi, J Hiipakka, RA Kokontis, JM Hsu, S Ko, AL Fitzgerald, ML Liao, ST TI Androgenic suppression of ATP-binding cassette transporter A1 expression in LNCaP human prostate cancer cells SO CANCER RESEARCH LA English DT Article ID CHOLESTEROL EFFLUX; PROTEIN; PROLIFERATION; DEPRIVATION; PROGRESSION; ACTIVATION; APOPTOSIS; RECEPTOR; DOMAIN; ACID AB Alteration of lipid metabolism is commonly observed in sex hormone-dependent cancer cells, yet its mechanistic involvement in cancer cell proliferation and progression is unclear. We have found that the expression of the cholesterol transporter, ATP-binding cassette transporter A1 (ABCA1), was 15- to 20-fold higher in androgen-dependent than in androgen-independent LNCaP human prostate cancer cells, indicating a possible relationship between the expression levels of ABCA1 and prostate cancer progression. On the basis of real-time quantitative PCR and Western blot analysis, expression of ABCA1 in androgen-dependent cells was inhibited by androgen. The antiandrogen Casodex blocked the effect of androgen, implicating the androgen receptor in regulation of ABCA1 expression by androgens. Using an ABCA1 promoter-reporter gene assay, androgenic suppression was observed at the transcriptional level in androgen-dependent but not in androgen-independent prostate cancer cells. ABCA1 appears to have a role in modulating cell proliferation because knockdown of ABCA1 expression by RNA interference in androgen-dependent cells increased their rate of proliferation. Therefore, a suppressive effect of androgen on ABCA1 expression may be one of the mechanisms by which androgens regulate proliferation in prostate cancer cells. Attenuated ABCA1 expression in androgen-independent cells thus may contribute, in part, to prostate cancer progression. C1 Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Liao, ST (reprint author), Univ Chicago, Ben May Inst Canc Res, MC6027,5841 S Maryland Ave, Chicago, IL 60637 USA. EM sliao@huggins.bsd.uchicago.edu RI Ko, Andrew/C-2077-2012 FU NCCIH NIH HHS [AT00850]; NCI NIH HHS [CA58073, R01 CA058073] NR 20 TC 44 Z9 47 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2004 VL 64 IS 21 BP 7682 EP 7685 DI 10.1158/0008-5472.CAN-04-2647 PG 4 WC Oncology SC Oncology GA 866RM UT WOS:000224790600008 PM 15520169 ER PT J AU Smolen, GA Vassileva, MT Wells, J Matunis, MJ Haber, DA AF Smolen, GA Vassileva, MT Wells, J Matunis, MJ Haber, DA TI SUMO-1 modification of the Wilms' tumor suppressor WT1 SO CANCER RESEARCH LA English DT Article ID SUBNUCLEAR LOCALIZATION; GENE WT1; COVALENT MODIFICATION; MODIFIER-1 SUMO-1; SPLICING FACTOR; PROTEIN SUMO-1; P53 ACTIVITY; C-JUN; NUCLEAR; PML AB SUMO-1 conjugation modulates numerous cellular functions, including the subnuclear localization of its target proteins. The WT1 tumor suppressor encodes a four-zinc ringer protein with distinct splicing isoforms. WT1(-KTS), encoding uninterrupted zinc ringers, functions as a transcription factor and has a diffusely nuclear distribution; WT1(+KTS), with an insertion of three amino acids (KTS) between zinc fingers three and four, localizes to discrete nuclear speckles, the function of which is unknown. Because the SUMO-1 E2-conjugating enzyme, Ubc9, interacts with WT1, we tested whether sumoylation modulates the cellular localization of WT1. We find here that both WT1 isoforms are directly sumoylated on lysine residues 73 and 177. Although RNA interference-mediated Ubc9 depletion effectively suppresses WT1 nuclear speckles, a SUMO-1-deficient WT1(+KTS)(K73,177R) double mutant retains localization to speckles. Thus, direct sumoylation of WT1 is not responsible for its cellular localization, and other sumoylated proteins may target WT1 to these nuclear structures. Identification of other components of WT1-associated speckles is likely to provide clues to their function. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu OI Matunis, Michael/0000-0002-9350-6611 FU NCI NIH HHS [CA58596]; NIGMS NIH HHS [R01 GM060980, R01 GM060980-04, R01 GM60980-01] NR 40 TC 26 Z9 28 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2004 VL 64 IS 21 BP 7846 EP 7851 DI 10.1158/0008-5472.CAN-04-1502 PG 6 WC Oncology SC Oncology GA 866RM UT WOS:000224790600029 PM 15520190 ER PT J AU Yuan, H Liddle, FJ Mahajan, S Frank, DA AF Yuan, H Liddle, FJ Mahajan, S Frank, DA TI IL-6-induced survival of colorectal carcinoma cells is inhibited by butyrate through down-regulation of the IL-6 receptor SO CARCINOGENESIS LA English DT Article ID LARGE-BOWEL CANCER; CHAIN FATTY-ACIDS; DIETARY FIBER; TRANSCRIPTION FACTORS; SIGNAL TRANSDUCER; MULTIPLE-MYELOMA; SODIUM-BUTYRATE; MELANOMA-CELLS; ONCOSTATIN-M; INTERLEUKIN-6 AB Colorectal carcinoma cells are characterized by over-expression of IL-6 and the IL-6 receptor, an autocrine loop that promotes the development of many tumors. To determine the importance of this pathway, we examined the role that IL-6 plays in the biology of 228 and RKO colorectal tumor cells. IL-6 induced prominent tyrosine phosphorylation of the transcription factor STAT1 in both cell types. Furthermore, IL-6 exerts functional effects in these cells in that it inhibited apoptosis induced by Fas ligation, and up-regulated Bcl-xl, a STAT target gene, which can promote cell survival. Butyrate, a compound formed in the intestines of people who consume a high-fiber diet, may confer protection against the development of colorectal cancer. Given the potential importance of IL-6 in the pathogenesis of colorectal tumors, we tested the hypothesis that butyrate acts by inhibiting IL-6-induced signaling events in colorectal carcinoma cells. Following treatment with butyrate, the activation of STAT1 in response to IL-6, but not interferon-gamma, was completely lost. Butyrate induced a prominent decrease of mRNA and cell surface expression of the IL-6 receptor alpha (IL-6Ralpha) chain. Introduction of a soluble form of the IL-6Ralpha chain restored IL-6-induced STAT1 activation and resistance to apoptosis of butyrate treated cells. These experiments indicate that IL-6 may play an important role in the pathogenesis of colorectal cancers, and that butyrate may exert its protective effect by specifically blocking IL-6-induced signaling events. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Frank, DA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu NR 49 TC 16 Z9 17 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2004 VL 25 IS 11 BP 2247 EP 2255 DI 10.1093/carcin/bgh246 PG 9 WC Oncology SC Oncology GA 873AO UT WOS:000225251200028 PM 15284182 ER PT J AU Shankar, S vanSonnenberg, E Silverman, SG Tuncali, K Banks, PA AF Shankar, S vanSonnenberg, E Silverman, SG Tuncali, K Banks, PA TI Imaging and percutaneous management of acute complicated pancreatitis SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review DE acute pancreatitis; pancreatic abscess; pseudocyst; endoscopic ultrasound; endoscopic retrograde cholangiopancreatography; CT; interventional radiology ID ACUTE NECROTIZING PANCREATITIS; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; PERIPANCREATIC FLUID COLLECTIONS; ENHANCED COMPUTED-TOMOGRAPHY; INTRAVENOUS CONTRAST-MEDIUM; MR CHOLANGIOPANCREATOGRAPHY; INTERVENTIONAL RADIOLOGY; PARENTERAL-NUTRITION; CATHETER DRAINAGE; BILIARY PANCREATITIS AB Acute pancreatitis varies from a mild, self-limited disease to one With significant morbidity and mortality in its most severe forms. While clinical criteria abound, imaging has become indispensable to diagnose the extent of the disease and its complications. as well as to guide and monitor therapy. Percutaneous interventional techniques offer options that can be life-saving, surgery-sparing or important adjuncts to operation. Close cooperation and communication between the surgeon, gastroenterologist and interventional radiologist enhance the likelihood of successful patient care. C1 Univ Massachusetts, Med Hlth Ctr, Dept Radiol, Worcester, MA 01655 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Shankar, S (reprint author), Univ Massachusetts, Med Hlth Ctr, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. NR 137 TC 29 Z9 32 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD NOV-DEC PY 2004 VL 27 IS 6 BP 567 EP 580 DI 10.1007/s00270-004-0037-1 PG 14 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 872PB UT WOS:000225218600001 PM 15578132 ER PT J AU Mori, M Burgess, DL Gefrides, LA Foreman, PJ Opferman, JT Korsmeyer, SJ Cavalheiro, EA Naffah-Mazzacoratti, MG Noebels, JL AF Mori, M Burgess, DL Gefrides, LA Foreman, PJ Opferman, JT Korsmeyer, SJ Cavalheiro, EA Naffah-Mazzacoratti, MG Noebels, JL TI Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Mcl1; neuronal cell death; seizure; hippocampus; genetics; modifier genes; neuroprotection ID PROGRAMMED CELL-DEATH; HUMAN MYELOMA CELLS; BCL-2 FAMILY-MEMBER; IMMUNOHISTOCHEMICAL ANALYSIS; NERVOUS-SYSTEM; PHOSPHATIDYLINOSITOL 3-KINASE; HIPPOCAMPAL-NEURONS; STATUS EPILEPTICUS; RAT HIPPOCAMPUS; GENE FAMILY AB Mcl1 is a Bcl2-related antiapoptotic protein originally isolated from human myeloid leukemia cells. Unlike Bcl2, expression has not been reported in CNS neurons. We isolated Mcl1 in a direct screen for candidate modifier genes of neuronal vulnerability by differential display of mRNAs upregulated following prolonged seizures in two mouse strains with contrasting levels of hippocampal cell death. Mcl1 is widely expressed in neurons, and transcription is rapidly induced in both strains. In resistant C57Bl/6J mice, Mcl1 protein levels remain persistently elevated in hippocampal pyramidal neurons after seizures, but fall rapidly in C3H/HeJ hippocampus, coinciding with extensive neuronal apoptosis. DNA damage and caspase-mediated cell death were strikingly increased in Mcl1-deficient mice when compared to +/+ littermates after similar seizures. We identify Mcl1 as a neuronal gene responsive to excitotoxic insult in the brain, and link relative levels of Mcl1 expression to inherited differences in neuronal thresholds for apoptosis. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Univ Fed Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil. RP Noebels, JL (reprint author), Baylor Coll Med, Dept Neurol, 1 Baylor Plaza, Houston, TX 77030 USA. EM jnoebels@bcm.tmc.edu OI Noebels, Jeffrey /0000-0002-2887-0839 NR 56 TC 28 Z9 28 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD NOV PY 2004 VL 11 IS 11 BP 1223 EP 1233 DI 10.1038/sj.cdd.4401483 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 862BX UT WOS:000224465700009 PM 15286683 ER PT J AU Hersh, CP DeMeo, DL Al-Ansari, E Carey, VJ Reilly, JJ Ginns, LC Silverman, EK AF Hersh, CP DeMeo, DL Al-Ansari, E Carey, VJ Reilly, JJ Ginns, LC Silverman, EK TI Predictors of survival in severe, early onset COPD SO CHEST LA English DT Article DE COPD; pulmonary emphysema; smoldng; survival analysis ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; WIDE LINKAGE ANALYSIS; CHRONIC-BRONCHITIS; BRONCHODILATOR RESPONSIVENESS; SPIROMETRIC PHENOTYPES; LUNG TRANSPLANTATION; OXYGEN-THERAPY; MORTALITY; PROGNOSIS AB Study objectives: Multiple risk factors for mortality in patients with COPD have been described, but most studies have involved older, primarily male subjects. The purpose of this study was to determine the mortality rate and predictors of survival in subjects with severe, early onset COPD. Design, setting, and participants: The cohort of 139 probands in the Boston Early-Onset COPD Study was recruited from lung transplant and general pulmonary clinics between September 1994 and July 2002. Subjects were < 53 years old, had an FEV1 of < 40% of predicted, did not have severe alpha(1)-antitrypsin deficiency, and had not undergone lung transplantation. The initial evaluation included a standardized respiratory questionnaire, spirometry, and a blood sample. A follow-up telephone interview was conducted between May and December 2002. Measurements and results: Subjects were young (mean age at enrollment, 47.9 years) and had severe airflow obstruction (mean baseline FEV1, 19.4% predicted). A total of 72.7% of the subjects were women (p < 0.0001 [comparison to equal gender distribution]). The median estimated survival time was 7.0 years from the time of study enrollment, determined by the Kaplan-Meier method. The majority of deaths were due to cardiorespiratory illness. In a multivariable Cox proportional hazards model, adjusting for age, gender, and baseline FEV1, lifetime cigarette consumption (hazard ratio [HR], 1.20 [per 10 pack-years]; 95% confidence interval [CI], 1.02 to 1.40) and recent smoking status (HR, 2.50; 95% CI, 1.03 to 6.05) were both significant predictors of mortality. Conclusion: In this cohort, recent smoking status predicted increased mortality independent of the effects of lifetime smoking intensity. Smoking cessation may confer a survival benefit even among patients,with very severe COPD. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Silverman, EK (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ed.silverman@channing.harvard.edu FU NHLBI NIH HHS [T32-HL07427, HL61575] NR 41 TC 39 Z9 40 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2004 VL 126 IS 5 BP 1443 EP 1451 DI 10.1378/chest.126.5.1443 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 872NU UT WOS:000225214700015 PM 15539711 ER PT J AU Gadjeva, M Paludan, SR Thiel, S Slavov, V Ruseva, M Eriksson, K Lowhagen, GB Shi, L Takahashi, K Ezekowitz, A Jensenius, JC AF Gadjeva, M Paludan, SR Thiel, S Slavov, V Ruseva, M Eriksson, K Lowhagen, GB Shi, L Takahashi, K Ezekowitz, A Jensenius, JC TI Mannan-binding lectin modulates the response to HSV-2 infection SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE complement; HSV-2; double knock-out mice; mannan-binding lectin; MBL ID HERPES-SIMPLEX-VIRUS; INFLUENZA-A VIRUSES; COMPLEMENT ACTIVATION; SERINE-PROTEASE; T-CELLS; STAPHYLOCOCCUS-AUREUS; TYPE-2 INFECTION; GENITAL HERPES; MICE; HEPATITIS AB Viruses have developed numerous strategies to escape recognition by the immune system. However, some viruses such as herpes simplex virus-2 (HSV-2) are recognized by initiators of the complement system, e.g. mannan-binding lectin (MBL). To study the effects of MBL deficiency during viral infection we have chosen a model of generalized HSV-2 infection. We infected MBL-A and MBL-C double knock-out mice (DKO) with HSV-2 via the intraperitoneal (i.p.) route. DKO mice cleared HSV-2 from the liver less efficiently than the comparable wild-type animals. The impairment to effectively neutralize HSV-2 correlated with compromised liver function as measured by increased plasma levels of alanine-amino transferase. No differences in the viral burden were found in other organs such as spleen or brain. Thus, MBL-mediated protection was limited to the effects of preservation of liver homeostasis. Reconstitution with recombinant human MBL before and during the HSV-2 infection dramatically lowered the viral titres in the liver. Taken together, the data show that MBL modulates the response to HSV-2 in mice by affecting neutralization of the virus. To analyse if MBL plays a role in establishment and progression of human HSV-2 infection we analysed MBL levels in the serum samples from asymptomatic (virus-exposed people who have never displayed symptoms of HSV-2 infection) and symptomatic HSV-2 patients (people with recurrent HSV-2 infections). We found that the frequency of the MBL deficiency (<100 ng/ml) was higher in the symptomatic group and significantly different from that in the asymptomatic group (P = 0.0369). This suggests that lack of MBL-mediated complement activation increases susceptibility to viral infection. C1 Aarhus Univ, Dept Med Microbiol & Immunol, DK-8000 Aarhus, Denmark. Univ Gothenburg, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden. Univ Gothenburg, Dept Dermatovenereol, Gothenburg, Sweden. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA USA. RP Gadjeva, M (reprint author), Aarhus Univ, Dept Med Microbiol & Immunol, Bartholin Bldg, DK-8000 Aarhus, Denmark. EM mg@immunology.au.dk NR 43 TC 54 Z9 55 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2004 VL 138 IS 2 BP 304 EP 311 DI 10.1111/j.1365-2249.2004.02616.x PG 8 WC Immunology SC Immunology GA 863VY UT WOS:000224592700016 PM 15498041 ER PT J AU Tien, PC Kovacs, A Bacchetti, P French, AL Augenbraun, M Cole, SR Hessol, N Justman, J AF Tien, PC Kovacs, A Bacchetti, P French, AL Augenbraun, M Cole, SR Hessol, N Justman, J TI Association between syphilis, antibodies to herpes simplex virus type 2, and recreational drug use and hepatitis B virus infection in the women's interagency HIV study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CORE ANTIGEN; HETEROSEXUAL TRANSMISSION; LIVER-DISEASE; UNITED-STATES; PREVALENCE; INDIVIDUALS; MORTALITY; IMPACT; RISK AB Background. Liver disease is a leading cause of death in human immunodeficiency virus (HIV)-infected women; however, risk factors for hepatitis B virus (HBV) infection in this population have not been well studied. Methods. We describe the seroprevalence and predictors of HBV infection in a cross-sectional analysis of 2132 women with and at risk for HIV infection enrolled in the Women's Interagency HIV Study during the periods 1994-95 and 2001-02. Any test result positive for antibody to hepatitis B core antigen defined infection; those women with serological evidence of vaccine immunity were excluded from analysis. Women were stratified into those with a history of injection drug use (IDU), those with a history of noninjection drug use (non- IDU), and those with no history of illicit drug use. Results. Of 1606 HIV-infected and 526 HIV-uninfected women, 7% and 12%, respectively, appeared to be vaccine immune. After exclusion of these women, 43% of 1500 HIV-infected and 22% of 461 HIV-uninfected women had HBV infection. HBV infection prevalence differed among the IDU, non- IDU, and no illicit drug use groups (76%, 30%, and 17%, respectively;). HBV infection was strongly associated with herpes simplex virus 2 (HSV-2) seropositivity in the IDU group (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.6-5.4) and with a history of syphilis in the non-IDU group (OR, 2.7; 95% CI, 1.4-5.0). Discussion. We found a high prevalence of HBV infection in our cohort of women with and at risk for HIV infection. HSV-2 seropositivity and a history of syphilis appeared to be important correlates of HBV infection. Sexual transmission of HBV, particularly in those with a history of genital ulcer disease, should be a major focus of education in all high-risk groups. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ So Calif, San Francisco Vet Affairs Med Ctr, Los Angeles, CA USA. Univ So Calif, Dept Med, Los Angeles, CA USA. Cook Cty Hosp, Rush Med Coll, CORE Ctr, Chicago, IL 60612 USA. Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. Bronx Lebanon Hosp Ctr, Bronx, NY 10456 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA. RP Tien, PC (reprint author), VAMC, Metab Sect, 111F,4150 Clement St, San Francisco, CA 94121 USA. EM ptien@medicine.ucsf.edu FU NIAID NIH HHS [U01 AI035004, AI-34989, R01 AI052065, R01 AI052065-01, U01 AI031834, U01 AI034989, U01 AI034993, U01 AI034994, U01 AI042590, U01-AI-31834, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590]; NICHD NIH HHS [U01 HD032632, U01-HD-32632] NR 24 TC 9 Z9 11 U1 1 U2 1 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 NOV 1 PY 2004 VL 39 IS 9 BP 1363 EP 1370 DI 10.1086/424879 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JG UT WOS:000227491800013 PM 15494914 ER PT J AU Muratoglu, OK Burroughs, BR Bragdon, CR Christensen, S Lozynsky, A Harris, WH AF Muratoglu, OK Burroughs, BR Bragdon, CR Christensen, S Lozynsky, A Harris, WH TI Knee simulator wear of polyethylene tibias articulating against explanted rough femoral components SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Joint Annual Meeting of the Knee-Society/Association-of-Hip-and-Knee-Surgeons CY 2004 CL New Orleans, LA SP Knee Soc, Assoc Hip & Knee Surg ID CROSS-LINKED POLYETHYLENE; INSERTS AB Highly cross-linked and melted polyethylene tibial inserts have recently been introduced for clinical use to reduce fatigue damage and adhesive wear in tibial inserts. Other authors have studied the effect of counterface roughness on the wear behavior of polyethylene tibial inserts in knee simulators using femoral components that were roughened artificially. They reported a higher wear rate with highly crosslinked polyethylene than with unirradiated polyethylene tibial inserts. Artificial roughening of femoral components may not be clinically relevant. To evaluate this concern, we studied the wear behavior of highly cross-linked and conventional polyethylene tibial inserts articulating in vitro against surgically retrieved femoral components that had become roughened in vivo. The wear rate of the highly cross-linked polyethylene (5.9 and 6.8 mg/1 million cycles with 100 and 50% serum) was 80% lower than the wear rate of the conventional polyethylene (33.5 and 32.2 mg/1 million cycles with 100 and 50% serum) tibial inserts after 2 million cycles of simulated gait. This study suggests that during in vivo use, scratches that are generated on the femoral components are likely to produce a higher wear rate with both cross-linked and conventional polyethylene than a smooth femoral component, but that this wear rate is likely to be higher with conventional polyethylene than with highly cross-linked polyethylene tibial inserts. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson 1206,55 Fruit St, Boston, MA 02114 USA. EM orhun@alum.mit.edu NR 13 TC 29 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2004 IS 428 BP 108 EP 113 DI 10.1097/01.blo.0000143801.41885.8b PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 870JV UT WOS:000225054300018 PM 15534529 ER PT J AU Temple, RO Horner, MD Taylor, RM AF Temple, RO Horner, MD Taylor, RM TI Relationship of MMPI-2 anxiety and defensiveness to neuropsychological test performance and psychotropic medication use SO COGNITION & EMOTION LA English DT Article ID ATTENTIONAL BIAS; TRAIT ANXIETY; RESPONSE SET; THREAT; MEMORY; INFORMATION; STRESS AB Research has suggested an adverse effect of anxiety on cognitive functioning, and high defensive individuals may have poorer control of their anxiety than low defensive individuals. Thus, these individuals may be more likely to have a prescription for psychotropic medication. The purpose of this study was to further delineate the effects of anxiety and defensiveness on neuropsychological test performance and psychotropic medication use. Participants were 143 US veterans referred for neuropsychological evaluation. Four groups were established based on median splits on MMPI-2 approximations of anxiety and defensiveness. Anxiety and defensiveness were unrelated to neuropsychological test performance. Defensive high anxious individuals were more likely than truly high anxious individuals to have anxiolytic and narcotic prescriptions. There was also a trend toward truly low anxious participants being more likely to be prescribed anxiolytics than repressor participants. Thus, defensiveness appears to attenuate the experience of anxiety in individuals who are low, but not high, in self-reported anxiety. C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Temple, RO (reprint author), Brown Med Sch, Phys Off Bldg,Suite 430,593 Eddy St, Providence, RI 02903 USA. EM rtemple@lifespan.org NR 27 TC 2 Z9 2 U1 2 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PD NOV PY 2004 VL 18 IS 7 BP 989 EP 998 DI 10.1080/02699930341000012 PG 10 WC Psychology, Experimental SC Psychology GA 861SA UT WOS:000224437700007 ER PT J AU Havrlikova, K Mellott, M Kaufman, AH Loredo, GA Peters, JH Colvin, RB Foster, CS AF Havrlikova, K Mellott, M Kaufman, AH Loredo, GA Peters, JH Colvin, RB Foster, CS TI Expression of fibronectin isoforms bearing the alternatively spliced EIIIA, EIIIB, and V segments in cornea alkali burn and keratectomy wound models in the rat SO CORNEA LA English DT Article DE fibronectin; keratectomy; alkali burn ID RABBIT CORNEA; CELLULAR PROLIFERATION; TOPICAL FIBRONECTIN; EDA SEGMENT; TENASCIN; INTEGRIN; ULCERATION; MIGRATION; ADHESION; PEPTIDE AB Purpose: To better understand the healing process in the Wounded cornea, fibronectin (FN) isoforms bearing the alternatively spliced EIIIA, EIIIB, and V segments (EIIIA(+), EIIIB(+), and V(+) FNs) were evaluated in alkali burn and keratectomy wound models in the rat. Methods: Alkali burn or keratectomy wounds (both 2 mm) were created, and corneas were harvested at various time points and analyzed by indirect immunofluorescence using antibodies specific for the EIIIA, EIIIB, and V segments as well as for the total pool of FN (total FN). Results: There was minimal staining for any variety of FN in the epithelium or basement membrane zone (BMZ) in normal cornea, but each antibody produced granular staining in the stroma. Bright staining for V(+) and total FNs was evident at the denuded stromal surface I day following keratectomy. In contrast, staining for EIIIA(+) and EIIIB(+) FNs was negligible at 24 hours but appeared on the wound surface under the migrating unstained epithelium by the second day. BMZ staining for FN then gradually subsided, such that there was little or no staining by 6 weeks. In contrast, alkali burn wounds exhibited very little BMZ staining throughout the time course. Although there was preferential staining of the anterior aspect of Descemet membrane by anti-EIIIA and anti-EIIIB antibodies under normal conditions. the staining intensity of the anterior and posterior aspects became similar following corneal wounding. Conclusion: Deposition of EIIIA(+) and EIIIB(+) FNs in the BMZ of the keratectomy wound occurs more slowly than deposition of V(+) and total FNs. EIIIA(+) FN is expressed in a distribution that overlaps with that previously described for the alpha9 integrin subunit following corneal debridement, suggesting that EIIIA-alpha9 interactions could occur during corneal wound healing. In contrast, the relative lack of FN deposition in alkali burn wounds suggests that proteolytic degradation of FN may occur; and this, along with impairment of new FN synthesis because of cellular damage, could play a role in the high prevalence of recurrent epithelial erosions in alkali-wounded corneas. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Hilles Immunol Lab,Dept Ophthalmol, Boston, MA 02115 USA. Univ Cincinnati, Ctr Med, Cincinnati, OH 45221 USA. Univ Calif Davis, Dept Med, Sch Med, Sacramento, CA 95817 USA. Sacramento VA Med Ctr, VA No Calif Hlth Care Syst, Mather, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Unite Immunopathol, Boston, MA 02115 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org FU NCI NIH HHS [R01CA208822] NR 35 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 2004 VL 23 IS 8 BP 812 EP 818 DI 10.1097/01.ico.0000133988.34274.24 PG 7 WC Ophthalmology SC Ophthalmology GA 867YU UT WOS:000224879800010 PM 15502483 ER PT J AU Iaccheri, B Roque, M Fiore, T Papadaki, T Mathew, B Baltatzis, S Emara, B Tokarewicz, AC Foster, CS AF Iaccheri, B Roque, M Fiore, T Papadaki, T Mathew, B Baltatzis, S Emara, B Tokarewicz, AC Foster, CS TI Ocular cicatricial pemphigoid, keratomycosis, and intravenous immunoglobulin therapy SO CORNEA LA English DT Article DE ocular cicatricial pemphigoid; keratomycosis; keratoprosthesis; intravenous immunoglobulin ID MYCOTIC KERATITIS; IMMUNOSUPPRESSIVE THERAPY; KERATOPROSTHESIS AB Purpose: To report the case of a patient developing fungal keratitis in the context of uncontrolled ocular cicatricial pemphigoid (OCP), which. despite intravenous immunoglobulin (IVIg) and other immunomodulatory therapy, progressed to end-stage pemphigoid, with corneal opacification, ankyloblepharon, and xerosis. Keratoprosthesis (KPro) restored functional vision for the patient. Methods: A 39-year-old man presented with uncontrolled CP and corneal ulcer in the left eye. Conjunctival biopsy diagnosed OCP; corneal scraping and biopsy diagnosed the cause of the corneal ulcer. OCP was treated with systemic steroids, immunosuppressive drugs, and IVIg. Visual rehabilitation was accomplished with Ahmed valve and a type II Dohlman KPro. Results: Immunohistology of the biopsied conjunctiva showed IgG at the epithelial basement membrane zone, confirming the clinical diagnosis of OCP. Microbiologic studies of the corneal biopsy specimen were negative for Acanthamoeba and herpes but positive for Aspergillus niger. The patient's keratomycosis resolved with topical antifungal therapy. Treatment with Dapsone, intravenous-pulse steroid, oral cyclophosphamide, and intravenous immunoglobulin (IVIg) failed to control the OCP, with resultant complete conjunctivization of the cornea. Keratoprosthesis improved the patient's visual acuity from hand movements to 20/20. Conclusions: Patients with uncontrolled OCP are at increased risk of corneal infection. The difficulty in diagnosing keratomycosis and the relatively rare occurrence of OCP explain the uniqueness of our reported case. OCP may progress to "end-stage" disease despite therapy. Keratoprosthesis can restore vision in selected otherwise seemingly hopeless cases. C1 Harvard Univ, Ocular Immunol & Uveitis Serv, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Univ Ottawa, Inst Eye, Ottawa, ON, Canada. Univ Western Ontario, Ivey Inst Ophthalmol, London, ON, Canada. RP Foster, CS (reprint author), Harvard Univ, Ocular Immunol & Uveitis Serv, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org NR 17 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 2004 VL 23 IS 8 BP 819 EP 822 DI 10.1097/01.ico.0000127483.08466.56 PG 4 WC Ophthalmology SC Ophthalmology GA 867YU UT WOS:000224879800011 PM 15502484 ER PT J AU Scott, JA Aziz, K Yasuda, T Gewirtz, H AF Scott, JA Aziz, K Yasuda, T Gewirtz, H TI Integration of clinical and imaging data to predict the presence of coronary artery disease with the use of neural networks SO CORONARY ARTERY DISEASE LA English DT Article DE neural network; myocardial perfusion imaging; coronary artery disease; radionuclide stress testing ID CARDIAC NORMALITY; SPECT; VALIDATION; TRIAL AB Aim To establish proof of the principle that a computer-based neural network method can be employed that will enhance diagnostic accuracy vis-a-vis image analysis alone in the interpretation of treadmill exercise tests performed in conjunction with myocardial perfusion imaging. Materials and methods One-hundred-and-two patients underwent myocardial perfusion imaging in association with the standard Bruce protocol. Twenty objective parameters describing each patient's exercise physiology, general clinical status and image appearance were used to train an artificial neural network. Classification accuracy of the neural network and clinical interpretation was determined by coronary angiography. We evaluated the ability of the neural network to integrate clinical, exercise and imaging data to determine the likelihood of coronary artery disease and compared these results with an optimized method of clinical image interpretation, which made use of all available clinical, angiographic and stress test data. Results The artificial neural network had a sensitivity of 88% and a specificity of 65% for detection of ischemic heart disease and was comparable to that of the optimized clinical method (sensitivity 80%, specificity 69%). Incorporation of clinical and exercise data significantly improved the predictive accuracy of the network compared to a network based on image data alone (P<0.05). Conclusion The results show a computer-based neural network can perform as well as expert readers working under optimal conditions including full knowledge of the patient's clinical, prior angiographic and stress test data. Thus, the method is promising as a diagnostic aid to the recognition of ischemic heart disease in the clinical setting of treadmill exercise testing in conjunction with myocardial perfusion imaging. (C) 2004 Lippincott Williams Wilkins. C1 Massachusetts Gen Hosp, Cardiac Unit, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gewirtz, H (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM hgewirtz@partners.org NR 21 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD NOV PY 2004 VL 15 IS 7 BP 427 EP 434 DI 10.1097/00019501-200411000-00010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 869IF UT WOS:000224975900010 PM 15492592 ER PT J AU Sheibani, N Grabowski, EF Schoenfeld, DA Whalen, MJ AF Sheibani, N Grabowski, EF Schoenfeld, DA Whalen, MJ TI Effect of granulocyte colony-stimulating factor on functional and histoplathologic outcome after traumatic brain injury in mice SO CRITICAL CARE MEDICINE LA English DT Article DE brain injury; mice; granulocyte colony-stimulating factor; inflammation; Morris water maze; growth factors ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; ACUTE INFLAMMATORY RESPONSE; SEVERE HEAD-INJURIES; CEREBRAL BLOOD-FLOW; BARRIER PERMEABILITY; MILD HYPOTHERMIA; ERYTHROPOIETIN; RATS; ISCHEMIA; INFECTIONS AB Objective: Granulocyte colony-stimulating factor has been used to reduce the risk of sepsis in patients with traumatic brain injury. However, granulocyte colony-stimulating factor exerts potent pro- and anti-inflammatory effects that could influence secondary injury, and outcome, after traumatic brain injury. Our objective was to determine the effect of granulocyte colony-stimulating factor on histopathologic, motor, and cognitive Design: Experimental study. Setting: Research laboratory at the Massachusetts General Hospital, Boston, MA. Subjects: Forty-eight adult male C57BI/6 mice. Interventions: Mice (8 wks of age, n = 16/group) were administered granulocyte colony-stimulating factor or saline subcutaneously twice per day for 7 days after controlled cortical impact or sham injury (n = 16). Absolute neutrophil counts, motor function, Morris water maze performance, and lesion volume were determined after controlled cortical impact or sham injury. Measurements and Main Results: At the time of controlled cortical impact, body weight, brain and body temperature, and systemic absolute neutrophil counts did not differ between groups. Compared with control, systemic absolute neutrophil count was increased more than ten-fold in granulocyte colony-stimulating factor-treated mice on posttrauma days 2 and 7 (p < .05, repeated-measures analysis of variance) but did not differ between groups by day 14. There. were no differences between groups in tests of motor function or histopathologic outcome. However, compared with control, mice given granulocyte colony-stimulating factor had improved Morris water maze performance after controlled cortical impact (p < .05, repeated-measures analysis of variance) but not sham injury. Conclusions: The data suggest a small beneficial effect of granulocyte colony-stimulating factor on functional outcome after traumatic brain injury in adult mice but do not show differences in histopathology or motor outcome between treated and control groups. C1 Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Epidemiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sheibani, N (reprint author), Massachusetts Gen Hosp, 149 13th St Room 6403, Charlestown, MA 02129 USA. FU NINDS NIH HHS [5K08NS41969] NR 37 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2004 VL 32 IS 11 BP 2274 EP 2278 DI 10.1097/01.CCM.0000145998.11686.ED PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 872MN UT WOS:000225211400014 PM 15640641 ER PT J AU Martin, TR AF Martin, TR TI Direct lung injury by bacteria: Clarifying the tools of the trade SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID ACUTE RESPIRATORY-DISTRESS; EPITHELIAL INJURY; VASCULAR LEAKAGE; TIDAL VOLUMES; RABBIT LUNGS; ENDOTOXIN; VENTILATION; EXPRESSION; PNEUMONIA; RESPONSES C1 Univ Washington, Dept Med, Div Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst,Med Res Serv, Seattle, WA USA. RP Martin, TR (reprint author), Univ Washington, Dept Med, Div Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst,Med Res Serv, Seattle, WA USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2004 VL 32 IS 11 BP 2360 EP 2361 DI 10.1097/01.CCM.0000146135.19642.72 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 872MN UT WOS:000225211400037 PM 15640664 ER PT J AU Cavendish, JJ Fugit, RV Safani, M AF Cavendish, JJ Fugit, RV Safani, M TI Role of antiplatelet therapy in cardiovascular disease I: acute coronary syndromes SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE acute coronary syndromes; antiplatelet; atherothrombosis; myocardial infarction; unstable angina ID PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; AMERICAN-COLLEGE; INTERVENTION; CLOPIDOGREL; MANAGEMENT; ASPIRIN; UPDATE AB The acute coronary syndromes (ACS), consisting of ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina, remain a leading cause of death in the United States. Through the process of atherothrombosis, underlying atherosclerosis can progress to an acute ischemic coronary event. This disease mechanism is also common to ischemic stroke and peripheral arterial disease. As ACS is a heterogeneous disease, accurate patient diagnosis and risk categorization is essential. Treatment approaches for both STEMI and NSTEMI ACS consist of a combination of surgical intervention and pharmacotherapy, with antiplatelet agents such as clopidogrel, aspirin and glycoprotein IIb/IIIa receptor antagonists playing an essential role. C1 USN, Ctr Med, Dept Cardiol, San Diego, CA 92134 USA. Denver Vet Affairs Med Ctr, Dept Pharm, Denver, CO USA. Univ Calif San Francisco, Long Beach Mem Med Ctr, CA & Volunteer Fac, Redondo Beach, CA USA. RP Cavendish, JJ (reprint author), USN, Ctr Med, Dept Cardiol, Bldg 3,3rd Floor,34800 Bob Wilson Dr, San Diego, CA 92134 USA. EM JJCavendish@nmcsd.med.navy.mil NR 12 TC 6 Z9 7 U1 0 U2 1 PU LIBRAPHARM PI NEWBURY PA C/O DR. PETER L CLARKE, 26-32 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD NOV PY 2004 VL 20 IS 11 BP 1839 EP 1843 DI 10.1185/030079904X10665 PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 876HX UT WOS:000225488600018 PM 15537484 ER PT J AU Fernando, D Garasic, J AF Fernando, D Garasic, J TI Percutaneous intervention for renovascular disease: rationale and patient selection SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE renovascular disease; magnetic resonance angiography; renal artery stenosis ID RENAL-ARTERY STENOSIS; SURGICAL REVASCULARIZATION; ANGIOPLASTY; HYPERTENSION; FAILURE; PROGRESSION; RECURRENT; RISK AB Purpose of review The anatomic diagnosis of renovascular disease is increasing in frequency due to the advent of sophisticated non-invasive imaging modalities such as MRA (Magnetic Resonance Angiography) and renal angiography at the time of cardiac catheterization. Despite this fact, the investigation and appropriate management of renovascular disease has remained a controversial topic. This review addresses the clinical syndromes associated with renal artery stenosis (RAS) and the published data guiding appropriate patient selection for revascularization. Recent findings There is a growing literature in support of renal revascularization as an aid in improving anti-hypertensive control, preserving renal function, and easing the management of congestive heart failure. Meanwhile, technological advances have allowed intervention in an expanding pool of eligible patients. One such technology is the atheroembolic protection device, which may soon allow renal salvage in patients with significant baseline renal impairment that were previously denied intervention for fear of worsening renal function. Summary The data reviewed herein helps to identify patients that will benefit from renal revascularization. Large-scale, randomized data further defining the role of renal revascularization and optimal patient selection is still needed. C1 Massachusetts Gen Hosp, Cardiac Unit, Div Cardiol, Boston, MA 02114 USA. RP Garasic, J (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Div Cardiol, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM jgarasic@partners.org NR 29 TC 8 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2004 VL 19 IS 6 BP 582 EP 588 DI 10.1097/01.hco.0000143392.80705.a2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 871HQ UT WOS:000225121500007 PM 15502502 ER PT J AU Kaunitz, JD Akiba, Y AF Kaunitz, JD Akiba, Y TI Gastroduodenal mucosal defense: role of endogenous mediators SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE stomach; duodenum; injury; Helicobacter pylori; nonsteroidal anti-inflammatory drugs; proteinase-activated receptors; prostaglandin; nitric oxide ID PROTEASE-ACTIVATED RECEPTOR-1; SENSITIVE SENSORY NEURONS; GASTRIC EPITHELIAL-CELLS; NO-RELEASING ASPIRIN; GENE-RELATED PEPTIDE; HELICOBACTER-PYLORI; DUODENAL-ULCER; GROWTH-FACTOR; VANILLOID RECEPTORS; RAT STOMACH AB Purpose of review The remarkable resistance of the mucosal lining of the upper gastrointestinal tract to concentrated gastric acid remains one of the biggest unsolved mysteries of upper gastrointestinal physiology. In the past year, there have been prominent findings regarding prostaglandin subtypes, growth factors, proteinase-activated receptors, peroxisome proliferator-activated receptors, and nitric oxide releasing nonsteroidal antiinflammatory agents. Recent findings The prostaglandin I receptor subtype is involved with the mucosal acid-sensing neural circuit termed the capsaicin pathway. Proteinase-activated receptors and peroxisome proliferator activated receptor-gamma are important components of host defense against acid injury. Nitric oxide releasing nonsteroidal antiinflammatory agents have potential usefulness in subjects with mucosal injury related to the use of nonsteroidal antiinflammatory agents and may be an important alternative to selective cyclooxygenase-2 inhibitors for patients who need aspirin cotherapy for the prevention of arterial thrombus formation. Summary Peptic ulcer disease, although declining in prevalence, appears to be increasing in virulence, perhaps because of the overall aging of the population and improved care in the intensive care unit. Although Helicobacter pylori and nonsteroidal antiinflammatory agents have been identified as key pro-ulcerogenic factors, many ulcers may also result from a deficiency of other, unknown host protective factors. A more detailed understanding of the host factors involved in mucosal protection will thus help identify novel therapeutic targets aimed at the prevention and treatment of upper gastrointestinal tract mucosal injury. C1 WLAVA Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Div Digest Dis, CURE,David Geffen Sch Med, Ctr Digest Dis,Dept Med, Los Angeles, CA USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), Bldg 114,Suite 217 W Los Angeles VAMC, Los Angeles, CA 90073 USA. EM jake@ucla.edu NR 53 TC 10 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2004 VL 20 IS 6 BP 526 EP 532 DI 10.1097/00001574-200411000-00004 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 866OY UT WOS:000224784000003 PM 15703677 ER PT J AU Kilbourne, AM Pincus, HA AF Kilbourne, AM Pincus, HA TI Improving quality of care for bipolar disorder SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE quality of care; mood disorders; bipolar; guidelines ID STAFF-MODEL HMO; BIOLOGICAL TREATMENT; BRITISH-ASSOCIATION; WFSBP GUIDELINES; ACUTE MANIA; I DISORDER; PART II; COSTS; LIFE; OLANZAPINE AB Purpose of review Bipolar disorder is a chronic illness associated with significant functional impairment and health care costs. Despite the existence of clinical guidelines, outcomes for this disease remain sub-optimal. We reviewed the relevant literature concerning current efforts to improve the quality of care for bipolar disorder, highlighting advances in quality measures, practice guidelines, care improvement strategies, and other emerging trends in this field. We evaluated the recent developments in the diagnosis and treatment of bipolar disorder. Recent findings Several emerging areas of research were evident from this recent literature review, encompassing issues including detection and diagnosis (e.g. bipolar II, use of secondary data), estimating costs and burden of bipolar disorder (including lost work productivity), treatment guideline updates, the need to develop strategies for implementing guidelines, and measuring quality. Summary Additional evidence is needed to clarify the criteria for diagnosing bipolar II disorder. More research is needed to clarify guidelines regarding the treatment of specific episodes, notably bipolar depression, and to compare the different guidelines. Given the adverse impact of bipolar disorder on lost work productivity, guidelines should also cover important followup care as well as recommend best practices in social services (e.g. vocational training). Finally, system-level interventions that promote continuity of care, provider decision support, and quality measurement are needed to implement practice guidelines and subsequently improve care. C1 Univ Pittsburgh, VA Pittsburgh Ctr Hlth Equ Res & Promot, Dept Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, VA Pittsburgh Ctr Hlth Equ Res & Promot, Dept Psychiat, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, RAND, Hlth Inst, Pittsburgh, PA USA. RP Kilbourne, AM (reprint author), Univ Pittsburgh, VA Pittsburgh Ctr Hlth Equ Res & Promot, Dept Med, VA Pittsburgh Healthcare Syst, Univ Dr C, Pittsburgh, PA 15240 USA. EM Amy.Kilbourne@med.va.gov NR 34 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD NOV PY 2004 VL 17 IS 6 BP 513 EP 517 DI 10.1097/00001504-200411000-00016 PG 5 WC Psychiatry SC Psychiatry GA 870TS UT WOS:000225081800015 ER PT J AU Khachennoune, A Yalamanchili, R Rodriguez, C AF Khachennoune, A Yalamanchili, R Rodriguez, C TI Bazex syndrome (Paraneoplastic acrokeratosis) SO CUTIS LA English DT Article AB Bazex syndrome (paraneoplastic acrokeratosis) is characterized by the presence of hyperkeratotic lesions on the nose, ears, palms, and soles that appear in association with malignancies of the upper aerodigestive tract, most often a squamous cell carcinoma. We present a case of Bazex syndrome and provide a review of the literature. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Austin Med Educ Program, Austin, TX USA. Univ Illinois, Coll Med, Chicago, IL USA. RP Khachennoune, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. EM amorkh@pol.net NR 15 TC 3 Z9 3 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI CHATHAM PA 26 MAIN ST, STE A, CHATHAM, NJ 07928-2402 USA SN 0011-4162 J9 CUTIS JI Cutis PD NOV PY 2004 VL 74 IS 5 BP 289 EP 292 PG 4 WC Dermatology SC Dermatology GA 872YD UT WOS:000225244500003 PM 15605965 ER PT J AU Dai, J Li, J Bos, E Porcionatto, M Premont, RT Bourgoin, S Peters, PJ Hsu, VW AF Dai, J Li, J Bos, E Porcionatto, M Premont, RT Bourgoin, S Peters, PJ Hsu, VW TI ACAP1 promotes endocytic recycling - Short article by recognizing recycling sorting signals SO DEVELOPMENTAL CELL LA English DT Article ID GTPASE-ACTIVATING PROTEINS; HUMAN TRANSFERRIN RECEPTOR; ARF6; INTERNALIZATION; COMPARTMENT; EXPRESSION; ENDOSOME; VESICLES; PATHWAY; CELLS AB Cargo sorting that promotes the transport of cargo proteins from a membrane compartment has been predicted to be unlikely in the endocytic recycling pathways. We now show that ACAP1 binds specifically and directly to recycling cargo proteins. Reducing this interaction for TfR inhibits its recycling. Moreover, ACAP1 binds to two distinct phenylalanine-based sequences in the cytoplasmic domain of TfR that function as recycling sorting signals to promote its transport from the recycling endosome. Taken together, these findings indicate that ACAP1 promotes cargo sorting by recognizing recycling sorting signals. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Quebec, Ctr Hosp, CHUL, Pavillion Rhumatol & Immunol, Quebec City, PQ G1V 4G2, Canada. Duke Univ, Ctr Med, Div Gastroenterol, Dept Pediat Oncol, Durham, NC 27710 USA. RP Hsu, VW (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. EM vhsu@rics.bwh.harvard.edu RI Porcionatto, Marimelia/C-3322-2012; Dai, Jun/J-9718-2015 OI Porcionatto, Marimelia/0000-0001-6287-916X; NR 22 TC 57 Z9 58 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD NOV PY 2004 VL 7 IS 5 BP 771 EP 776 DI 10.1016/j.devcel.2004.10.002 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 872HA UT WOS:000225197100018 PM 15525538 ER PT J AU Hong, YK Shin, JW Detmar, M AF Hong, YK Shin, JW Detmar, M TI Development of the lymphatic vascular system: A mystery unravels SO DEVELOPMENTAL DYNAMICS LA English DT Review DE lymphatics; Prox-1; LYVE-1; lymphedema; lymphangiogenesis; lymphatic development ID ENDOTHELIAL GROWTH-FACTOR; LYMPHEDEMA-DISTICHIASIS SYNDROME; VEGF-C; TRANSGENIC MICE; BREAST-CANCER; TUMOR LYMPHANGIOGENESIS; TRANSCRIPTION FACTOR; PROX1 FUNCTION; IN-VIVO; HEREDITARY LYMPHEDEMA AB The blood vascular and the lymphatic system play complementary roles in tissue perfusion and fluid reabsorption. Despite its critical role in mediating tissue fluid homeostasis, intestinal lipid absorption, and the immune response, the lymphatic system has not received as much attention as the blood vascular system, largely due to a lack of lymphatic-specific markers and to the dearth of knowledge about the molecular regulation of lymphatic development and function. A series of recent landmark studies now significantly has advanced our understanding of the lymphatic system. Based upon the discovery and characterization of lymphatic-specific growth factors, receptors, and transcriptional regulators, the mystery of lymphatic vascular system development begins to be unraveled. The successful isolation and cultivation of blood vascular and lymphatic endothelial cells has enabled comparative molecular and cellular analyses of these two genetically and developmentally closely related cell lineages. Moreover, studies of several genetic mouse models have set the framework for a new molecular model of embryonic lymphatic vascular development and have identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Although these rapid advances already have led to development of the first lymphatic-targeted molecular therapies, there still remain many unanswered questions regarding almost every aspect of lymphatic vascular biology, making the lymphatic system a highly exciting and rewarding field of study. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Hong, YK (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM young.hong@cbrc2.mgh.harvard.edu FU NCI NIH HHS [CA 69184, CA 86410, CA 91861] NR 107 TC 54 Z9 58 U1 1 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2004 VL 231 IS 3 BP 462 EP 473 DI 10.1002/dvdy.20179 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 864QH UT WOS:000224647500002 PM 15376314 ER PT J AU Green, JBA Dominguez, I Davidson, LA AF Green, JBA Dominguez, I Davidson, LA TI Self-organization of vertebrate mesoderm based on simple boundary conditions SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Xenopus; gastrulation; convergent extension; hoop stress; polarity; vegetal alignment zone; activin ID SEA-URCHIN GASTRULATION; ANIMAL CAP ASSAY; XENOPUS-LAEVIS; CONVERGENT EXTENSION; CELL INTERCALATION; PATTERN-FORMATION; INDUCTION; MOVEMENTS; POLARITY; ACTIVIN AB Embryonic development requires cell movements whose coordination is robust and reproducible. A dramatic example is the primary body axis of vertebrates: despite perturbation, cells in prospective axial tissue coordinate their movements to make an elongated body axis. The spatial cues coordinating these movements are not known. We show here that cells deprived of preexisting spatial cues by physical dissociation and reaggregation nonetheless organize themselves into an axis. Activin-induced cells that are reaggregated into a flat disc initially round up into a ball before elongating perpendicular to the disc. Manipulations of the geometry of the disc and immunofluorescence micrography reveal that the edge of the disc provides a circumferential alignment zone. This finding indicates that physical boundaries provide alignment cues and that circumferential "hoop stress" drives the axial extrusion in a manner resembling late-involuting mesoderm of Xenopus and archenteron elongation in other deuterostome species such as sea urchins. Thus, a population of cells finds its own midline based on the form of the population's boundaries using an edge-aligning mechanism. This process provides a remarkably simple organizing principle that contributes to the reliability of embryonic development as a whole. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Virginia, Dept Biol, Charlottesville, VA USA. Univ Virginia, Dept Cell Biol, Charlottesville, VA USA. RP Green, JBA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM jeremy_green@dfci.harvard.edu RI Green, Jeremy/F-3630-2010; OI Green, Jeremy/0000-0002-6102-2620; Dominguez, Maria Isabel/0000-0001-9617-4141 FU NICHD NIH HHS [R01 HD 036426, R01 HD 25594, R01 HD 26402, R01 HD 36345] NR 34 TC 14 Z9 14 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2004 VL 231 IS 3 BP 576 EP 581 DI 10.1002/dvdy.20163 PG 6 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 864QH UT WOS:000224647500012 PM 15376320 ER PT J AU Bluher, S Moschos, S Bullen, J Kokkotou, E Maratos-Flier, E Wiegand, SJ Sleemann, MW Mantzoros, CS AF Bluher, S Moschos, S Bullen, J Kokkotou, E Maratos-Flier, E Wiegand, SJ Sleemann, MW Mantzoros, CS TI Ciliary neurotrophic factor (AX15) alters energy homeostasis, decreases body weight, and improves metabolic control in diet-induced obese and UCP1-DTA mice SO DIABETES LA English DT Article ID HYPOTHALAMIC NEUROPEPTIDE-Y; TRANSGENIC MICE; LEPTIN; FAT; EXPRESSION; CORTICOSTERONE; RESISTANCE; ABLATION AB Ciliary neurotrophic factor (CNTF) potently reduces appetite and body weight in rodents and humans. We studied the short- and long-term effects of CNTFAx15, a second-generation CNTF analog, in diet-induced obese C57BL/6J mice and brown adipose tissue (BAT)-deficient obese UCP1-DTA (uncoupling protein 1-diphtheria toxin A) mice. CNTFAx15 administration (0.1, 0.3, or 1.0 mug (.) g(-1) (.) day(-1) s.c.) for 3 or 7 days reduced food intake and body weight (mainly body fat mass). The effect of CNTFAx15 on food intake and body weight was more pronounced in CNTFAx15-treated diet-induced obese C57BL/6J mice compared with pair-fed controls and was associated with suppressed expression of hypothalamic neuropeptide Y and agouti gene-related protein. Moreover, CNTFAx15 increased uncoupling protein 1 mRNA expression in BAT and energy expenditure in diet-induced obese C57BL/6J mice. Longitudinal observations revealed a sustained reduction in body weight for several days post-CNTFAx15 treatment of CNTFAx15-treated but not pair-fed mice, followed by a gradual regain in body weight over 28 days. Finally, CNTFAx15 administration improved the metabolic profile in both diet-induced obese C57BL/6J and UCP1-DTA mice and resulted in a significantly improved glycemic response to oral glucose tolerance tests in CNTFAx15-treated UCP1-DTA compared with pair-fed mice of similar body weight. These data suggest that CNTFAx15 may act through a pathway downstream of the putative point responsible for leptin resistance in diet-induced obese C57BL/6J and UCP1-DTA mice to alter food intake, body weight, body composition, and metabolism. CNTFAx15 has delayed and persistent effects in diet-induced obese C57BL/6J mice, which account for a reduction in body weight over and above what would be expected based on decreased foot intake alone. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. RP Bluher, S (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 99 Brookline Ave, Boston, MA 02215 USA. EM sblueher@caregroup.havard.edu FU NIDDK NIH HHS [DK 56113, DK 56116, P30 DK 57521-3, R01 DK 58785] NR 19 TC 47 Z9 52 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2004 VL 53 IS 11 BP 2787 EP 2796 DI 10.2337/diabetes.53.11.2787 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867EV UT WOS:000224826000007 PM 15504958 ER PT J AU Vence, L Benoist, C Mathis, D AF Vence, L Benoist, C Mathis, D TI Fas deficiency prevents type 1 diabetes by inducing hyporesponsiveness in islet beta-cell-reactive T-cells SO DIABETES LA English DT Article ID NEONATAL-RAT; LIGAND; MICE; ACTIVATION; APOPTOSIS; DEATH; ANTIGEN; PROLIFERATION; PATHOGENESIS; MECHANISMS AB Type 1 diabetes is an autoimmune disease wherein autoreactive T-cells promote the specific destruction of pancreatic islet beta-cells. Evidence for a crucial role for Fas/FasL interactions in this destruction has been highly controversial because of the pleiotropic effects of Fas deficiency on the lymphoid and other systems. Fas-deficient mice are protected from spontaneous development of diabetes not because Fas has a role in the destruction of beta-cells, but rather because insulitis is abrogated. Fas may somehow be involved in the series of events provoking insulitis; for example, it may play a role in the physiological wave of beta-cell death believed to result in the export of pancreatic antigens to the pancreatic lymph nodes and, thereby, to circulating, naive, diabetogenic T-cells for the first time. To explore the implication of Fas in these events, we crossed the lpr mutation into the BDC2.5 model of type 1 diabetes to make it easier to monitor direct effects on the pathogenic specificity. We demonstrated that BDC2.5/NODlpr/lpr mice have qualitatively and quantitatively less aggressive insulitis than do BDC2.5/NOD mice. In vitro proliferation assays showed that BDC2.5/NODlpr/lpr splenocytes proliferated less vigorously than those from control mice in the presence of islet extracts, which reflects their inability to produce interleukin-2, resulting in weaker pathogenicity. C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Benoist, C (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.havard.edu FU NIDDK NIH HHS [1R-01-DK-59658] NR 47 TC 15 Z9 15 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2004 VL 53 IS 11 BP 2797 EP 2803 DI 10.2337/diabetes.53.11.2797 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867EV UT WOS:000224826000008 PM 15504959 ER PT J AU Utzschneider, KM Carr, DB Hull, RL Kodama, K Shofer, JB Retzlaff, BM Knopp, RH Kahn, SE AF Utzschneider, KM Carr, DB Hull, RL Kodama, K Shofer, JB Retzlaff, BM Knopp, RH Kahn, SE TI Impact of intra-abdominal fat and age on insulin sensitivity and beta-cell function SO DIABETES LA English DT Article ID PANCREATIC B-CELL; GLUCOSE-TOLERANCE; BODY-FAT; JAPANESE-AMERICANS; VISCERAL ADIPOSITY; MINIMAL MODEL; RESISTANCE; INTOLERANCE; SECRETION; MEN AB The prevalence of glucose intolerance and type 2 diabetes increases with age. To determine whether the hyperbolic relationship between insulin sensitivity and the insulin response is affected by age and whether the decline in beta-cell function with age is related to increases in intra-abdominal fat or age per se, we studied 220 healthy subjects with fasting glucose <6.1 mmol/l (89 men and 131 women, aged 26-75 years, BMI 18.7-40.4 kg/m(2)). The insulin sensitivity index (S-i) and the acute insulin response to glucose (AIRg) were determined, and from these beta-cell function was estimated as the disposition index (S-i x AIRg). Intra-abdominal fat and subcutaneous fat areas were quantified by computed tomography. S-i (5.40 +/- 0.5 vs. 7.86 +/- 0.7 x 10(-5) min(-1)/[pmol/l]), P < 0.01) was decreased and intra-abdominal fat (117 +/-10 vs. 81 +/- 9 cm(2), P < 0.05) was increased in the oldest (age 60-75 years) versus the youngest (age 26-44 years) quartile. The hyperbolic relationship between S-i and AIRg was present independent of age; thus, beta-cell function measured as the disposition index (1,412 +/- 120 vs. 2,125 +/- 150 x 10(-5) min(-1) P < 0.01) was lower in the oldest versus the youngest quartile. In multiple regression, intra-abdominal fat (r = -0.470, P < 0.001) but not age was associated with S-i, but both intra-abdominal fat (r = -0.198, P = 0.003) and age (r = -0.131, P = 0.05) were correlated with the disposition index. These data suggest that although intra-abdominal fat is a strong determinant of insulin sensitivity and beta-cell function, age has an independent effect on beta-cell function that may contribute to the increased prevalence of type 2 diabetes in older populations. C1 VA Puget Sound Hlth Care Syst, Harborview Med Ctr, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Div Maternal Fetal Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Rehabil & Res & Dev, Seattle, WA 98108 USA. RP Utzschneider, KM (reprint author), VA Puget Sound Hlth Care Syst, Harborview Med Ctr, Dept Med, Div Metab Endocrinol & Nutr, 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM kutzschn@u.washington.edu FU NCRR NIH HHS [RR-37]; NHLBI NIH HHS [HL-07028, HL-30086]; NIDDK NIH HHS [DK-35747, DK-35816, DK-02654, DK-17047, DK-59417, DK-02456] NR 35 TC 42 Z9 45 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2004 VL 53 IS 11 BP 2867 EP 2872 DI 10.2337/diabetes.53.11.2867 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867EV UT WOS:000224826000016 PM 15504967 ER PT J AU Miljanovic, B Glynn, RJ Nathan, DM Manson, JE Schaumberg, DA AF Miljanovic, B Glynn, RJ Nathan, DM Manson, JE Schaumberg, DA TI A prospective study of serum lipids and risk of diabetic macular edema in type 1 diabetes SO DIABETES LA English DT Article ID SEVERE VISUAL-LOSS; INTENSIVE THERAPY; HARD EXUDATE; RETINOPATHY; COMPLICATIONS; PROGRESSION; MELLITUS; CHOLESTEROL; PHOTOCOAGULATION; NEPHROPATHY AB We evaluated the relationships between serum lipid levels and clinically significant macular edema (CSME), hard exudates, and other diabetic retinopathy (DR) end points in a population with type 1 diabetes. We studied data from serum lipids that were measured annually among the 1,441 Diabetes Control and Complications Trial (DCCT) participants. We used proportional hazards regression models to examine the relationship of the cumulative average of lipid levels (total, LDL, and HDL cholesterol, total-to-HDL cholesterol ratio, and triglycerides) with development of CSME, hard exudate, DR progression, and development of proliferative DR (PDR). In models controlling for primary prevention versus secondary intervention subgroup, randomized treatment assignment, HbA(1c), and other risk factors, both total-to-HDL cholesterol ratio and LDL predicted development of CSME (rate ratio [RR] for extreme quintiles 3.84, P for trend = 0.03 for total-to-HDL cholesterol ratio, and RR 1.95, P for trend = 0.03 for LDL) and hard exudate (RR 2.44, P for trend = 0.0004 for total-to-HDL cholesterol ratio, and RR 2.77, P for trend = 0.002 for LDL). Relationships of lipids with progression of DR and development of PDR were weaker and not significant after adjustment for HbA(1c). Higher serum lipids are associated with increased risk of CSME and retinal hard exudate. Lipid-lowering treatment among type 1 diabetic subjects, recommended to prevent cardiovascular disease, may also decrease risk of CSME, an important cause of vision loss. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Ctr,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP Schaumberg, DA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM dschaumberg@rics.bwh.havard.edu NR 42 TC 88 Z9 93 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD NOV PY 2004 VL 53 IS 11 BP 2883 EP 2892 DI 10.2337/diabetes.53.11.2883 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867EV UT WOS:000224826000018 PM 15504969 ER PT J AU Hood, KK Butler, DA Volkening, LK Anderson, BJ Laffel, LMB AF Hood, KK Butler, DA Volkening, LK Anderson, BJ Laffel, LMB TI The blood glucose monitoring communication questionnaire SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GLYCEMIC CONTROL; METABOLIC-CONTROL; ADOLESCENTS; ADHERENCE; CHILDREN; YOUTH AB OBJECTIVE- The aim of this study was to present the psychometric properties of a new tool for evaluating affective response to blood glucose monitoring (BGM) in youths with type 1 diabetes and their parents. RESEARCH DESIGN AND METHODS- Study participants included 153 youths with type 1 diabetes and their parents. Each youth and parent completed the Blood Glucose Monitoring Communication (BGMC) questionnaire, Diabetes Family Conflict Scale, and Pediatric Quality of Life Inventory. Statistical analyses evaluated the psychometric properties of the BGMC questionnaires and their association with glycemic outcomes. RESULTS- Youth and parent BGMC questionnaires had acceptable internal consistency (youth, alpha = 0.77; parent, alpha = 0.82) and 1-year test-retest reliability (youth, r = 0.60; parent, r = 0.80). Higher BGMC questionnaire scores (indicating more negative affect) showed a strong association with higher levels of diabetes-specific family conflict (youth, r = 0.33; parent, r = 0.44) and poorer health-related psychosocial quality of life (youth, r = -0.50; parent, r -0.42). Higher BGMC questionnaire scores were also associated with poorer glycerine control (youth, r = 0.28; parent, r = 0.20), even when the effects of diabetes-specific family conflict and psychosocial quality of life were controlled. Youths with BGMC questionnaire scores in the upper quartile had Ale values 1 percentage point higher (9.1%) than youths with scores in the lowest quartile (8.0%). CONCLUSIONS- The BGMC questionnaires have strong psychometric properties and are convenient measures of affect specific to BGM. Further, BGM affect is associated with glycemic outcomes and may provide a unique contribution to factors associated with glycemic control in youths. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat & Adolescent Unit,Genet & Epidemiol Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Behav Res & Mental Hlth Sect, Boston, MA 02215 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Laffel, LMB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat & Adolescent Unit,Genet & Epidemiol Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [DK-46887] NR 26 TC 22 Z9 23 U1 2 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2004 VL 27 IS 11 BP 2610 EP 2615 DI 10.2337/diacare.27.11.2610 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867ET UT WOS:000224825800007 PM 15504994 ER PT J AU Meigs, JB AF Meigs, JB TI Metabolic syndrome - In search of a clinical role SO DIABETES CARE LA English DT Editorial Material ID GLUCOSE-TOLERANCE TEST; TYPE-2 DIABETES RISK; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; PREDICTION; IDENTIFICATION; MANAGEMENT; MELLITUS C1 Massachusetts Gen Hosp, Div Gen Med, 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 NR 20 TC 29 Z9 32 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2004 VL 27 IS 11 BP 2761 EP 2763 DI 10.2337/diacare.27.11.2761 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867ET UT WOS:000224825800033 PM 15505020 ER PT J AU Wen, LK Shepherd, MD Parchman, ML AF Wen, LK Shepherd, MD Parchman, ML TI Family support, diet, and exercise among older Mexican Americans with type 2 diabetes SO DIABETES EDUCATOR LA English DT Article ID SELF-CARE BEHAVIORS; SOCIAL SUPPORT; MANAGEMENT; ADULTS; ADHERENCE; RECOMMENDATIONS; POPULATION; MELLITUS; EFFICACY; ENVIRONMENT AB PURPOSE The purpose of this study was to examine the relationship between diabetes-specific family support and other psychosocial factors with regard to diet and exercise self-care behavior among older Mexican Americans with type 2 diabetes. METHODS Adults aged 55 years and older who presented for care in a primary care clinic for type 2 diabetes (N= 138) completed a survey to assess family support specific to diabetes barriers to, self-management, self-efficacy, and diabetes self-care activities. Multivariate regression analyses were conducted to evaluate the relationship between family support and self-care activities for diet and exercise. RESULTS Higher levels of perceived family support and greater self-efficacy were associated with higher reported levels of diet and exercise self-care. As the barriers to exercise increased, the levels of exercise self-care decreased. Living with family members (more than just a spouse or significant other) was associated with higher levels of diet self-care, as was older age. CONCLUSIONS Family behavior is associated with diet and exercise self-care. Diabetes educators and healthcare providers should consider involving the entire family in the management of older patients with type 2 diabetes. Interventions designed to improve diabetes self-management should address family support specific to diabetes, self-efficacy, and barriers to self-care. C1 Pfizer Inc, San Antonio, TX 78258 USA. S Texas Vet Hlth Care Syst, Vet Evidence Based Res Dissemination & Implementa, VERDICT, San Antonio, TX USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX USA. RP Wen, LK (reprint author), Pfizer Inc, 17827 Salado Draw, San Antonio, TX 78258 USA. EM lonnie.k.wen@pfizer.com NR 48 TC 88 Z9 92 U1 1 U2 11 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD NOV-DEC PY 2004 VL 30 IS 6 BP 980 EP 993 DI 10.1177/014572170403000619 PG 14 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 886LQ UT WOS:000226229200009 PM 15641619 ER PT J AU Yokoe, DS Noskin, GA Cunningham, SM Zuccotti, G Plaskett, T Fraser, VJ Olsen, MA Tokars, JI Solomon, S Perl, TM Cosgrove, SE Tilson, RS Greenbaum, M Hooper, DC Sands, KE Tully, J Herwaldt, LA Diekema, DJ Wong, ES Climo, M Platt, R AF Yokoe, DS Noskin, GA Cunningham, SM Zuccotti, G Plaskett, T Fraser, VJ Olsen, MA Tokars, JI Solomon, S Perl, TM Cosgrove, SE Tilson, RS Greenbaum, M Hooper, DC Sands, KE Tully, J Herwaldt, LA Diekema, DJ Wong, ES Climo, M Platt, R TI Enhanced identification of postoperative infections among inpatients SO EMERGING INFECTIOUS DISEASES LA English DT Article ID ANTIBIOTIC EXPOSURE; SURVEILLANCE; RISK AB We evaluated antimicrobial exposure, discharge diagnoses, or both to identify surgical site infections (SSI). This retrospective cohort study in 13 hospitals involved weighted, random samples of records from 8,739 coronary artery bypass graft (CABG) procedures, 7,399 cesarean deliveries, and 6,175 breast procedures. We compared routine surveillance to detection through inpatient antimicrobial exposure ( 9 days for CABG, greater than or equal to2 days for cesareans, and greater than or equal to6 days for breast procedures), discharge diagnoses, or both. Together, all methods identified SSI after 7.4% of CABG, 5.0% of cesareans, and 2.0% of breast procedures. Antimicrobial exposure had the highest sensitivity, 88%-91%, compared with routine surveillance, 38%-64%. Diagnosis codes improved sensitivity of detection of antimicrobial exposure after cesareans. Record review confirmed SSI after 31% to 38% of procedures that met antimicrobial surveillance criteria. Sufficient antimicrobial exposure days, together with diagnosis codes for cesareans, identified more postoperative SSI than routine surveillance methods. This screening method was efficient, readily standardized, and suitable for most hospitals. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Washington Univ, Sch Med, St Louis, MO USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Salem Hosp, N Shore Med Ctr, Salem, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mt Auburn Med Ctr, Cambridge, MA USA. Univ Iowa, Carver Coll Med, Iowa City, IA USA. McGuire Vet Affairs Med Ctr, Richmond, VA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. RP Yokoe, DS (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM deborah.yokoe@channing.harvard.edu OI Diekema, Daniel/0000-0003-1273-0724 FU CCR NIH HHS [URCCU-315092, URCCU-315346]; ODCDC CDC HHS [UR8CCU-515081, UR8CCU-115079, UR8CCU-215090, UR8CCU-715087, UR8CCU-715091] NR 7 TC 80 Z9 80 U1 1 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2004 VL 10 IS 11 BP 1924 EP 1930 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 869PY UT WOS:000224997700005 PM 15550201 ER PT J AU Carroll, D Gardner, P Kay, BA Osterholm, M Ryan, ET AF Carroll, D Gardner, P Kay, BA Osterholm, M Ryan, ET TI Transformation of the developing world: Socioeconomic matrix SO EMERGING INFECTIOUS DISEASES LA English DT Meeting Abstract CT 4th International Conference on Emerging Infectious Diseases CY FEB 29-MAR 03, 2004 CL Atlanta, GA SP Ctr Dis Control & Prevent, Amer Soc Microbiol, Assoc Public Hlth Labs, Council State & Territorial Epidemiologists, WHO C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. US Agcy Int Dev, Washington, DC 20523 USA. NIH, Bethesda, MD 20892 USA. WHO, Lyon, France. Univ Minnesota, Minneapolis, MN USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. EM etryan@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2004 VL 10 IS 11 BP 2049 EP 2049 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 869PY UT WOS:000224997700039 PM 16010742 ER PT J AU Papasani, MR Gensure, RC Yan, YL Gunes, Y Postlethwait, JH Ponugoti, B John, MR Juppner, H Rubin, DA AF Papasani, MR Gensure, RC Yan, YL Gunes, Y Postlethwait, JH Ponugoti, B John, MR Juppner, H Rubin, DA TI Identification and characterization of the zebrafish and fugu genes encoding tuberoinfundibular peptide 39 SO ENDOCRINOLOGY LA English DT Article ID PARATHYROID-HORMONE PTH; MULTIPLE SEQUENCE ALIGNMENT; 39 RESIDUES; RECEPTOR FAMILY; PEPTIDE; EXPRESSION; AGONIST; RAT; ANTAGONIST; HEDGEHOG AB Although the PTH type 2 receptor (PTH2R) has been isolated from mammals and zebrafish, only its mammalian agonist, tuberoinfundibular peptide 39 (TIP39), has been characterized thus far. To determine whether zebrafish TIP39 (zTIP39) functions similarly with the zebrafish PTHR (zPTH2R) and human PTH2Rs and to determine its tissue-specific expression, fugu (Takifugu rubripes) and zebrafish (Danio rerio) genomic databases were screened with human TIP39 (hTIP39) sequences. A single TIP39 gene was identified for each fish species, which showed significant homology to mammalian TIP39. Using standard molecular techniques, we isolated cDNA sequences encoding zTIP39. The fugu TIP39 precursor was encoded by a gene comprising at least three exons. It contained a hydrophobic signal sequence and a predicted pro-sequence with a dibasic cleavage site, similar to that found in mammalian TIP39 ligands. Phylogenetic analyses suggested that TIP39 forms the basal group from which PTH and PTHrP have been derived. Functionally, subtle differences in potency could be discerned between hTIP39 and zTIP39. The human PTH2R and zPTH2R were stimulated slightly better by both hTIP39 and zTIP39, whereas zTIP39 had a higher potency at a previously isolated zPTH2R splice variant. Whole-mount in situ hybridization of zebrafish revealed strong zTIP39 expression in the region of the hypothalamus and in the heart of 24- and 48-h-old embryos. Similarly, zPTH2R expression was highly expressed throughout the brain of 48- and 72-h-old embryos. Because the mammalian PTH2R was also most abundantly expressed in these tissues, the TIP39-PTH2R system may serve conserved physiological roles in mammals and fishes. C1 Illinois State Univ, Dept Sci Biol, Normal, IL 61790 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Novartis Inst Biomed Res, Bone Metab Res, CH-4002 Basel, Switzerland. RP Rubin, DA (reprint author), Illinois State Univ, Dept Sci Biol, Normal, IL 61790 USA. EM adavid@ilstu.edu RI PONUGOTI, BHASKAR/H-2230-2011 FU NCRR NIH HHS [R01RR10715]; NICHD NIH HHS [P01HD22486]; NIDDK NIH HHS [DK60513, DK11794] NR 60 TC 21 Z9 22 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2004 VL 145 IS 11 BP 5294 EP 5304 DI 10.1210/en.2004-0159 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 862SB UT WOS:000224510100061 PM 15297442 ER PT J AU Garshick, E Laden, F Hart, JE Rosner, B Smith, TJ Dockery, DW Speizer, FE AF Garshick, E Laden, F Hart, JE Rosner, B Smith, TJ Dockery, DW Speizer, FE TI Lung cancer in railroad workers exposed to diesel exhaust SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID HEALTHY-HUMAN VOLUNTEERS; RETROSPECTIVE COHORT; AIR-POLLUTION; EFFECT MODIFIERS; TERM EXPOSURE; MORTALITY; SMOKING; OCCUPATION; RISK; ASSOCIATION AB Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30-1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort. C1 Vet Affairs Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA 02132 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. RP Garshick, E (reprint author), Vet Affairs Boston Healthcare Syst, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, Boston, MA 02132 USA. EM eric.garshick@med.va.gov FU NCI NIH HHS [CA79725, R01 CA079725] NR 57 TC 107 Z9 108 U1 0 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2004 VL 112 IS 15 BP 1539 EP 1543 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 869GX UT WOS:000224972500042 PM 15531439 ER PT J AU Wang, XR Zhang, HX Sun, BX Dai, HL Pan, LD Eisen, EA Wegman, DH Olenchock, SA Christiani, DC AF Wang, XR Zhang, HX Sun, BX Dai, HL Pan, LD Eisen, EA Wegman, DH Olenchock, SA Christiani, DC TI Is chronic airway obstruction from cotton dust exposure reversible? SO EPIDEMIOLOGY LA English DT Article ID ACROSS-SHIFT DROP; TEXTILE WORKERS; PULMONARY-FUNCTION; RESPIRATORY SYMPTOMS; LUNG-FUNCTION; EXPERIMENTAL CARDROOM; ENDOTOXIN; FEV(1); DISEASE AB Background: Exposure to cotton dust is known to cause chronic airway obstruction, but there is little information on whether the obstructive impairment is reversible after the exposure stops. Methods: Longitudinal changes in lung function were evaluated among 429 cotton textile workers and 449 silk workers in Shanghai, China, beginning in 1981. Both active and retired workers were tested every 4 to 6 years for 15 years. Results: Overall, cotton workers had greater annual declines in forced expiratory volume in I second (FEV1) and forced vital capacity (FVC). Compared with active workers, retired cotton workers had lower annual loss of FEV1, although the retired workers had a greater loss during their active employment than the currently active workers. No such trends were detected in silk workers. Annual declines in FEV1 in retired cotton workers were smaller with increasing time since retirement. Multivariate analysis showed that retirement was a substantial contributing factor for improved FEV1 and FVC in the cotton workers, especially among those who did not smoke. Correspondingly, remission of airflow obstruction, defined as a ratio of FEV1 and FVC of less than 70%, was more common in retirees than in the active workers, and more common in nonsmokers than in smokers. Conclusion: Chronic airway obstruction related to long-term exposure to cotton dust may be partially reversible after the exposure ceases, although lung function does not return to the level found in unexposed workers. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. First Hosp Shanghai Text Bur, Shanghai, Peoples R China. Univ Massachusetts Lowell, Dept Work Environm, Lowell, MA USA. NIOSH, Morgantown, WV USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Lin, Sihao/A-8412-2012 FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R01OH02421] NR 23 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2004 VL 15 IS 6 BP 695 EP 701 DI 10.1097/01.ede.0000142141.28139.25 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 865IZ UT WOS:000224697200007 PM 15475718 ER PT J AU Holmes, LB Wyszynski, DF AF Holmes, LB Wyszynski, DF TI North American Antiepileptic drug pregnancy registry SO EPILEPSIA LA English DT Article C1 Massachusetts Gen Hosp Childrens, Genet & Teratol Unit, Dept Pediat, AED Pregnancy Reg, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp Childrens, Genet & Teratol Unit, Dept Pediat, AED Pregnancy Reg, Warren 801,55 Fruit St, Boston, MA 02114 USA. EM holmes.lewis@mgh.harvard.edu NR 3 TC 32 Z9 32 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2004 VL 45 IS 11 BP 1465 EP 1465 DI 10.1111/j.0013-9580.2004.451102.x PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 868JA UT WOS:000224908700023 PM 15509251 ER PT J AU Gibson, CM Dumaine, RL Gelfand, EV Murphy, SA Morrow, DA Wiviott, SD Giugliano, RP Cannon, CP Antman, EM Braunwald, E AF Gibson, CM Dumaine, RL Gelfand, EV Murphy, SA Morrow, DA Wiviott, SD Giugliano, RP Cannon, CP Antman, EM Braunwald, E CA TIMI Study Grp TI Association of glomerular filtration rate on presentation with subsequent mortality in non-ST-segment elevation acute coronary syndrome; observations in 13307 patients in five TIMI trials SO EUROPEAN HEART JOURNAL LA English DT Article DE kidney disease; acute coronary syndromes; prognosis; TIMI risk score ID ACUTE MYOCARDIAL-INFARCTION; STAGE RENAL-DISEASE; NATRIURETIC PEPTIDE; UNSTABLE ANGINA; ARTERY-DISEASE; FRAME COUNT; CREATININE CLEARANCE; CLINICAL-OUTCOMES; RISK; INSUFFICIENCY AB Aims To determine the association of glomerular filtration rate (GFR) with clinical outcomes in the setting of non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Methods and results Data were pooled from five NSTE-ACS TIMI trials (TIMI 11 A and B, TIMI 12, OPUS-TIMI 16 and TACTICS-TIMI 18) and were available in 13 307 patients. GFR was assessed as a continuous and a categorical variable (normal: greater than or equal to 90 mL/ min/1.73 m(2), n = 4952; mildly decreased: 60-89 mL/min/1.73 m(2), n = 6262; and moderately to severely decreased GFR: < 60 mL/min/1.73 m(2), n = 2093). There was an independent association between decreasing GFR and mortality at 30 days (OR 1.19, 95% CI 1.12-1.27, p < 0.001) and at 6 months (OR 1.16, 95% CI 1.11-1.22, p < 0.001). The combination of TIMI risk score (TRS) and decreasing GFR provided further mortality risk stratification with highest 30-day and 6-month mortality rates among patients with the lowest GFR who also had a TRS greater than or equal to 5 (9.1% and 15.4%, respectively). Decreasing GFR was also independently associated with stroke and recurrent ischaemia at 30-days as well as with major bleeding (p < 0.001). Conclusion In the setting of NSTE-ACS, impaired GFR is associated with higher mortality as well as higher rates of thrombotic and major bleeding events, independent of TRS. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gibson, CM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, 350 Longwood Ave, Boston, MA 02115 USA. EM mgibson@timi.org NR 41 TC 90 Z9 99 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD NOV PY 2004 VL 25 IS 22 BP 1998 EP 2005 DI 10.1016/j.ehj.2004.08.016 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 875KP UT WOS:000225419400007 PM 15541835 ER PT J AU Elentuck, D Palmer, WE AF Elentuck, D Palmer, WE TI Direct magnetic resonance arthrography SO EUROPEAN RADIOLOGY LA English DT Article DE arthrography; contrast media; joints; magnetic resonance; arthrography ID DIRECT MR ARTHROGRAPHY; ULNAR COLLATERAL LIGAMENT; ROTATOR CUFF; GLENOID LABRUM; HISTOLOGIC CORRELATION; GLENOHUMERAL JOINT; ACETABULAR LABRUM; POSTERIOR INSTABILITY; ARTHROSCOPIC REPAIR; WRIST ARTHROGRAPHY AB Magnetic resonance (MR) arthrography has gained increasing popularity as a diagnostic tool in the assessment of intra-articular derangements. Its role has been studied extensively in the shoulder, but it also has been explored in the hip, elbow, knee, wrist and ankle. This article reviews the current role of direct MR arthrography in several major joints, with consideration of pertinent anatomy, techniques and applications. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Palmer, WE (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 515, Boston, MA 02114 USA. EM paimer.william@mgh.harvard.edu NR 78 TC 45 Z9 48 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD NOV PY 2004 VL 14 IS 11 BP 1956 EP 1967 DI 10.1007/s00330-004-2449-3 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 879AS UT WOS:000225689400002 PM 15351900 ER PT J AU Zaspel, U Denning, DW Lemke, AJ Greene, R Schurmann, D Maschmeyer, G Ruhnke, M Herbrecht, R Ribaud, P Lortholary, O Zonderland, H Rabe, KF Rottgen, R Bittner, R Neumann, K Oestmann, JW AF Zaspel, U Denning, DW Lemke, AJ Greene, R Schurmann, D Maschmeyer, G Ruhnke, M Herbrecht, R Ribaud, P Lortholary, O Zonderland, H Rabe, KF Rottgen, R Bittner, R Neumann, K Oestmann, JW TI Diagnosis of IPA in HIV: the role of the chest X-ray and radiologist SO EUROPEAN RADIOLOGY LA English DT Article DE aspergillosis; fungal lung disease; HIV infections; acquired immunodeficiency syndrome; ROC analysis; ROC curve ID INVASIVE PULMONARY ASPERGILLOSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL HISTORY; RADIOGRAPH INTERPRETATION; OBSERVER PERFORMANCE; AIDS; ROC; CT; ABNORMALITIES; DISEASE AB The role of clinical information and chest film for the discrimination between invasive pulmonary aspergillosis (IPA) and its differential diagnoses in human immunodeficiency virus (HIV) infection was studied. The diagnostic performance of clinical information and chest film alone and in combination was studied for eight internists and eight radiologists with regular exposure to IPA patients. The multicenter case sample consisted of 25 patients with proven IPA and 25 with other pulmonary diseases typical for HIV. The cases were presented on a CDROM. Receiver operating characteristics (ROC) methodology was employed. With clinical information alone, internists achieved the highest diagnostic performance (area under curve/AUC=0.84). Viewing the chest films did not contribute to their performance (AUC=0.80, P=0.26). The radiologist's performance on the basis of viewing the chest film (AUC=0.75) increased significantly (P=0.012) when clinical information (AUC=0.83) was supplied. IPA cases with characteristic radiological appearance were correctly identified in 90% with chest film. For radiologists with regular exposure to HIV patients, chest films hold relevant information and contribute to the determination in cases with characteristic radiological appearance. Overall and especially in cases with less characteristic radiological appearance, they have significant profit from full access to the clinical data. For internists with regular exposure to HIV patients, chest films do not provide information essential for the verification or differentiation of potential IPA. C1 Charite Univ Med Berlin, Inst Radiol, D-10117 Berlin, Germany. Univ Manchester, Wythenshawe Hosp, Educ & Res Ctr, Manchester, Lancs, England. Charite Univ Med Berlin, Klin Strahlenheilkunde, D-10117 Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Charite Univ Med Berlin, Med Klin Schwerpunkt Infektiol & Asthma Poliklin, D-10117 Berlin, Germany. Charite Univ Med Berlin, Med Klin Schwerpunkt Hamatol & Onkol, D-10117 Berlin, Germany. Hop Hautepiere, Dept Hematol & Oncol, Strasbourg, France. Hop St Louis, Serv Hematol, Paris, France. Univ Paris 05, Hop Necker, Serv Malad Infect & Trop,Inst Pasteur, Ctr Natl Reference Mycoses & Antifong, Paris, France. Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Pulmol, Leiden, Netherlands. Krankenhaus & Herzzentrum Bernau, Bernau, Germany. RP Zaspel, U (reprint author), Charite Univ Med Berlin, Inst Radiol, Campus Mitte,Schuhmannstr 20-21, D-10117 Berlin, Germany. EM uta.zaspel@charite.de RI Herbrecht, Raoul/D-3471-2013; OI Herbrecht, Raoul/0000-0002-9381-4876; Denning, David/0000-0001-5626-2251 NR 46 TC 7 Z9 8 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD NOV PY 2004 VL 14 IS 11 BP 2030 EP 2037 DI 10.1007/s00330-004-2447-5 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 879AS UT WOS:000225689400012 PM 15309496 ER PT J AU Ramchandran, RS Manoach, DS Cherkasova, MV Lindgren, KA Goff, DC Barton, JJS AF Ramchandran, RS Manoach, DS Cherkasova, MV Lindgren, KA Goff, DC Barton, JJS TI The relationship of saccadic peak velocity to latency: evidence for a new prosaccadic abnormality in schizophrenia SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE saccade; antisaccade; schizophrenia; peak velocity; latency; visual transient ID GUIDED VOLUNTARY SACCADES; EYE-MOVEMENTS; SMOOTH-PURSUIT; BIOLOGICAL RELATIVES; SUPERIOR COLLICULUS; ANTISACCADES; TASK; DISTRACTIBILITY; INITIATION; INHIBITION AB Antisaccades have not only longer latencies but also lower peak velocities than prosaccades. It is not known whether these latency and velocity differences are related. Studies of non-human primates suggest that prosaccade peak velocity declines as latency from target appearance increases. We examined whether a similar relationship between peak velocity and latency existed in human saccades, whether it accounted for the difference in peak velocity between antisaccades and prosaccades, and whether it was affected by schizophrenia, a condition that affects antisaccade performance. Sixteen control and 21 schizophrenia subjects performed prosaccade and antisaccade trials in the same test session. In both groups antisaccades had lower peak velocities than prosaccades. Latency did not influence the peak velocities of antisaccades in either subject group. At short latencies, the peak velocities of prosaccades were also similar in the two groups. However, while prosaccade peak velocities declined minimally with increasing latency in control subjects, those in the schizophrenia group declined significantly until they reached a value similar to antisaccade peak velocities. We conclude that, in normal subjects, the effect of latency on prosaccade peak velocity is minimal and cannot account for the lower velocity of antisaccades. In schizophrenia, we hypothesize that the latency-related decline in prosaccade peak velocity may reflect either an increased rate of decay of the effect of the transient visual signal at the saccadic goal, or a failure of the continuing presence of the target to sustain neural activity in the saccadic system. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,KS 452, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Ophthalmol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. RP Barton, JJS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,KS 452, 330 Brookline Ave, Boston, MA 02215 USA. EM jbarton@bidmc.harvard.edu RI Barton, Jason/A-6362-2012 NR 46 TC 3 Z9 4 U1 1 U2 4 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 NOV PY 2004 VL 159 IS 1 BP 99 EP 107 DI 10.1007/s00221-004-1940-z PG 9 WC Neurosciences SC Neurosciences & Neurology GA 864DK UT WOS:000224613500011 PM 15480590 ER PT J AU Cheng, GC Schulze, PC Lee, RT Sylvan, J Zetter, BR Huang, H AF Cheng, GC Schulze, PC Lee, RT Sylvan, J Zetter, BR Huang, H TI Oxidative stress and thioredoxin-interacting protein promote intravasation of melanoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE metastasis; thioredoxin; cell migration; reactive oxygen species ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-CELLS; TRANSENDOTHELIAL MIGRATION; BREAST-CANCER; EXPRESSION; METASTASIS; ADHESION; CARCINOMA; INVASION; GENE AB Although intravasation may be a critical rate-limiting step in the metastatic cascade, the role of oxidative stress in intravasation is unknown. We tested the hypothesis that reactive oxygen species (ROS), regulated by thioredoxin interacting protein (Txnip) through the action of thioredoxin (Trx), influence human SK-MEL-28 melanoma cell reverse (basolateral-to-apical) transendothelial migration (TEM) in vitro as a model for intravasation. Reverse transendothelial migration was dose-dependently induced by hydrogen peroxide 2.4-fold for 0.1 muM (P<0.01) and 3.9-fold for 1 muM (P<0.001) vs. control, and this effect was blocked by the antioxidant N-acetylcysteine. Overexpression of Txnip by infecting melanoma cells with adenovirus increased TEM 3-fold vs. control (P<0.001), and this increase was blocked by N-acetylcysteine, indicating a redox-sensitive mechanism. Conversely, thioredoxin overexpression blocked hydrogen peroxide-induced TEM. Exposure to ultraviolet-A radiation increased ROS 1.8-fold (P<0.01), and this was accompanied by a 45% reduction (P<0.05) in thioredoxin activity and an 11.4-fold (P<0.001) increase in Txnip gene expression. These data suggest that TEM of melanoma cells during intravasation is in part mediated by ROS-sensitive cellular signaling cascades, may be controlled by Txnip and its interaction with thioredoxin that in turn modulates cellular levels of oxidative stress, and may be initiated by ultraviolet-A induction of this cascade. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Dept Cardiol, Brigham & Womens Hosp, Sch Med,Dept Med,Cardiovasc Div, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Surg Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst,Joint Ctr Radiat Therapy, Brigham & Womens Hosp,Beth Israel Deaconess Med C, Boston, MA 02215 USA. RP Huang, H (reprint author), Harvard Univ, Dept Cardiol, Brigham & Womens Hosp, Sch Med,Dept Med,Cardiovasc Div, 65 Landsdowne St,Rm 283, Cambridge, MA 02139 USA. EM hhuang@rics.bwh.harvard.edu NR 48 TC 34 Z9 35 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 1 PY 2004 VL 300 IS 2 BP 297 EP 307 DI 10.1016/j.yexcr.2004.07.014 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 864UC UT WOS:000224657400004 PM 15474995 ER PT J AU Barabino, S Chen, W Dana, MR AF Barabino, S Chen, W Dana, MR TI Tear film and ocular surface tests in animal models of dry eye: uses and limitations SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE tear film; ocular surface; dry eye; animal models; apoptosis ID CANINE KERATOCONJUNCTIVITIS SICCA; SJOGRENS-SYNDROME; LISSAMINE-GREEN; ROSE-BENGAL; STAINING CHARACTERISTICS; CONJUNCTIVAL EPITHELIA; GENERAL-ANESTHESIA; BARRIER FUNCTION; LACRIMAL GLAND; RABBIT MODEL AB Many ocular surface tests have been developed for the clinical diagnosis of keratoconjunctivitis sicca, and several have been used to 'validate' animal models of Sjogren's and non-Sjogren's dry eye. However, many of these tests themselves have not been systematically studied or standardized, and yet their use in animal models of dry eye is common. This review provides a rational approach and systematic review of the tear film and ocular surface tests described in the literature that may be applicable to the current animal models of dry eye, with particular emphasis on their limitations, along with some suggestions regarding their standardization and applications in eye research. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Stephen Eye Res Inst,Lab Immunol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, Boston, MA 02114 USA. Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Stephen Eye Res Inst,Lab Immunol, 20 Staniford St, Boston, MA 02114 USA. EM barabino@vision.eri.harvard.edu; dana@vision.eri.harvard.edu NR 60 TC 42 Z9 45 U1 0 U2 11 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2004 VL 79 IS 5 BP 613 EP 621 DI 10.1016/j.exer.2004.07.002 PG 9 WC Ophthalmology SC Ophthalmology GA 871IV UT WOS:000225125200002 PM 15500820 ER PT J AU Dedeoglu, A Cormier, K Payton, S Tseitlin, KA Kremsky, JN Lai, L Li, XH Moir, RD Tanzi, RE Bush, AI Kowall, NW Rogers, JT Huang, XD AF Dedeoglu, A Cormier, K Payton, S Tseitlin, KA Kremsky, JN Lai, L Li, XH Moir, RD Tanzi, RE Bush, AI Kowall, NW Rogers, JT Huang, XD TI Preliminary studies of a novel bifunctional metal chelator targeting Alzheimer's amyloidogenesis SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT 7th International Symposium on the Neurobiology and Neuroendocrinology of Aging CY JUL 18-23, 2004 CL Bregenz, AUSTRIA DE Alzheimer's disease; amyloid precursor protein (APP); A beta amyloid; metals; metal chelator ID AMYLOID-BETA-PROTEIN; A-BETA; PRECURSOR PROTEIN; DRUG DISCOVERY; 5'-UNTRANSLATED REGION; HYDROGEN-PEROXIDE; TRANSGENIC MICE; SENILE PLAQUES; DISEASE; ZINC AB A growing body of evidence indicates that dysregulation of cerebral biometals (Fe, Cu, Zn) and their interactions with APP and Abeta amyloid may contribute to the Alzheimer's amyloid pathology, and thus metal chelation could be a rational therapeutic approach for interdicting AD pathogenesis. However, poor target specificity and consequential clinical safety of current metal-complexing agents have limited their widespread clinical use. To develop the next generation of metal chelators, we have designed and synthesized a new bifunctional molecule-XH1, based on a novel 'pharmacophore conjugation' concept. This lipophilic molecule has both amyloid-binding and metal-chelating moieties covalently connected by amide bonds. It achieved a putative binding geometry with Abeta1-40 peptide by the computational chemistry modeling and reduced Zn(II)-induced Abeta1-40 aggregation in vitro as determined by turbidometry. Moreover, our pilot data indicated that XH1 has no significant neurotoxicity at low micromolar concentrations and acute animal toxicity. XH1 specifically reduced APP protein expression in human SH-SY5Y neuroblastoma cells and attenuated cerebral Abeta amyloid pathology in PS1/APP transgenic mice without inducing apparent toxicity and behavior disturbances. Collectively, these preliminary findings carry implication for XH1 being a BBB-permeable lead compound for AD therapeutics targeting Alzheimer's amyloidogenesis, although further studies are needed. (C) 2004 Elsevier Inc. All rights reserved. C1 Bedford Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Prime Organ Inc, Lowell, MA 01851 USA. Harvard Univ, Sch Med, Inst Chem & Chem Biol, Boston, MA 02115 USA. RP Huang, XD (reprint author), Massachusetts Gen Hosp E, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM huangx@helix.mgh.harvard.edu RI Kowall, Neil/G-6364-2012; Bush, Ashley/A-1186-2007; OI Kowall, Neil/0000-0002-6624-0213; Bush, Ashley/0000-0001-8259-9069; Dedeoglu, Alpaslan/0000-0003-1156-0874 FU NIA NIH HHS [AG13846, AG21081]; NIMH NIH HHS [5K01MH02001] NR 41 TC 92 Z9 94 U1 2 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 2004 VL 39 IS 11-12 BP 1641 EP 1649 DI 10.1016/j.exger.2004.08.016 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 880WM UT WOS:000225820700010 PM 15582280 ER PT J AU Di Giovanni, S Faden, AI Yakovlev, A Duke-Cohan, JS Finn, T Thouin, M Knoblach, S De Biase, A Bregman, BS Hoffman, EP AF Di Giovanni, S Faden, AI Yakovlev, A Duke-Cohan, JS Finn, T Thouin, M Knoblach, S De Biase, A Bregman, BS Hoffman, EP TI Neuronal plasticity after spinal cord injury: identification of a gene cluster driving neurite outgrowth SO FASEB JOURNAL LA English DT Article DE SCI; microtubule-associated proteins; GAP-43 ID CENTRAL-NERVOUS-SYSTEM; OLIGODENDROCYTE GLYCOPROTEIN MOG; FOCAL CEREBRAL-ISCHEMIA; PROTEIN 1A; ADULT-RAT; FUNCTIONAL RECOVERY; AXONAL PLASTICITY; IN-VIVO; GROWTH; REGENERATION AB Functional recovery after spinal cord injury (SCI) may result in part from axon outgrowth and related plasticity through coordinated changes at the molecular level. We employed microarray analysis to identify a subset of genes the expression patterns of which were temporally coregulated and correlated to functional recovery after SCI. Steady-state mRNA levels of this synchronously regulated gene cluster were depressed in both ventral and dorsal horn neurons within 24 h after injury, followed by strong re-induction during the following 2 wk, which paralleled functional recovery. The identified cluster includes neuritin, attractin, microtubule-associated protein 1a, and myelin oligodendrocyte protein genes. Transcriptional and protein regulation of this novel gene cluster was also evaluated in spinal cord tissue and in single neurons and was shown to play a role in axonal plasticity. Finally, in vitro transfection experiments in primary dorsal root ganglion cells showed that cluster members act synergistically to drive neurite outgrowth. C1 Georgetown Univ, Sch Med, Dept Neurosci, Washington, DC 20057 USA. Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. Dana Farber Canc Inst D1526, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Faden, AI (reprint author), Georgetown Univ, Sch Med, Dept Neurosci, 3900 Reservoir Rd NW, Washington, DC 20057 USA. EM fadena@georgetown.edu OI Duke-Cohan, Jonathan/0000-0002-9478-9609 NR 56 TC 2 Z9 2 U1 0 U2 0 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 NOV PY 2004 VL 18 IS 14 BP 153 EP + DI 10.1096/fj.04-2694fje PG 29 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 876FO UT WOS:000225482100026 ER PT J AU Dhanasekaran, SM Dash, A Yu, JJ Maine, IP Laxman, B Tomlins, SA Creighton, CJ Menon, A Rubin, MA Chinnaiyan, AM AF Dhanasekaran, SM Dash, A Yu, JJ Maine, IP Laxman, B Tomlins, SA Creighton, CJ Menon, A Rubin, MA Chinnaiyan, AM TI Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty SO FASEB JOURNAL LA English DT Article DE BPH; microarray; androgen ID IN-SITU HYBRIDIZATION; RAT VENTRAL PROSTATE; GROWTH-FACTOR-BETA; ANDROGEN RECEPTOR; CANCER CELLS; FINASTERIDE; HYPERPLASIA; MICROARRAY; STROMA; CARCINOGENESIS AB Testosterone production surges during puberty and orchestrates massive growth and reorganization of the prostate gland, and this glandular architecture is maintained thereafter throughout adulthood. Benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCA) are common diseases in adulthood that do not develop in the absence of androgens. Our objective was to gain insight into gene expression changes of the prostate gland at puberty, a crucial juncture in prostate development that is androgen dependent. Understanding the role played by androgens in normal prostate development may provide greater insight into androgen involvement in prostatic diseases. Benign prostate tissues obtained from pubertal and adult age group cadaveric organ donors were harvested and profiled using 20,000 element cDNA microarrays. Statistical analysis of the microarray data identified 375 genes that were differentially expressed in pubertal prostates relative to adult prostates including genes such as Nkx3.1, TMEPAI, TGFBR3, FASN, ANKH, TGFBR2, FAAH, S100P, HoxB13, fibronectin, and TSC2 among others. Comparisons of pubertal and BPH expression profiles revealed a subset of genes that shared the expression pattern between the two groups. In addition, we observed that several genes from this list were previously demonstrated to be regulated by androgen and hence could also be potential in vivo targets of androgen action in the pubertal human prostate. Promoter searches revealed the presence of androgen response elements in a cohort of genes including tumor necrosis factor-alpha induced adipose related protein, which was found to be induced by androgen. In summary, this is the first report that provides a comprehensive view of the molecular events that occur during puberty in the human prostate and provides a cohort of genes that could be potential in vivo targets of androgenic action during puberty. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Bioinformat Program, Ann Arbor, MI 48109 USA. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Dept Pathol & Urol, Michigan Urol Ctr, MSI Rm 4237,1301 Catherine Rd, Ann Arbor, MI 48109 USA. EM arul@umich.edu OI Rubin, Mark/0000-0002-8321-9950 NR 48 TC 4 Z9 4 U1 0 U2 0 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 NOV PY 2004 VL 18 IS 14 BP 243 EP + DI 10.1096/fj.04-2415fje PG 23 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 876FO UT WOS:000225482100013 ER PT J AU Roefaro, J Daryanani, AA AF Roefaro, J Daryanani, AA TI Treatment options for the management of chronic obstructive pulmonary disease SO FORMULARY LA English DT Article ID STABLE COPD; FLUTICASONE PROPIONATE; INFLUENZA VACCINATION; INHALED BUDESONIDE; MULTICENTER TRIAL; DOUBLE-BLIND; SALMETEROL; TIOTROPIUM; THERAPY; FORMOTEROL AB Chronic obstructive pulmonary disease (COPD) is a disease state characterized by the progressive development of airflow limitation that is not fully reversible. The airflow limitation is associated with an abnormal inflammatory response of the lungs to noxious particles or gases. It affects approximately 15 million Americans and is associated with high morbidity and mortality. Previously, pharmacologic therapeutic options were limited by relatively short durations of action in the first-line medications and limited efficacy data and/or a high rate of adverse effects in the second-line medications. Today, there are several new and emerging medications to treat this disease state, and new guidelines have been published for disease management. This review examines current therapeutic options, compares efficacy data., and highlights the recommendations from international guidelines. C1 VA Boston Healthcare Syst, Boston, MA USA. RP Roefaro, J (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM john.roefaro@med.va.gov NR 40 TC 1 Z9 1 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1082-801X J9 FORMULARY JI Formulary PD NOV PY 2004 VL 39 IS 11 BP 542 EP + PG 10 GA 874YZ UT WOS:000225387900014 ER PT J AU Hur, C Gazelle, GS Zalis, ME Podolsky, DK AF Hur, C Gazelle, GS Zalis, ME Podolsky, DK TI An analysis of the potential impact of computed tomographic colonography (virtual colonoscopy) on colonoscopy demand SO GASTROENTEROLOGY LA English DT Article ID COLORECTAL-CANCER; CT COLONOGRAPHY; CONVENTIONAL COLONOSCOPY; ASYMPTOMATIC ADULTS; POLYPS; NEOPLASIA; SCREEN; RECOMMENDATIONS; GUIDELINES; ADHERENCE AB Background & Aims: There has been much speculation about the potential impact on the use of conventional colonoscopy if "virtual" computed tomographic colonography (CTC) became a widely accepted modality for colorectal cancer (CRC) screening. However, no formal analysis of the impact of CTC on colonoscopy demand has been reported. Methods: A mathematical model to predict colonoscopy demand based on several relevant input parameters was constructed. Current national colonoscopy practice, estimated using various published reports, was used as the foundation to project colonoscopy demand if CTC were implemented as the primary CRC screening modality. Results: In the base-case analysis, if CTC were used as the primary modality for CRC screening, 1.78 million colonoscopies could be eliminated from the total 6.47 million in 2003. Depending on the polyp size threshold used to define a CTC study as positive (6 or 10 mm), this loss would be partially offset by 1.21 million (6 mm) or .34 million (10 mm) follow-up colonoscopies for CTC examinations with positive findings, resulting in a net loss of .57 million (8.8% decrease) (6 mm) or 1.44 million (22.3% decrease) (10 mm). Extensive sensitivity analyses showed that the findings of this model were robust and insensitive to most parameters tested but were sensitive to a few parameters, including the percentage of CTC examinations with positive findings. Conclusions: Wide-scale implementation of CTC for CRC screening would likely lead to a decrease in use of conventional colonoscopy. The percentage of CTC studies with positive findings seemed to be a pivotal variable, which would be determined in large part by the polyp size ultimately established to define a positive finding. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Hur, C (reprint author), 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 NR 30 TC 40 Z9 41 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 BP 1312 EP 1321 DI 10.1053/j.gastro.2004.07.018 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 870IC UT WOS:000225049800006 PM 15521000 ER PT J AU Davila, JA Morgan, RO Shaib, Y McGlynn, KA El-Serag, HB AF Davila, JA Morgan, RO Shaib, Y McGlynn, KA El-Serag, HB TI Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: A population-based study SO GASTROENTEROLOGY LA English DT Article ID CHRONIC LIVER-DISEASE; UNITED-STATES; INTERFERON THERAPY; DIABETES-MELLITUS; VIRAL-HEPATITIS; VIRUS-INFECTION; RISK-FACTORS; CIRRHOSIS; CANCER AB Background & Aims: A significant increase in the incidence of hepatocellular carcinoma (HCC) has been reported in the United States. The risk factors underlying this increase remain unclear. Methods: By using Surveillance, Epidemiology, and End-Results program (SEER)-Medicare-linked data, we conducted a population-based study to examine temporal changes in risk factors for patients 65 years and older diagnosed with HCC between 1993 and 1999. Only patients with continuous Medicare enrollment for 2 years before and up to 2 years after HCC diagnosis were examined. Univariate and multiple logistic regression analyses were used to evaluate changes in risk factors over time (January 1993-June 1996 and July 1996-December 1999). Results: The age-adjusted incidence of HCC among persons 65 years of age and older significantly increased from 14.2 per 100,000 in 1993 to 18.1 per 100,000 in 1999. We identified 2584 patients with continuous Medicare enrollment 2 years before and up to 2 years after HCC diagnosis. The proportion of hepatitis C virus (HCV)-related HCC increased from 11% during January of 1993 to June of 1996 to 21% during July of 1996 to December of 1999, whereas hepatitis B virus (HBV)-related HCC increased from 6% to 11% (P < .0001). In multiple logistic regression analyses that adjusted for age, sex, race, and geographic region, the risk for HCV-related HCC and HBV-related HCC increased by 226% and 67%, respectively. Idiopathic HCC decreased from 43% to 39%. This decrease did not fully account for the significant increases observed for HCV and HBV. No significant changes over time were observed for alcohol-induced liver disease, nonspecific cirrhosis, or nonspecific hepatitis. Conclusions: There has been a significant recent increase in HCV- and HBV-related HCC. Increasing rates of HCV-related HCC can explain a substantial proportion of the reported increase in HCC incidence during recent years. C1 Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu RI Morgan, Robert/A-8577-2009 NR 23 TC 284 Z9 296 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 BP 1372 EP 1380 DI 10.1053/j.gastro.2004.07.020 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 870IC UT WOS:000225049800012 PM 15521006 ER PT J AU McFarland, EG Zalis, ME AF McFarland, EG Zalis, ME TI CT colonography: Progress toward colorectal evaluation without catharsis SO GASTROENTEROLOGY LA English DT Editorial Material ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; CONVENTIONAL COLONOSCOPY; VIRTUAL COLONOSCOPY; FEASIBILITY; POLYPS C1 Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO 63130 USA. St Lukes Hosp, Dept Radiol, Chesterfield, MO USA. Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP McFarland, EG (reprint author), Washington Univ, Mallinckrodt Inst Radiol, Campus Box 8131, St Louis, MO 63130 USA. NR 17 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 BP 1623 EP + DI 10.1053/j.gastro.2004.09.060 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 870IC UT WOS:000225049800033 PM 15521027 ER PT J AU El-Serag, HB AF El-Serag, HB TI Hepatocellular carcinoma: Recent trends in the United States SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Workshop on Hepatocellular Carcinoma CY APR 01-03, 2004 CL Bethesda, MD ID PRIMARY LIVER-CANCER; HEPATITIS-C VIRUS; DIABETES-MELLITUS; RISK-FACTORS; NONALCOHOLIC STEATOHEPATITIS; VIRAL-HEPATITIS; DISEASE; POPULATION; PREVALENCE; INFECTION AB Hepatocellular carcinoma (HCC) is increasing in frequency in the United States. The age-adjusted incidence rates have doubled over the past 2 decades. Similar increases have affected the mortality and hospitalization rates. Although there has been a small recent improvement in survival, it remains generally dismal (median, 8 months). It is estimated that 8500 to 11,500 new cases of HCC occur annually in the United States. There are striking differences in the incidence of HCC related to age, gender, race, and geographic region. Although it remains an affliction of the elderly (mean age, 65 years) population, there has been a shift toward relatively younger age cases. Men are affected 3 times more frequently than women, Asians are affected 2 times more than blacks, and Hispanics are affected 2 times more often than whites. However, the recent increase has disproportionately affected white (and Hispanic) men between ages 45 and 65 years. The temporal changes of risk factors among HCC cases in the United States remain unclear. However, available studies indicate that hepatitis C virus (HCV) infection acquired 2-4 decades ago explains at least half of the observed increase in HCC; HCV-related HCC is likely to continue to increase for the next decade. A variable but significant proportion of cases (15% to 50%) do not have evidence of the risk factors of viral hepatitis or heavy alcohol consumption, The insulin resistance syndrome, manifesting as obesity and diabetes, is emerging as a risk factor for HCC in the United States; however, its impact on the current trend in HCC remains unclear. C1 Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu RI Jepsen, Peter/A-2593-2010 OI Jepsen, Peter/0000-0002-6641-1430 NR 37 TC 601 Z9 614 U1 3 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 SU 1 BP S27 EP S34 DI 10.1053/j.gastro.2004.09.013 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 871TJ UT WOS:000225156200004 PM 15508094 ER PT J AU Yates, WR Mitchell, J Rush, AJ Trivedi, MH Wisniewski, SR Warden, D Hauger, RB Fava, M Gaynes, BN Husain, MM Bryan, C AF Yates, WR Mitchell, J Rush, AJ Trivedi, MH Wisniewski, SR Warden, D Hauger, RB Fava, M Gaynes, BN Husain, MM Bryan, C TI Clinical features of depressed outpatients with and without co-occurring general medical conditions in STAR*D SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE depression; STAR*D; major depressive disorder; general medical conditions ID ILLNESS RATING-SCALE; FORM HEALTH SURVEY; MAJOR DEPRESSION; SYMPTOMATOLOGY IDS; ELDERLY-PATIENTS; COMORBIDITY; DISORDERS; CARE; PREVALENCE; INVENTORY AB Background: A significant percentage of patients with major depressive disorder (MDD) suffer from concurrent general medical conditions (GMCs). Objective: The objective of this preliminary report was to describe the rates of co-occurring significant GMCs and the clinical correlates and symptom features associated with the presence of GMCs. Design: Baseline cross-sectional case-control study of patients enrolling in a prospective randomized multistage treatment study of MDD. Setting: Fourteen regional U.S. centers representing 19 primary care and 22 psychiatric practices. Patients: One thousand five hundred outpatients with DSM-IV nonpsychotic MDD. Measurements: Sociodemographic status, medical illness ratings, psychiatric status, quality of life and DSM-IV depression symptom ratings. Results: The prevalence of significant medical comorbidity in this population was 52.8% (95% Cl 50.3-55.3%). Concurrent significant medical comorbidity was associated with older age, lower income, unemployment, limited education, longer duration of index depressive episode and absence of self-reported family history of depression. Somatic symptoms common in MDD were endorsed at a higher rate in those with GMCs. Those without a GMC had higher rates of endorsement of impaired mood reactivity, distinct mood quality and interpersonal sensitivity. Conclusions: Concurrent GMCs are common among outpatients with MDD in both primary care and specialty settings. Concurrent GMCs appear to influence the severity and symptom patterns in MDD and describe a vulnerable population with sociodemographic challenges to effective assessment and treatment. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK 74135 USA. Laureate Psychiat Clin & Hosp, Tulsa, OK 74136 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. Warren Clin, Tulsa, OK 74136 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. RP Yates, WR (reprint author), Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK 74135 USA. EM william-yates@ouhsc.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH90003] NR 53 TC 55 Z9 56 U1 1 U2 5 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 NOV-DEC PY 2004 VL 26 IS 6 BP 421 EP 429 DI 10.1016/j.genhosppsych.2004.06.008 PG 9 WC Psychiatry SC Psychiatry GA 879SD UT WOS:000225738300001 PM 15567207 ER PT J AU Su, XY Busson, M Della Valle, V Ballerini, P Dastugue, N Talmant, P Ferrando, AA Baudry-Bluteau, D Romana, S Berger, R Bernard, OA AF Su, XY Busson, M Della Valle, V Ballerini, P Dastugue, N Talmant, P Ferrando, AA Baudry-Bluteau, D Romana, S Berger, R Bernard, OA TI Various types of rearrangements target TLX3 locus in T-cell acute lymphoblastic leukemia SO GENES CHROMOSOMES & CANCER LA English DT Article ID HOX11L2 EXPRESSION; CDK6 GENE; TRANSLOCATION; T(5/14)(Q35,Q32); DYSREGULATION; ACTIVATION; CANCER AB Most chromosomal translocations observed in T-cell acute lymphoblastic leukemia (T-ALL) often produce transcriptional activation of transcription factor oncogenes. Ectopic expression of the TLX3 (also known as HOXIIL2) gene has been shown to be associated with a cryptic t(5; 14)(q35;q32) translocation specific for a subtype of T-ALL. Here we report several examples of variant and alternative translocations resulting in expression of TLX3 in T-ALL, and we describe three of these translocations in detail. In particular, the CDK6 gene was rearranged in two t(5;7)(q35;q21) translocations. In two additional instances, fusion of the BCLIIB (also known as CTIP2) and RANBP17/TLX3 loci were shown to result from subtle genomic insertion/deletion within these loci. This study further underscores that TLX3 expression in T-ALL is strongly associated with the presence of genomic rearrangements. (C) 2004 Wiley-Liss, Inc. C1 Hop Necker Enfants Malad, INSERM EMI 0210, IRNEM, F-75015 Paris, France. Hop Enfants Armand Trousseau, Serv Hematol BIol, Paris, France. Hop Purpan, Hematol Lab, Toulouse, France. Hop Hotel Dieu, Lab Cytogenet, Nantes, France. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bernard, OA (reprint author), Hop Necker Enfants Malad, INSERM EMI 0210, IRNEM, 149 Rue Sevres, F-75015 Paris, France. EM olivier.bernard@necker.fr RI Bernard, Olivier/E-5721-2016 NR 20 TC 32 Z9 32 U1 0 U2 0 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 NOV PY 2004 VL 41 IS 3 BP 243 EP 249 DI 10.1002/gc.20088 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 857LU UT WOS:000224119000007 PM 15334547 ER PT J AU Keller, C Arenkiel, BR Coffin, CM El-Bardeesy, N DePinho, RA Capecchi, MR AF Keller, C Arenkiel, BR Coffin, CM El-Bardeesy, N DePinho, RA Capecchi, MR TI Alveolar rhabdomyosarcomas in conditional Pax3 : Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function SO GENES & DEVELOPMENT LA English DT Article DE alveolar rhabdomyosarcoma; Pax3 : Fkhr; Pax3; Fkhr; FoxO1A; chromosome translocation; satellite cell ID SKELETAL-MUSCLE DEVELOPMENT; CHILDHOOD RHABDOMYOSARCOMA; SATELLITE CELLS; PAX7 EXPRESSION; GENE-EXPRESSION; FUSION PROTEIN; HUMAN CANCER; MUTANT MICE; STEM-CELLS; MUTATIONS AB Alveolar rhabdomyosarcoma is an aggressive childhood muscle cancer for which outcomes are poor when the disease is advanced. Although well-developed mouse models exist for embryonal and pleomorphic rhabdomyosarcomas, neither a spontaneous nor a transgenic mouse model of alveolar rhabdomyosarcoma has yet been reported. We report the first mouse model of alveolar rhabdomyosarcoma using a conditional Pax3.Fkhr knock-in allele whose activation in late embryogenesis and postnatally is targeted to terminally differentiating Myf6-expressing skeletal muscle. In these mice, alveolar rhabdomyosarcomas occur but at low frequency, and Fkhr haploinsufficiency does not appear to accelerate tumorigenesis. However, Pax3.Fkhr homozygosity with accompanying Ink4a/ARF or Trp53 pathway disruption, by means of conditional Trp53 or Ink4a/ARF loss of function, substantially increases the frequencies of tumor formation. These results of successful tumor generation postnatally from a target pool of differentiating myofibers are in sharp contrast to the birth defects and lack of tumors for mice with prenatal and postnatal satellite cell triggering of Pax3.Fkhr. Furthermore, these murine alveolar rhabdomyosarcomas have an immunohistochemical profile similar to human alveolar rhabdomyosarcoma, suggesting that this conditional mouse model will be relevant to study of the disease and will be useful for preclinical therapeutic testing. C1 Univ Utah, Div Pediat Hematol Oncol, Salt Lake City, UT 84112 USA. Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. Univ Utah, Div Pediat Pathol, Salt Lake City, UT 84112 USA. Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA. Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Capecchi, MR (reprint author), Univ Utah, Div Pediat Hematol Oncol, Salt Lake City, UT 84112 USA. EM mario.capecchi@genetics.utah.edu OI Keller, Charles/0000-0003-2505-7487 FU NCI NIH HHS [1K08 CA90438-01, K08 CA090438, P30 CA042014, P30 CA42014] NR 55 TC 187 Z9 196 U1 0 U2 2 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 NOV 1 PY 2004 VL 18 IS 21 BP 2614 EP 2626 DI 10.1101/gad.1244004 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 867YM UT WOS:000224878900006 PM 15489287 ER PT J AU Hieronymus, H Yu, MC Silver, PA AF Hieronymus, H Yu, MC Silver, PA TI Genome-wide mRNA surveillance is coupled to mRNA export SO GENES & DEVELOPMENT LA English DT Article DE mRNA export; mRNA surveillance; DNA repair; nuclear exosome; Lrp1; Rrp6 ID SACCHAROMYCES-CEREVISIAE GENOME; NUCLEOTIDE EXCISION-REPAIR; HUMAN PM-SCL; POLYMERASE-II; INTERACTION NETWORK; QUALITY-CONTROL; NUCLEAR EXPORT; YEAST EXOSOME; RIBOSOMAL-RNA; THO COMPLEX AB Nuclear export of mRNA is a central step in gene expression that shows extensive coupling to transcription and transcript processing. However, little is known about the fate of mRNA and its export under conditions that damage the DNA template and RNA itself. Here we report the discovery of four new factors required for mRNA export through a screen of all annotated nonessential Saccharomyces cerevisiae genes. Two of these factors, mRNA surveillance factor Rrp6 and DNA repair protein Lrp1, are nuclear exosome components that physically interact with one another. We find that Lrp1 mediates specific mRNA degradation upon DNA-damaging UV irradiation as well as general mRNA degradation. Lrp1 requires Rrp6 for genomic localization to genes encoding its mRNA targets, and Rrp6 genomic localization in turn correlates with transcription. Further, Rrp6 and Lrp1 are both required for repair of UV-induced DNA damage. These results demonstrate coupling of mRNA surveillance to mRNA export and suggest specificity of the RNA surveillance machinery for different transcript populations. Broadly, these findings link DNA and RNA surveillance to mRNA export. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM Pamela_Silver@dfci.harvard.edu NR 55 TC 80 Z9 82 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 NOV 1 PY 2004 VL 18 IS 21 BP 2652 EP 2662 DI 10.1101/gad.1241204 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 867YM UT WOS:000224878900009 PM 15489286 ER PT J AU Wang, G Maher, E Brennan, C Chin, L Leo, C Kaur, M Zhu, P Rook, M Wolfe, JL Makrigiorgos, GM AF Wang, G Maher, E Brennan, C Chin, L Leo, C Kaur, M Zhu, P Rook, M Wolfe, JL Makrigiorgos, GM TI DNA amplification method tolerant to sample degradation SO GENOME RESEARCH LA English DT Article ID WHOLE-GENOME AMPLIFICATION; ROLLING-CIRCLE AMPLIFICATION; PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYMERASE CHAIN-REACTION; GENE-EXPRESSION PATTERNS; BREAST-CANCER; CELL-LINES; DISPLACEMENT AMPLIFICATION; MICROSATELLITE INSTABILITY; AMPLIFIED DNA AB Despite recent advances in linear whole genome amplification of intact DNA/RNA, amplification of degraded nucleic acids in all unbiased fashion remains a serious challenge for genetic diagnosis. We describe a new whole genome amplification procedure, RCA-RCA (Restriction and Circularization-Aided Rolling Circle Amplification), which retains the allelic differences among degraded amplified genomes while achieving almost complete genome coverage. RCA-RCA utilizes restriction digestion and whole genome circularization to generate genomic sequences amenable to rolling circle amplification. When intact genomic DNA is used, RCA-RCA retains gene-amplification differences (twofold or higher) between complex genomes on a genome-wide scale providing highly improved concordance with unamplified material as compared with other amplification methodologies including multiple displacement amplification. Using RCA-RCA, formalin-fixed samples of modest or substantial DNA degradation were successfully amplified and screened via array-CGH or Taqman PCR that displayed retention of the principal gene amplification features of the original material. Microsatellite analysis revealed that RCA-RCA amplified genomic DNA is representative of the original material at the nucleotide level. Amplification of cDNA is successfully performed via RCA-RCA and results to unbiased gene expression analysis (R-2 = 0.99). The simplicity and universal applicability of RCA-RCA make it a powerful new tool for genome analysis With unique advantages over previous amplification technologies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Rochelle Belfer Canc Genom Ctr, Boston, MA 02115 USA. Variagen Inc, Cambridge, MA 02140 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [P50 CA 93638, P50 CA093683] NR 38 TC 55 Z9 59 U1 4 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 NOV PY 2004 VL 14 IS 11 BP 2357 EP 2366 DI 10.1101/gr.2813404 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 868LC UT WOS:000224914100017 PM 15520297 ER PT J AU Newburg, DS Polak, JJ Wilhelm, SN Stepans, MB Jacewicz, MS Newburg, DS AF Newburg, DS Polak, JJ Wilhelm, SN Stepans, MB Jacewicz, MS Newburg, DS TI Comparative analysis of oligosaccharides in human milk and feces using high performance thin layer chromatography SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 Massachusetts Gen Hosp, Program Glycobiol, Mucosal Immunol Lab, Boston, MA 02129 USA. Univ Nebraska, Coll Nursing, Scottsbluff, NE 69361 USA. Univ Massachusetts, Sch Med, Shriver Ctr, Waltham, MA 02452 USA. NR 0 TC 1 Z9 1 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 353 BP 1152 EP 1152 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400361 ER PT J AU Lee, CW Matulonis, UA Castells, MC AF Lee, CW Matulonis, UA Castells, MC TI Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-mediated reactions SO GYNECOLOGIC ONCOLOGY LA English DT Article DE carboplatin hypersensitivity; carboplatin desensitization; carboplatin skin test ID SINGLE-AGENT CARBOPLATIN; OVARIAN-CANCER; RANDOMIZED-TRIAL; CISPLATIN; PACLITAXEL; EXPERIENCE; PLATINUM; WOMEN; CYCLOPHOSPHAMIDE; CHEMOTHERAPY AB Objectives. The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 12-step desensitization protocol and to characterize the immune mechanism of carboplatin HR. Methods. We analyzed 10 consecutive patients who had documented HR to carboplatin and in whom continued treatment with carboplatin was considered advantageous. The patients were treated with carboplatin using a 6-h, 12-step desensitization protocol with a 30-min premedication regimen. Skin tests were performed on five patients. Results. Ten patients successfully completed 35 planned courses of desensitizations to carboplatin, 31 of which were without reactions. Four patients had symptoms during their first (n = 3) and third (n = 1) desensitizations but tolerated the re-administration of infusions without further reactions. For subsequent courses, the protocol was modified for two patients who had extracutaneous symptoms during desensitization and was unchanged for the patient who had mild urticaria. These three patients tolerated subsequent courses of desensitizations without reactions. The fourth patient with symptoms during desensitization no longer required carboplatin due to progressive disease. Of the five patients who were skin tested to carboplatin, four had positive wheal and flare reactions. In one patient, the skin test response to carboplatin became negative after desensitization. Conclusion. The 6-h, 12-step desensitization protocol is safe and effective for treating patients with carboplatin HR. Positive skin tests to carboplatin suggest a mast cell/IgE-mediated mechanism. Conversion of the positive skin test to a negative response after desensitization supports antigen-specific mast cell desensitization. (C) 2004 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Castells, MC (reprint author), 850 Boylston St,Suite 540, Chestnut Hill, MA 02467 USA. EM mcastells@partners.org NR 29 TC 75 Z9 77 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 NOV PY 2004 VL 95 IS 2 BP 370 EP 376 DI 10.1016/j.ygyno.2004.08.002 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 868TX UT WOS:000224937000014 PM 15491759 ER PT J AU Ring, D AF Ring, D TI Open reduction and internal fixation of fractures of the radial head SO HAND CLINICS LA English DT Article ID ABSORBABLE POLYGLYCOLIDE PINS; SILICONE-RUBBER REPLACEMENT; ELBOW FOLLOWING EXCISION; INTRAARTICULAR FRACTURES; LIGAMENTOUS INJURIES; ROTATORY INSTABILITY; OPERATIVE TREATMENT; DISLOCATION; JOINT; STABILITY AB Early reports of open reduction and internal fixation of fractures of the radial head were positive, perhaps because of the prevalence of isolated partial head fractures for which good results would be expected. Subsequent reports have found that complex fractures of the radial head are prone to early failure, nonunion, and poor forearm rotation after operative fixation. Combined with increased availability and use of metal radial head prosthesis for complex fractures of the radial head, the role of open reduction and internal fixation is being redefined. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Wang Ambulatory Ctr 525, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Wang Ambulatory Ctr 525, 15 Parkman St, Boston, MA 02114 USA. EM dring@partners.org NR 79 TC 32 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD NOV PY 2004 VL 20 IS 4 BP 415 EP + DI 10.1016/j.hcl.2004.06.001 PG 14 WC Orthopedics SC Orthopedics GA 876BA UT WOS:000225469200006 PM 15539097 ER PT J AU Carey, K Dor, A AF Carey, K Dor, A TI Trends in contract management: The hidden evolution in hospital organization SO HEALTH AFFAIRS LA English DT Article ID MARKET-STRUCTURE; COMPETITION; EMPLOYMENT; IMPACT AB Contract management is an arrangement whereby the day-to-day operation of the hospital is contracted to an outside organization. In the past two decades there has been dramatic growth in the number of hospitals opting for contract management, yet surprisingly little attention has been paid to this phenomenon. Using national data, we report trends and demonstrate that adoption of contracts results in decreases in service offerings more often than increases. Since contract-managed hospitals tend to be located in rural areas, this raises concerns regarding access to care. On the other hand, contract management may allow distressed hospitals to survive. C1 Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. US Dept Vet Affairs, Management Sci Grp, Bedford, MA USA. Case Western Reserve Univ, Weatherhead Sch Management, Cleveland, OH 44106 USA. Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Carey, K (reprint author), Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. EM Kathleen.Carey@med.va.gov OI Carey, Kathleen/0000-0002-7924-431X NR 22 TC 4 Z9 4 U1 1 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2004 VL 23 IS 6 BP 192 EP 199 DI 10.1377/hlthaff.23.6.192 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 909CF UT WOS:000227835800026 PM 15537598 ER PT J AU Blumenthal, D AF Blumenthal, D TI Decisions, decisions: Why the quality of medical decisions matters SO HEALTH AFFAIRS LA English DT Article AB Questions about the process leading to particular medical decisions are Seldom addressed in discussions of health care quality. In some cases, strict adherence to treatment protocols may overlook important elements in the clinical decision-making process, such as physicians' judgment and patients' preferences. Papers by Annette O'Connor and colleagues and Karen Sepucha and colleagues are welcome additions to this debate because they highlight the importance of the medical decision-making process; they suggest that the quality of this process should be considered when evaluating health care quality. I explore some key limitations and uncertainties that must be addressed before work in this area can become broadly applicable. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Partners Hlth Care Syst, Boston, MA USA. RP Blumenthal, D (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM dblumenthal@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2004 VL 23 IS 6 BP VAR124 EP VAR127 DI 10.1377/hlthaff.var.124 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 909CF UT WOS:000227835800077 ER PT J AU Sepucha, KR Fowler, FJ Mulley, AG AF Sepucha, KR Fowler, FJ Mulley, AG TI Policy support for patient centered care: The need for measurable improvements in decision quality SO HEALTH AFFAIRS LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; SMALL-AREA VARIATIONS; GEOGRAPHIC VARIATIONS; REGIONAL-VARIATIONS; SURGICAL-PROCEDURES; APPROPRIATENESS; PROSTATECTOMY; SATISFACTION; SERVICES; OUTCOMES AB The phenomenon of practice variation draws attention to the need for better management of clinical decision making as a means of ensuring quality. Different policies to address variations, including guidelines and measures of appropriateness, have had little demonstrable impact on variation itself or on the underlying quality problems. Variations in rates of interventions raise questions about the patient-centeredness of decisions that determine what care is provided to whom. Policies that support the development and routine use of measures of decision quality will provide opportunities to measurably improve the quality of decisions, thereby leading to more patient-centered and efficient health care. C1 Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. Fdn Informed Med Decis Making, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Sepucha, KR (reprint author), Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. EM ksepucha@partners.org NR 27 TC 5 Z9 5 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2004 VL 23 IS 6 BP VAR54 EP VAR62 DI 10.1377/hlthaff.var.54 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 909CF UT WOS:000227835800066 ER PT J AU Mansour, M Mela, T Ruskin, J Keane, D AF Mansour, M Mela, T Ruskin, J Keane, D TI Successful release of entrapped circumferential mapping catheters in patients undergoing pulmonary vein isolation for atrial fibrillation SO HEART RHYTHM LA English DT Article DE atrial fibrillation; pulmonary vein ID MITRAL-VALVE APPARATUS; ABLATION; ENTRAPMENT AB OBJECTIVES The purpose of this study was to demonstrate a method for successful and safe release of an entrapped circular catheter. BACKGROUND Segmental pulmonary vein (PV) isolation is widely practiced for patients with symptomatic drug-refractory atrial fibrillation. A circular mapping catheter is sometimes used with this technique to map the electrical connection between the left atrium (LA) and the PVs. This catheter reportedly can become entrapped in the mitral valve apparatus. Attempts to free the entrapped catheter can result in serious complications, including damage to the mitral valve chordae tendineae or fracture of the catheter itself. METHODS Three patients were referred for PV isolation for atrial fibrillation. A circular mapping catheter was used to map the sites of LA-PV electrical connections. RESULTS During the procedure, the circular mapping catheter became entrapped in the mitral valve apparatus in two patients and in the PV in one patient. A series of maneuvers, which included use of another catheter and guiding sheaths as well as pushing forward rather than pulling back on the entrapped catheter, allowed safe and successful release of the entrapped catheter in all patients. CONCLUSIONS Entrapment of the circular mapping in the mitral valve apparatus or the PVs during PV isolation is a rare complication associated with use this catheter. We describe a series of maneuvers that may allow safe and successful release of the entrapped catheter. (C) 2004 Heart Rhythm Society. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Boston, MA USA. RP Keane, D (reprint author), St James Hosp, Cardiac Arrhythmia Serv, St Jamess St, Dublin 8, Ireland. EM dkeane@stjames.ie NR 6 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2004 VL 1 IS 5 BP 558 EP 561 DI 10.1016/j.hrthm.2004.07.004 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 888TD UT WOS:000226396200006 PM 15851219 ER PT J AU Zembowicz, A Mihm, MC AF Zembowicz, A Mihm, MC TI Dermal dendritic melanocytic proliferations: an update SO HISTOPATHOLOGY LA English DT Review ID CELLULAR BLUE NEVUS; EQUINE MELANOTIC DISEASE; PILAR NEUROCRISTIC HAMARTOMA; ANIMAL-TYPE MELANOMA; MALIGNANT-MELANOMA; CARNEY COMPLEX; MONGOLIAN SPOT; VARIANT; TUMOR; NEOPLASMS AB Dermal dendritic melanocytic proliferations are a broad group of congenital and acquired melanocytic lesions characterized by the presence of dermal spindled and dendritic cells resembling melanocytes migrating from the neural crest to the epidermis. Historically, they were subdivided into dermal melanocytoses (naevus of Ota, Ito, Mongolian spot and related conditions), blue naevi and malignant blue naevi. The purpose of this review is to provide an update on recent developments in the field with emphasis on new entities and their differential diagnosis. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Warren 820,55 Fruit St, Boston, MA 02114 USA. EM azembowicz@partners.org NR 94 TC 70 Z9 71 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD NOV PY 2004 VL 45 IS 5 BP 433 EP 451 DI 10.1111/j.1365-2559.2004.01975.x PG 19 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 864LE UT WOS:000224634200001 PM 15500647 ER PT J AU Davis-Michaud, M Yurk, R Lansky, D Asch, S Wu, AW AF Davis-Michaud, M Yurk, R Lansky, D Asch, S Wu, AW TI Quality care for people with HIV/AIDS: Patients perspectives SO HIV CLINICAL TRIALS LA English DT Article DE evaluation studies; focus groups; human immunodeficiency virus; outcomes assessment (health care); patient satisfaction; quality of care ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED ADULTS; UNITED-STATES; DRUG-THERAPY; OF-LIFE; HEALTH; SERVICES; DISEASE; RELIABILITY; STRATEGIES AB Purpose: To explore patient preferences to aid in the development of quality measures to assess quality of health care for people living with human immunodeficiency virus/acquired immunodeficiency disease (HIV/AIDS). Method: This study involved three 2-hour focus groups with 29 people living with HIV/AIDS in Portland, Oregon, and San Francisco, California. Eighteen quality of care indicators for HlV/AlDS health care were presented to each group and quantitative rankings were obtained. Aggregated weightings were used to rank and prioritize the quality measures for further exploration. Results: Participants identified 38 themes relevant to high-quality care for HIV/AIDS. Patients ranked the following candidate measures most important: effective relationship with provider, prevention of opportunistic infections, involvement in care and treatment decisions, being offered antiretroviral treatment, and access to health care services. We observed attitudinal differences among focus group participants that corresponded to gender and race/ethnicity. Conclusion: Participants favored quality information that rated the experience of care and outcome measures including indicators of access to services, standard treatments, and competence of the providers. Patient perspectives can inform the development of quality measures that are meaningful to consumers and can assist in the design of services that meet patients' demographic and socioeconomic needs. C1 Johns Hopkins Univ, Hlth Serv Res, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Portland VA Med Ctr, Med Serv, Portland, OR USA. Fdn Accountabil, Portland, OR USA. RAND Corp, Los Angeles, CA USA. Vet Adm Healthcare Syst, Los Angeles, CA USA. RP Wu, AW (reprint author), Johns Hopkins Univ, Hlth Serv Res, Bloomberg Sch Publ Hlth, 624 N Broadway, Baltimore, MD 21205 USA. EM awu@jhsph.edu NR 40 TC 8 Z9 9 U1 0 U2 0 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD NOV-DEC PY 2004 VL 5 IS 6 BP 406 EP 415 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 894NY UT WOS:000226800000006 PM 15682354 ER PT J AU Meeker, JD Singh, NP Ryan, L Duty, SM Barr, DB Herrick, RF Bennett, DH Hauser, R AF Meeker, JD Singh, NP Ryan, L Duty, SM Barr, DB Herrick, RF Bennett, DH Hauser, R TI Urinary levels of insecticide metabolites and DNA damage in human sperm SO HUMAN REPRODUCTION LA English DT Article DE comet assay; DNA damage; exposure; insecticides ID DOUBLE-STRAND BREAKS; CARBARYL-EXPOSED EMPLOYEES; COMET ASSAY; IN-VITRO; SPINDLE DISTURBANCES; MAMMALIAN-CELLS; C-MITOSIS; RATS; PESTICIDES; REPAIR AB Background: Members of the general population are exposed to non-persistent insecticides at low levels. The present study explored whether environmental exposures to carbaryl and chlorpyrifos are associated with DNA damage in human sperm. Methods: Subjects (n=260) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary metabolite concentrations of chlorpyrifos [3,5,6-trichloro-2-pyridinol (TCPY)] and carbaryl [1-naphthol (1N)], adjusted using specific gravity. Sperm DNA integrity was assessed by neutral comet assay and reported as comet extent, percentage DNA in comet tail (Tail%) and tail distributed moment (TDM). Results: A statistically significant increase in Tail% was found for an interquartile range (IQR) increase in both 1N [coefficient = 4.1; 95% confidence interval (CI) 1.9-6.3] and TCPY (2.8; 0.9-4.6), while a decrease in TDM was associated with IQR changes in 1N (-2.2; -4.9 to 0.5) and TCPY (-2.5; -4.7 to -0.2). A negative correlation between Tail% and TDM was present only when stratified by comet extent, suggesting that Tail% and TDM may measure different types of DNA damage within comet extent strata. Conclusions: Environmental exposure to carbaryl and chlorpyrifos may be associated with increased DNA damage in human sperm, as indicated by a change in comet assay parameters. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Simmons Coll, Sch Hlth Studies, Nursing Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1 Room 1405,665 Huntington Ave, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu RI Ryan, Louise/A-4562-2009; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013; OI Ryan, Louise/0000-0001-5957-2490; Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [ES00002, ES09718] NR 52 TC 54 Z9 62 U1 4 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 2004 VL 19 IS 11 BP 2573 EP 2580 DI 10.1093/humrep/deh444 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 865LB UT WOS:000224703500024 PM 15333606 ER PT J AU Franco, V Chen, YF Oparil, S Feng, JA Wang, DJ Hage, F Perry, G AF Franco, V Chen, YF Oparil, S Feng, JA Wang, DJ Hage, F Perry, G TI Atrial natriuretic peptide dose-dependently inhibits pressure overload-induced cardiac remodeling SO HYPERTENSION LA English DT Article DE atrial natriuretic factor; natriuretic peptides; receptors, atrial natriuretic factor; hypertrophy, cardiac; remodeling; extracellular matrix; collagen ID CLEARANCE-RECEPTOR GENE; GUANYLYL CYCLASE-A; MATRIX METALLOPROTEINASES; ESSENTIAL-HYPERTENSION; INDEPENDENT ENHANCEMENT; TRANSGENIC MICE; DEFICIENT MICE; NITRIC-OXIDE; HYPERTROPHY; EXPRESSION AB We hypothesized that a single copy of the proatrial natriuretic peptide gene (Nppa(+/-)) would not be adequate to protect heterozygous mice against exaggerated cardiac hypertrophy and remodeling after pressure-overload stress. Nppa(+/+), Nppa(+/-), and Nppa(-/-) mice were subjected to sham surgery or transverse aortic constriction and fed a basal salt diet. Heart weight varied inversely with Nppa gene load by 1 week after either surgery. Fractional shortening did not differ among genotypes at baseline and fell in Nppa(-/-) mice only after transverse aortic constriction. There was a graded response in collagen deposition related to atrial natriuretic peptide (ANP) expression after either surgery. A robust interstitial and perivascular fibrosis was noted in Nppa(-/-) and Nppa(+/-) but not in Nppa(+/+) mice after transverse aortic constriction. Our findings are consistent with a growing body of evidence that ANP is an important modulator of cardiac hypertrophy and remodeling in response to hemodynamic stress. The observation that partial ANP deficiency results in exaggerated hypertrophy and remodeling after pressure overload suggests that genetic or environmental variation in ANP levels may play a role in the development of cardiac hypertrophy, remodeling, and failure in humans. C1 Univ Alabama, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Franco, V (reprint author), Univ Alabama, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, ZRB 1024,703 19th St S, Birmingham, AL 35294 USA. EM vfranco@uab.edu RI Franco, Veronica/E-3080-2011; OI Hage, Fadi/0000-0002-1397-4942 FU NHLBI NIH HHS [HL07457, HL44195] NR 34 TC 50 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2004 VL 44 IS 5 BP 746 EP 750 DI 10.1161/01.HYP.0000144801.09557.4c PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866GI UT WOS:000224761500029 PM 15452027 ER PT J AU Ding, D Cooper, RA Guo, SF Corfman, TA AF Ding, D Cooper, RA Guo, SF Corfman, TA TI Analysis of driving backward in an electric-powered wheelchair SO IEEE TRANSACTIONS ON CONTROL SYSTEMS TECHNOLOGY LA English DT Article DE directional stability control; electric-powered wheelchair; reverse driving; simulation; wheelchair dynamics model ID STABILITY; MODEL AB The purpose of this study was to examine the influences of caster orientations and driving speeds on the reverse directional stability of electric-powered wheelchairs. An experiment was set up to record wheelchair trajectories and ground reaction forces/moments for the front caster wheels and rear wheels when a wheelchair initiates reverse motions at six initial caster orientations and three desired driving speeds. A kinematic model as well as a dynamic model were developed to simulate the wheelchair motion and conduct a parametric study of different factors on wheelchair reverse directional stability. The experimental and simulation results show agreement, both of which indicate that different caster orientations at the start of reverse driving introduce disturbances and the faster the intended speed, the less deviation of the wheelchair from its desired heading. The center of gravity (CG) was also found to be a dominant influence on the reverse directional stability of power wheelchairs. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15026 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Human Engn Res Labs, Pittsburgh, PA 15026 USA. Univ Pittsburgh, Sch Engn, Dept Bioengn, Pittsburgh, PA 15260 USA. RP VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15026 USA. EM dad5@pitt.edu; rcooper@pitt.edu; sguo@pitt.edu; corfmant@herlpitt.org NR 21 TC 18 Z9 18 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1063-6536 EI 1558-0865 J9 IEEE T CONTR SYST T JI IEEE Trans. Control Syst. Technol. PD NOV PY 2004 VL 12 IS 6 BP 934 EP 943 DI 10.1109/TCST.2004.833638 PG 10 WC Automation & Control Systems; Engineering, Electrical & Electronic SC Automation & Control Systems; Engineering GA 865GI UT WOS:000224690200011 ER PT J AU Zalis, ME Perumpillichira, J Hahn, PE AF Zalis, ME Perumpillichira, J Hahn, PE TI Digital subtraction bowel cleansing for CT colonography using morphological and linear filtration methods SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE computed tomography; segmentation; virtual colonoscopy ID COLONOSCOPY AB We describe a method to perform postacquisition processing of computed tomography colonography (virtual colonoscopy) datasets that results in electronic removal of opacified, ingested bowel contents while reconstructing natural appearing boundaries of colon lumen and thereby permitting three-dimensional visual analyses of the resulting colon models. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Zalis, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mzalis@partners.org NR 16 TC 53 Z9 56 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD NOV PY 2004 VL 23 IS 11 BP 1335 EP 1343 DI 10.1109/TMI.2004.826050 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 868QY UT WOS:000224929300002 PM 15554122 ER PT J AU Kalliomaki, MA Isolauri, E AF Kalliomaki, MA Isolauri, E TI Probiotics and down-regulation of the allergic response SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID INDUCED AIRWAY HYPERREACTIVITY; INTESTINAL EPITHELIAL-CELLS; LACTOBACILLUS-RHAMNOSUS GG; ANTHROPOSOPHIC LIFE-STYLE; PLACEBO-CONTROLLED TRIAL; BIRCH-POLLEN ALLERGY; LACTIC-ACID BACTERIA; GROWTH-FACTOR-BETA; ATOPIC DISEASE; DENDRITIC-CELL AB The first clinical trials with probiotics, especially in the treatment of atopic eczema, have yielded encouraging results. Experimental studies have found that probiotics exert strain-specific effects in the intestinal lumen and on epithelial cells and immune cells with anti-allergic potential. These effects include enhancement in antigen degradation and gut barrier function and induction of regulatory and proinflammatory immune responses, the latter of which occurs more likely beyond the intestinal epithelium. Future studies should address more accurately how these and other possible mechanisms operate in the complex gastrointestinal macroenvironment in vivo and how these mechanisms are related to the clinical effects in a dose-dependent manner. C1 Univ Turku, Dept Pediat, FIN-20521 Turku, Finland. Turku Univ Hosp, FIN-20521 Turku, Finland. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02139 USA. RP Kalliomaki, MA (reprint author), Univ Turku, Dept Pediat, POB 52, FIN-20521 Turku, Finland. EM marko.kalliomaki@utu.fi RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 89 TC 41 Z9 48 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD NOV PY 2004 VL 24 IS 4 BP 739 EP + DI 10.1016/j.iac.2004.06.006 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA 992XC UT WOS:000233916300013 PM 15474869 ER PT J AU LaVela, SL Smith, B Weaver, FM Legro, MW Goldstein, B Nichol, K AF LaVela, SL Smith, B Weaver, FM Legro, MW Goldstein, B Nichol, K TI Attitudes and practices regarding influenza vaccination among healthcare workers providing services to individuals with spinal cord injuries and disorders SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; NOSOCOMIAL INFLUENZA; NURSING-HOMES; PNEUMOCOCCAL VACCINATION; ADVERSE REACTIONS; ELDERLY PATIENTS; WORKING ADULTS; MORTALITY AB OBJECTIVE: To examine influenza vaccination status and predictors for vaccine receipt among healthcare workers (HCWs) caring for patients with spinal cord injuries and disorders. DESIGN: Cross-sectional, nationwide anonymous survey. SETTING: Twenty-three Veterans Affairs spinal cord injury centers. PARTICIPANTS: One thousand five hundred fifty-six HCWs. METHODS: the primary outcome was staff vaccination status. Independent variables included staff demographic and employment characteristics, health status, attitudes and beliefs about the vaccine, and implications for its use. RESULTS: The staff vaccination rate was 51%. Leading motivators of vaccine receipt were self-protection (77%) and patient protection (49%). The most common reasons for nonreceipt were concerns about side effects (49%), preventive quality (20%), and inconvenience (14%). Logistic regression results suggested that age of 50 years or older (OR, 1.47; P =.021), male gender (OR, 2.50; P <.001), strong belief in vaccine effectiveness (OR, 19.03; P =.008), and importance of HCW vaccination (OR, 20.50; P =.005) significantly increased the probability of vaccination. Recommending the vaccine to coworkers, patients, or patients' families was also associated with HCW vaccination (OR, 3.20; P <.001). Providers who did not believe the vaccine was protective (P <.001) or effective (P <.001) were less likely to recommend it to patients. CONCLUSIONS: Strategies to increase vaccination rates among HCWs should address concerns about side effects, effectiveness, and protective value of the vaccine and access to it. The impact of provider recommendations should be stressed. Vaccination and subsequent prevention of illness may limit morbidity and mortality, thus benefiting HCWs, healthcare facilities, and patients (Infect Control Hosp Epidemiol 2004;25:933-940). C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Spinal Cord Injury Quality Enhancement Res Initia, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Chicago, IL 60611 USA. Puget Sound Hlth Care Syst, Spinal Cord Injury Qual Enhancement Res Initiat, Hlth Serv Res & Dev, Seattle, WA USA. US Dept Vet Affairs, Spinal Cord Injury & Disorders Strateg Healthcare, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. US Dept Vet Affairs, Dept Rehabil Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. US Dept Vet Affairs, Minneapolis Vet Affairs Med Ctr, Med Serv, Minneapolis, MN USA. RP LaVela, SL (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Spinal Cord Injury Quality Enhancement Res Initia, Midwest Ctr Hlth Serv & Policy Res, 151-H, Hines, IL 60141 USA. NR 68 TC 57 Z9 60 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD NOV PY 2004 VL 25 IS 11 BP 933 EP 940 DI 10.1086/502323 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 870TA UT WOS:000225079800015 PM 15566027 ER PT J AU Jubran, A AF Jubran, A TI Pulse oximetry SO INTENSIVE CARE MEDICINE LA English DT Article C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. RP Jubran, A (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111 N, Hines, IL 60141 USA. EM ajubran@lumc.edu NR 11 TC 58 Z9 59 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 2004 VL 30 IS 11 BP 2017 EP 2020 DI 10.1007/s00134-004-2399-x PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 869AZ UT WOS:000224956000005 PM 15278272 ER PT J AU Zhong, WM Reinherz, EL AF Zhong, WM Reinherz, EL TI In vivo selection of a TCR V beta repertoire directed against an immunodominant influenza virus CTL epitope SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE influenza virus; repertoire; T cell receptor; vaccination ID T-CELL-RECEPTOR; NUCLEOPROTEIN EPITOPE; AFFINITY MATURATION; ANTIGEN RECEPTOR; RECALL RESPONSES; VIRAL-INFECTION; ALPHA-BETA; PEPTIDE; MEMORY; DIVERSITY AB Little is known about the mechanisms governing TCR repertoire selection in response to foreign antigens. Here, we evaluate the molecular features of the murine C57BL/6 (B6) TCR Vbeta repertoire directed at the NP366-374 immunodominant epitope of the influenza virus nucleoprotein. Common or 'public' beta chains are shared among individuals following either primary or secondary infection. Importantly, repertoire diversity decreases substantially after a second viral exposure due to enrichment of TCRs sharing Vbeta CDR3 loops of identical length and highly related amino acid sequences. TCRs from these secondary T cell populations possess greater overall avidity for the NP366-374/D-b complex compared to those from the primary repertoire. Thus, expansion of CD8(+) T cells expressing a favored germline Vbeta gene segment in the primary response and further selection for CDR3beta loops during the secondary response, contribute to optimization of immune recognition against certain viral epitopes. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Lab Immunobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA USA. RP Zhong, WM (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Lab Immunobiol, Boston, MA 02114 USA. EM weimin_zhong@dfci.harvard.edu; ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI50900] NR 36 TC 29 Z9 29 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2004 VL 16 IS 11 BP 1549 EP 1559 DI 10.1093/intimm/dxh156 PG 11 WC Immunology SC Immunology GA 862HT UT WOS:000224482300001 PM 15351787 ER PT J AU Siegler, G Meyer, B Dawson, C Brachtel, E Lennerz, J Koch, C Kremmer, E Niedobitek, E Gonnella, R Pilch, BZ Young, LS Niedobitek, G AF Siegler, G Meyer, B Dawson, C Brachtel, E Lennerz, J Koch, C Kremmer, E Niedobitek, E Gonnella, R Pilch, BZ Young, LS Niedobitek, G TI Expression of tumor necrosis factor receptor-associated factor 1 in nasopharyngeal carcinoma: Possible upregulation by Epstein-Barr virus latent membrane protein 1 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Epstein-Barr virus; LMP1; TRAF1; nasopharyngeal carcinoma ID MEMBRANE-PROTEIN 1; NF-KAPPA-B; HODGKINS-DISEASE; GENE-EXPRESSION; CELL-DEATH; TRAF1; LMP1; ACTIVATION; INFECTION; KINASE AB EBV infection is associated with virtually all cases of undifferentiated NPC, and the EBV-encoded LMP1 is expressed in a proportion of cases. LMP1 has transforming functions similar to members of the TNF receptor family and activates intracellular signaling cascades through interaction with TRAFs. In B cells, expression of TRAF1 is in turn upregulated by LMP1. LMP1 signaling in epithelial cells may be affected by the presence or absence of TRAF1. By immunohistochemistry, we detected TRAF1 expression in 17 of 42 (40%) EBV+ undifferentiated NPCs. All 7 LMP1(+) NPC biopsies were also TRAF1(+). Using an RNAse protection assay, high-level TRAF1 expression was detected in an LMP1-expressing NPC-derived cell line (C IS) and expression was weaker in 2 LMP1(-) cell lines (C17, C19). Finally, LMP1 upregulated TRAF1 expression in an EBV- keratinocyte cell line. Our results demonstrate that TRAF1 is expressed in NPC tumor cells in vivo and suggest that TRAF1 expression may be upregulated by LMP1 in NPC. An antiapoptotic function has been proposed for TRAF1, and this may be relevant for the pathogenesis of NPC. (C) 2004 Wiley-Liss, Inc. C1 Univ Erlangen Nurnberg, Inst Pathol, D-91054 Erlangen, Germany. Univ Birmingham, Inst Canc Studies, Birmingham, W Midlands, England. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Gesell Strahlen, Inst Mol Immunol, Munich, Germany. Univ Hosp, Dept Med 1, Erlangen, Germany. Gesell Strahlenforsch, Inst Clin Mol Biol & Tumor Genet, Munich, Germany. RP Niedobitek, G (reprint author), Univ Erlangen Nurnberg, Inst Pathol, Krankenhausstr 8-10, D-91054 Erlangen, Germany. EM gerald.niedobitek@patho.imed.uni-erlangen.de RI Gonnella, Roberta/R-2028-2016; OI Gonnella, Roberta/0000-0003-4894-4986; Niedobitek, Gerald/0000-0003-4474-1882 NR 37 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2004 VL 112 IS 2 BP 265 EP 272 DI 10.1002/ijc.20367 PG 8 WC Oncology SC Oncology GA 854YJ UT WOS:000223939500013 PM 15352039 ER PT J AU Boseley, ME Hartnick, CJ AF Boseley, ME Hartnick, CJ TI Assessing the outcome of surgery to correct velopharyngeal insufficiency with the pediatric voice outcomes survey SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE velopharyngeal insufficiency; pediatric voice outcomes survey (PVOS); voice; surgery ID SPHINCTER PHARYNGOPLASTY; PHARYNGEAL FLAP; WALL AUGMENTATION; MANAGEMENT AB Objective: To assess the functional outcome of surgery for velopharyngeal insufficiency (VPI) by administering the pediatric voice outcomes survey (PVOS) to the parents of the affected children. Design: Prospective longitudinal study. Setting: Tertiary referral pediatric otolaryngology office. Subjects: Twelve children who underwent surgery to correct VPI during the 12-month-period between 1 January 2002 and 31 December 2002. Methods: Parents of the 12 children were administered the PVOS prior to surgery and again 6 weeks post-operatively. The PVOS is a validated instrument designed to measure voice-related quality of life (V-RQOL). The score has been transformed to range from 0 (low V-RQOL) to 100 (high V-RQOL). Results: The mean age of the children was 5 years (standard deviation [S.D.], 2.3 years). Seven children underwent sphincteroplasty and five had a superior based pharyngeal flap as a primary procedure. Three children required secondary procedures to correct their underlying VPI and one of those had a third procedure consisting of a posterior wall fat injection. The mean pre-operative PVOS score was 38.3 (S.D., 12) and the mean 6 weeks post-operative score was 72.3 (S.D., 22.7) (paired t-test; P < 0.001). Conclusion: The PVOS represents a valid clinical tool to measure the functional impact of surgery to correct pediatric velopharyngeal insufficiency. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM cboseley@satx.rr.com NR 17 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD NOV PY 2004 VL 68 IS 11 BP 1429 EP 1433 DI 10.1016/j.ijporl.2004.06.002 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 868BB UT WOS:000224885800012 PM 15488976 ER PT J AU Taghian, A Jagsi, R Makris, A Goldberg, S Ceilley, E Grignon, L Powell, S AF Taghian, A Jagsi, R Makris, A Goldberg, S Ceilley, E Grignon, L Powell, S TI Results of a survey regarding irradiation of internal mammary chain in patients with breast cancer: Practice is culture driven rather than evidence based SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 18-23, 2003 CL Salt Lake City, UT SP Amer Soc Therapeut Radiol Oncol DE breast cancer; radiotherapy; internal mammary lymph nodes; survey; practice patterns ID RADICAL-MASTECTOMY; LYMPH-NODES; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; AMERICAN-SOCIETY; STAGE-II; DISSECTION; CARCINOMA; RISK AB Purpose: To examine the self-reported practice patterns of radiation oncologists in North America and Europe regarding radiotherapy to the internal mammary lymph node chain (IMC) in breast cancer patients. Methods and Materials: A survey questionnaire was sent in 2001 to physician members of the American Society for Therapeutic Radiology and Oncology and European Society for Therapeutic Radiology and Oncology regarding their management of breast cancer. Respondents were asked whether they would treat the IMC in several clinical scenarios. Results: A total of 435 responses were obtained from European and 702 responses from North American radiation oncologists. Respondents were increasingly likely to report IMC irradiation in scenarios with greater axillary involvement. Responses varied widely among different European regions, the United States, and Canada (p < 0.01). European respondents were more likely to treat the IMC (p < 0.01) than their North American counterparts. Academic physicians were more likely to treat the IMC than those in nonacademic positions (p < 0.01). Conclusion: The results of this study revealed significant international variation in attitudes regarding treatment of the IMC. The international patterns of variation mirror the divergent conclusions of studies conducted in the different regions, indicating that physicians may rely preferentially on evidence from local studies when making difficult treatment decisions. These variations in self-reported practice patterns indicate the need for greater data in this area, particularly from international cooperative trials. The cultural predispositions documented in this study are important to recognize, because they may continue to affect physician attitudes and practices, even as greater evidence accumulates. (C) 2004 Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mt Vernon Hosp, Acad Oncol Unit, Northwood HA6 2RN, Middx, England. RP Taghian, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 54 TC 42 Z9 46 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2004 VL 60 IS 3 BP 706 EP 714 DI 10.1016/j.ijrobp.2004.04.027 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 860NS UT WOS:000224350900002 PM 15465186 ER PT J AU Lawenda, BD Gagne, HM Gierga, DP Niemierko, A Womg, WM Tarbell, NJ Chen, GTY Hochberg, FH Loeffler, JS AF Lawenda, BD Gagne, HM Gierga, DP Niemierko, A Womg, WM Tarbell, NJ Chen, GTY Hochberg, FH Loeffler, JS TI Permanent alopecia after cranial irradiation: Dose-response relationship SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiotherapy; dose-response; alopecia; cranial irradiation ID RADIATION-INDUCED ALOPECIA; HUMAN HAIR-FOLLICLES; IONIZING-RADIATION; LINEAR-ACCELERATOR; HUMAN SCALP; STEM-CELLS; RADIOTHERAPY; MICE; PROTECTS; PROSTAGLANDIN-E2 AB Purpose: To develop a dose-response relationship for the occurrence of permanent alopecia after cranial irradiation and to analyze potential confounding variables that may contribute to this unwanted and often unavoidable complication of treatment. Methods and Materials: Twenty-six patients were enrolled in this study. Three reviewers independently assessed 61 scalp regions and assigned a score for the degree of alopecia in each region using a 4-point scale. Patient and treatment data were collected using a patient questionnaire and outpatient medical chart review. The hair follicle dose was calculated for each scalp region and correlated with the alopecia score for that region. A dose-response relationship was established using the data from these correlations. Results: Permanent alopecia correlated significantly with the follicle dose only (p < 0.001). A personal history of alopecia and the use of chemotherapy correlated with permanent alopecia with borderline statistical significance (p = 0.059 and p = 0.068, respectively). Patient age, family history of baldness, gender, tobacco use, diabetes, and beam energy did not correlate with alopecia. Conclusion: We report the first human dose-response relationship describing the effect of the follicle dose on the subsequent development of permanent scalp alopecia after cranial irradiation. This information will assist the radiation oncologist, physicist, and dosimetrist in designing a treatment plan that might minimize the risk of this untoward side effect of cranial irradiation. (C) 2004 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Loeffler, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. EM jloeffler@partners.org FU NCI NIH HHS [CA 21239, CA 50628] NR 30 TC 32 Z9 34 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2004 VL 60 IS 3 BP 879 EP 887 DI 10.1016/j.ijrobp.2004.04.031 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 860NS UT WOS:000224350900022 PM 15465206 ER PT J AU Paganetti, H Jiang, HY Adams, JA Chen, GT Rietzel, E AF Paganetti, H Jiang, HY Adams, JA Chen, GT Rietzel, E TI Monte Carlo simulations with time-dependent geometries to investigate effects of organ motion with high temporal resolution SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE protons; Monte Carlo; organ motion; dose calculation; 4D CT ID CELL LUNG-CANCER; CONFORMAL RADIOTHERAPY; DOSE CALCULATIONS; PROTON RADIOTHERAPY; RESPIRATORY MOTION; RADIATION-THERAPY; UNCERTAINTIES; TUMORS; CT; DESIGN AB Purpose: To calculate the dose in time-dependent geometry, the results of three-dimensional calculations are usually performed separately and combined. This approach becomes cumbersome when high temporal resolution is required, if the geometry is complex, or if interplay effects between different, independently moving systems are to be studied. The purpose of this project was the implementation of continuous (four-dimensional [4D]) Monte Carlo simulation to study the irradiation of tumors under respiratory motion. Methods and Materials: In taking advantage of object-oriented programming, we implemented 4D Monte Carlo dose calculation. Local dose depositions in the patient are calculated while beam configuration and organ positions are changed continuously. Deformable image registration is used to describe the CT voxel displacement over time. Results: The 4D Monte Carlo technique is applied to a lung cancer case planned for proton therapy. We show that the effect of motion on the dose distribution can be simulated effectively based on statistical motion parameterizations acting on the geometry or based on patient-specific 4D CT information. Conclusion: We present a novel method able to calculate dose with underlying time-dependent geometry. The technique allows 4D dose calculation in arbitrary time scales in a single simulation even for double-dynamic systems (e.g., time-dependent beam delivery under organ motion). (C) 2004 Elsevier Inc. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@partners.org FU NCI NIH HHS [P01 CA 21239-24] NR 38 TC 59 Z9 61 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2004 VL 60 IS 3 BP 942 EP 950 DI 10.1016/j.ijrobp.2004.06.024 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 860NS UT WOS:000224350900029 PM 15465213 ER PT J AU Chang, SM Kuhn, J Wen, P Greenberg, H Schiff, D Conrad, C Fink, K Robins, HI Cloughesy, T De Angelis, L Razier, J Hess, K Dancey, J Prados, MD AF Chang, SM Kuhn, J Wen, P Greenberg, H Schiff, D Conrad, C Fink, K Robins, HI Cloughesy, T De Angelis, L Razier, J Hess, K Dancey, J Prados, MD CA N Amer Brain Tumor Consortium Natl Canc Inst TI Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE chemotherapy; rapamycin; CCI-779; toxicity ID GLIOBLASTOMA-MULTIFORME; MAMMALIAN TARGET; CANCER-THERAPY; RAPAMYCIN; INHIBITOR; MTOR; PTEN; PROGNOSIS; PATHWAY AB Objectives: CCI-779 is an ester of the immunosuppressive agent sirolimus ( rapamycin) that causes cell-cycle arrest at G1 via inhibition of key signaling pathways resulting in inhibition of RNA translation. Antitumor activity has been demonstrated using cell lines and animal models of malignant glioma. Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs) can have altered metabolism of drugs like CCI-779 that are metabolized through the hepatic cytochrome P450 enzyme system. The objectives of this study were to determine the pharmacokinetic profile and the maximum tolerated dose of CCI-779 in patients with recurrent malignant gliioma taking EIAEDs. Study design: The starting dose of CCI-779 was 250 mg intravenously (IV) administered weekly on a continuous basis. Standard dose escalation was performed until the maximum tolerated dose was established. Toxicity was assessed using the National Cancer Institute common toxicity criteria. Results: Two of 6 patients treated at the second dose level of 330 mg sustained a dose-limiting toxicity: grade III stomatitis, grade 3 hypercholesterolemia, or grade 4 hypertriglyceridemia. The maximum tolerated dose was reached at 250 mg IV. Pharmacokinetic profiles were similar to those previously described, but the area under the whole blood concentration-time curve of rapamycin was 1.6 fold lower for patients on EIAEDs. Conclusions: The recommended phase II dose of CCI 779 for patients on enzyme-inducing antiepileptic drugs is 250 mg IV weekly. A phase II study is ongoing to determine the efficacy of this agent. C1 Univ Calif San Francisco, Neuroloncol Serv, San Francisco, CA 94143 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Virginia, Charlottesville, VA 22903 USA. MD Anderson Canc Ctr, Houston, TX USA. Univ Texas San Antonio SW, Dallas, TX USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Chang, SM (reprint author), Univ Calif San Francisco, Neuroloncol Serv, 400 Parnassus Ave,A808, San Francisco, CA 94143 USA. EM changs@neurosurg.ucsf.edu FU NCI NIH HHS [CA62399, CA62422, CA62426, CA16672, CA62455-08, U01 CA62399-09, U01 CA62421-08, U01CA62407-08]; NCRR NIH HHS [M01 RR00042, M01 RR00079, M01 RR00633, M01 RR03186] NR 25 TC 64 Z9 65 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 2004 VL 22 IS 4 BP 427 EP 435 DI 10.1023/B:DRUG.0000036685.72140.03 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 843GB UT WOS:000223065400008 PM 15292713 ER PT J AU Nishiguchi, KM Sokal, I Yang, LL Roychowdhury, N Palczewski, K Berson, EL Dryja, MP Baehr, W AF Nishiguchi, KM Sokal, I Yang, LL Roychowdhury, N Palczewski, K Berson, EL Dryja, MP Baehr, W TI A novel mutation (I143NT) in guanylate cyclase-activating protein 1 (GCAP1) associated with autosomal dominant cone degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RECESSIVE RETINITIS-PIGMENTOSA; CGMP-GATED CHANNEL; LEBERS CONGENITAL AMAUROSIS; BETA-SUBUNIT; ALPHA-SUBUNIT; MOLECULAR CHARACTERIZATION; CA2+-BINDING PROTEINS; TOTAL COLOURBLINDNESS; MAMMALIAN RETINAS; ROD DYSTROPHY AB PURPOSE. To identify pathogenic mutations in the guanylate cyclase-activating protein 1 (GCAP1) and GCAP2 genes and to characterize the biochemical effect of mutation on guanylate cyclase (GC) stimulation. METHODS. The GCAP1 and GCAP2 genes were screened by direct sequencing for mutations in 216 patients and 421 patients, respectively, with various hereditary retinal diseases. A mutation in GCAP1 segregating with autosomal dominant cone degeneration was further evaluated biochemically by employing recombinant proteins, immunoblotting, Ca2+-dependent stimulation of GC, fluorescence emission spectra, and limited 21 proteolysis in the absence and presence of Ca2+. RESULTS. A novel GCAP1 mutation, I143NT (substitution of Ile at codon 143 by ASH and Thr), affecting the EF4 Ca2+-binding loop, was identified in a heterozygote father and son with autosomal dominant cone degeneration. Both patients had much greater loss of cone function versus rod function; previous histopathologic evaluation of the father's eyes at autopsy (age 75 years) showed no foveal cones but a few, scattered cones remaining in the peripheral retina. Biochemical analysis showed that the GCAP1-I143NT mutant adopted a conformation susceptible to proteolysis, and the mutant inhibited GC only partially at high Ca2+ concentrations. Individual patients with atypical or recessive retinitis pigmentosa (RP) had additional heterozygous GCAP1-T114I and GCAP2 gene changes (V85M and F150C) of unknown pathogenicity. CONCLUSIONS. A novel GCAP1 mutation, I143NT, caused a form of autosomal dominant cone degeneration that destroys foveal cones by mid-life but spares some cones in the peripheral retina up to 75 years. Properties of the GCAP1-I143NT mutant protein suggested that it is incompletely inactivated by high Ca2+ concentrations as should occur with dark adaptation. The continued activity of the mutant GCAP1 likely results in higher-than-normal scotopic cGMP levels which may, in turn, account for the progressive loss of cones. C1 Univ Utah, Hlth Sci Ctr, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84112 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Chem, Seattle, WA 98195 USA. Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT USA. RP Baehr, W (reprint author), Univ Utah, Hlth Sci Ctr, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, 15N-2030E EIHG, Salt Lake City, UT 84112 USA. EM wbaehr@hsc.utah.edu FU NEI NIH HHS [R01 EY008123-17, R01 EY009339, R37 EY000169, R01 EY008123, EY08123, EY08683, EY00169, R01 EY000169, R01 EY008683, EY09339] NR 50 TC 41 Z9 43 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 NOV PY 2004 VL 45 IS 11 BP 3863 EP 3870 DI 10.1167/iovs.04-0590 PG 8 WC Ophthalmology SC Ophthalmology GA 865BT UT WOS:000224678200003 PM 15505030 ER PT J AU Stelmack, JA Szlyk, JP Stelmack, BR Demers-Turco, P Williams, RT Moran, D Massof, RW AF Stelmack, JA Szlyk, JP Stelmack, BR Demers-Turco, P Williams, RT Moran, D Massof, RW TI Psychometric properties of the Veterans Affairs low-vision visual functioning questionnaire SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INDEPENDENT MOBILITY; OUTCOMES; REHABILITATION; CATARACT; ABILITY; INDEX AB PURPOSE. To describe psychometric properties of a self-report questionnaire, the Veterans Affairs (VA) Low-Vision Visual Functioning Questionnaire (LV VFQ-48), which was designed to measure the difficulty visually impaired persons have performing daily activities and to evaluate low-vision outcomes. METHODS. The VA LV VFQ-48 was administered by telephone interview to subjects with visual acuity ranging from near normal to total blindness at five sites in the VA and private sector. Rasch analysis with the Andrich rating scale model was applied to difficulty ratings from 367 subjects, to evaluate measurement properties of the instrument. RESULTS. High intercenter correlations for item measure estimates (intraclass correlation coefficient [ICC] = 0.97) justified pooling the data from these sites. The person measure fit statistics (mean square residuals) confirm that the data fit the assumptions of the model. The item measure fit statistics indicate that responses to 19% of the items were confounded by factors other than visual ability. The separation reliabilities for pooled data (0.94 for persons and 0.98 for items) demonstrate that the estimated measures discriminate persons and items well along the visual ability dimension. ICCs for test-retest data (0.98 for items and 0.84 for persons) confirm temporal stability. Subjects used the rating categories in the same way at all five centers. Ratings of slight and moderate difficulty were used interchangeably, suggesting that the instrument could be modified to a 4-point scale including not difficult, slightly/moderately difficult, extremely difficult, and impossible. Fifty additional subjects were administered the questionnaire with a 4-point scale to confirm that the scale was used in the same way when there were four rather than five difficulty ratings. CONCLUSIONS. The VA LV VFQ-48 is valid and reliable and has the range and precision necessary to measure visual ability of low-vision patients with moderate to severe vision loss across diverse clinical settings. C1 Edward Hines Jr Vet Adm Hosp, Blind Rehabil Ctr, Hines, IL 60141 USA. Illinois Coll Optometry, Chicago, IL USA. Univ Illinois, Coll Med, Dept Ophthalmol & Visual Sci, Chicago, IL USA. Jessie Brown VA Med Ctr, Chicago, IL USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Lois & Edwin Deicke Ctr Vis Rehabil, Wheaton, IL USA. Loyola Univ, Sch Med, Dept Ophthalmol, Maywood, IL 60153 USA. Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. RP Stelmack, JA (reprint author), Edward Hines Hosp, Blind Rehabil Ctr 124, Hines, IL 60141 USA. EM joan.stelmack@med.va.gov FU NEI NIH HHS [EY-012045] NR 33 TC 66 Z9 66 U1 2 U2 6 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 NOV PY 2004 VL 45 IS 11 BP 3919 EP 3928 DI 10.1167/iovs.04-0208 PG 10 WC Ophthalmology SC Ophthalmology GA 865BT UT WOS:000224678200010 PM 15505037 ER PT J AU Miller, MW Kaloupek, DG Dillon, AL Keane, TM AF Miller, MW Kaloupek, DG Dillon, AL Keane, TM TI Extemalizing and internalizing subtypes of combat-related PTSD: A replication and extension using the PSY-5 scales SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; COMMON MENTAL-DISORDERS; SUBSTANCE USE DISORDERS; DSM-III-R; PERSONALITY-TYPES; PSYCHOPATHOLOGY; CHILDHOOD; VETERANS; DEPRESSION AB This study replicated and extended prior findings of internalizing and externalizing subtypes of posttraumatic response (M. W. Miller, J. L. Greif, & A. A. Smith, 2003). Cluster analyses of the Minnesota Multiphasic Personality Inventory-2 Personality Psychopathology-Five (MMPI-2 PSY-5; A. R. Harkness, J. L. McNulty, Y. S. Ben-Porath, 1995) profiles obtained from 736 veterans with posttraumatic stress disorder (PTSD) partitioned the sample into a low pathology cluster defined by personality scores in the normal range, an externalizing cluster characterized by low constraint and high negative emotionality, and an internalizing cluster with high negative emotionality and low positive emotionality. Externalizers showed the highest rates of alcohol-related and antisocial personality disorders; internalizers, the highest rates of panic and major depressive disorder. These findings support the development of a personality-based typology of posttraumatic response designed to account for heterogeneity in the expression of PTSD and associated psychopathology. C1 Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Miller, MW (reprint author), Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-2, Boston, MA 02130 USA. EM mark.miller5@med.va.gov RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 FU NIMH NIH HHS [MH63959, MH66324] NR 47 TC 100 Z9 101 U1 4 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2004 VL 113 IS 4 BP 636 EP 645 DI 10.1037/0021-843X.113.4.636 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 866JO UT WOS:000224770000014 PM 15535795 ER PT J AU Kradin, R AF Kradin, R TI The placebo response complex SO JOURNAL OF ANALYTICAL PSYCHOLOGY LA English DT Article DE placebo response; self; neurobiology; psychoanalysis ID POWERFUL PLACEBO; TRIALS AB Placebo effects contribute to beneficial therapeutic responses and are common in anxiety and depressive disorders. It is posited that placebo effects are yielded by autonomous feeling-toned complexes capable of re-establishing background self-states of well-being. The relationship between the placebo response complex and modern neurobiological models of self is explored. The psychological roots of the placebo response complex in implicit memories of organized attachment between child and early caretakers and in Sandler's conception of the benign superego are examined. The relationships between the negative placebo (nocebo) response complex, Freud's negative therapeutic reaction, and Fordham's defence of the self are explored. Finally, it is suggested that approaches fundamental to the analytic encounter, e.g., mirroring, affectual exchanges, attunement, and containment are likely to optimize the salutary effects of both psychological and somatic therapeutic interventions. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kradin, R (reprint author), Massachusetts Gen Hosp, Dept Med, Warren 5, Boston, MA 02114 USA. EM rkradin@partners.org NR 62 TC 9 Z9 9 U1 1 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0021-8774 J9 J ANAL PSYCHOL JI J. Anal. Psychol. PD NOV PY 2004 VL 49 IS 5 BP 617 EP 634 DI 10.1111/j.0021-8774.2004.00492.x PG 18 WC Psychology, Psychoanalysis SC Psychology GA 869VY UT WOS:000225013800002 PM 15533195 ER PT J AU Coviello, AD Bremner, WJ Matsumoto, AM Herbst, KL Amory, JK Anawalt, BD Yan, XH Brown, TR Wright, WW Zirkin, BR Jarow, JP AF Coviello, AD Bremner, WJ Matsumoto, AM Herbst, KL Amory, JK Anawalt, BD Yan, XH Brown, TR Wright, WW Zirkin, BR Jarow, JP TI Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen SO JOURNAL OF ANDROLOGY LA English DT Article DE intratesticular androgens; spermatogenesis; gonadotropins; progestogens ID FOLLICLE-STIMULATING-HORMONE; EXOGENOUSLY ADMINISTERED TESTOSTERONE; GONADOTROPIN-RELEASING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; CYPROTERONE-ACETATE; LUTEINIZING-HORMONE; INDUCED AZOOSPERMIA; ADULT-RATS; SPERMATOGENESIS; SUPPRESSION AB Intratesticular testosterone (ITT) is thought to play a key role in the control of spermatogenesis in man but is rarely measured. The purposes of this study were 1) to examine the relationship between intratesticular fluid and serum testosterone (T) at baseline and during treatment with a contraceptive regimen known to suppress spermatogenesis and 2) to measure intratesticular fluid androgenic bioactivity. Seven men received 6 months of T enanthate (TE) 100 mg weekly intramuscularly plus levonorgestrel (LNG) 62.5 or 31.25 mug orally daily. Testicular fluid was obtained by percutaneous aspiration at baseline and during month 6. Mean luteinizing hormone (LH) was suppressed 98% from 3.79 +/- 0.80 IU/L at baseline to 0.08 +/- 0.03 IU/L. Mean follicle stimulating hormone (FSH) was suppressed 97%, from 3.29 +/- 0.67 IU/ L to 0.10 +/- 0.03 IU/L. Mean serum T levels were similar before (22.8 +/- 1.9 nmol/L) and during treatment (28.7 +/- 2.0 nmol/L) (P = .12). ITT (822 +/- 136 nmol/L) was similar to40X higher than serum T (P < .001) at baseline. ITT was suppressed 98% during treatment to 13.1 +/- 4.5 nmol/L, a level similar to baseline serum T (P = .08) but significantly lower than on-treatment serum T (P = .01). At baseline, intratesticular fluid androgenic bioactivity (583 +/- 145 nmol/L) was 70% of the ITT concentration measured by radioimmunoassay. Intratesticular androgenic bioactivity was suppressed 93% to 40 +/- 22 nmol/L (P < .01) during treatment, but was 3X higher than ITT (13.1 +/- 4.5 nmol/L). Sperm counts declined from 65 +/- 15 million/mL to 1.3 +/- 1.3 million/mL. In summary, TE plus LNG dramatically suppressed ITT (98%) and intratesticular androgenic bioactivity (93%) to levels approximating those in serum. ITT levels comparable with serum T were insufficient to support normal spermatogenesis. Intratesticular androgenic bioactivity was higher than ITT during treatment, suggesting that other androgens may be prevalent in the low-ITT environment. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Johns Hopkins Sch Publ Hlth, Dept Biochem, Baltimore, MD USA. Johns Hopkins Sch Publ Hlth, Dept Biol Mol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD USA. RP Coviello, AD (reprint author), Northwestern Univ, Feinberg Sch Med, Tarry 15-751,303 Chicago Ave, Chicago, IL 60611 USA. EM a-coviello@northwestern.edu FU NICHD NIH HHS [HD44258, U54HD42454, U54HD12629, T32HD07453, U54 HD36209] NR 32 TC 43 Z9 43 U1 0 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD NOV-DEC PY 2004 VL 25 IS 6 BP 931 EP 938 PG 8 WC Andrology SC Endocrinology & Metabolism GA 865NE UT WOS:000224709000015 PM 15477366 ER PT J AU Drouin, EE Glickstein, LJ Steere, AC AF Drouin, EE Glickstein, LJ Steere, AC TI Molecular characterization of the OspA(161-175) T cell epitope associated with treatment-resistant Lyme arthritis: differences among the three pathogenic species of Borrelia burgdorferi sensu lato SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE antigen presentation; autoimmunity; bacterial; human; MHC ID SURFACE PROTEIN-A; CLASS-II MOLECULES; PEPTIDE-FLANKING RESIDUES; MONOCLONAL-ANTIBODIES; SEQUENCE-ANALYSIS; CRYSTAL-STRUCTURE; SP-NOV; OSPA; COMPLEX; BINDING AB Treatment-resistant Lyme arthritis, which may result from infection-induced autoinimunity, is associated with reactivity to a T cell epitope of outer-surface protein A (OspA(161-175)) of Borrelia burgdorferi sensu stricto (Bb). This syndrome has been noted primarily in the United States where only Bb is present, and rarely in Europe where Borrelia garinii (Bg) and Borrelia afzelii (Ba) predominate. To gain a better understanding of this epitope, we identified its species-specific polymorphisms, determined their immunogenicity, and characterized the contribution of individual amino acids. Based on published sequences the Bb peptide differed from the Ba peptide in six of the nine core residues (amino acids 165-173), whereas the Bg peptide usually differed in three of the nine residues. Lymphocytes from seven patients with treatment-resistant Lyme arthritis proliferated in response to the Bb peptide, but not to the Ba or Bg peptide. Substitution analysis showed,that valine(166) and threonine(172) were critical for the immunogenicity of the Bb peptide. Thus, consistent with the geographic distribution of the illness, the European causative agents of Lyme borreliosis usually lack the putative pathogenic OspA epitope. These observations are consistent with the hypothesis that T cell recognition of this epitope is important in the induction of autoinimunity in treatment-resistant Lyme arthritis. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflamatory Dis,Div Rheumatol Aller, Boston, MA 02114 USA. RP Drouin, EE (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM edrouin@partners.org FU NIAMS NIH HHS [AR-20358, AR-07570] NR 48 TC 18 Z9 19 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD NOV PY 2004 VL 23 IS 3 BP 281 EP 292 DI 10.1016/j.jaut.2004.06.005 PG 12 WC Immunology SC Immunology GA 870JB UT WOS:000225052300010 PM 15501399 ER PT J AU Garsin, DA Urbach, J Huguet-Tapia, JC Peters, JE Ausubel, FM AF Garsin, DA Urbach, J Huguet-Tapia, JC Peters, JE Ausubel, FM TI Construction of an Enterococcus faecalis Tn917-mediated-gene-disruption library offers insight into Tn917 insertion patterns SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TARGET SITE SELECTION; RNA-POLYMERASE-III; STREPTOCOCCUS-FAECALIS; BACILLUS-SUBTILIS; TRANSPOSON TN917; ESCHERICHIA-COLI; DNA-REPLICATION; PSEUDOMONAS-AERUGINOSA; YEAST RETROTRANSPOSON; STAPHYLOCOCCUS-AUREUS AB Sequencing the insertion sites of 8,865 Tn917 insertions in Enterococcus faecalis strain OG1RF identified a hot spot in the replication terminus region corresponding to 6% of the genome where 65% of the transposons had inserted. In E. faecalis, Tn917 preferentially inserted at a 29-bp consensus sequence centered on TATAA, a 5-bp sequence that is duplicated during insertion. The regional insertion site preference at the chromosome terminus was not observed in another low-G+C gram-positive bacterium, Listeria monocytogenes, although the consensus insertion sequence was the same. The 8,865 Tn917 insertion sites sequenced in E. faecalis corresponded to only similar to610 different open reading frames, far fewer than the predicted number of 2,400, assuming random insertion. There was no significant preference in orientation of the Tn917 insertions with either transcription or replication. Even though OG1RF has a smaller genome than strain V583 (2.8 Mb versus 3.2 Mb), the only E. faecalis strain whose sequence is in the public domain, over 10% of the Tn917 insertions appear to be in a OG1RF-specific sequence, suggesting that there are significant genomic differences among E. faecalis strains. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Cornell Univ, Dept Microbiol, Ithaca, NY USA. RP Garsin, DA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Genet & Microbiol, 6431 Fannin St,JFB 1-711, Houston, TX 77030 USA. EM Danielle.A.Garsin@uth.tmc.edu OI Peters, Joseph/0000-0001-8309-3297 FU NHLBI NIH HHS [U01 HL 66678, U01 HL066678] NR 45 TC 39 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2004 VL 186 IS 21 BP 7280 EP 7289 DI 10.1128/JB.186.7280-7289.2004 PG 10 WC Microbiology SC Microbiology GA 863QA UT WOS:000224575500026 PM 15489440 ER PT J AU Most, E Axe, J Rubash, H Li, G AF Most, E Axe, J Rubash, H Li, G TI Sensitivity of the knee joint kinematics calculation to selection of flexion axes SO JOURNAL OF BIOMECHANICS LA English DT Article DE knee; kinematics; flexion axis; biomechanics ID TRANSEPICONDYLAR AXIS; FEMORAL COMPONENT; ARTHROPLASTY; MOVEMENT; FEMUR; ALIGNMENT; ROTATION; MOTIONS; MRI AB Various flexion axes have been used in the literature to describe knee joint kinematics. This study measured the passive knee kinematics of six cadaveric human knee specimens using two widely accepted flexion axes; transepicondylar axis and the geometric center axis. These two axes were found to form an angle of 4.0degrees +/- 0.8degrees. The tibial rotation calculated using the transepicondylar axis was significantly different than the rotation obtained using the geometric center axis for the same knee motion. At 90degrees of flexion, the tibial rotation obtained using the transepicondylar axis was 4.8degrees +/- 9.4degrees whereas the rotation recorded using the geometric center axis at the same flexion angle was 13.8degrees +/- 10.2degrees. At 150degrees of knee flexion, the rotations obtained from the transepicondylar and the geometric center axes were 7.2degrees +/- 5.7degrees and 19.9degrees +/- 6.9degrees, respectively. The data suggest that a clear definition of the flexion axis is necessary when reporting knee joint kinematics. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthoped Bioengn Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthoped Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org OI Axe, Jeremie/0000-0002-9302-0822 NR 23 TC 83 Z9 85 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD NOV PY 2004 VL 37 IS 11 BP 1743 EP 1748 DI 10.1016/j.jbiomech.2004.01.025 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 863YH UT WOS:000224599000013 PM 15388317 ER PT J AU Saad, L Spector, M AF Saad, L Spector, M TI Effects of collagen type on the behavior of adult canine annulus fibrosus cells in collagen-glycosaminoglycan scaffolds SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE collagen scaffold; annulus fibrosus; tissue engineering ID INTERVERTEBRAL DISC CELLS; MATRICES IN-VITRO; II COLLAGEN; EXTRACELLULAR-MATRIX; CHONDROCYTES; PROTEOGLYCANS; REGENERATION; TGF-BETA-1; METABOLISM; ALGINATE AB The healing of intervertebral disc defects may be improved by the implantation of cell-seeded collagen-based scaffolds. The present study evaluated in vitro the effects of the collagen type (type I vs type II) from which the scaffolds were fabricated on the behavior of adult canine annulus fibrosus cell-seeded collagen-glycosaminoglycan (GAG) scaffolds. Protein and GAG biosynthesis continued through the 8-week period of the experiment, demonstrating the viability of the cells in type I and type II collagen-GAG scaffolds. Statistical analysis revealed no significant effect of the type of collagen that makes up the scaffold on the biosynthetic activity. For both scaffold types, the amount of retained newly synthesized proteins increased from 1 to 2 weeks and from 6 to the 8 weeks. In contrast, the rate of GAG retention increased to a maximum at 4 weeks for both types of scaffolds, then decreased to about 50% of that level after 8 weeks. The number of cells generally increased the first week but then decreased in type I scaffolds while remaining constant in type II scaffolds. It could be assumed that most newly synthesized protein was lost to the medium, as the quantity of protein and collagen remained constant. Cell-mediated contraction of the scaffolds contributed to folds that formed in the constructs and to create an oriented architecture tissue. These findings commend the use of a type II collagen-GAG scaffold for further study on the basis of its maintenance of cell number and the slightly higher accumulated GAG content. (C) 2004 Wiley Periodicals, Inc. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mspector@rics.bwh.harvard.edu NR 19 TC 21 Z9 29 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD NOV 1 PY 2004 VL 71A IS 2 BP 233 EP 241 DI 10.1002/jbm.a.30150 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 861LW UT WOS:000224419000006 PM 15368219 ER PT J AU Ring, D Allende, C Jafarnia, K Allende, BT Jupiter, JB AF Ring, D Allende, C Jafarnia, K Allende, BT Jupiter, JB TI Ununited diaphyseal forearm fractures with segmental defects: Plate fixation and autogenous cancellous bone-grafting SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SKELETAL DEFECTS; LONG BONES; RADIUS; NONUNION; ULNA; RECONSTRUCTION; OSTEOSYNTHESIS; MANAGEMENT; TIBIA AB Background: With current techniques of plate-and-screw fixation, diaphyseal nonunions of the radius and ulna are unusual. The few reports that have been published have discussed the use of structural corticocancellous bone grafts for the treatment of atrophic nonunions that are associated with osseous defects. We reviewed the rate of union and the functional results in association with the use of plate-and-screw fixation and autogenous cancellous (nonstructural) bone grafts. Methods: Thirty-five patients with an atrophic ununited diaphyseal fracture of the forearm were treated with 3.5-mm plate-and-screw fixation and autogenous cancellous bone-grafting. A segmental osseous defect with an average size of 2.2 cm (range, 1 to 6 cm) was present in each patient. Twenty of the original fractures had been open. Eleven patients had had treatment of a deep infection before referral to us. The nonunion involved both forearm bones in eight patients, the radius alone in sixteen patients, and the ulna alone in eleven patients. Results: The atrophic nonunion was associated with an open fracture in twenty patients, suboptimal fixation in twenty-two, a fracture-dislocation of the forearm in nine, and infection in eleven. All fractures healed without additional intervention within six months. Two patients had a subsequent Darrach resection of the distal part of the ulna for the treatment of arthrosis of the distal radioulnar joint. After an average duration of follow-up of forty-three months, the final arc of motion averaged 121degrees in the forearm, 131degrees at the elbow, and 137degrees at the wrist, with an average grip strength of 83% compared with that of the contralateral limb. According to the system of Anderson and colleagues, five patients had an excellent result, eighteen had a satisfactory result, eleven had an unsatisfactory result (because of elbow stiffness related to associated elbow injuries in three and because of wrist stiffness in eight), and one had a poor result (because of malunion). Conclusions: When the soft-tissue envelope is compliant, has limited scar, and consists largely of healthy muscle with a good vascular supply, autogenous cancellous bone-grafting and stable internal plate fixation results in a high rate of union and improved upper limb function in patients with diaphyseal nonunion of the radius and/or ulna. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Sanatorio Allende, Dept Orthopaed Surg & Rehabil, RA-5000 Cordoba, Argentina. Baylor Coll Med, Dept Orthopaed, Houston, TX 77090 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, ACC 525 & ACC 527,15 Parkman St, Boston, MA 02114 USA. EM dring@partners.org OI jafarnia, kourosh/0000-0002-8106-4705 NR 28 TC 38 Z9 41 U1 0 U2 2 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 NOV PY 2004 VL 86A IS 11 BP 2440 EP 2445 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 868QL UT WOS:000224928000013 PM 15523016 ER PT J AU Herndon, JH AF Herndon, JH TI The future of specialization within orthopaedics SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID UNITED-STATES; SURGERY; VOLUME; FELLOWSHIPS; EXPERIENCE; EDUCATION; OUTCOMES C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, 55 Fruit St,Gray 624, Boston, MA 02114 USA. EM jherndon@partners.org NR 30 TC 2 Z9 2 U1 1 U2 1 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 NOV PY 2004 VL 86A IS 11 BP 2560 EP 2566 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 868QL UT WOS:000224928000032 PM 15523032 ER PT J AU Heist, EK Doshi, SK Singh, JP Di Salvo, T Semigran, MJ Reddy, VY Keane, D Ruskin, JN Mansour, M AF Heist, EK Doshi, SK Singh, JP Di Salvo, T Semigran, MJ Reddy, VY Keane, D Ruskin, JN Mansour, M TI Catheter ablation of atrial flutter after orthotopic heart transplantation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial flutter; heart transplant; catheter ablation ID CRITICAL ISTHMUS; TACHYCARDIA; ARRHYTHMIAS; REJECTION; RECIPIENT; ENTRAINMENT; CONDUCTION; BICAVAL AB Ablation of Atrial Flutter after Heart Transplant. Introduction: Atrial arrhythmias, including atrial flutter, are common in orthotopic heart transplant recipients. However, only a small number of individual case reports describe the electrical circuit and catheter ablation of atrial flutter after heart transplantation. Methods and Results: Detailed electrophysiologic evaluation and radiofrequency ablation of atrial flutter were performed in three patients after orthotopic heart transplantation. All cases involved a counterclockwise flutter circuit around the tricuspid annulus. All were successfully ablated at the isthmus between the tricuspid valve and the atrial anastomosis adjacent to the inferior vena cava. Conclusion: Atrial flutter involving a counterclockwise circuit around the tricuspid annulus is common in the heart transplant population. Based on the patients described in this study and other cases reported in the literature, this arrhythmia often is treated successfully by ablation of the isthmus between the tricuspid valve and the atrial anastomosis near the inferior vena cava. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA 02114 USA. RP Mansour, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 17 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD NOV PY 2004 VL 15 IS 12 BP 1366 EP 1370 DI 10.1046/j.1540-8167.2004.04440.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 878ZN UT WOS:000225686300006 PM 15610280 ER PT J AU Mian, SI Jarade, EF Scally, A Azar, DT AF Mian, SI Jarade, EF Scally, A Azar, DT TI Combined ICRS insertion and LASIK to maximize postoperative residual bed thickness in high myopia SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID IN-SITU KERATOMILEUSIS; INTRASTROMAL CORNEAL RING; PHAKIC INTRAOCULAR-LENS; EUROPEAN MULTICENTER; INTRACORNEAL RINGS; LASER; SEGMENTS; ASTIGMATISM; INTACS; COMPLICATIONS AB Purpose: To describe a new technique and early outcomes of combined intrastromal corneal ring segment (ICRS) insertion and laser in situ keratomileusis (LASIK) to treat patients with moderate to high myopia and thin corneas. Setting: University-based academic practice, Boston, Massachusetts, USA. Methods: Combined ICRS insertion and LASIK was performed in 2 stages: ICRS channel formation (stage I) followed by LASIK and ICRS insertion (stage II). Results: Fifteen eyes of 11 patients with a mean preoperative spherical equivalent of -9.98 diopters; (D) +/- 2.60 (SD) (range -7.13 to -16.25 D) and mean preoperative astigmatism of 1.11 +/- 0.75 D (range 0.00 to -3.00 D) were treated with combined ICRS insertion and LASIK The mean central pachymetry was 526.13 +/- 35.69 mum (472 to 579 mum). The uncorrected visual acuity was 20/40 or better in 7 of 15 eyes (46.67%) at 1 month, 6 of 12 eyes (50.00%) at 3 months, 5 of 12 eyes (41.67%) at 6 months, and 6 of 12 eyes (50.00%) at 12 months. The best spectacle-corrected visual acuity was 20/40 or better at all times. Postoperative maps confirmed the absence of ectasia. The postoperative spherical equivalent was within +/- 1.00 D of the intended refraction in 11 of 15 eyes (73.33%) at 1 month, 9 of 12 eyes at 3 and 6 months, and 8 of 12 eyes (66.67%) at 12 months. Conclusions: Results of combined ICRS insertion and LASIK in moderately to highly myopic patients with relatively thin corneas were good. Long-term studies are needed to determine whether this procedure will decrease the risk of LASIKinduced keratectasia in these patients. (C) 2004 ASCRS and ESCRS. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, Boston, MA 02114 USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, 243Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu NR 29 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD NOV PY 2004 VL 30 IS 11 BP 2383 EP 2390 DI 10.1016/j.jcrs.2004.02.069 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 873IB UT WOS:000225272000041 PM 15519093 ER PT J AU Proano, CE Azar, DT Mocan, MC Redmond, RW Kochevar, IE AF Proano, CE Azar, DT Mocan, MC Redmond, RW Kochevar, IE TI Photochemical keratodesmos as an adjunct to sutures for bonding penetrating keratoplasty corneal incisions SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID BIOLOGIC TISSUE GLUE; GRAFT FAILURE; MICROBIAL KERATITIS; CATARACT INCISIONS; MONOFILAMENT; CLOSURE; EYES AB Purpose: To evaluate the benefit of photochemical keratodesmos (PKD) in acute wound closure of penetrating keratoplasty (PKP) corneal incisions in vivo. Setting: Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. Methods: Penetrating keratoplasty incisions were performed in both eyes of 6 New Zealand white rabbits, followed by application of 1.5 mM rose bengal dye at the wound edges. The incision in 1 eye of each rabbit was irradiated with neodymium:YAG laser light at 532 nm and fluence of 40 J/cm(2); the contralateral control eye was untreated. Intraocular pressure at which fluid leaked at the edges (IOPL) was determined immediately after surgery. Results: The mean IOPL was 410 mm Hg +/- 70 (SD) in the PKID-treated eyes and 250 +/- 150 mm Hg in the unirradiated eyes. The difference was statistically significant by paired t test (P<.05). Conclusions: Photochemical keratodesmos may be a useful adjunct to sutures for approximating PKP corneal incisions in the immediate postoperative period. This process does not induce high temperature, and thus denaturation can be avoided and structural integrity restored. (C) 2004 ASCRS and ESCRS. C1 Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Wellman Labs Photomed, Boston, MA 02115 USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu OI Mocan, Cem/0000-0002-3419-9105 NR 34 TC 20 Z9 22 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD NOV PY 2004 VL 30 IS 11 BP 2420 EP 2424 DI 10.1016/j.jcrs.2004.02.068 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 873IB UT WOS:000225272000047 PM 15519099 ER PT J AU Mehrotra, M Krane, SM Walters, K Pilbeam, C AF Mehrotra, M Krane, SM Walters, K Pilbeam, C TI Differential regulation of platelet-derived growth factor stimulated migration and proliferation in osteoblastic cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MN SP Amer Soc Bone & Mineral Res DE signaling pathways; MAP kinase; ERK; p38 kinase; JNK; CFSE ID ACTIVATED PROTEIN-KINASE; N-TERMINAL KINASE; P38 MAP KINASE; SIGNALING PATHWAYS; PDGF-BB; CROSS-TALK; BONE; EXPRESSION; RECEPTOR; ERK AB Osteoblastic migration and proliferation in response to growth factors are essential for skeletal development, bone remodeling, and fracture repair, as well as pathologic processes, such as metastasis. We studied migration in response to platelet-derived growth factor (PDGF, 10 ng/ml) in a wounding model. PDGF stimulated a twofold increase in migration of osteoblastic MC3T3-E1 cells and murine calvarial osteoblasts over 24-48 h. PDGF also stimulated a tenfold increase in H-3-thymidine (H-3-TdR) incorporation in MC3T3-E1 cells. Migration and DNA replication, as measured by BrdU incorporation, could be stimulated in the same cell. Blocking DNA replication with aphiclicolin did not reduce the distance migrated. To examine the role of mitogen-activated protein (MAP) kinases in migration and proliferation, we used specific inhibitors of p38 MAP kinase, extracellular signal regulated kinase (ERK), and c-jun N-terminal kinase (JNK). For these signaling studies, proliferation was measured by carboxyfluorescein diacetate succinimidyl ester (CFSE) using flow cytometry. Inhibition of the p38 MAP kinase pathway by SB203580 and SB202190 blocked PDGF-stimulated migration but had no effect on proliferation. Inhibition of the ERK pathway by PD98059 and U0126 inhibited proliferation but did not inhibit migration. Inhibition of JNK activity by SP600125 inhibited both migration and proliferation. Hence, the stimulation of migration and proliferation by PDGF occurred by both overlapping and independent pathways. The JNK pathway was involved in both migration and proliferation, whereas the p38 pathway was predominantly involved in migration and the ERK pathway predominantly involved in proliferation. (C) 2004 Wiley-Liss, Inc. C1 Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Pilbeam, C (reprint author), Univ Connecticut, Ctr Hlth, Dept Med, Room AM047,263 Farmington Ave, Farmington, CT 06030 USA. EM pilbeam@nso.uchc.edu FU NIAMS NIH HHS [R01 AR47673, AR-44815] NR 49 TC 44 Z9 50 U1 1 U2 6 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 NOV 1 PY 2004 VL 93 IS 4 BP 741 EP 752 DI 10.1002/jcb.20138 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868SL UT WOS:000224933200012 PM 15660418 ER PT J AU Schurgin, S Canavan, B Koutkia, P DePaoli, AM Grinspoon, S AF Schurgin, S Canavan, B Koutkia, P DePaoli, AM Grinspoon, S TI Endocrine and metabolic effects of physiologic r-metHuLeptin administration during acute caloric deprivation in normal-weight women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LUTEINIZING-HORMONE; RECOMBINANT LEPTIN; ANOREXIA-NERVOSA; SERUM LEPTIN; NEUROENDOCRINE; OBESE; GENE AB Leptin is a nutritionally regulated hormone that may modulate neuroendocrine function during caloric deficit. We hypothesized that administration of low-dose leptin would prevent changes in neuroendocrine function resulting from short-term caloric restriction. We administered physiologic doses of r-metHuLeptin [(0.05 mg/kg sc daily or identical placebo in divided doses (0800, 1400, 2000, and 0200 h)] to 17 healthy, normal-weight, reproductive-aged women during a 4-d fast. Leptin levels were lower in the placebo-treated group during fasting (3.3 +/- 0.2 vs. 9.6 +/- 1.0 ng/ml, P < 0.001, placebo vs. leptin-treated at end of study). Fat mass decreased more in the leptin than the placebo-treated group (-0.6 +/- 0.1 vs. -0.2 +/- 0.1 kg, P = 0.03). Both overnight LH area (38.9 +/- 21.5 vs. 1.2 +/- 11.1 mu IU/ml.min, P = 0.05) and LH peak width increased (15.8 +/- 7.1 vs. -2.3 +/- 6.7 min, P = 0.06) and LH pulsatility decreased (-2.0 +/- 0.9 vs. 1.0 +/- 0.8 peaks/12 h, P = 0.03) more in the leptin vs. placebo group. LH pulse regularity was higher in the leptin-treated group (P = 0.02). Twenty-four-hour mean TSH decreased more in the placebo than the leptin-treated group, respectively (-1.06 +/- 0.27 vs. -0.32 +/- 0.18 mu IU/ml, P = 0.03). No differences in 24-h mean GH, cortisol, IGF binding protein-1, and IGF-I were observed between the groups. Hunger was inversely related to leptin levels in the subjects randomized to leptin (r = -0.76, P = 0.03) but not placebo (r = -0.18, P = 0.70) at the end of the study. Diminished hunger was seen among subjects achieving the highest leptin levels. Our data provide new evidence of the important role of physiologic leptin regulation in the neuroendocrine response to acute caloric deprivation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02114 USA. Amgen Inc, Thousand Oaks, CA 91319 USA. RP Grinspoon, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01 RR01066] NR 20 TC 28 Z9 28 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 NOV PY 2004 VL 89 IS 11 BP 5402 EP 5409 DI 10.1210/jc.2004-1102 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 868XL UT WOS:000224946300019 PM 15531489 ER PT J AU Lee, SD Kearney, DJ AF Lee, SD Kearney, DJ TI A randomized controlled trial of gastric lavage prior to endoscopy for acute upper gastrointestinal bleeding SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy CY MAY 20-23, 2001 CL ATLANTA, GA SP Amer Soc Gastrointestinal Endoscopy DE upper gastrointestinal bleeding; gastric lavage; endoscopy; esophagogastroduodenoscopy ID HEMORRHAGE AB Goals: We hypothesized that large volume gastric lavage prior to endoscopy for acute upper gastrointestinal bleeding would improve the quality of endoscopic examination. Background: Blood retained in the stomach can impair visualization during esophagogastroduodenoscopy. Patients with acute upper gastrointestinal bleeding and a retained gastric fundic pool during endoscopy may have worse outcomes than patients without a retained fundic pool. No trials to date have evaluated if large volume gastric lavage prior to endoscopy improves visualization during acute upper gastrointestinal bleeding. Study Methods: Patients with acute upper gastrointestinal bleeding were randomized to esophagogastroduodenoscopy alone or large volume tap water gastric lavage prior to esophagogastroduodenoscopy. The quality of endoscopic visualization was assessed using a 5-point scale. Clinical outcomes were compared for lavaged and nonlavaged patients. Results: A total of 39 patients were randomized. In 1 patient, lavage was unsuccessful. The quality of visualization was not significantly different between groups for the esophagus, gastric antrum, or duodenum but was significantly better for the gastric fundus for patients randomized to lavage (P = 0.02). There was no significant difference between groups for ability to define a bleeding source, achieve hemostasis, recurrent bleeding, need for repeat endoscopy, and length of stay or death. There were no complications. Conclusions: Large volume gastric lavage prior to esophagogastroduodenoscopy for acute upper gastrointestinal bleeding is safe and provides better visualization of the gastric fundus. C1 Univ Washington, Sch Med, Med Ctr, Div Gastroenterol,Gastroenterol Sect, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lee, SD (reprint author), Univ Washington, Sch Med, Med Ctr, Div Gastroenterol,Gastroenterol Sect, 1959 NE Pacific Ave,Box 356424, Seattle, WA 98195 USA. EM leesd@u.washington.edu NR 9 TC 27 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2004 VL 38 IS 10 BP 861 EP 865 DI 10.1097/00004836-200411000-00005 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 865QR UT WOS:000224718100005 PM 15492601 ER PT J AU Barbie, DA Mangi, AA Lauwers, GY AF Barbie, DA Mangi, AA Lauwers, GY TI Eosinophilic gastroenteritis associated with systemic lupus erythematosus SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE eosinophilic gastroenteritis; systemic lupus erythematosus; connective tissue disease ID OF-THE-LITERATURE; SODIUM CROMOGLYCATE; REVISED CRITERIA; ABDOMINAL-PAIN; DISEASE; CLASSIFICATION; ENTEROPATHY; MONTELUKAST; VASCULITIS; COLITIS AB Eosinophilic gastroenteritis is an uncommon disease with an obscure etiology, although associations with allergy, the idiopathic hypereosinophilic syndrome, and connective tissue disease have been reported. We present the case of a 37-year-old woman with a history of idiopathic thrombocytopenic purpura who presented with refractory nausea, vomiting, and abdominal pain. Imaging studies were significant for bowel wall thickening and ascites, while laboratory studies revealed a positive antinuclear antibody (ANA), a positive anti-double stranded (DS) DNA antibody, low complement, and proteinuria. Exploratory laparotomy with gastric and small bowel biopsies established the diagnosis of eosinophilic gastroenteritis. In addition, the patient met clinical criteria for the diagnosis of systemic lupus crythematosus. Previous studies have described cosinophilic gastroenteritis in patients with scleroderma, polymyositis, or dermatomyositis. This is the first report to our knowledge of an individual with eosinophilic gastroenteritis and systemic lupus erythematosus. C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Barbie, DA (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Wang ACC 625,15 Parkman St, Boston, MA 02114 USA. EM dbarbie@partners.org NR 32 TC 28 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2004 VL 38 IS 10 BP 883 EP 886 DI 10.1097/00004836-200411000-00010 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 865QR UT WOS:000224718100010 PM 15492606 ER PT J AU Sarantopoulos, S Lu, LR Cantor, H AF Sarantopoulos, S Lu, LR Cantor, H TI Qa-1 restriction of CD8(+) suppressor T cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN BASIC-PROTEIN; HEAT-SHOCK-PROTEIN; CLASS IB MOLECULES; NEGATIVE SELECTION; AUTOIMMUNE-DISEASE; TRANSPLANTATION TOLERANCE; INHIBITORY RECEPTORS; POSITIVE SELECTION; ADJUVANT ARTHRITIS AB There is increasing evidence that the immune response can be inhibited by several T cell subsets, including NK T cells, CD25(+)CD4(+) T cells, and a subpopulation of CD8(+) T cells. Animal model studies of multiple sclerosis have suggested an important role for suppressor CD8(+) T cells in protection against disease recurrence and exacerbation. The molecular lynchpin of CD8(+) suppressive activity is the murine MHC molecule Qa-1, termed HLA-E in humans. Here we summarize findings from work on Qa-1 that have begun to delineate suppressor CD8(+) T cells and their mechanisms of action in the context of self tolerance and autoimmune disease. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Harvey_Cantor@dfci.harvard.edu RI Lu, Linrong/A-1429-2013 FU NCI NIH HHS [T32 CA009172] NR 55 TC 87 Z9 92 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 NOV PY 2004 VL 114 IS 9 BP 1218 EP 1221 DI 10.1172/JCI200423152 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 867WC UT WOS:000224872400007 PM 15520850 ER PT J AU O'Garra, A Vieira, PL Vieira, P Goldfeld, AE AF O'Garra, A Vieira, PL Vieira, P Goldfeld, AE TI IL-10-producing and naturally occurring CD4(+) Tregs: limiting collateral damage SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID REGULATORY T-CELLS; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; PULMONARY TUBERCULOSIS PATIENTS; IN-VIVO; IMMUNE-RESPONSES; LEISHMANIA-MAJOR; DENDRITIC CELLS; TH2 CELLS; TGF-BETA AB Effective immune responses against pathogens are sometimes accompanied by strong inflammatory reactions. To minimize damage to self, the activation of the immune system also triggers anti-inflammatory circuits. Both inflammatory and anti-inflammatory reactions are normal components of the same immune response, which coordinately fight infections while preventing immune pathology. IL-10 is an important suppressive cytokine, produced by a large number of immune cells in addition to the antigen-driven IL-10-producing regulatory and the naturally occurring suppressor CD4(+) T cells, which is a key player in anti-inflammatory immune responses. However, additional mechanisms have evolved to ensure that pathogen eradication is achieved with minimum damage to the host. Here we discuss those mechanisms that operate to regulate effector immune responses. C1 Natl Inst Med Res, Div Immunoregulat, London NW7 1AA, England. CNRS, URA 1961, Unite Dev Lymphocytes, Paris, France. Harvard Univ, Sch Med, Biomed Res Inst, CBR, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP O'Garra, A (reprint author), Natl Inst Med Res, Div Immunoregulat, Mill Hill,Ridgeway, London NW7 1AA, England. EM aogarra@nimr.mrc.ac.uk RI Vieira, Paulo/D-4500-2013; OI O'Garra, Anne/0000-0001-9845-6134 NR 105 TC 310 Z9 325 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2004 VL 114 IS 10 BP 1372 EP 1378 DI 10.1172/JCI200423215 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 871EU UT WOS:000225113200003 PM 15545984 ER PT J AU Taghian, A Jeong, JH Mamounas, E Anderson, S Bryant, J Deutsch, M Wolmark, N AF Taghian, A Jeong, JH Mamounas, E Anderson, S Bryant, J Deutsch, M Wolmark, N TI Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: Results from five national surgical adjuvant breast and bowel project randomized clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 04-08, 2001 CL SAN FRANCISCO, CA SP Amer Soc Therapeut Radiol & Oncol ID PREMENOPAUSAL WOMEN; RADIATION-THERAPY; DOXORUBICIN-CYCLOPHOSPHAMIDE; POSTOPERATIVE RADIOTHERAPY; PREOPERATIVE CHEMOTHERAPY; RISK; IRRADIATION; FLUOROURACIL; METHOTREXATE; PNEUMONITIS AB Purpose To assess patterns of locoregional failure (LRF) in lymph node-positive (LN+) breast cancer patients treated with mastectomy and adjuvant chemotherapy ( tamoxifen) and without postmastectomy radiotherapy (PMRT) in five National Surgical Adjuvant Breast and Bowel Project trials. Patients and Methods \We examined 5,758 patients enrolled onto the B-15, B-16, B-18, B-22, and B-25 trials. Median follow-up time was 11.1 years. Distribution of pathologic tumor size was less than or equal to2 cm, 2.1 to 5 cm, and more than 5 cm in 30%, 52%, and 11% of patients, respectively. Distribution of the number of LN+ was one to three, four to nine, and greater than or equal to10 in 51 %, 32%, and 16% of patients, respectively. Ninety percent of patients received doxorubicin-based chemotherapy. Results The overall 10-year cumulative incidences of isolated LRF, LRF with or without distant failure (DR and DF alone as first event were 12.2%, 19.8%, and 43.3%, respectively. Cumulative incidences for LRF as first event with or without DF for patients with one to three, four to nine, and greater than or equal to: 10 LN+ were 13.0%, 24.4%, and 31.9%, respectively (P < .0001). For patients with a tumor size of greater than or equal to2 cm, 2.1 to 5.0 cm, and more than 5.0 cm, these incidences were 14.9%, 21.3%, and 24.6%, respectively (P < .0001). Multivariate analysis showed age, tumor size, premenopausal status, number of LN+, and number of dissected LN as significant predictors for LRF as first event. Conclusion In patients with large tumors and four or more LN+, LRF as first event remains a significant problem. Although PMRT is currently recommended for patients with four or more LN+, it may also have value in selected patients with one to three LN+. However, in the absence of a randomized trial examining the worth of radiotherapy in this group of patients, the value of PMRT remains unknown. (C) 2004 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Med Presbyterian, Dept Radiat Oncol, Pittsburgh, PA USA. Boston Med Ctr, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Aultman Canc Ctr, Canton, OH USA. RP Taghian, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ataghian@partners.org FU NCI NIH HHS [U10CA-69974, U10CA-12027, U10CA-69651-10] NR 30 TC 206 Z9 221 U1 0 U2 1 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 NOV 1 PY 2004 VL 22 IS 21 BP 4247 EP 4254 DI 10.1200/JCO.2004.01.042 PG 8 WC Oncology SC Oncology GA 867LU UT WOS:000224844900004 PM 15452182 ER PT J AU Puduvalli, VK Yung, WKA Hess, KR Kuhn, JG Groves, MD Levin, VA Zwiebel, J Chang, SM Cloughesy, TF Junck, L Wen, P Lieberman, F Conrad, CA Gilbert, MR Meyers, CA Liu, V Mehta, MP Nicholas, MK Prados, M AF Puduvalli, VK Yung, WKA Hess, KR Kuhn, JG Groves, MD Levin, VA Zwiebel, J Chang, SM Cloughesy, TF Junck, L Wen, P Lieberman, F Conrad, CA Gilbert, MR Meyers, CA Liu, V Mehta, MP Nicholas, MK Prados, M TI Phase II study of Fenretinide (NSC 374551) in adults with recurrent malignant gliomas: A North American brain tumor consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER PATIENTS; N-(4-HYDROXYPHENYL) RETINAMIDE; CHEMOPREVENTION TRIAL; CLINICAL-TRIALS; RETINOIC ACID; CELL-LINES; APOPTOSIS; PHARMACOKINETICS; INDUCTION; PLASMA AB Purpose Fenretinide induces apoptosis in malignant gliomas in vitro. This two-stage phase 11 trial was conducted to determine the efficacy of fenretinide in adults with recurrent malignant gliomas. Patients and Methods Twenty-two patients with anaplastic gliomas (AG) and 23 patients with glioblastoma (GBM) whose tumors had recurred after radiotherapy and no more than two chemotherapy regimens were enrolled. Fenretinide was given orally on days I to 7 and 22 to 28 in 6-week cycles in doses of 600 or 900 mg/m(2) bid. Results Six of 21 (29%) patients in the AG arm and two of 23 (9%) patients in the GBM arm had stable disease at 6 months. One patient with AG treated at 900 mg/m(2) bid dosage had a partial radiologic response. Median progression-free survival (PFS) was 6 weeks for the AG arm and 6 weeks for the GBM arm. PFS at 6 months was 10% for the AG arm and 0% for the GBM arm. Grade I or 2 fatigue, dryness of skin, anemia, and hypoalbuminemia were the most frequent toxicities reported. The trial was closed after the first stage because of the inadequate activity at the fenretinide doses used. The first-administration mean plasma Cm ex for fenretinide was 832 +/- 360 ng/mL at the 600 mg/m(2) bid dosage and 1,213 +/- 261 ng/mL at the 900 mg/m(2) bid dosage. Conclusion Fenretinide was inactive against recurrent malignant gliomas at the dosage used in this trial. However, additional studies using higher doses of the agent are warranted based on the tolerability of the agent and the potential for activity of a higher fenretinde dosage, as suggested in this trial. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Wisconsin, Madison, WI 53706 USA. RP Puduvalli, VK (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 431, Houston, TX 77030 USA. EM vpuduval@mdanderson.org RI Puduvalli, Vinay/A-2411-2016; Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA62426, CA16672, CA62399, CA62412, CA62422, CA62455, P30 CA016672, R21 CA097767, R21 CA097767-02, U01 CA062399, U01 CA062405, U01 CA062407, U01 CA062412, U01 CA062421, U01 CA062422, U01 CA062426, U01CA62399, U01CA62405, U01CA62407-08, U01CA62421]; NCRR NIH HHS [M01 RR000042, M01 RR000056, M01 RR000079, M01 RR000633, M01 RR000865, M01 RR003186, M01-RR00042, M01-RR00056, M01-RR00079, M01-RR00633, M01-RR03186, M01-RR0865] NR 30 TC 47 Z9 48 U1 1 U2 2 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 NOV 1 PY 2004 VL 22 IS 21 BP 4282 EP 4289 DI 10.1200/JCO.2004.09.006 PG 8 WC Oncology SC Oncology GA 867LU UT WOS:000224844900008 PM 15514370 ER PT J AU Haffajee, AD Bogren, A Hasturk, H Feres, M Lopez, NJ Socransky, SS AF Haffajee, AD Bogren, A Hasturk, H Feres, M Lopez, NJ Socransky, SS TI Subgingival microbiota of chronic periodontitis subjects from different geographic locations SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE geographic location; periodontal diseases; periodontal health; periodontitis; subgingival microbiota ID ADULT; MICROFLORA; PREVALENCE; CHINESE; PLAQUE AB Background: Most clinical studies assume that the subgingival microbiota is similar from one geographic location to another. The purpose of the present investigation was to examine the composition of the subgingival microbiota in chronic periodontitis subjects from four countries. Method: Subjects with chronic periodontitis (N, Sweden=101; USA=115; Brazil=58; Chile=26) were recruited. Subjects were measured at baseline for plaque, gingivitis, bleeding on probing (BOP), suppuration, pocket depth (PD) and attachment level (AL) at six sites per tooth. Subgingival plaque samples taken from the mesial aspect of each tooth at baseline were individually analyzed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization (total samples=6036). % DNA probe counts comprised by each species was determined for each site and averaged across sites in each subject. Significance of differences in proportions of each species among countries was determined using ANCOVA adjusting for age, mean pocket depth, gender and smoking status. p-Values were adjusted for multiple comparisons. Results: On average, all species were detected in samples from subjects in the four countries. Thirteen species differed significantly in adjusted mean proportions among countries even after adjusting for multiple comparisons. Porphyromonas gingivalis, one species that differed in proportions among countries, comprised adjusted means of 7.5, 11.9, 1.6 and 6.6% of the microbiota in subjects from Brazil, Chile, Sweden and USA (p<0.001), while mean proportions of Treponema denticola were 6.7, 4.2, 0.8 and 2.3, respectively (p<0.001). In contrast, a key periodontal pathogen, Tannerella forsythensis, exhibited mean proportions ranging from 6.2-8.5% and did not differ significantly among countries. Besides these species, prominent species in Brazil were Actinomyces naeslundii genospecies 1 and 2 (8.4%, 7.2%) and Prevotella intermedia (6.5%); in Chile, Prevotella melaninogenica (6.4%) and Neisseria mucosa (5.3%); in Sweden A. naeslundii genospecies 2 (8.4%), Capnocytophaga gingivalis (7.1%) and Peptostreptococcus micros (5.0%); in USA A. naeslundii genospecies 2 (7.5%), P. intermedia (6.8%) and C. gingivalis (6.1%). Conclusions: The microbial profiles of subgingival plaque samples from chronic periodontitis subjects in four countries showed surprisingly marked differences. These differences persisted after adjusting for age, mean pocket depth, gender and smoking status. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. Gothenburg Univ, Dept Periodontol, S-41124 Gothenburg, Sweden. Boston Univ, Dept Periodontol, Boston, MA 02215 USA. Guarulhos Univ, Dept Periodontol, Sao Paulo, Brazil. Univ Chile, Dept Periodontol, Santiago, Chile. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. EM ahaffajee@forsyth.org RI Feres, Magda/H-7964-2012 FU NIDCR NIH HHS [DE-10977, DE-12108, DE-1286, DE-13232] NR 13 TC 113 Z9 127 U1 1 U2 9 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD NOV PY 2004 VL 31 IS 11 BP 996 EP 1002 DI 10.1111/j.1600-051X.2004.00597.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 862XV UT WOS:000224525700012 PM 15491316 ER PT J AU Wilhelm, S Tolin, DF Steketee, G AF Wilhelm, S Tolin, DF Steketee, G TI Challenges in treating obsessive-compulsive disorder: Introduction SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE obsessive-compulsive disorder; obsessions; compulsions; cognitive behavioral therapy; exposure; response prevention; pharmacotherapy AB This issue of In Session is devoted to challenges in the treatment of obsessive-compulsive disorder (OCD). The remarkable diversity of symptoms and the comorbidity in OCD pose substantial challenges to practitioners seeking to treat this disorder. After briefly reviewing the clinical features of OCD and its typical treatment, we provide brief descriptions of the six articles this issue comprises. Articles focus on the treatment of OCD with comorbid depression, compulsive hoarding, incompleteness, and repugnant obsessions, and on treatment of children who have OCD. The final article describes pharmacotherapy for OCD. All articles feature case vignettes and provide practitioners with clinical recommendations. (C) 2004 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, OCD Clin, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Connecticut, Sch Med, Storrs, CT 06269 USA. Boston Univ, Boston, MA 02215 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, OCD Clin, Bldg 149,13th St, Charlestown, MA 02129 USA. EM wilhelm@psych.mgh.harvard.edu NR 16 TC 2 Z9 2 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 NOV PY 2004 VL 60 IS 11 BP 1127 EP 1132 DI 10.1002/jclp.20077 PG 6 WC Psychology, Clinical SC Psychology GA 865FE UT WOS:000224687100001 PM 15389623 ER PT J AU Dougherty, DD Rauch, SL Jenike, MA AF Dougherty, DD Rauch, SL Jenike, MA TI Pharmacotherapy for obsessive-compulsive disorder SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE obsessive-compulsive disorder; pharmacotherapy; serotonin reuptake inhibitors; neuroleptics; neurosurgery ID DOUBLE-BLIND; CINGULOTOMY AB Pharmacotherapeutic options for obsessive-compulsive disorder (OCD) have expanded over the past half-century since medications were first found to be effective for the treatment of OCD. Currently, the serotonin reuptake inhibitors (SRIs) represent the first-line pharmacotherapy for OCD. High dosages and long trials of the SRIs are needed for adequate treatment of OCD. The use of SRIs for the treatment of OCD is reviewed, then other pharmacotherapeutic treatment options, including SRI augmentation and alternative monotherapies, are discussed. The preponderance of data demonstrates that SRI augmentation with neuroleptics is efficacious for treatment-refractory OCD. There is substantially less evidence supporting other alternative strategies. Finally, neurosurgical and device-based approaches for treatment-refractory OCD are reviewed. (C) 2004 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St,CNY-2612, Charlestown, MA 02129 USA. EM ddougherty@partners.org NR 14 TC 34 Z9 36 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD NOV PY 2004 VL 60 IS 11 BP 1195 EP 1202 DI 10.1002/jclp.20083 PG 8 WC Psychology, Clinical SC Psychology GA 865FE UT WOS:000224687100007 PM 15389617 ER PT J AU Hussein, MR Al-Badaiwy, ZH Guirguis, MN AF Hussein, MR Al-Badaiwy, ZH Guirguis, MN TI Analysis of p53 and bcl-2 protein expression in the non-tumorigenic, pretumorigenic, and tumorigenic keratinocytic hyperproliferative lesions SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ORAL LICHEN-PLANUS; NONMELANOMA SKIN CANCERS; EPIDERMODYSPLASIA-VERRUCIFORMIS; ACTINIC KERATOSIS; SOLAR KERATOSIS; APOPTOSIS; PROLIFERATION; GENE; DNA AB Background: The hyperproliferative keratinocytic lesions encompass a wide range of non-tumorigenic, pretumorigenic, and tumorigenic conditions. The aim of this work was to examine the expression patterns of apoptosis-linked molecules (bcl-2 and p53) in these lesions. Methods: Immunoperoxidase staining methods were applied to analyze p53 and bcl-2 protein expression in a total of 66 cases, including 12 squamous cell carcinomas (both in situ and invasive SCC), 11 actinic keratoses (AK), 13 psoriasis vulgaris (PV), eight verruca vulgaris (VV), six chronic dermatitis (CD), five seborrheic keratosis (SK), four lichen planus (LP), three epidermodysplasia verruciformis (EDV), two condyloma acuminata (CA), two lichen simplex chronicus (LSC), and 10 specimens from normal skin. Results: As compared to normal skin (0.70 +/- 0.26), the bcl-2 average weighted scores in the non-tumorigenic (0.76 +/- 0.16), pretumorigenic (1.45 +/- 0.28), and tumorigenic lesions (2.83 +/- 0.50 and 2.92 +/- 0.50 for in situ and invasive SCC, respectively) showed significant up-regulation (p = 0.001). In the non-tumorigenic lesions, the bcl-2 expression values decreased in the following order: SK > EDV > CD > LP > CA > PV > VV (1.40 +/- 0.24 > 1.33 +/- 0.67 > 0.83 +/- 0.40 > 0.67 +/- 0.21 > 0.50 +/- 0.20 > 0.46 +/- 0.22 > 0.13 +/- 0.01, respectively). As compared to normal skin (1.10 +/- 0.23), the p53 average weighted scores in the non-tumorigenic (1.86 +/- 0.18), pretumorigenic (3.64 +/- 0.53), and tumorigenic lesions (5.00 +/- 1.00 and 5.08 +/- 0.86 for in situ and invasive SCC, respectively) showed significant up-regulation (p = 0.021). In the non-tumorigenic lesions, p53 average weighted scores decreased in the following order: SK > PV > CA > LP > CD > VV > EDV (3.20 +/- 0.49 > 2.38 +/- 0.27 > 2.0 +/- 0.0 > 1.83 +/- 0.48 > 1.0 +/- 0.37 > 1.0 +/- 0.33 > 1.0 0.0, respectively). There was a positive correlation between bcl-2 and p53 protein expression in normal skin (r = 0.966, p = 0.0001), non-tumorigenic (r = 0.775, p = 0.0001), pretumorigenic (r = 0.830, p = 0.001), and tumorigenic lesions (r = 0.757, p = 0.003). Conclusions: Bcl-2 and p53 proteins are altered in the keratinocytic hyperproliferative lesions. Determination of whether these alterations reflect underlying gene mutations will require further investigations. C1 Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. S Valley Univ, Fac Med, Assiut, Egypt. Univ Wisconsin, Sch Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Hussein, MR (reprint author), Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. EM mrh17@swissinfo.org NR 63 TC 44 Z9 45 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD NOV PY 2004 VL 31 IS 10 BP 643 EP 651 DI 10.1111/j.0303-6987.2004.00244.x PG 9 WC Dermatology; Pathology SC Dermatology; Pathology GA 867SM UT WOS:000224862500002 PM 15491323 ER PT J AU Pawlik, TM Poon, RT Abdalla, EK Sarmiento, JM Ikai, I Curley, SA Nagorney, DM Belghiti, J Ng, IOL Yamaoka, Y Lauwers, GY Vauthey, JN AF Pawlik, TM Poon, RT Abdalla, EK Sarmiento, JM Ikai, I Curley, SA Nagorney, DM Belghiti, J Ng, IOL Yamaoka, Y Lauwers, GY Vauthey, JN TI Hepatitis serology predicts tumor and liver-disease characteristics but not prognosis after resection of hepatocellular carcinoma SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 15-19, 2004 CL New Orleans, LA SP Soc Surg Alimentary Tract DE hepatitis; hepatocellular carcinoma; resection ID B SURFACE-ANTIGEN; C VIRUS-INFECTION; RISK-FACTORS; CLINICAL-SIGNIFICANCE; VIRAL-INFECTION; JAPAN; PERSISTENCE; RECURRENCE; CIRRHOSIS; SURVIVAL AB The impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on survival rates after resection of hepatocellular carcinoma (HCC) is controversial. The objective of this study was to determine whether serologic evidence of HBV or HCV infection ("hepatitis serology") can predict underlying liver disease, tumor factors, and survival rates in patients with HCC. Using a multicenter international database, we identified 446 patients with complete HBV and HCV serology. One hundred twenty-six patients were negative for HBV and HCV, 163 patients had HBV infection only, 79 patients had HCV infection only, and 78 patients had coinfection with HBV and HCV. Patients with hepatitis were more likely to have tumors smaller than 5 cm, and bilateral HCC involvement. Hepatitis status (negative vs. HBV vs. HCV vs. coinfection with HBV and HCV) did not predict tumor grade or the presence of multiple tumor nodules. Patients with HCV or coinfection with HBV and HCV exhibited a lower incidence of vascular invasion, but worse fibrosis than patients with negative serology or HBV. The median survival rate was 47.9 months. The presence of hepatitis did not significantly affect the survival rate, but hepatic fibrosis and vascular invasion predicted a decreased survival rate. The prognosis after resection of HCC is influenced by tumor factors and liver disease, but not by HBV or HCV infection. The treatment for HCC should be dictated by the extent of underlying liver disease rather than by hepatitis serology. (C) 2004 The Society for Surgery of the Alimentary Tract. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Int Cooperat Study Grp Hepatocellular Carcinoma, Houston, TX 77030 USA. Univ Hong Kong, Med Ctr, Dept Surg, Queen Marys Hosp, Hong Kong, Hong Kong, Peoples R China. Kyoto Univ, Dept Surg, Grad Sch Med, Kyoto, Japan. Mayo Clin, Dept Gastroenterol & Gen Surg, Rochester, MN USA. Beaujon Hosp, Dept Surg, Paris, France. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Int Cooperat Study Grp Hepatocellular Carcinoma, 1515 Holcombe Blvd,Unit 444, Houston, TX 77030 USA. EM jvauthey@mdanderson.org RI Poon, Ronnie/C-4383-2009 NR 50 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD NOV PY 2004 VL 8 IS 7 BP 794 EP 804 DI 10.1016/j.gassur.2004.06.013 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 878FV UT WOS:000225633000007 PM 15531232 ER PT J AU Peck, BM Ubel, PA Roter, DL Goold, SD Asch, DA Jeffreys, AS Grambow, SC Tulsky, JA AF Peck, BM Ubel, PA Roter, DL Goold, SD Asch, DA Jeffreys, AS Grambow, SC Tulsky, JA TI Do unmet expectations for specific tests, referrals, and new medications reduce patients' satisfaction? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient expectations; patient satisfaction; veterans ID PATIENTS DESIRES; PHYSICIAN RELATIONSHIP; REQUEST FULFILLMENT; DECISION-MAKING; OFFICE PRACTICE; CARE; PERCEPTIONS; OUTCOMES; INTERVIEW; ENCOUNTER AB BACKGROUND: Patient-centered care requires clinicians to recognize and act on patients' expectations. However, relatively little is known about the specific expectations patients bring to the primary care visit. OBJECTIVE: To describe the nature and prevalence of patients' specific expectations for tests, referrals, and new medications, and to examine the relationship between fulfillment of these expectations and patient satisfaction. DESIGN: Prospective cohort study. SETTING: VA general medicine clinic. PATIENTS/PARTICIPANTS: Two hundred fifty-three adult male outpatients seeing their primary care provider for a scheduled visit. MEASUREMENTS AND MAIN RESULTS: Fifty-six percent of patients reported at least 1 expectation for a test, referral, or new medication. Thirty-one percent had 1 expectation, while 25% had 2 or more expectations. Expectations were evenly distributed among tests, referrals, and new medications (37%, 30%, and 33%, respectively). Half of the patients who expressed an expectation did not receive one or more of the desired tests, referrals, or new medications. Nevertheless, satisfaction was very high (median of 1.5 for visit-specific satisfaction on a 1 to 5 scale, with 1 representing "excellent"). Satisfaction was not related to whether expectations were met or unmet, except that patients who did not receive desired medications reported lower satisfaction. CONCLUSIONS: Patients' expectations are varied and often vague. Clinicians trying to implement the values of patient-centered care must be prepared to elicit, identify, and address many expectations. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Hlth Adm & Policy, Coll Publ Hlth, Oklahoma City, OK 73104 USA. Vet Adm Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Ann Arbor VA Med Ctr, Ann Arbor, MI USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. RP Peck, BM (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Hlth Adm & Policy, Coll Publ Hlth, 801 NE 13th St, Oklahoma City, OK 73104 USA. EM bmitchellpeck@tamu.edu RI Roter, Debra/N-8830-2014; Grambow, Steven/E-1422-2015; OI Grambow, Steven/0000-0001-6037-3253; Goold, Susan Dorr/0000-0002-0258-9774 NR 50 TC 41 Z9 41 U1 0 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2004 VL 19 IS 11 BP 1080 EP 1087 DI 10.1111/j.1525-1497.2004.30436.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 867TJ UT WOS:000224864900002 PM 15566436 ER PT J AU Budoff, JE AF Budoff, JE TI The prevalence of rotator cuff weakness in patients with injured hands SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE hand injury; rotator cuff; weakness; shoulder-hand ID HELD DYNAMOMETRY; REHABILITATION PROGRAM; ISOKINETIC DYNAMOMETRY; SHOULDER STRENGTH; MUSCLE STRENGTH; BREAK TESTS; RELIABILITY; INHIBITION; REFLEX; TORQUE AB Purpose: The purpose of this study was to document bilateral rotator cuff strength in patients with unilateral hand or wrist disorders. Methods: Fifty-seven patients who had suffered a unilateral injury or disorder isolated to their hand or wrist, distal to the distal radius, had their bilateral rotator cuff strength measured. Results: A statistically significant decrease in strength was found in the ipsilateral shoulder for both elevation in the plane of the scapula (supraspinatus) and for elevated external rotation (infraspinatus). Younger patients and the nondominant extremity were affected more adversely. Conclusions: An increased prevalence of rotator cuff weakness is shown proximal to ipsilateral hand injuries or disorders. Copyright (C) 2004 by the American Society for Surgery of the Hand. C1 Baylor Coll Med, Dept Orthopaed Surg, Hand & Upper Extrem Inst, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Budoff, JE (reprint author), Baylor Coll Med, Dept Orthopaed Surg, Hand & Upper Extrem Inst, Houston Vet Affairs Med Ctr, 6550 Fannin,2525, Houston, TX 77030 USA. RI Lempereur, Mathieu/G-5470-2012 NR 37 TC 4 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 2004 VL 29A IS 6 BP 1154 EP 1159 DI 10.1016/j.jhsa.2004.06.006 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 876SQ UT WOS:000225518200027 PM 15576231 ER PT J AU Kaphingst, KA DeJong, W Rudd, RE Daltroy, LH AF Kaphingst, KA DeJong, W Rudd, RE Daltroy, LH TI A content analysis of direct-to-consumer television prescription drug advertisements SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID PROMOTION; HEALTH; INFORMATION; PHYSICIANS; APPEALS AB This article reports the results of a content analysis of 23 direct-to-consumer (DTC) product-specific television prescription drug advertisements broadcast during 2001. A majority of ads used both medical and lay terms to convey medical ideas. Most gave consumers somewhat more time to absorb facts about benefits than those about risks, which could have implications for the "fair balance'' requirement. Complete references to additional product information were given only in text, casting doubt on whether these ads are making "adequate provision'' for dissemination of detailed product information. Overall, our results call into question the potential of these ads to educate consumers. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. Brigham & Womens Hosp, RBB Arthrit Res Ctr, Boston, MA 02115 USA. RP Kaphingst, KA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kimberly_kaphingst@dfci.harvard.edu OI DeJong, William/0000-0003-4964-0466 FU NIAMS NIH HHS [P60AR47782] NR 51 TC 53 Z9 54 U1 1 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD NOV-DEC PY 2004 VL 9 IS 6 BP 515 EP 528 DI 10.1080/10810730490882586 PG 14 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 875BI UT WOS:000225394300004 PM 15764450 ER PT J AU Roberts, DH Wain, JC Chang, YC Ginns, LC AF Roberts, DH Wain, JC Chang, YC Ginns, LC TI Donor-recipient gender mismatch in lung transplantation: Impact on obliterative bronchiolitis and survival SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article; Proceedings Paper CT 97th International Conference of the American-Thoracic-Society CY MAY 18-23, 2001 CL SAN FRANCISCO, CA SP Amer Thorac Soc ID RISK-FACTORS; MANAGEMENT; HISTORY; HEART; HLA AB Background: Because of the shortage of donor lungs, liberalization of donor selection criteria in terms of age, gas exchange, and smoking history has been proposed. Methods: We evaluated a single-institution population of lung transplant recipients (n = 98) for donor-recipient gender matching. We measured overall survival, time to acute allograft rejection, and time to development of obliterative bronchiolitis (OB). Results: We found significant improvement in overall survival for gender-mismatched donor and recipient pairs (p = 0.078) and a significantly shorter OB-free period for male donor and female recipient pairs (p = 0.017). Conclusion: These findings suggest that donor organ allocation based on gender may affect long-term survival and other outcomes after lung transplantation. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Gen Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ginns, LC (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Gen Med Serv, White 905,Fruit St, Boston, MA 02114 USA. EM lginns@partners.org NR 22 TC 35 Z9 35 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 NOV PY 2004 VL 23 IS 11 BP 1252 EP 1259 DI 10.1016/j.healun.2003.09.014 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 871QR UT WOS:000225148900006 PM 15539123 ER PT J AU Alter, G Malenfant, JM Altfeld, M AF Alter, G Malenfant, JM Altfeld, M TI CD107a as a functional marker for the identification of natural killer cell activity SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE natural killer cells; IFN-gamma; TNF-alpha; CD107a; cytotoxicity; degranulation ID GLYCOPROTEINS; SPECIFICITY; PERFORIN AB Natural killer (NK) cells are a subset of lymphocytes that play a central role in the innate immune response to tumors and infections. An important limitation in the field of NK research is attributable to the deficit of assays available for the detection of the functional activity of NK cells. Recently, lysosomal-associated membrane protein-1 (LAMP-1 or CD107a) has been described as a marker of CD8(+) T-cell degranulation following stimulation. Here we describe CD107a as a marker of NK cell functional activity using multi-parameter flow cytometry. CD107a is significantly upregulated on the surface of NK cells following stimulation with MHC devoid targets. Additionally, CD107a expression correlates with both cytokine secretion and NK cell-mediated lysis of target cells. However, as well as being coordinately expressed on nearly all cytokine secreting cells, CD107a was also expressed on a large subset of NK cells that did not secrete cytokine following stimulation. These data suggest that employing CD107a as a marker of NK cell functional activity may allow for the identification of a large fraction of activated NK cells that may degranulate in the absence of cytokine secretion. Cumulatively, the data presented here demonstrate that CD107a is a sensitive marker of NK cell activity. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. EM maltfeld@partners.org NR 15 TC 561 Z9 583 U1 1 U2 20 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 NOV PY 2004 VL 294 IS 1-2 BP 15 EP 22 DI 10.1016/j.jim.2004.08.008 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 881UU UT WOS:000225895700002 PM 15604012 ER PT J AU Rosen, HR Hinrichs, DJ Leistikow, RL Callender, GC Wertheimer, AM Nishimura, MI Lewinsohn, DM AF Rosen, HR Hinrichs, DJ Leistikow, RL Callender, GC Wertheimer, AM Nishimura, MI Lewinsohn, DM TI Cutting edge: Identification of hepatitis C virus-specific CD8(+) T cells restricted by donor HLA alleles following liver transplantation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULES; INFECTION; LYMPHOCYTES; MECHANISMS; ANTIGEN AB By necessity, human liver transplantation is performed across HLA barriers. As a result, intracellular infection of the allograft presents a unique immunologic challenge for the recipient's immune system. In this study, we describe the presence of HLA-A2-restricted, hepatitis C virus (HCV)-specific CD8(+) T cells in liver transplant recipients in whom the allograft is HLA-A2 positive and the recipient is HLA-A2 negative. These memory-effector T cells are recipient derived and recognize HCV peptide uniquely in the context of HLA-A2. Furthermore, these cells were absent before the transplant, suggesting that the allograft is capable of selectively expanding naive CD8(+) T cells. The in vitro specificity to donor HLA allele-restricted CD8(+) T cells suggests that these cells may function to control HCV spread in the allograft. C1 Oregon Hlth Sci Univ, Hepatol & Liver Transplantat Program, Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. Portland Vet Affairs Med Ctr, Res Serv, Portland, OR 97207 USA. Portland Vet Affairs Med Ctr, Div Pulm & Crit Care, Portland, OR 97207 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Hepatol & Liver Transplantat Program, Portland Vet Affairs Med Ctr, 3710 SW US Vet Hosp Rd,P3-GI, Portland, OR 97207 USA. EM rosenhu@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NCI NIH HHS [CA90873, CA102280]; NIDDK NIH HHS [R01 DK060590] NR 20 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2004 VL 173 IS 9 BP 5355 EP 5359 PG 5 WC Immunology SC Immunology GA 864XH UT WOS:000224665900005 PM 15494481 ER PT J AU Hurley, BP Siccardi, D Mrsny, RJ McCormick, BA AF Hurley, BP Siccardi, D Mrsny, RJ McCormick, BA TI Polymorphonuclear cell transmigration induced by Pseudomonas aeruginosa requires the eicosanoid hepoxilin A(3) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; PROTEIN-KINASE-C; NEUTROPHIL MIGRATION; CYSTIC-FIBROSIS; ARACHIDONATE 12-LIPOXYGENASE; MOLECULAR MECHANISMS; LUNG; MODEL; TRANSLOCATION; RECRUITMENT AB Lung inflammation resulting from bacterial infection of the respiratory mucosal surface in diseases such as cystic fibrosis and pneumonia contributes significantly to the pathology. A major consequence of the inflammatory response is the recruitment and accumulation of-polymorphonuclear cells (PMNs) at the infection site. It is currently unclear what bacterial factors trigger this response and exactly how PMNs are directed across the epithelial barrier to the airway lumen. An in vitro model consisting of human PMNs and alveolar epithelial cells (A549) grown on inverted Transwell filters was used to determine whether bacteria are capable of inducing PMN migration across these epithelial barriers. A variety of lung pathogenic bacteria, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa are indeed capable of inducing PMN migration across A549 monolayers. This phenomenon is not mediated by LPS, but requires live bacteria infecting the apical surface. Bacterial interaction with the apical surface of A549 monolayers results in activation of epithelial responses, including the phosphorylation of ERK1/2 and secretion of the PMN chemokine IL-8. However, secretion of IL-8 in response to bacterial infection is neither necessary nor sufficient to mediate PMN transepithelial migration. Instead, PMN transepithelial migration is mediated by the eicosanoid hepoxilin A(3), which is a PMN chemoattractant secreted by A549 cells in response to bacterial infection in a protein kinase G dependent manner. These data suggest that bacterial-induced hepoxilin A(3) secretion may represent a previously unrecognized inflammatory mechanism occurring within the lung epithelium during bacterial infections. C1 Massachusetts Gen Hosp, Musosal Immunol Labs, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02155 USA. Cardiff Univ, Sch Pharm, Cardiff, S Glam, Wales. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Musosal Immunol Labs, CNY 114,114-3503, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK 56754] NR 40 TC 40 Z9 40 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2004 VL 173 IS 9 BP 5712 EP 5720 PG 9 WC Immunology SC Immunology GA 864XH UT WOS:000224665900047 PM 15494523 ER PT J AU Gadjeva, M Tomczak, MF Zhang, M Wang, YY Dull, K Rogers, AB Erdman, SE Fox, JG Carroll, M Horwitz, BH AF Gadjeva, M Tomczak, MF Zhang, M Wang, YY Dull, K Rogers, AB Erdman, SE Fox, JG Carroll, M Horwitz, BH TI A role for NF-kappa B subunits p50 and p65 in the inhibition of lipopolysaccharide-induced shock SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; INTERFERON-GAMMA; IMMUNE-RESPONSES; MICE LACKING; IFN-GAMMA; INTERLEUKIN-12; TRANSCRIPTION; INFLAMMATION; NF-KAPPA-B1 AB To evaluate the possibility that NF-kappaB subunits p50 and p65 have a role in limiting the systemic inflammatory response induced by endotoxin, we compared the susceptibility of wild-type (WT), p65(+/-), p50(-/-), and p50(-/-)p65(+/-) (3X) mice to LPS-induced shock. Interestingly, whereas p65(+/-) mice were no more sensitive than WT mice to LPS-induced shock, 3X mice were exquisitely sensitive to the toxic effects of LPS. Mice lacking p50 alone displayed an intermediate phenotype. Sensitivity to LPS was a property of the innate immune system and was characterized by elevated circulating levels of TNF in both p50(-/-) and 3X mice. The ability of LPS to induce shock depended upon TNF, and 3X mice were significantly more sensitive to the toxic effects of TNF than were p50-deficient mice. The expression of several LPS-inducible proinflammatory genes, including IFN-gamma, was significantly higher within the spleens of p50(-/-) mice than in the spleens of WT mice, and interestingly, the expression of IFN-gamma was augmented still further within the spleens of 3X mice. These results demonstrate that NF-kappaB subunits p50 and p65 have critical inhibitory functions during the systemic response to LPS and raise the possibility that these functions could be essential in preventing mortality associated with systemic inflammatory response syndromes. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Immunol Res Div, Boston, MA 02115 USA. Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. RP Horwitz, BH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Blood Res, NHRB 630E,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM bhorwitz@rics.bwh.harvard.edu FU NCI NIH HHS [CA67529]; NIAID NIH HHS [AI50952, AI052267] NR 35 TC 52 Z9 55 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2004 VL 173 IS 9 BP 5786 EP 5793 PG 8 WC Immunology SC Immunology GA 864XH UT WOS:000224665900055 PM 15494531 ER PT J AU Kikuchi, T Akasaki, Y Abe, T Fukuda, T Saotome, H Ryan, JL Kufe, DW Ohno, T AF Kikuchi, T Akasaki, Y Abe, T Fukuda, T Saotome, H Ryan, JL Kufe, DW Ohno, T TI Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE immunotherapy; dendritic cells; glioma; brain tumor; interleukin 12 ID IN-VITRO; TUMORS; IMMUNIZATION; CYTOKINES; IMMUNITY AB Despite aggressive treatment, the median survival of patients with high-grade malignant astrocytoma is about I year. The authors investigated the safety and clinical response to immunotherapy using fusions of dendritic and glioma cells combined with recombinant human interleukin 12 (rhIL-12) for the treatment of malignant glioma. Fifteen patients with malignant glioma participated in this study. Dendritic cells were generated from peripheral blood. Cultured autologous glioma cells were established from surgical specimens in each case. Fusion cells were prepared from dendritic and glioma cells using polyethylene glycol. All patients received fusion cells intradermally on day 1. rhIL-12 was injected subcutaneously at the same site on days 3 and 7. Response to the treatment was evaluated by clinical observations and radiologic findings. No serious adverse effects were observed. In four patients, magnetic resonance imaging showed a greater than 50% reduction in tumor size. One patient had a mixed response. These results show that administration of fusion cells and rhIL-12 safely induces clinical antitumor effects in some patients with malignant glioma. C1 Jikei Univ, Dept Oncol, Inst DNA Med, Tokyo, Japan. Jikei Univ, Dept Neurosurg, Tokyo, Japan. Jikei Univ, Div Neuropathol, Dept Neurosci, Tokyo, Japan. AHP Serv Japan Co Ltd, Wyeth Res Dept, Tokyo, Japan. Wyeth Pharmaceut, Experimental Med Res & Dev, Cambridge, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kikuchi, T (reprint author), 3-25-8 Nishishinbashi,Minato Ku, Tokyo 1058461, Japan. EM tkikuchi@jikei.ac.jp NR 17 TC 138 Z9 146 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP 452 EP 459 DI 10.1097/00002371-200411000-00005 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800005 PM 15534489 ER PT J AU Cho, D Signoretti, S Regan, M Ko, YJ McDermott, D Lechpammer, M Polivy, A Youmans, A Stanbridge, E Atkins, M AF Cho, D Signoretti, S Regan, M Ko, YJ McDermott, D Lechpammer, M Polivy, A Youmans, A Stanbridge, E Atkins, M TI Carbonic anyhydrase IX (CAIX) expression does not correlate with the renal cell cancer (RCC) patient response to CCI-779 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Renal Canc Program, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Dept Microbiol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Dept Mol Genet, Boston, MA 02115 USA. Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S12 EP S12 DI 10.1097/00002371-200411000-00048 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800049 ER PT J AU Febbo, P Signoretti, S Regan, M Mier, J McDermott, D Hirsh, M Genega, E Youmans, A Polivy, A Atkins, M AF Febbo, P Signoretti, S Regan, M Mier, J McDermott, D Hirsh, M Genega, E Youmans, A Polivy, A Atkins, M TI Gene expression patterns associated with renal cancer (RCC) response and resistance to IL-2-based therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Renal Canc Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S12 EP S13 DI 10.1097/00002371-200411000-00049 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800050 ER PT J AU Klyushnenkova, E Link, J Oberle, W Kodak, J Rich, C Vandenbark, A Alexander, R AF Klyushnenkova, E Link, J Oberle, W Kodak, J Rich, C Vandenbark, A Alexander, R TI Identification of HLA-DRB1*1501-restricted T cell epitopes from prostate-specific antigen (PSA) using DR2b transgenic mice SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 VA Maryland Hlth Care Syst, Urol Sect, Baltimore, MD USA. Univ Maryland, Sch Med, Div Urol, Baltimore, MD 21201 USA. Portland VA Med Ctr, Dept Neuroimmunol, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S25 EP S25 DI 10.1097/00002371-200411000-00091 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800092 ER PT J AU Resick, PA AF Resick, PA TI A suggested research agenda on treatment-outcome research for female victims of violence SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE violence against women; research agenda; treatment outcome ID POSTTRAUMATIC-STRESS-DISORDER; EXPOSURE THERAPY; NATIONAL SAMPLE; RAPE VICTIMS; PTSD; ABUSE; WOMEN; COMORBIDITY; DEPENDENCE; ASSAULT C1 VA Boston Healthcare Syst, Boston, MA USA. Univ Missouri, St Louis, MO 63121 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 26 TC 8 Z9 8 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD NOV PY 2004 VL 19 IS 11 BP 1290 EP 1295 DI 10.1177/0886260504271339 PG 6 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 865PL UT WOS:000224714900008 PM 15534332 ER PT J AU Corless, CL McGreevey, L Town, A Schroeder, A Bainbridge, T Harrell, P Fletcher, JA Heinrich, MC AF Corless, CL McGreevey, L Town, A Schroeder, A Bainbridge, T Harrell, P Fletcher, JA Heinrich, MC TI KIT gene deletions at the intron 10 exon 11 boundary in GI stromal tumors SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID OF-FUNCTION MUTATIONS; GERMLINE MUTATION; C-KIT; TYROSINE KINASE; JUXTAMEMBRANE REGION; PHASE-I; IMATINIB; DOMAIN; ASSOCIATION; ACTIVATION AB Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in the KIT gene, and the majority of these mutations affect the juxtamembrane domain of the kinase encoded by exon 11. Screening GIST' for KIT gene mutations is important for translational research studies and for providing prognostic information on the likelihood of tumor response to treatment with the kinase inhibitor imatinib mesylate (Gleevec). In a series of GIST' analyzed in our laboratory by a combination of denaturing HPLC and direct DNA sequencing, we identified 19 cases with KIT exon 11 deletions that included from 1 to 14 by of intron 10 sequence and resulted in loss of the normal splice acceptor site at the beginning of exon 11. Predicted use of the next potential splice-acceptor site was confirmed by cDNA sequencing in 4 cases. Thus, the resulting mutant isoform, deletion KPMYEVQWK 550-558, was the same in all 19 cases. Only two other examples of deletions across the intron 10-exon 11 boundary have been reported, yet among 722 GIST' analyzed in our laboratories these deletions were not uncommon, accounting for 3.9% of exon 11 mutations and 2.6% of all tumors. Loss of KIT intron 10 sequences may be under-recognized if the forward primer is too close to exon 11, or if cases are examined exclusively at the cDNA level. Laboratories that offer clinical screening for KIT mutations in GI stromal tumors should be aware of this class of mutations. C1 Oregon Hlth Sci Univ, Inst Canc, Dept Pathol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Hematol & Oncol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Corless, CL (reprint author), Oregon Hlth Sci Univ, Inst Canc, Dept Pathol, L471,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM corlessc@ohsu.edu NR 31 TC 29 Z9 31 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 BP 366 EP 370 DI 10.1016/S1525-1578(10)60533-8 PG 5 WC Pathology SC Pathology GA 885XG UT WOS:000226190000012 PM 15507676 ER PT J AU Whitney, D Skoletsky, J Moore, K Boynton, K Kann, L Brand, R Syngal, S Lawson, M Shuber, A AF Whitney, D Skoletsky, J Moore, K Boynton, K Kann, L Brand, R Syngal, S Lawson, M Shuber, A TI Enhanced retrieval of DNA from human fecal samples results in improved performance of colorectal cancer screening test SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID CELL-LINES; P53 GENE; MUTATIONS; STOOL; TUMORS; PCR; RATIONALE; GERMLINE; DATABASE; BAT-26 AB Colorectal cancer accounts for more than 10% of all cancer deaths but is curable, if detected early. We reported previously on a stool-based screening test in which DNA from stool samples is subjected to genome analysis; sensitivity of the test has been limited in part by inefficiency of retrieving DNA from stool. Our aim was to test the impact of a new purification method that would increase the yield of human DNA from stool. DNA from 86 cancer and 100 non-cancer subjects (diagnosed by colonoscopy) were purified from stool with a new method for DNA recovery based on sequence-specific capture with acrylamide gel immobilized capture probes as well as with a previously developed magnetic bead-capture procedure. The new purification method gives an average 5.4-fold increase in the quantity of human DNA that can routinely be retrieved from fecal samples. The increased recovery of DNA corresponds with an increase in assay sensitivity from 53% (CI: 42 to 64%) to 70% (CI: 59 to 79%); P = 0.0005 (by McNemar's test), with no change in specificity. The newly developed sample preparation method mitigates a major problem in detecting rare cancer-associated genetic changes in heterogeneous clinical samples such as stool. C1 EXACT Sci Corp, Appl Res Grp, Marlborough, MA USA. Evanston NW Healthcare, Evanston, IL USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kaiser Permanente, Sacramento, CA USA. RP Shuber, A (reprint author), EXACT Sci Corp, Appl Res Grp, 100 Campus Dr, Marlborough, MA USA. EM tshuber@exactsciences.com NR 27 TC 45 Z9 48 U1 1 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 BP 386 EP 395 DI 10.1016/S1525-1578(10)60536-3 PG 10 WC Pathology SC Pathology GA 885XG UT WOS:000226190000015 PM 15507679 ER PT J AU Ogino, S Wilson, RB Hawley, P Grody, WW AF Ogino, S Wilson, RB Hawley, P Grody, WW TI Bayesian analysis for cystic fibrosis risks in prenatal and carrier screening SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 10-13, 2004 CL Los Angeles, CA SP Assoc Mole Pathol C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 MA G1 BP 408 EP 408 PG 1 WC Pathology SC Pathology GA 885XG UT WOS:000226190000019 ER PT J AU Ogino, S Wilson, RB Gold, B Grody, WW AF Ogino, S Wilson, RB Gold, B Grody, WW TI Genetic risk assessment for cystic fibrosis in neonatal screening by immunoreactive trypsinogen and CFTR tests SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 10-13, 2004 CL Los Angeles, CA SP Assoc Mole Pathol C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NCI, Human Genet Sect, Frederick, MD 21701 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 MA G2 BP 408 EP 408 PG 1 WC Pathology SC Pathology GA 885XG UT WOS:000226190000020 ER PT J AU Ogino, S Kirkner, G Cantor, M Brahmandam, M Kawasaki, T Namgyal, C Giovannucci, EL Loda, M Fuchs, CS AF Ogino, S Kirkner, G Cantor, M Brahmandam, M Kawasaki, T Namgyal, C Giovannucci, EL Loda, M Fuchs, CS TI Family history and risks of colorectal cancer with MSI, 18q LOH, or KRAS, BRAF or TP53 mutation: Molecular epidemiologic data from Nurses' Health Study SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 10-13, 2004 CL Los Angeles, CA SP Assoc Mole Pathol C1 Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 MA ST14 BP 429 EP 429 PG 1 WC Pathology SC Pathology GA 885XG UT WOS:000226190000157 ER PT J AU Ozen, M Ittmann, M DeBakey, ME AF Ozen, M Ittmann, M DeBakey, ME TI Increased CDC25C phosphatase activity in prostate cancer: Correlation to biochemical recurrence SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 10-13, 2004 CL Los Angeles, CA SP Assoc Mole Pathol C1 Baylor Coll Med, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 MA ST22 BP 431 EP 431 PG 1 WC Pathology SC Pathology GA 885XG UT WOS:000226190000165 ER PT J AU Coffey, BJ Biederman, J Geller, D Frazier, J Spencer, T Doyle, R Gianini, L Small, A Frisone, DF Magovcevic, M Stein, N Faraone, SV AF Coffey, BJ Biederman, J Geller, D Frazier, J Spencer, T Doyle, R Gianini, L Small, A Frisone, DF Magovcevic, M Stein, N Faraone, SV TI Reexamining tic persistence and tic-associated impairment in Tourette's Disorder - Findings from a naturalistic follow-up study SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Tourette's disorder; natural history; prospective follow-up; remission rates ID SEVERITY; PREVALENCE; CHILDREN; ADULTS AB The objective of this study was to assess tic persistence and tic-associated impairment in referred youth with Tourette's Disorder (TD). Subjects were 50 youth (ages 6-17 years) who met DSM-IV diagnostic criteria for TD, were referred to a specialized TD program, and were evaluated by clinical and structured diagnostic interview. Tic severity and impairment was measured using the Yale Global Tic Severity Scale. The total tic score at or above minimal range defined tic persistence, and a TD impairment score at or above moderate range defined tic-associated impairment. Results were assessed during administration of the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiological Version. Mean age of onset of TD was 5.1 +/- 2.3 years, and mean illness duration was 5.6 +/- 3.2 years. At baseline, 88% of subjects met threshold criteria for at least mild tics, but only 30% met criteria for tic-associated impairment. At 2-year follow-up, 82% of these subjects met criteria for tic persistence (NS change from baseline), but only 14% met criteria for TD-associated impairment (p < .04 change from baseline). Although tics followed a persistent course in the majority of youth with TD, they were infrequently associated with impairment. There was a significant reduction in the proportion of youth with TD impairment from baseline to follow-up. These results support the view that TD is a persistent disorder, but suggest a dissociation between tic persistence and tic-associated dysfunction. C1 NYU, Ctr Child Study, Inst Study Tourettes & Movement Disorders, New York, NY 10016 USA. Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. RP Coffey, BJ (reprint author), NYU, Ctr Child Study, Inst Study Tourettes & Movement Disorders, 577 1st Ave, New York, NY 10016 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH01415-05] NR 23 TC 44 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 2004 VL 192 IS 11 BP 776 EP 780 DI 10.1097/01.nmd.0000144696.14555.c4 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 870SR UT WOS:000225078700007 PM 15505522 ER PT J AU McMillan, PJ Wilkinson, CW Greenup, L Raskind, MA Peskind, ER Leverenz, JB AF McMillan, PJ Wilkinson, CW Greenup, L Raskind, MA Peskind, ER Leverenz, JB TI Chronic cortisol exposure promotes the development of a GABAergic phenotype in the primate hippocampus SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE brain-derived neurotrophic factor; calbindin; dentate gyrus; GABAergic; glucocorticoid; glutamic acid decarboxylase ID MESSENGER-RNA EXPRESSION; ACTIVITY-DEPENDENT EXPRESSION; GRANULE CELL DEGENERATION; CALCIUM-BINDING PROTEINS; AMINOBUTYRIC-ACID LEVELS; MOSSY FIBER PATHWAY; NEUROTROPHIC FACTOR; RAT HIPPOCAMPUS; GENE-EXPRESSION; PYRAMIDAL NEURONS AB Glucocorticoids regulate plasticity and survival of hippocampal neurons. Aberrant exposure to this steroid hormone can result in neurodegeneration, perhaps secondary to disruption of calcium homeostasis. Calbindin, a calcium-binding protein that buffers excess calcium, may protect against neurodegeneration resulting from overabundance of intracellular calcium. In this study, we examined whether chronic treatment (1 year) with cortisol enhances hippocampal calbindin expression in primates. Calbindin is a marker for inhibitory neurons and the dentate gyrus is known to adopt an inhibitory phenotype in response to extreme conditions such as seizures. Thus, we hypothesized that chronic cortisol exposure may also promote a GABAergic phenotype. Therefore, we examined the expression of the GABA-synthesizing enzyme glutamic acid decarboxylase. The expression of brain-derived neurotrophic factor, which is responsive to glucocorticoids, was also examined. Our results demonstrate significant increases in calbindin, glutamic acid decarboxylase and brain-derived neurotrophic factor in several regions of the primate hippocampus, including the dentate gyrus and CA3, in response to chronic cortisol exposure. These results suggest that chronic cortisol exposure may shift the balance towards a GABAergic phenotype, perhaps as part of a compensatory feedback mechanism to dampen the initial excitatory effects of glucocorticoids in the hippocampus. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. Univ Washington, Sch Med, Dept Behav Sci, Seattle, WA USA. RP McMillan, PJ (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, GRECC S-182,Box 358280,1660 S Columbian Way, Seattle, WA 98108 USA. EM pammcm@u.washington.edu FU NIA NIH HHS [AG06136] NR 78 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2004 VL 91 IS 4 BP 843 EP 851 DI 10.1111/j.1471-4159.2004.02760.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 867TI UT WOS:000224864800009 PM 15525338 ER PT J AU Alberici, A Gobbo, C Panzacchi, A Nicosia, F Ghidoni, R Benussi, L Hock, C Papassotiropoulos, A Liberini, P Growdon, JH Frisoni, GB Villa, A Zanetti, O Cappa, S Fazio, F Binetti, G AF Alberici, A Gobbo, C Panzacchi, A Nicosia, F Ghidoni, R Benussi, L Hock, C Papassotiropoulos, A Liberini, P Growdon, JH Frisoni, GB Villa, A Zanetti, O Cappa, S Fazio, F Binetti, G TI Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; LOBAR DEGENERATION; PROTEIN-TAU; DIAGNOSIS; DYSFUNCTION; PREVALENCE; FREQUENCY; MISSENSE; CRITERIA AB Frontotemporal dementia (FTD) is the second commonest form of dementia after Alzheimer's disease, but its clinical and biological features are less well known. To uncover its earliest signs, we studied the main clinical, neuroimaging, and biochemical findings in an asymptomatic carrier from a three generation FTD family, bearing the P301L pathogenic mutation in the tau gene. Except for selective impairment on the Verbal Fluency Test for letters, all cognitive tests were normal. The brain computed tomography scan was normal, but the brain single photon emission computed tomography and statistical parametric mapping ( SPECT-SPM) scan revealed bilateral frontal lobe hypoperfusion. Levels of total tau, 181P-tau, and Abeta1-42 in the cerebrospinal fluid were increased compared with control values. We conclude that detection of these distinctive abnormalities should improve early diagnostic accuracy for FTD and help distinguish it from Alzheimer's disease. C1 IRCCS S Giovanni Dio FBF, Neurobiol Lab, I-25123 Brescia, Italy. Inst HS Raffaele, Dept Nucl Med, Milan, Italy. Univ Zurich, Dept Psychiat Res, Zurich, Switzerland. Spedali Civil Brescia, Dept Neurol, I-25125 Brescia, Italy. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. IRCCS S Giovanni Dio FBF, Epidemiol & Neuroimaging Lab, I-25123 Brescia, Italy. IRCCS S Giovanni Dio FBF, Alzheimer Res Unit, I-25123 Brescia, Italy. Univ Milan Bicocca, CNR, INB, Milan, Italy. IRCCS S Giovanni Dio FBF, Memory Clin, I-25123 Brescia, Italy. RP Binetti, G (reprint author), IRCCS S Giovanni Dio FBF, Neurobiol Lab, Via Pilastroni 4, I-25123 Brescia, Italy. EM gbinetti@oh-fbf.it RI Frisoni, Giovanni B/K-1360-2016; BENUSSI, LUISA/K-4409-2016; Ghidoni, Roberta/K-4507-2016; Binetti, Giuliano/K-4519-2016; Zanetti, Orazio/K-9967-2016 OI Frisoni, Giovanni B/0000-0002-6419-1753; BENUSSI, LUISA/0000-0003-2836-8141; Ghidoni, Roberta/0000-0002-7691-1957; Binetti, Giuliano/0000-0003-2759-5844; Zanetti, Orazio/0000-0002-5408-0048 NR 29 TC 17 Z9 17 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 2004 VL 75 IS 11 BP 1607 EP 1610 DI 10.1136/jnnp.2003.021295 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 867PT UT WOS:000224855200022 PM 15489396 ER PT J AU Dreyer, M Vucic, S Cros, DP Chong, PST AF Dreyer, M Vucic, S Cros, DP Chong, PST TI Multiple painful sensory mononeuropathies (MPSM), a novel pattern of sarcoid neuropathy SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Editorial Material ID PERIPHERAL NEUROPATHY C1 Neurol Consultants PC, Bennington, VT 05210 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Dreyer, M (reprint author), Neurol Consultants PC, Suite 210,140 Hosp Dr, Bennington, VT 05210 USA. EM PSIAO@PARTNERS.ORG NR 5 TC 6 Z9 6 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 2004 VL 75 IS 11 BP 1645 EP 1646 DI 10.1136/jnnp.2003.028134 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 867PT UT WOS:000224855200034 PM 15489408 ER PT J AU Paintlia, MK Paintlia, AS Barbosa, E Singh, I Singh, AK AF Paintlia, MK Paintlia, AS Barbosa, E Singh, I Singh, AK TI N-acetylcysteine prevents endotoxin-induced degeneration of oligodendrocyte progenitors and hypomyelination in developing rat brain SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE periventricular leukomalacia; cerebral palsy; N-acetylcysteine; oligodendrocyte progenitors; hypomyelination ID NECROSIS-FACTOR-ALPHA; PRETERM PREMATURE RUPTURE; FOCAL CEREBRAL-ISCHEMIA; PERIVENTRICULAR LEUKOMALACIA; IMMUNE-SYSTEM; WHITE-MATTER; TNF-ALPHA; KAPPA-B; INJURY; INFLAMMATION AB Periventricular leukomalacia (PVL), the dominant form of brain injury in premature infants, is characterized by diffuse white matter injury and is associated with cerebral palsy (GP). Maternal and placental infections are major causes of prematurity and identifiable etiology of PVL and CP. Here we have evaluated the therapeutic efficacy of N-acetylcysteine (NAC), a potent antioxidant and precursor of glutathione, to attenuate lipopolysaccharide (LPS)-induced white matter injury and hypomyelination in the developing rat brain, an animal model of PVL. Intraperitoneal pretreatment of pregnant female rats with NAC (50 mg/kg), 2 hr prior to administration of LIPS at embryonic day 18 (E18), attenuated the LIPS-induced expression of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta, and inducible nitric oxide synthase in fetal rat brains. There were significantly reduced numbers of TUNEL+ nuclei coimmunostained for platelet-derived growth factor-alphaR(+) [a surface marker for oligodendrocyte progenitor cells (OPCs)] at E20 in the subventricular zone of fetal rat brain in the NAC + LPS group compared with the untreated LIPS group. Interestingly, immunostaining for O4 and O1 as markers for late OPCs and immature oligodendrocytes demonstrated fewer O4(+) and O1(+) cells in the LIPS group compared with the NAC + LIPS and control groups. Consistent with O4(+)/O1(+) cell counts, the expression of myelin proteins such as myelin basic protein, proteolipid protein, and 2'3'-cyclic nucleotide phosphodiesterase, including transcription factors such as MyT1 and Gtx, was less in the LIPS group at late postnatal days, indicating severe hypomyelination in the developing rat brain when compared with NAC + LIPS and control groups. Collectively, these data support the hypothesis that NAC may provide neuroprotection and attenuate the degeneration of OPCs against LIPS evoked inflammatory response and white matter injury in developing rat brain. Moreover, these data suggest the possible use of NAC as a treatment for pregnant women with maternal or placental infection as a means of minimizing the risk of PVL and CP. (C) 2004 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 96 Jonathan Lucas St,CSB-316, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40144, NS-40810] NR 44 TC 101 Z9 102 U1 1 U2 8 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 NOV 1 PY 2004 VL 78 IS 3 BP 347 EP 361 DI 10.1002/jnr.20261 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 869GP UT WOS:000224971700005 PM 15389835 ER PT J AU Marracci, GH McKeon, GP Marquardt, WE Winter, RW Riscoe, MK Bourdette, DN AF Marracci, GH McKeon, GP Marquardt, WE Winter, RW Riscoe, MK Bourdette, DN TI alpha lipoic acid inhibits human T-cell migration: Implications for multiple sclerosis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE antioxidant; matrix metalloproteinase-9; transmigration ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; KAPPA-B ACTIVATION; ADHESION MOLECULE EXPRESSION; MATRIX-METALLOPROTEINASE; INTERFERON BETA-1B; IN-VITRO; TRANSENDOTHELIAL MIGRATION; CONTROLLED-TRIAL; FLOW CONDITIONS AB We have demonstrated previously the ability of the antioxidant a lipoic acid (ALA) to suppress and treat a model of multiple sclerosis (MS), relapsing experimental autoimmune encephalomyelitis (EAE). We describe the effects of ALA and its reduced form, dihydrolipoic acid (DHLA), on the transmigration of human Jurkat T cells across a fibronectin barrier in a transwell system. ALA and DHLA inhibited migration of Jurkat cells in a dose-dependent fashion by 16-75%. ALA and DHLA reduced matrix metalloproteinase-9 (MMP-9) activity by 18-90% in Jurkat cell supernatants. GM6001, a synthetic inhibitor of MMP, reduced Jurkat cell migration, but not as effectively as ALA and DHLA did. Both ALA and DHLA down-modulated the surface expression of the alpha4beta1 integrin (very late activation-4 antigen; VLA-4), which binds fibronectin and its endothelial cell ligand vascular cell adhesion molecule-1 (VCAM-1). Moreover, ALA, but not DHLA, reduced MMP-9-specific mRNA and extracellular MMP-9 from Jurkat cells and their culture supernatants as detected by relative reverse transcriptase-polymerise chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. ALA and DHLA inhibited Jurkat cell migration and have different mechanisms for inhibiting MMP-9 activity. These data, coupled with its ability to treat relapsing EAE, suggest that ALA warrants investigation as a therapy for MS. (C) 2004 Wiley-Liss, Inc. C1 Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Biochem, Portland, OR USA. Portland State Univ, Portland, OR 97207 USA. RP Bourdette, DN (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,L226, Portland, OR 97239 USA. EM bourdett@ohsu.edu FU NCCIH NIH HHS [P50AT00066-01] NR 47 TC 34 Z9 38 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 NOV 1 PY 2004 VL 78 IS 3 BP 362 EP 370 DI 10.1002/jnr.20255 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 869GP UT WOS:000224971700006 PM 15389837 ER PT J AU Schouten, JW Fulp, CT Royo, NC Saatman, KE Watson, DJ Snyder, EY Trojanowski, JQ Prockop, DJ Maas, AIR McIntosh, TK AF Schouten, JW Fulp, CT Royo, NC Saatman, KE Watson, DJ Snyder, EY Trojanowski, JQ Prockop, DJ Maas, AIR McIntosh, TK TI A review and rationale for the use of cellular transplantation as a therapeutic strategy for traumatic brain injury SO JOURNAL OF NEUROTRAUMA LA English DT Review DE cell death; cell replacement; head injury; progenitor cells; stem cells ID NEURAL STEM-CELLS; MARROW STROMAL CELLS; CENTRAL-NERVOUS-SYSTEM; CONTROLLED CORTICAL IMPACT; RAT SPINAL-CORD; ADULT BONE-MARROW; FACTOR GENE-TRANSFER; LONG-TERM SURVIVAL; DIFFERENTIATION FOLLOWING TRANSPLANTATION; AMYOTROPHIC-LATERAL-SCLEROSIS AB Experimental research during the past decade has greatly increased our understanding of the pathophysiology of traumatic brain injury (TBI) and allowed us to develop neuroprotective pharmacological therapies. Encouraging results of experimental pharmacological interventions, however, have not been translated into successful clinical trials, to date. Traumatic brain injury is now believed to be a progressive degenerative disease characterized by cell loss. The limited capacity for self-repair of the brain suggests that functional recovery following TBI is likely to require cellular transplantation of exogenous cells to replace those lost to trauma. Recent advances in central nervous system transplantation techniques involve technical and experimental refinements and the analysis of the feasibility and efficacy of transplantation of a range of stem cells, progenitor cells and postmitotic cells. Cellular transplantation has begun to be evaluated in several models of experimental TBI, with promising results. The following is a compendium of these new and exciting studies, including a critical discussion of the rationale and caveats associated with cellular transplantation techniques in experimental TBI research. Further refinements in future research are likely to improve results from transplantation-based treatments for TBI. C1 Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Erasmus Med Ctr, Dept Neurosurg, Rotterdam, Netherlands. Burnham Inst, Program Dev & Regenerat Cell Biol, La Jolla, CA 92037 USA. Tulane Univ, Hlth Sci Ctr, Ctr Gene Therapy, New Orleans, LA USA. Univ Penn, Sch Med, Dept Neurosurg, Traumat Brain Injury Lab, Philadelphia, PA 19104 USA. RP McIntosh, TK (reprint author), Univ Penn, Sch Med, Dept Neurosurg, Traumat Brain Injury Lab, 105C Hayden Hall,3320 Smith Walk, Philadelphia, PA 19104 USA. EM mcintosh@seas.upenn.edu RI Maas, Andrew/C-5584-2013 OI Maas, Andrew/0000-0003-1612-1264 FU NINDS NIH HHS [P50-NS08803, R01-NS40978] NR 312 TC 41 Z9 47 U1 0 U2 10 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV PY 2004 VL 21 IS 11 BP 1501 EP 1538 DI 10.1089/0897715042441774 PG 38 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 872IL UT WOS:000225200800001 PM 15684646 ER PT J AU Ponte, PR AF Ponte, PR TI Nurse-physician co-leadership - A model of interdisciplinary practice governance\ SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article C1 Brigham & Womens Hosp, Patient Care Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, BMT, Boston, MA 02115 USA. RP Ponte, PR (reprint author), 44 Binney St,D1624, Boston, MA 02115 USA. EM preidponte@partners.org NR 2 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD NOV PY 2004 VL 34 IS 11 BP 481 EP 484 DI 10.1097/00005110-200411000-00001 PG 4 WC Nursing SC Nursing GA 871XP UT WOS:000225170200001 PM 15586066 ER PT J AU Kim, JY Magari, SR Herrick, RF Smith, TJ Christiani, DC AF Kim, JY Magari, SR Herrick, RF Smith, TJ Christiani, DC TI Comparison of fine particle measurements from a direct-reading instrument and a gravimetric sampling method SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE aerosol sampling methods; DUSTTRAK aerosol monitor; fine particulate matter (PM2.5); occupational exposure ID PARTICULATE MATTER; AEROSOL MONITORS; AIR-POLLUTION; PM2.5; BALTIMORE; EXPOSURE; ASSOCIATION; POLLUTANTS; MORTALITY; COAL AB Particulate air pollution, specifically the fine particle fraction (PM2.5), has been associated with increased cardiopulmonary morbidity and mortality in general population studies. Occupational exposure to fine particulate matter can exceed ambient levels by a large factor. Due to increased interest in the health effects of particulate matter many particle sampling methods have been developed. fit this study, two such measurement methods were used simultaneously and compared. PM2.5 was sampled using a filter-based gravimetric sampling method and a direct-reading instrument, the TSI Inc. model 8520 DUSTTRAK aerosol monitor Both sampling methods were used to determine the PM2.5 exposure in a group of boilermakers exposed to welding fumes and residual fuel oil ash. The geometric mean PM2.5 concentration was 0.30 mg/m(3) (GSD 3.25) and 0.31 mg/m(3) (GSD 2.90)from the DUSTTRAK and gravimetric method, respectively The Spearman rank correlation coefficient for the gravimetric and DUSTTRAK PM2.5 concentrations was 0.68. Linear regression models indicated that log, DUSTTRAK PM2.5 concentrations significantly predicted log(e) gravimetric PM2.5 concentrations (p < 0.01). The association between log, DUSTTRAK and log, gravimetric PM2.5 concentrations was found to be modified by surrogate measures for seasonal variation and type of aerosol. PM2.5 measurements from the DUSTTRAK are well correlated and highly predictive of measurements from the gravimetric sampling method for the aerosols in these work environments. However, results from this study suggest that aerosol particle characteristics may affect the relationship between the gravimetric and DUSTTRAK PM2.5 measurements. Recalibration of the DUSTTRAK for the specific aerosol, as recommended by the manufacturer, may be necessary to produce valid measures of airborne particulate matter. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm & Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm & Hlth, Bldg 1,Room 1402,665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu FU NIEHS NIH HHS [ES00002, ES09860]; NIOSH CDC HHS [OH00152] NR 24 TC 37 Z9 38 U1 2 U2 21 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PD NOV PY 2004 VL 1 IS 11 BP 707 EP 715 DI 10.1080/15459620490515833 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 866OB UT WOS:000224781700006 PM 15673091 ER PT J AU Susarla, SM Dodson, TB AF Susarla, SM Dodson, TB TI Risk factors for third molar extraction difficulty SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ALVEOLAR NERVE INJURY; SURGERY; CLASSIFICATION AB Purpose: The purpose of this study was to measure the difficulty of third molar (M3) extractions and to identify demographic, anatomic, and operative variables associated with extraction difficulty. Materials and Methods: To address the research purpose, we implemented a prospective cohort study and enrolled a sample composed of patients presenting for M3 removal. Predictor variables were categorized as demographic, anatomic, and operative. The primary outcome variable was difficulty of extraction, measured as extraction time per tooth. The secondary outcome variable was the surgeon's postoperative estirriate of M3 extraction difficulty, measured on a 100-mm visual analog scale (VAS). Appropriate univariate, bivariate, and multivariate statistics were computed. Results: The sample was composed of 82 subjects, having 250 M3s (53.2% mandibular) extracted, with a mean age of 26.2 +/- 10.7 years; 57.3% were female, 72.0% were white. The mean operating time per M3 extraction vas 6.9 +/- 7.6 minutes. The mean estimate of difficulty was 39.6 +/- 24.7 mm and was significantly correlated (r = 0.68) with extraction time (P < .01). Surgical experience, M3 location (maxillary versus mandibular), procedure type, tooth position, number of teeth extracted, and tooth morphology were statistically associated (P less than or equal to .05) with extraction time in a multivariate model. Conclusion: Our model indicates that the difficulty of M3 extractions is governed primarily by anatomic and operative factors with minimal influence from demographic factors. (C) 2004 American Association, of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Dent Med, Boston, MA USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU NIDCR NIH HHS [K23-DE000448] NR 25 TC 42 Z9 47 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2004 VL 62 IS 11 BP 1363 EP 1371 DI 10.1016/j.joms.2004.05.214 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 869PW UT WOS:000224997500006 PM 15510357 ER PT J AU Moreland, EC Tovar, A Zuehlke, JB Butler, DA Milaszewski, K Laffel, LMB AF Moreland, EC Tovar, A Zuehlke, JB Butler, DA Milaszewski, K Laffel, LMB TI The impact of physiological, therapeutic and psychosocial variables on glycemic control in youth with type 1 diabetes mellitus SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE type 1 diabetes mellitus; family involvement adolescents; continuous subcutaneous insulin infusion; psychosocial factors ID LONGITUDINAL FOLLOW-UP; GROWTH-FACTOR-I; INSULIN-RESISTANCE; METABOLIC-CONTROL; GLYCOSYLATED HEMOGLOBIN; FAMILY CONFLICT; ADOLESCENTS; CHILDREN; HORMONE; ADHERENCE AB Objective: Intensive management of type I diabetes mellitus (DM1) in youth is challenging. We evaluated the relative impact of variables related to DM1 among groups of pre/early pubertal, midpubertal and postpubertal youths with DM1. Methods: In this cross-sectional study of 153 youth with DM1, we ascertained Tanner stage, insulin dose and delivery modality (CSII vs NIDI), daily blood glucose monitoring (BGM) frequency, and most recent hemoglobin A(1c) (HbA(1c)). We collected questionnaires from patients and their parents on diabetes-specific family conflict and family involvement in diabetes management tasks. We assessed predictors of glycemic control according to pubertal status. Results: Insulin doses increased between pre/ early puberty and midpuberty (p <0.0001); daily BGM frequency (p = 0.02) and family involvement for DM management (p <0.001) were lowest in the postpubertal group. Hb(1c) was similar among all three puberty groups (8.4 +/- 1.4). Lower levels of child-reported DM-specific family conflict, more frequent BGM, and CSII use were significantly associated with lower HbA(1c) (R-2 = 0.20, p <0.001). Conclusion: Although glycemic control was not significantly worse in midpubertal and post-pubertal patients, family involvement for DM management and adherence to BGM were lower in late adolescence. Interventions to optimize glycemic control may include minimizing DM-specific conflict, increasing BGM frequency, and implementing CSII use. C1 Harvard Univ, Joslin Diabet Ctr, Sch Med,Behav Res & Mental Hlth Sect, Dept Pediat,Pediat & Adolescent Unit, Boston, MA 02215 USA. Harvard Univ, Joslin Diabet Ctr, Sch Med,Genet & Epidemiol Sect, Dept Pediat,Pediat & Adolescent Unit, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Harvard Univ, Joslin Diabet Ctr, Sch Med,Behav Res & Mental Hlth Sect, Dept Pediat,Pediat & Adolescent Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM Lori.Laffel@joslin.harvard.edu FU NIDDK NIH HHS [DK 46887] NR 37 TC 34 Z9 34 U1 6 U2 12 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD NOV PY 2004 VL 17 IS 11 BP 1533 EP 1544 PG 12 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 870YS UT WOS:000225095600010 PM 15570991 ER PT J AU Ponce, BA Hedequist, DJ Zurakowski, D Atkinson, CC Waters, PM AF Ponce, BA Hedequist, DJ Zurakowski, D Atkinson, CC Waters, PM TI Complications and timing of follow-up after closed reduction and percutaneous pinning of supracondylar humerus fractures - Follow-up after percutaneous pinning of supracondylar humerus fractures SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE fracture; humerus; supracondylar; percutaneous pinning; complications ID K-WIRE FIXATION; CHILDREN; MANAGEMENT; ELBOW; EXPERIENCE; EXTENSION; TRACTION AB The purpose of this study was to evaluate the need for clinical evaluation with radiographs within 10 days of closed reduction and percutancous pinning for the treatment of displaced supracondylar humerus fractures. Between May I and December 31, 2001, the authors evaluated the complications with closed reduction and percutancous pinning of 104 displaced supracondylar humerus fractures. Fifty-two of the patients had the initial follow-up examination with radiographs 10 days or less after pinning; the other 52 patients had the initial follow-up examination with radiographs either after 10 days or on the day of pin removal. The overall complication rate for the series was 7.7% (8/104). All eight complications were in type III fractures. The early follow-up group had six complications; the late follow-up group had two complications. Baumann's angle, lateral humerocapitellar angle, and lateral rotational percentage were not significantly different between the two groups. The only variable tested that was associated with a complication was pin configuration, No association between late follow-up and complications was identified. The authors conclude that clinical and radiographic evaluation of routine displaced supracondylar humerus fractures requiring closed reduction and percutaneous pinning may be safely delayed until pin removal. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Combined Orthopaed Surg Program, Boston, MA 02114 USA. RP Waters, PM (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Orthopaed Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM peter.waters@tch.harvard.edu NR 32 TC 21 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD NOV-DEC PY 2004 VL 24 IS 6 BP 610 EP 614 PG 5 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 865RF UT WOS:000224719600002 PM 15502556 ER PT J AU Donahoe, PK AF Donahoe, PK TI Sustained inquiry: In the clinic and at the beach SO JOURNAL OF PEDIATRIC SURGERY LA English DT Editorial Material ID MULLERIAN-INHIBITING SUBSTANCE; CONGENITAL DIAPHRAGMATIC-HERNIA; HUMAN OVARIAN-CANCER; CHRONIC MYELOGENOUS LEUKEMIA; II RECEPTOR; DEVELOPMENTAL EXPRESSION; SEX DETERMINATION; DUCT REGRESSION; FETAL TESTIS; IN-VIVO C1 Harvard Univ, Sch Med, Pediat Surg Serv, Boston, MA USA. Harvard Univ, Sch Med, Pediat Surg Res Lab, Massachusetts Gen Hosp,MassGen Hosp Children, Boston, MA USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 11, Boston, MA 02114 USA. NR 40 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD NOV PY 2004 VL 39 IS 11 BP 1601 EP 1606 DI 10.1016/j.jpedsurg.2004.07.006 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 875TQ UT WOS:000225445100001 PM 15547820 ER PT J AU Frazer-Abel, AA Baksh, S Fosmire, SP Willis, D Pierce, AM Meylemans, H Linthicum, DS Burakoff, SJ Coons, T Bellgrau, D Modiano, JF AF Frazer-Abel, AA Baksh, S Fosmire, SP Willis, D Pierce, AM Meylemans, H Linthicum, DS Burakoff, SJ Coons, T Bellgrau, D Modiano, JF TI Nicotine activates nuclear factor of activated T cells c2 (NFATc2) and prevents cell cycle entry in T cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID IMMUNE-RESPONSE; CIGARETTE-SMOKING; ANTIGEN RECEPTOR; CHRONIC EXPOSURE; IN-VITRO; EXPRESSION; LYMPHOCYTES; PROLIFERATION; THYMUS; DIFFERENTIATION AB We used primary peripheral blood T cells, a population that exists in G(0) and can be stimulated to enter the cell cycle synchronously, to define more precisely the effects of nicotine on pathways that control cell cycle entry and progression. Our data show that nicotine decreased the ability of T cells to transit through the G(0)/G(1) boundary (acquire competence) and respond to progression signals. These effects were due to nuclear factor of activated T cells c2 (NFATc2)-dependent repression of cyclin-dependent kinase 4 (CDK4) expression. Growth arrest at the G(0)/G(1) boundary was further enforced by inhibition of cyclin D2 expression and by increased expression and stabilization of p27Kip1. Intriguingly, T cells from habitual users of tobacco products and from NFATc2-deficient mice constitutively expressed CDK4 and were resistant to the antiproliferative effects of nicotine. These results indicate that nicotine impairs T cell cycle entry through NFATc2-dependent mechanisms and suggest that, in the face of chronic nicotine exposure, selection may favor cells that can evade these effects. We postulate that cross talk between nicotinic acetylcholine receptors and growth factor receptor-activated pathways offers a novel mechanism by which nicotine may directly impinge on cell cycle progression. This offers insight into possible reasons that underlie the unique effects of nicotine on distinct cell types and identifies new targets that may be useful control tobacco-related diseases. C1 Univ Colorado, Hlth Sci Ctr, AMC Canc Ctr, Denver, CO 80214 USA. Univ Colorado, Hlth Sci Ctr, Integrated Dept Immunol, Denver, CO USA. Donald Monk Canc Res Fdn, Denver, CO USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Saccomanno Res Inst, Grand Junction, CO USA. Landcare Res, Mannaki Whenua, Lincoln, New Zealand. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. RP Modiano, JF (reprint author), Univ Colorado, Hlth Sci Ctr, AMC Canc Ctr, 2 Diamond Bldg,1600 Pierce St, Denver, CO 80214 USA. EM modianoj@amc.org RI Meylemans, Heather/G-4511-2012; OI Meylemans, Heather/0000-0001-9141-1478; Modiano, Jaime/0000-0001-6398-7648 FU NCI NIH HHS [R25 CA 49981, P30 CA 46934, R55 CA 86432]; NIAID NIH HHS [F32 AI 50392] NR 40 TC 17 Z9 17 U1 0 U2 3 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 NOV PY 2004 VL 311 IS 2 BP 758 EP 769 DI 10.1124/jpet.104.070060 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 861ZE UT WOS:000224456400040 PM 15231866 ER PT J AU Chang, JS Van Remmen, H Ward, WF Regnier, FE Richardson, A Cornell, J AF Chang, JS Van Remmen, H Ward, WF Regnier, FE Richardson, A Cornell, J TI Processing of data generated by 2-dimensional gel electrophoresis for statistical analysis: Missing data, normalization, and statistics SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE 2-D PAGE; missing data; normalization; mitochondria; permutation test; false discovery rates ID MANGANESE SUPEROXIDE-DISMUTASE; COMPARATIVE PROTEOMICS; MESSENGER-RNA; PROTEIN; IDENTIFICATION; COMPLEX; DAMAGE; GENES; MOUSE; MICE AB Several high-throughput statistical methods were evaluated for processing data generated by two-dimensional polyacrylamide gel electrophoresis, including how to handle missing data, normalization, and statistical analysis of data obtained from 2-D gels. Quantile normalization combined with a nonparametric permutation test based on minimizing false discover rates gave the highest yield of proteins that changed with genotype and detected the anticipated 50% decrease in Mn-superoxide dismutase (MnSOD) protein levels in mitochondrial extracts obtained from MnSOD-deficient mice. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev Studies, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. RP Cornell, J (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. EM cornell@uthscsa.edu FU NCI NIH HHS [CA P30 54174]; NEI NIH HHS [R01 EY 11733]; NIA NIH HHS [P01 AG 20591, 1P30 AG 13319, R01 AG 23843] NR 30 TC 41 Z9 42 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV-DEC PY 2004 VL 3 IS 6 BP 1210 EP 1218 DI 10.1021/pr049886m PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 881EX UT WOS:000225847300013 PM 15595730 ER PT J AU Lefler, DM Pafford, RG Black, NA Raymond, JR Arthur, JM AF Lefler, DM Pafford, RG Black, NA Raymond, JR Arthur, JM TI Identification of proteins in slow continuous ultrafiltrate by reversed-phase chromatography and proteomics SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proteomics; dialysate; 2D gel; continuous renal replacement therapy ID CONTINUOUS VENOVENOUS HEMOFILTRATION; LIPID-MOBILIZING FACTOR; D-BINDING PROTEIN; PANCREATITIS; CLEARANCE; MEDIATORS; TOXICITY; THERAPY; PLASMA AB Continuous modes of renal replacement therapy (CRRT) are increasingly being utilized in the intensive care unit. The removal of cytokines and other inflammatory proteins during ultrafiltration may be responsible for some of the beneficial effects of CRRT. We used proteomic tools to identify proteins found in the ultrafiltrate from a patient with acute renal failure. Identification of these proteins could help elucidate the mechanism(s) of improved outcome with continuous renal replacement therapy. Protein was loaded on a reversed-phase C4 column and eluted with stepwise isocratic flows starting with 0%, 5%, 10%, 25%, and 50% of acetonitrile. Effluent was collected, pooled, desalted, and separated by two-dimensional gel electrophoresis (2DE). Reversed-phase separation improved the resolution and the number of spots seen on the gels. Protein spots were digested with trypsin and spotted onto MALDI plates. Proteins were identified by either peptide mass fingerprinting using a MALDI-TOF mass spectrometer or by peptide sequencing using a MALDI-TOF/TOF tandem mass spectrometer. From 196 spots cut, 47 were identified, representing multiple charge forms of 10 different proteins. Proteins identified were albumin, apolipoprotein A-IV, beta-2-microglobulin, lithostathine, mannose-binding lectin associated serine protease 2 associated protein, plasma retinol-binding protein, transferrin, transthyretin, vitamin D-binding protein and Zn alpha-2 glycoprotein. Continuous renal replacement therapy is frequently used in acutely ill patients with renal failure. Removal of proteins occurs during this process. The physiological significance of this protein removal is unclear. Identification of these proteins will lead to better understanding of the role of protein removal in continuous renal replacement therapy. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. EM arthurj@musc.edu FU NHLBI NIH HHS [N01 HV 28181] NR 21 TC 22 Z9 23 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV-DEC PY 2004 VL 3 IS 6 BP 1254 EP 1260 DI 10.1021/pr0498640 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 881EX UT WOS:000225847300018 PM 15595735 ER PT J AU Nierenberg, AA Trivedi, MH Ritz, L Burroughs, D Greist, J Sackeim, H Kornstein, S Schwartz, T Stegman, D Fava, M Wisniewski, SR AF Nierenberg, AA Trivedi, MH Ritz, L Burroughs, D Greist, J Sackeim, H Kornstein, S Schwartz, T Stegman, D Fava, M Wisniewski, SR TI Suicide risk management for the sequenced treatment alternatives to relieve depression study: applied NIMH guidelines SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID MAJOR DEPRESSION; TRIALS AB NIMH guidelines to manage subjects who are suicidal during their participation in clinical trials include a full range of procedures to minimize suicidal risk, yet no reports to date have shown how researchers should best implement these guidelines. The architects of the sequenced treatment alternatives to relieve depression (STAR*D) study operationalized and implemented the NIMH guidelines by developing a comprehensive set of procedures to detect, monitor, and manage suicidal subjects during a large, complex, multisite clinical trial. Because of the large size of the study (anticipated n = 4000), the wide geographic distribution, the large number of treating STAR*D clinicians, the broad array of subjects with psychiatric and medical comorbidities, and the focus on treatment-resistant depression, along with the complexity of multiple treatment steps and randomization points in STAR*D, the risk of suicide, safety monitoring of suicidal subjects presented a unique challenge. This paper describes methods derived from the NIMH guidelines used to manage suicidal risk in STAR*D including the use of an interactive voice response system to alert clinicians, regional center directors, and safety officers. (C) 2004 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Clin Res Program, Boston, MA 01224 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Clin Res Program, ACC 812,15 Parkman St, Boston, MA 01224 USA. EM anierenberg@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH90003] NR 18 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD NOV-DEC PY 2004 VL 38 IS 6 BP 583 EP 589 DI 10.1016/j.jpsychires.2004.03.004 PG 7 WC Psychiatry SC Psychiatry GA 864YP UT WOS:000224669600005 PM 15458854 ER PT J AU Wilens, TE Biederman, J Kwon, A Ditterline, J Forkner, P Moore, H Swezey, A Snyder, L Henin, A Wozniak, J Faraone, SV AF Wilens, TE Biederman, J Kwon, A Ditterline, J Forkner, P Moore, H Swezey, A Snyder, L Henin, A Wozniak, J Faraone, SV TI Risk of substance use disorders in adolescents with bipolar disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE mania; bipolar disorder; substance abuse ID DEFICIT HYPERACTIVITY DISORDER; PROSPECTIVE FOLLOW-UP; CONDUCT DISORDER; NOVELTY SEEKING; EARLY-ONSET; MANIA; CHILDREN; ADHD; CHILDHOOD; ILLNESS AB Objective: Previous work in adults and youths has suggested that juvenile onset bipolar disorder (BPD) is associated with an elevated risk of substance use disorders (SUD). Considering the public health importance of this issue, the authors now report on a controlled study of adolescents with and without BPD to evaluate the risk of SUD. Method: Probands with DSM-IV BPD (n = 57, mean age +/- SD = 13.3 +/- 2.4 years) and without DSM-IV BPD (n = 46, 13.6 +/- 2.2 years) were studied. Structured psychiatric interviews and multiple measures of SUD were collected. Results: Bipolar disorder was associated with a highly significant risk factor for SUD (32% versus 7%, Z = 2.9, p = .004) that was not accounted for by conduct disorder (adjusted odds ratio = 5.4, p = .018). Adolescent-onset BPD (greater than or equal to 13 years) was associated with a higher risk of SUD compared with those with child-onset BPD (chi(1)(2) = 9.3, p = .002). Conclusions: These findings strongly indicate that BPD, especially adolescent onset, is a significant risk factor for SUD independently of conduct disorder. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Res Unit, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM twilens@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [R01 DA12945] NR 49 TC 76 Z9 76 U1 3 U2 6 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 NOV PY 2004 VL 43 IS 11 BP 1380 EP 1386 DI 10.1097/01.chi.0000140454.89323.99 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 864JX UT WOS:000224630900015 PM 15502597 ER PT J AU Geller, DA Wagner, KD Emslie, G Murphy, T Carpenter, DJ Wetherhold, E Perera, P Machin, A Gardiner, C AF Geller, DA Wagner, KD Emslie, G Murphy, T Carpenter, DJ Wetherhold, E Perera, P Machin, A Gardiner, C TI Paroxetine treatment in children and adolescents with obsessive-compulsive disorder: A randomized, multicenter, double-blind, placebo-controlled trial SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; selective serotonin reuptake inhibitor; paroxetine; pediatric ID CLOMIPRAMINE; SERTRALINE; FLUOXETINE; VALIDITY; FAMILY AB Objective: To assess the efficacy and safety of paroxetine for the treatment of pediatric obsessive-compulsive disorder. Method: Children (7-11 years of age) and adolescents (12-17 years of age) meeting DSM-IV criteria for obsessive-compulsive disorder were randomized to paroxetine (10-50 mg/day) or placebo for 10 weeks. The primary efficacy measure was change from baseline in the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) total score at week 10 last observation carried forward end point. Safety was assessed primarily through adverse event monitoring. Results: A total of 207 patients were randomized to treatment. Of these, 203 were included in the intention-to-treat population. Adjusted mean changes from baseline at week 10 observation carried forward end point in CY-BOCS total score for patients receiving paroxetine and placebo were -8.78 (SE = 0.82) and -5.34 points (SE = 0.77), respectively. The adjusted mean difference, -3.45 in favor of paroxetine, was statistically significant (95% confidence interval = -5.60 to -1.29, p = .002). Adverse events were generally mild to moderate in intensity. A total of 10.2% (10/98) of patients in the paroxetine group and 2.9% (3 of 105) in the placebo group discontinued treatment because of adverse events. Conclusions: Paroxetine is an effective and generally well-tolerated treatment for obsessive-compulsive disorder in children and adolescents. C1 Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Texas SW, Dallas, TX USA. Univ Florida, Gainesville, FL USA. GlaxoSmithKline, King Of Prussia, PA USA. GlaxoSmithKline, Harlow, Essex, England. RP Geller, DA (reprint author), Massachusetts Gen Hosp, OCD Clin, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM dageller@partners.org NR 32 TC 102 Z9 103 U1 3 U2 9 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 NOV PY 2004 VL 43 IS 11 BP 1387 EP 1396 DI 10.1097/01.chi.0000138356.29099.f1 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 864JX UT WOS:000224630900016 PM 15502598 ER PT J AU Tsao, H Niendorf, K AF Tsao, H Niendorf, K TI Genetic testing in hereditary melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID OF-CLINICAL-ONCOLOGY; CDKN2A MUTATIONS; GERMLINE MUTATIONS; FAMILIAL MELANOMA; CANCER SUSCEPTIBILITY; PANCREATIC-CANCER; TUMOR-SUPPRESSOR; STATEMENT; SURVEILLANCE; INDIVIDUALS AB Advances in our understanding of molecular genetics bring about unique challenges in our ability to practice molecular medicine. With the availability of commercial testing for various genetic cancer syndromes, including hereditary melanoma, specific issues regarding its use and limitations require attention before full translation of this tool into the clinical setting. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Boston, MA 02114 USA. NR 24 TC 14 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2004 VL 51 IS 5 BP 803 EP 808 DI 10.1016/j.jaad.2004.04.045 PG 6 WC Dermatology SC Dermatology GA 867BB UT WOS:000224816000023 PM 15523363 ER PT J AU Hester, EJ Johnson, KR Crane, LA Schilling, LM Dellavalle, RP AF Hester, EJ Johnson, KR Crane, LA Schilling, LM Dellavalle, RP TI Indoor UV tanning operator opinion regarding youth access: An electronic survey SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; FACILITIES; RISK; ADOLESCENTS; SUNSCREEN; SUNLAMPS; SUNBEDS; DEVICES; STATE AB Background: Adolescents frequently use indoor tanning facilities, but little is known about tanning facility operator opinions regarding this use. Objective: To assess indoor tanning operator attitudes and stated practices regarding youth access. Methods: We electronically surveyed 89 indoor tanning facilities and 130 spas with active e-mail addresses. Results. The survey response rate was 21% for both indoor tanning facilities (19/89) and spas (27/130). Most tanning operators (92%) felt that a client can be too young to receive indoor tanning, and most felt that written parental permission should be required (80%). Most facilities required adult accompaniment (92%), and most operators had discouraged a customer from receiving indoor tanning based on age (77%). The reported age of the youngest patron receiving indoor tanning ranged from 5 to 21 years. Conclusion. Our sample of indoor tanning facility operators believed that minimum age and parental consent regulations for indoor tanning should be required. C1 Univ Colorado, Hlth Sci Ctr, Dept Dermatol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. RP Dellavalle, RP (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Dermatol, 4200 E 9th Ave,Box B-153, Denver, CO 80262 USA. EM robert.dellavaIle@uchsc.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X FU NCI NIH HHS [CA92550]; NIAMS NIH HHS [T32 AR07411] NR 26 TC 6 Z9 6 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2004 VL 51 IS 5 BP 814 EP 816 DI 10.1016/j.jaad.2004.05.023 PG 3 WC Dermatology SC Dermatology GA 867BB UT WOS:000224816000027 PM 15523366 ER PT J AU Bevona, C Fewkes, J Liu, V Sober, AJ AF Bevona, C Fewkes, J Liu, V Sober, AJ TI Prolonged evolution of a lentigo maligna SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MOHS MICROGRAPHIC SURGERY; SKIN-GRAFT; MELANOMA; NECK; HEAD; FRECKLE; PROGRESSION AB Lentigo maligna (LM) is a melanocytic lesion which is a potential precursor to melanoma and often has a prolonged intraepidermal growth phase before evolving into lentigo maligna melanoma (LMM). LM is also noted for its tendency to locally recur after treatment. We present a patient who had a persistent LM on her left cheek which, despite multiple excisions, persisted and transformed into a partially amelanotic LMM roughly three decades later. Our patient's course was also notable for this melanoma recurring at the edge of, and subsequently migrating into, a previously placed skin graft. C1 Massachusetts Gen Hosp, Melanoma Ctr, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Sober, AJ (reprint author), Massachusetts Gen Hosp, Melanoma Ctr, Dept Dermatol, 55 Fruit St,Bartlett Hall 622, Boston, MA 02114 USA. EM asober@partners.org NR 30 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2004 VL 51 IS 5 BP 830 EP 835 DI 10.1016/j.jaad.2002.09.002 PG 6 WC Dermatology SC Dermatology GA 867BB UT WOS:000224816000032 PM 15523371 ER PT J AU Shrank, WH Ettner, SL Glassman, P Asch, SM AF Shrank, WH Ettner, SL Glassman, P Asch, SM TI A bitter pill: Formulary variability and the challenge to prescribing physicians SO JOURNAL OF THE AMERICAN BOARD OF FAMILY PRACTICE LA English DT Article ID PRESCRIPTION DRUGS AB Background: Multitiered, incentive-based formularies have been increasingly used as a mechanism to control prescription drug expenditures. Prescribing physicians who manage patients from multiple insurers must be familiar with the variability in their patients' formulary incentives to help patients choose therapy wisely. However, the degree of formulary variability among and within health plans over time is unclear. Methods: In 6 major health plans in California, we evaluated formulary incentive variability in 4 of the 5 drug classes with the highest expenditures in California: proton pump inhibitors, hydroxymethylglutaryl coenzyme A reductase inhibitors ("statins"), calcium channel blockers, and angiotensin-converting enzyme inhibitors. We categorized 20 branded members of these classes into either "preferred" or nonpreferred/uncovered categories. We calculated the consistency that brands were preferred across health plans and the frequency of changes in formulary status for each drug within plans between 2000 and 2002. Results: None of the branded drugs evaluated were preferred on all formularies in 2002, and 10% were not available on any of the formularies. Formulary status varied greatly across plans, and more than 60% of drugs were preferred on 2 to 4 of the 6 formularies studied. Formulary status within health plans varied between 2000 and 2002 in more than half of the plans in the drug classes evaluated. Conclusions: In the drug classes evaluated, over a 2-year period, considerable variability was seen among and within formularies over time. This variability poses a challenge to physicians who wish to reduce patients' expenditures by prescribing the least expensive among similarly effective drugs within a drug class. This variability is especially relevant because recent legislation increases the likelihood that more Medicare beneficiaries will receive their medications from private health plans. C1 VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med 111G, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. RP Shrank, WH (reprint author), VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med 111G, 11301 Wilshire Blkvd, Los Angeles, CA 90073 USA. EM william.shrank@med.va.gov NR 21 TC 18 Z9 18 U1 0 U2 0 PU AMER BOARD FAMILY PRACTICE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 0893-8652 J9 J AM BOARD FAM PRACT JI J. Am. Board Fam. Pract. PD NOV-DEC PY 2004 VL 17 IS 6 BP 401 EP 407 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 875YE UT WOS:000225458200001 PM 15575031 ER PT J AU Lawrence, VA Hazuda, HP Cornell, JE Pederson, T Bradshaw, PT Mulrow, CD Page, CP AF Lawrence, VA Hazuda, HP Cornell, JE Pederson, T Bradshaw, PT Mulrow, CD Page, CP TI Functional independence after abdominal surgery in the elderly SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT Symposium on Surgery in the Elderly Patient CY 2004 CL Galveston, TX SP Univ Texas Med Branch, Sealy Ctr Aging, Dept Surg ID QUALITY-OF-LIFE; HIP FRACTURE REPAIR; HAND GRIP STRENGTH; PULMONARY COMPLICATIONS; INSTRUMENTAL ACTIVITIES; ELECTIVE SURGERY; CONTROLLED TRIAL; AORTIC-ANEURYSM; MUSCLE STRENGTH; OLDER PERSONS AB BACKGROUND: Elders undergo approximately 40% of more than 1 million major abdominal operations annually. Yet evidence about recovery to preoperative levels of functional independence is limited. This study details course and predictors of functional recovery after elective major abdominal operations in the elderly. STUDY DESIGN: This was a prospective cohort of 372 consecutive patients, 60 years old or more, enrolled from surgeons in private practice and two university-affiliated hospitals, assessed preoperatively and postoperatively at 1, 3, and 6 weeks, 3 and 6 months, using self-report and performance-based measures (Activities of Daily Living [ADL], Instrumental Activities of Daily Living [IADL], Medical Outcomes Study Short Form-36 Physical Component and Mental Component Scales [PCS, MCS], Geriatric Depression Scale [GDS], Folstein Mini-Mental State Exam [MMSE], timed walk, functional reach, hand grip strength). RESULTS: Mean age was 69 +/- 6 years with 56% men, 47% nonHispanic Caucasian, and 42% Mexican American; hospital distribution was 49% private, 51% university-affiliated. Maximum functional declines (95% Cl) occurred 1 week postoperatively: ADL, 2.8 points (2.4 to 3.2); IADL, 7.6 points (7 to 8.3); SF-36 PCS, 6.5 points (5.4 to 7.6); Mini-Mental State Exam, 0.5 points (0.2 to 0.7); timed walk, 6.8 seconds (5.2 to 8.4); functional reach, 1.7 inches (1.2 to 2.2); grip strength, 2 kilograms (1.3 to 2.7) (p < 0.001 for all). SF-36 mental component scale and Geriatric Depression Scale scores did not worsen. Mean recovery times were: Mini-Mental State Exam, 3 weeks; timed walk, 6 weeks; ADL, SF-36 PCS, and functional reach, 3 months; and IADL, 6 months. Mean grip strength did not return to preoperative status by 6 months. The incidence of persistent disability at 6 months, compared with preoperative status, was: ADL, 9%; IADL, 19%; PCS, 16%; mental component scale, 17%; timed walk, 39%; functional reach, 58%; and grip strength, 52%. Potentially modifiable independent predictors of ADL and IADL recovery were preoperative physical conditioning and depression plus serious postoperative complications. CONCULSIONS: The clinical course of functional recovery varied across different measures. Protracted disability at 6 months after operation was substantial. Several potentially modifiable factors consistently predicted recovery. ((C) 2004 by the American College of Surgeons). C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, VERDICT, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Gen Med, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Div Clin Epidemiol, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Ctr Biostat & Epidemiol, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78285 USA. RP Lawrence, VA (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, VERDICT, Ambulatory Care 11C-67400 Merton Minter Blvd, San Antonio, TX USA. FU NIA NIH HHS [P20 AG12044, R01 AG10444, R01 AG14304, R01 AG16518] NR 49 TC 100 Z9 101 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD NOV PY 2004 VL 199 IS 5 BP 762 EP 772 DI 10.1016/j.jamcollsurg.2004.05.280 PG 11 WC Surgery SC Surgery GA 868TW UT WOS:000224936900017 PM 15501119 ER PT J AU Goodson, JM Palys, MD Carpino, E Regan, EO Sweeney, M Socransky, SS AF Goodson, JM Palys, MD Carpino, E Regan, EO Sweeney, M Socransky, SS TI Microbiological changes associated with dental prophylaxis SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID EXPERIMENTAL GINGIVITIS; PLAQUE; DISEASE; CARIES AB Background: Despite the common application of dental prophylaxis as part of patient therapy, there is little reported that describes the.. microbiological impact of this treatment. Methods. The authors gave 20 healthy college-aged subjects three dental prophylaxes with a fluoride-containing prophylaxis paste during a two-week period and instructed them in oral hygiene. They evaluated the microbiological composition of dental plaque samples collected before and after treatment using DNA probe analysis. They analyzed 40 representative bacterial species in seven bacterial complexes by checkerboard DNA-DNA hybridization assay techniques. Results. After three dental prophylaxes, the patients' mean Gingival Index score decreased from 0.82 to 0.77, the mean Plaque Index score decreased from 0.72 to zero; and the total number of bacteria per tooth decreased to approximately one-third of the original number. The authors computed two different measures of bacterial presence. The reduction in bacterial numbers was statistically significant and occurred in many species. Bacterial proportion (DNA percentage or percentage of the bacteria per tooth) did not change significantly. Greater reductions in bacterial count occurred in species that showed high numbers before treatment. The total bacterial count decreased by approximately 72 percent of its original level before prophylaxis was initiated. Conclusions: Professional dental prophylaxis did not target any particular bacteria or bacterial groups but removed bacteria nonspecifically and in proportion to their initial numbers. Clinical Implications. Repeated dental prophylaxes effect a reduction in bacterial. amount that is commensurate with the initial amount, but they do does not alter composition. This suggests that mild gingivitis may be a bacterially nonspecific effect of plaque accumulation and emphasizes the need for regular plaque removal to maintain optimal gingival health. C1 Forsyth Inst, Clin Res, Boston, MA 02115 USA. Harvard Univ, Hlth Serv, Dent Serv, Sch Med, Cambridge, MA USA. RP Goodson, JM (reprint author), Forsyth Inst, Clin Res, 140 Fenway, Boston, MA 02115 USA. EM mgoodson@forsyth.org FU NIDCR NIH HHS [P30-DE11814] NR 15 TC 6 Z9 7 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 2004 VL 135 IS 11 BP 1559 EP 1564 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 873JZ UT WOS:000225277200017 PM 15622660 ER PT J AU Naik, AD Concato, J Gill, TM AF Naik, AD Concato, J Gill, TM TI Bathing disability in community-living older persons: Common, consequential, and complex SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MD SP Amer Geriatr Soc DE bathing; disability; activities of daily living; geriatric epidemiology ID MEDICAL CONDITIONS; PEOPLE; RISK; PATTERNS; OUTCOMES; HEALTH; ADULTS; HOME; ADL; AGE AB Objectives: To identify the specific bathing subtasks that are affected in community-living-older persons with bathing disability and to determine the self-reported reasons for bathing disability. Design: Cross-sectional study. Setting: General community of greater New Haven, Connecticut. Participants: A total of 626 community-living persons, aged 73 and older, who completed a comprehensive assessment, including a detailed evaluation of bathing disability. Measurements: Trained research nurses assessed bathing disability (defined as requiring personal assistance or having difficulty washing and drying the whole body), the specific bathing subtasks that were affected, and the main reasons (up to three) for bathing disability. Results: Disability in bathing was present in 195 (31%) participants; of these, 97 required personal assistance (i.e., dependence), and 98 had difficulty bathing. Participants with bathing disability reported a mean+/-standard deviation of 4.0+/-2.4 affected subtasks. The prevalence rate of disability for the eight prespecified bathing subtasks ranged from 25% for taking off clothes to 75% for leaving the bathing position. The majority of participants (59%) provided more than one reason for bathing disability. The most common reasons cited by participants for their bathing disability were balance problems (28%), arthritic complaints (26%), and fall or fear of falling (23%). Conclusion: For community-living older persons, disability in bathing is common, involves multiple subtasks, and is attributable to an array of physical and psychological problems. Preventive and restorative interventions for bathing disability will need to account for the inherent complexity of this essential activity of daily living. C1 Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, VA Med Ctr 152, Houston, TX 77030 USA. Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. W Haven Vet Adm, Clin Epidemiol Res Ctr, West Haven, CT USA. RP Naik, AD (reprint author), Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bmc.tmc.edu FU NIA NIH HHS [R01 AG 17560, K23 AG 00759, K24 AG 021507, K23 AG000759] NR 30 TC 38 Z9 39 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2004 VL 52 IS 11 BP 1805 EP 1810 DI 10.1111/j.1532-5415.2004.52513.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100002 PM 15507055 ER PT J AU Boockvar, KS Litke, A Penrod, JD Halm, EA Morrison, RS Silberzweig, SB Magaziner, J Koval, K Siu, AL AF Boockvar, KS Litke, A Penrod, JD Halm, EA Morrison, RS Silberzweig, SB Magaziner, J Koval, K Siu, AL TI Patient relocation in the 6 months after hip fracture: Risk factors for fragmented care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE patient transfer; hospitalization; hip fracture; risk factors ID POST-HOSPITAL CARE; TRANSITIONAL CARE; ADVERSE EVENTS; OUTCOMES; DISCHARGE; SETTINGS; SYSTEM; CRACKS; ELDERS; COSTS AB Objectives: To describe the incidence and patterns of patient relocation after hip fracture, identify factors associated with relocation, and examine effect of relocation on outcomes. Design: Prospective cohort study. Setting: Four hospitals in the New York metropolitan area. Participants: A total of 562 patients hospitalized for hip fracture discharged alive in 1997 to 1998. Measurements: Patient characteristics and hospital course were ascertained using patient or surrogate interview, research nurse assessment, and medical record review. Patient location was ascertained at five time points using patient or surrogate interview, and hospital readmissions were identified using New York state and hospital admission databases. Mobility was measured using patient or surrogate report using the Functional Independence Measure. Results: During 6 months of follow-up, the mean number of relocations per patient+/-standard deviation was 3.5+/-1.5 (range 2-10). Forty-one percent of relocations were between home and hospital, 36% between rehabilitation or nursing facility and hospital, 17% between rehabilitation or nursing facility and home, and 4% between two rehabilitation/nursing facilities. In a Poisson regression model that controlled for patient characteristics, hospital course, and length of follow-up, factors associated with relocation (P<.05) were absence of dementia, in-hospital delirium, one or more new impairments at hospital discharge, hospital discharge other than to home, and not living at home alone prefracture. Relocation was not significantly associated with immobility or mortality at 6 months (odds ratio=1.14, 95% confidence interval=0.97-1.35). Conclusion: Subgroups of patients with elevated risk of relocation after hip fracture may be target groups for intensive care coordination and care planning interventions. C1 Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NYU, Sch Med, Dept Orthoped Surg, New York, NY USA. RP Boockvar, KS (reprint author), Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, 130 W Kingsbridge Rd,Rm 4 A-17, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU AHRQ HHS [HS 09973, R01 HS009973, U18 HS 09459, U18 HS009459]; NIA NIH HHS [K24 AG000918, R01 AG021992] NR 29 TC 18 Z9 19 U1 4 U2 7 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2004 VL 52 IS 11 BP 1826 EP 1831 DI 10.1111/j.1532-5415.2004.52512.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100005 PM 15507058 ER PT J AU Caterino, JM Emond, JA Camargo, CA AF Caterino, JM Emond, JA Camargo, CA TI Inappropriate medication administration to the acutely ill elderly: A nationwide emergency department study, 1992-2000 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY, 2004 CL Orlando, FL SP Soc Acad Emergency Med DE emergency services; prescribing; geriatrics; inappropriate; Beers criteria ID ADVERSE DRUG-REACTIONS; NURSING-HOMES; EXPLICIT CRITERIA; BEERS CRITERIA; OLDER PERSONS; HIP FRACTURE; OUTPATIENTS; RISK; FACILITIES; EVENTS AB Objectives: To determine the national rate and trend of inappropriate medication administration to elderly emergency department (ED) patients. Secondary objectives were to identify risk factors for receiving an inappropriate medication and to determine whether administration is sometimes justified based on diagnosis. Design: Retrospective analysis of ED visits in the 1992-2000 National Hospital Ambulatory Medical Care Survey. Inappropriate medications identified using Beers' 1997 explicit criteria. Setting: EDs of U.S. noninstitutionalized general and short-stay hospitals. Participants: ED survey patients aged 65 and older. Measurements: Magnitude and rate of administration of 36 medications. Results: Inappropriate medications were administered in an estimated 16.1 million (95% confidence interval (CI)=14.9-17.3 million) or 12.6% (95% CI=11.6-13.5%) of elderly ED visits from 1992 to 2000. The rate of inappropriate administration was unchanged throughout the study period (P=.40). Six drugs accounted for 70.8% of inappropriate administration: promethazine (22.2%), meperidine (18.0%), propoxyphene (17.2%), hydroxyzine (10.3%), diphenhydramine (7.1%), and diazepam (6.0%). In multivariate analysis, number of ED medications was the strongest predictor, with an odds ratio for two to three medications of 6.0 (95% CI=5.3-6.7) and for four to six medications of 8.1 (95% CI=7.2-9.2). Diagnoses indicating potentially appropriate uses of these medications were rarely present. For example, only 42.4% of patients receiving diphenhydramine and 7.4% receiving hydroxyzine were diagnosed with an allergic process. Conclusion: Elderly ED patients are frequently administered inappropriate medications. Potentially appropriate uses of generally inappropriate drugs cannot account for such administrations. Inappropriate administration rates remain unchanged despite the 1997 publication of explicit criteria. C1 Allegheny Gen Hosp, Dept Emergency Med, Pittsburgh, PA 15212 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. RP Caterino, JM (reprint author), Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA. EM jeffreycaterino@hotmail.com NR 49 TC 47 Z9 50 U1 2 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2004 VL 52 IS 11 BP 1847 EP 1855 DI 10.1111/j.1532-5415.2004.52503.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100008 PM 15507061 ER PT J AU Kurella, M Chertow, GM Luan, J Yaffe, K AF Kurella, M Chertow, GM Luan, J Yaffe, K TI Cognitive impairment in chronic kidney disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognitive impairment; chronic kidney disease; end-stage renal disease; dementia ID CHRONIC-HEMODIALYSIS PATIENTS; QUALITY-OF-LIFE; NEUROPSYCHOLOGICAL FUNCTION; ALZHEIMERS-DISEASE; DIALYSIS PATIENTS; ELDERLY PERSONS; NORMATIVE DATA; RISK-FACTORS; DEMENTIA; PREVALENCE AB Objectives: To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD. Design: Cross-sectional study. Setting: University-affiliated ambulatory nephrology and dialysis practices. Participants: Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end-stage renal disease (ESRD)) with a mean age+/-standard deviation of 62.5+/-14.3. Measurements: Three standardized cognitive tests, the Modified Mini-Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six-variable Modification of Diet in Renal Disease equation. Results: There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms (P<.001 for all comparisons). Scores on the Trails B (P<.001) and CVLT immediate (P=.01) and delayed (P<.001) recall were significantly worse for subjects with CKD not requiring dialysis than for published norms. In addition, the fraction of subjects with impairment on the 3MS and Trails B increased with decreasing kidney function. Conclusion: Cognitive impairment is associated with the severity of kidney disease. Further studies are needed to determine the reasons for cognitive impairment in subjects with CKD and ESRD. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Moffitt Long Hosp, Mt Zion Med Ctr, Dept Med,Div Nephrol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Moffitt Long Hosp, Mt Zion Med Ctr, Dept Med,Div Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Moffitt Long Hosp, Mt Zion Med Ctr, Dept Med,Div Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Moffitt Long Hosp, Mt Zion Med Ctr, Dept Med,Div Epidemiol, San Francisco, CA 94143 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Box 181, San Francisco, CA 94143 USA. EM kyaffe@itsa.ucsf.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU NIA NIH HHS [AG 00888, R01 AG 021918]; NIDDK NIH HHS [R01 DK 01005, R01 DK 58411] NR 36 TC 181 Z9 187 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2004 VL 52 IS 11 BP 1863 EP 1869 DI 10.1111/j.1532-5415.2004.52508.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100010 PM 15507063 ER PT J AU Casarett, DJ Crowley, RL Hirschman, KB AF Casarett, DJ Crowley, RL Hirschman, KB TI How should clinicians describe hospice to patients and families? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospice; end-of-life; decision-making ID ADVANCE DIRECTIVES; TERMINAL CARE; LAST YEAR; LIFE; CANCER; DECISIONS; DEATH; PAIN; END AB Objectives: To describe hospice enrollment from the perspective of bereaved family members and to identify information about hospice that would encourage patients and families to enroll sooner. Design: Cross-sectional interviews. Setting: Three Medicare-certified hospice organizations. Participants: One hundred family members of 100 patients who died in hospice. Measurements: Semistructured interviews assessed prior knowledge of hospice, patients' and physicians' involvement in the enrollment process, features of hospice that motivated enrollment, and features that patients and families wished they had learned about sooner. Results: Almost all family members (n=92) and patients (n=71) knew about hospice before the patient's illness. Almost half the patients (n=44) were not involved at all in the hospice enrollment decision. The patient's physician (n=51) or the patient or family (n=34) initiated most hospice discussions, but patients and families usually obtained information about hospice from a hospice representative (n=75) rather than from the patient's physician (n=22). Family members identified several kinds of information about hospice that were particularly helpful in deciding whether to enroll and described several aspects of hospice that they wished they had known about sooner. Conclusion: Many patients and families learn about hospice from someone other than the patient's physician, and most learn about valuable hospice features and services only after enrollment. By providing more information about hospice earlier in the illness course, clinicians may be able to facilitate more-informed and more-timely decisions about hospice enrollment. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. RP Casarett, DJ (reprint author), Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu FU NIA NIH HHS [T32 AG 00255] NR 29 TC 52 Z9 53 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2004 VL 52 IS 11 BP 1923 EP 1928 DI 10.1111/j.1532-5415.2004.52520.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100020 PM 15507073 ER PT J AU Sohn, L Harada, ND AF Sohn, L Harada, ND TI Time since immigration and health services utilization of Korean-American older adults living in Los Angeles County SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE older persons; healthcare utilization; Korean American; minority; health services ID INSURANCE COVERAGE; AMBULATORY-CARE; UNITED-STATES; ACCESS; ACCULTURATION; POPULATION; NEEDS AB The aim of this study was to characterize ambulatory healthcare utilization of older Korean Americans and its association with length of time since immigration. It was hypothesized that older Korean Americans who were recent immigrants would use outpatient physician visits less often than early immigrants. The data are from the 2000 Korean-American Health Survey, which assessed the health status and medical needs of Korean Americans living in Los Angeles County. The dependent variable was the number of visits to a physician for check-up or consultation. Multivariate regression modeling was used to assess the influence of length of time since immigration on the dependent variable controlling for predisposing, enabling, and need variables for a sample of 208 Koreans Americans aged 65 and older. Results indicated that high school education in Korea and health insurance status were significant predictors of number of visits to a physician during the previous year (P<.05). The main variable of interest, the number of years living in the United States, approached significance at P=.09. It was concluded that enabling variables such as education and health insurance significantly influenced use of healthcare services in the older Korean-American population. The lack of studies regarding older minority populations and their access to healthcare further highlight theneed not only to characterize the access of these often-vulnerable populations, but also to generate interest for further studies. C1 VA Greater Los Angeles Healthcare Syst, Special Fellowship Program Adv Geriatr, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med & Publ Hlth, Los Angeles, CA USA. RP Sohn, L (reprint author), VA Greater Los Angeles Healthcare Syst, Special Fellowship Program Adv Geriatr, 11G,11301 Wilshire Blvd,Bldg 220,Room 334, Los Angeles, CA 90073 USA. EM Linda.sohn@med.va.gov NR 26 TC 14 Z9 14 U1 0 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2004 VL 52 IS 11 BP 1946 EP 1950 DI 10.1111/j.1532-5415.2004.52524.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100024 PM 15507077 ER PT J AU Abrass, CK AF Abrass, CK TI Overview: Obesity: What does it have to do with kidney disease? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID GLOMERULAR MESANGIAL CELLS; RENAL-DISEASE; INSULIN-RESISTANCE; ESSENTIAL-HYPERTENSION; MICROALBUMINURIA; HYPERINSULINEMIA; LIPIDS; GLOMERULOSCLEROSIS; CONSEQUENCES; PROGRESSION C1 Univ Washington, Sch Med, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Abrass, CK (reprint author), Univ Washington, Sch Med, Dept Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM cabrass@u.washington.edu NR 52 TC 47 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2004 VL 15 IS 11 BP 2768 EP 2772 DI 10.1097/01.ASN.0000141963.04540.3E PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 865EB UT WOS:000224684200001 PM 15504929 ER PT J AU Odden, MC Whooley, MA Shlipak, MG AF Odden, MC Whooley, MA Shlipak, MG TI Association of chronic kidney disease and anemia with physical capacity: The heart and soul study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; CHRONIC RENAL-INSUFFICIENCY; SEATTLE ANGINA QUESTIONNAIRE; EXERCISE CAPACITY; HEMODIALYSIS-PATIENTS; FUNCTIONAL STATUS; ELDERLY PERSONS; ERYTHROPOIETIN; PERFORMANCE; HEMOGLOBIN AB Chronic kidney disease (CKD) and anemia are common conditions in the outpatient setting, but their independent and additive effects on physical capacity have not been well characterized. The association of CKD and anemia with self-reported physical function was evaluated and exercise capacity was measured in patients with coronary disease. A cross-sectional study of 954 outpatients enrolled in the Heart and Soul study was performed. CKD was defined as a measured creatinine clearance <60 ml/min, and anemia was defined as a hemoglobin level of <12g/dl. Physical function was self-assessed using the physical limitation subscale of the Seattle Angina Questionnaire (0 to 100), and exercise capacity was defined as metabolic equivalent tasks achieved at peak exercise. In unadjusted analyses, CKD was associated with lower self-reported physical function (67.6 versus 74.9; P < 0.001) and lower exercise capacity (5.5 versus 7.9; P < 0.001). Similarly, anemia was associated with lower self-reported physical function (62.6 versus 74.3; P < 0.001) and exercise capacity (5.7 versus 7.5; P < 0.001). After multivariate adjustment, CKD (69.4 versus 74.2; P = 0.003) and anemia (67.5 versus 73.6; P = 0.009) each remained associated with lower mean self-reported physical function. In addition, patients with CKD (6.3 versus 7.7; P < 0.001) or anemia (6.5 versus 7.4; P = 0.004) had lower adjusted mean exercise capacities. Participants with both CKD and anemia had lower self-reported physical function and exercise capacity than those with either alone. CKD and anemia are independently associated with physical limitation and reduced exercise capacity in outpatients with coronary disease, and these effects are additive. The broad impact of these disease conditions merits further study. C1 San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 4150 Clement St,111A-1, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu FU NHLBI NIH HHS [R01 HL079235-01A1, R01 HL079235] NR 30 TC 41 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2004 VL 15 IS 11 BP 2908 EP 2915 DI 10.1097/01.ASN.0000143743.78092.E3 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 865EB UT WOS:000224684200016 PM 15504944 ER PT J AU Wright, CD Grillo, HC Wain, JC Wong, DR Donahue, DM Gaissert, HA Mathisen, DJ AF Wright, CD Grillo, HC Wain, JC Wong, DR Donahue, DM Gaissert, HA Mathisen, DJ TI Anastomotic complications after tracheal resection: Prognostic factors and management SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 04-07, 2003 CL BOSTON, MA SP Amer Assoc Thorac Surg ID LARYNGOTRACHEAL RESECTION; RECONSTRUCTION; STENOSIS; PREVENTION; REPAIR AB Objective: We sought to identify risk factors for anastomotic complications after tracheal resection and to describe the management of these patients. Methods: This was a single-institution, retrospective review of 901 patients who underwent tracheal resection. Results: The indications for tracheal resection were postintubation tracheal stenosis in 589 patients, tumor in 208, idiopathic laryngotracheal stenosis in 83, and tracheoesophageal fistula in 21. Anastornotic complications occurred in 81 patients (9%). Eleven patients (1%) died after operation, 6 of anastomotic complications and 5 of other causes (odds ratio 13.0, P =.0001 for risk of death after anastomotic complication). At the end of treatment, 853 patients (95%) had a good result, whereas 37 patients (4%) had an airway maintained by tracheostomy or T-tube. The treatments of patients with an anastomotic complication were as follows: multiple dilations (n = 2), temporary tracheostomy (n = 7), temporary T-tube (n = 16), permanent tracheostomy (n = 14), permanent T-tube (n = 20), and reoperation (n = 16). Stepwise multivariable analysis revealed the following predictors of anastomotic complications: reoperation (odds ratio 3.03, 95% confidence interval 1.69-5.43, P =.002), diabetes (odds ratio 3.32, 95% confidence interval 1.76-6.26, P =.002), lengthy ( greater than or equal to4 cm) resections (odds ratio 2.01, 95% confidence interval 1.21 - 3.35, P =.007), laryngotracheal resection (odds ratio 1.80, 95% confidence interval 1.07-3.01, P =.03), age 17 years or younger (odds ratio 2.26, 95% confidence interval 1.09-4.68, P =.03), and need for tracheostomy before operation (odds ratio 1.79, 95% confidence interval 1.03-3.14, P =.04). Conclusions: Tracheal resection is usually successful and has a low mortality. Anastornotic complications are uncommon, and important risk factors are reoperation, diabetes, lengthy resections, laryngotracheal resections, young age (pediatric patients), and the need for tracheostomy before operation. C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, Blake 1570, Boston, MA 02114 USA. EM Wright.Cameron@mgh.harvard.edu NR 14 TC 101 Z9 110 U1 0 U2 8 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2004 VL 128 IS 5 BP 731 EP 739 DI 10.1016/j.jtcvs.2004.07.005 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 867JO UT WOS:000224839100011 PM 15514601 ER PT J AU Mangi, AA Torchiana, DF AF Mangi, AA Torchiana, DF TI A technique for repair of mitral paravalvular leak SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID VALVE-REPLACEMENT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Surg Unit, Bullfinch 208, Boston, MA 02114 USA. EM dtorchiana@partners.org NR 5 TC 13 Z9 14 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2004 VL 128 IS 5 BP 771 EP 772 DI 10.1016/j.jtcvs.2004.04.035 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 867JO UT WOS:000224839100023 PM 15514613 ER PT J AU Grillo, HC Athanasoulis, CA AF Grillo, HC Athanasoulis, CA TI Tracheal obstruction from mediastinal arteriovenous malformation SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM pguerriero@partners.org NR 4 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2004 VL 128 IS 5 BP 780 EP 782 DI 10.1016/j.jtcvs.2004.03.019 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 867JO UT WOS:000224839100027 PM 15514617 ER PT J AU Block, M Lefkowitz, T Ravenel, J Leon, S Hannegan, C AF Block, M Lefkowitz, T Ravenel, J Leon, S Hannegan, C TI Endovascular coil embolization for acute management of traumatic pulmonary artery pseudoaneurysm SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 Med Univ S Carolina, Div Cardiothorac Surg, Dept Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA. RP Block, M (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Dept Surg, 96 Jonathan Lucas St,409 CSB, Charleston, SC 29425 USA. EM blockm@musc.edu NR 5 TC 9 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2004 VL 128 IS 5 BP 784 EP 785 DI 10.1016/j.jtcvs.2004.03.028 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 867JO UT WOS:000224839100029 PM 15514619 ER PT J AU Stoyioglou, A Jaff, MR AF Stoyioglou, A Jaff, MR TI Medical treatment of peripheral arterial disease: A comprehensive review SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; ACUTE CORONARY SYNDROMES; ANKLE-ARM INDEX; INTERMITTENT CLAUDICATION; OCCLUSIVE DISEASE; DOUBLE-BLIND; CARDIOVASCULAR-DISEASE; SMOKING-CESSATION; MYOCARDIAL-INFARCTION; VASCULAR-DISEASE AB Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis that affects more than 10 million people in the United States. The risk factors associated with PAD are similar to those found in patients with coronary artery disease and cerebrovascular disease. Medical therapy of PAD must include modification of cardiovascular risk factors with application of strict secondary prevention guidelines. For improvement in quality of life, a structured exercise rehabilitation program remains the most effective nortinterventional treatment strategy, but it is difficult to employ from economic and patient-compliance perspectives. Newer pharmacologic therapies have demonstrated efficacy in patients with intermittent claudication. Emerging strategies for management of these patients include revascularization and maximal medical therapy for improvement of physical function as well as reduction in risk for subsequent major cardiovascular events. This article will review the clinical data supporting aggressive medical interventions for patients with PAD. C1 Lenox Hill Hosp, Dept Cardiol, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Vasc Surg, Boston, MA 02114 USA. RP Jaff, MR (reprint author), 62 Staniford St, Boston, MA 02114 USA. EM mjaff@partners.org NR 96 TC 34 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2004 VL 15 IS 11 BP 1197 EP 1207 DI 10.1097/01.RVI.0000137978.15352.C6 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906XS UT WOS:000227678800003 PM 15525738 ER PT J AU Meissner, OA Verrel, F Tato, F Siebert, U Ramirez, H Ruppert, V Schoenberg, SO Reiser, M AF Meissner, OA Verrel, F Tato, F Siebert, U Ramirez, H Ruppert, V Schoenberg, SO Reiser, M TI Magnetic resonance angiography in the follow-up of distal lower-extremity bypass surgery: Comparison with duplex ultrasound and digital subtraction angiography SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID INFRAINGUINAL VEIN GRAFTS; 3-DIMENSIONAL MR-ANGIOGRAPHY; ARTERIAL OCCLUSIVE DISEASE; LIMB-THREATENING ISCHEMIA; BOLUS-CHASE; SURVEILLANCE; AORTA; FEMOROPOPLITEAL; RECONSTRUCTION; ARTERIOGRAPHY AB PURPOSE: The danger of limb loss as a consequence of acute occlusion of infrapopliteal bypasses underscores the requirement for careful patient follow-up. The objective of this study was to determine the agreement and accuracy of contrast material-enhanced moving-table magnetic resonance (MR) angiography and duplex ultrasonography (US) in the assessment of failing bypass grafts. In cases of discrepancy, digital subtraction angiography (DSA) served as the reference standard. MATERIALS AND METHODS: MR angiography was performed in 24 consecutive patients with 26 femorotibial or femoropedal bypass grafts. Each revascularized limb was divided into five segments-M native arteries proximal to the graft; (ii) proximal anastomosis; (iii) graft course; (iv) distal. anastomosis; and (v) native arteries distal to the graft-resulting in 130 vascular segments. Three readers evaluated all MR angiograms for image quality and the presence of failing grafts. The degree of stenosis was compared to the findings of duplex US, and in case of discrepancy, to DSA findings. Two separate analyses were performed with use of DSA only and a combined diagnostic endpoint as the reference standard. RESULTS: Image quality was rated excellent or intermediate in 119 of 130 vascular segments (92%). Venous overlay was encountered in 26 of 130 segments (20%). In only two segments was evaluation of the outflow region not feasible. One hundred seventeen of 130 vascular segments were available for quantitative analysis. In 109 of 117 segments (93%), MR angiography and duplex US showed concordant findings. In the eight discordant segments in seven patients, duplex US overlooked four high-grade stenoses that were correctly identified by MR angiography and confirmed by DSA. Percutaneous transluminal angioplasty was performed in these cases. In no case did MR angiography miss an area of stenosis of sufficient severity to require treatment. Total accuracy for duplex US ranged from 0.90 to 0.97 depending on the reference standard used, whereas MR angiography was completely accurate (1.00) regardless of the standard definition. CONCLUSION: Our data strongly suggest that the accuracy of MR angiography for identifying failing grafts in the infrapopliteal circulation is equal to that of duplex US and superior to that of duplex US in cases of complex revascularization. MR angiography should be included in routine follow-up of patients undergoing infrapopliteal bypass surgery. C1 Univ Munich, Inst Clin Radiol, D-81377 Munich, Germany. Univ Munich, Div Vasc Surg, D-81377 Munich, Germany. Univ Munich, Div Angiol, D-81377 Munich, Germany. Univ Munich, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany. Harvard Univ, Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA USA. RP Meissner, OA (reprint author), Univ Munich, Inst Clin Radiol, Marchioninistr 15, D-81377 Munich, Germany. EM oliver.meissner@med.uni-muenchen.de NR 35 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2004 VL 15 IS 11 BP 1269 EP 1277 DI 10.1097/01.RVI.0000137404.44683.75 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906XS UT WOS:000227678800012 PM 15525747 ER PT J AU Bush, RL Lin, PH Bates, JT Mureebe, L Zhou, W Lumsden, AB AF Bush, RL Lin, PH Bates, JT Mureebe, L Zhou, W Lumsden, AB TI Pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis: Safety and feasibility study SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Venous-Forum CY FEB 26-29, 2004 CL Orlando, FL SP Amer Venous Forum ID VEIN THROMBOSIS AB Purpose: The current standard of care for deep venous thromboembolism (DVT) is anticoagulation; however, this treatment method does not rapidly relieve clot burden or clinical symptoms. We describe a rapid and effective method of thrombus removal, with simultaneous percutaneous mechanical thrombectomy (PMT) and thrombolysis. Methods. Over 26 months 20 patients (22 men, 2 women; mean age, 52 +/- 6 years [range, 38-79 years]) with extensive lower extremity DVT were treated with PMT with the AngioJet thrombectomy device in combination with lytic agent (urokinase, tissue plasminogen activator, or reteplase) added to the infusion. Three patients underwent treatment twice, because of recurrent DVT. The primary end point was angiographic evidence. of restoration of venous patency at completion of the procedure. Complications, recurrent ipsilateral DVT, and improvement in clinical symptoms were evaluated. Results. Complete thrombus removal was obtained in 15 procedures (65%), and partial resolution in the remaining 8 procedures (35%). Inciting occlusive lesions responsible for acute DVT were revealed in 14 patients (61%), and angioplasty with or without stenting was performed when necessary. In the 8 procedures with partial resolution additional catheter-directed thrombolysis was carried out on average for 5.7 hours, with further thrombus reduction. Overall, immediate (<24 hours) improvement in clinical symptoms was noted in 17 patients (74%). There were no complications related to either PMT or the short duration of lytic agent infusion. At average follow-up of 10.2 +/- 0.3 months (range, 3-26 months), 3 patients had recurrent ipsilateral DVT, and underwent repeat treatment. Conclusions. Addition of lytic agent to PMT facilitates thrombus extraction, decreases overall interventional treatment time, and improves patient outcomes. In addition, definitive management of underlying anatomic lesions can be performed in the same setting. Further outcome measures are necessary to study the long-term efficacy of this treatment method on preservation of valve function, reduction of chronic venous insufficiency, and improved quality of life. C1 Baylor Coll Med, Michael E De Bakey Dept Surg, Houston VAMC, Div Vasc Surg & Envovasc Therapy, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. New York Presbyterian Hosp, Columbia Weill Cornell Div Vasc Surg, New York, NY USA. RP Bush, RL (reprint author), Baylor Coll Med, Michael E De Bakey Dept Surg, Houston VAMC, Div Vasc Surg & Envovasc Therapy, 2002 Holcomb Blvd 112, Houston, TX 77030 USA. EM rbush@bcm.tmc.edu RI Mureebe, Leila/C-2132-2009 OI Mureebe, Leila/0000-0001-5272-2871 NR 10 TC 64 Z9 69 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2004 VL 40 IS 5 BP 965 EP 970 DI 10.1016/j.jvs.2004.08.025 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 902XD UT WOS:000227389100027 PM 15557912 ER PT J AU Zennou, W Perez-Caballero, D Gottlinger, H Bieniasz, PD AF Zennou, W Perez-Caballero, D Gottlinger, H Bieniasz, PD TI APOBEC3G incorporation into human immunodeficiency virus type 1 particles SO JOURNAL OF VIROLOGY LA English DT Article ID VIF PROTEIN; ANTIVIRAL ACTIVITY; HIV-1 DNA; DEGRADATION; RNA; HYPERMUTATION; EXPRESSION; INFECTION; CELLS; CEM15 AB APOBEC3G is promiscuous with respect to its antiretroviral effect, requiring that it be packaged into diverse retrovirus particles. Here, we show that most virally encoded human immunodeficiency virus type 1 particle components are dispensable for APOPEC3G incorporation. However, replacement of the nucleocapsid (NC) Gag domain with a leucine zipper abolished APOBEC3G incorporation. Moreover, coprecipitation analysis showed that APOBEC3G-Gag interaction requires NC and nonspecific RNA. These observations suggest that APOBEC3G exploits an essential property of retroviruses, namely, RNA packaging, to infiltrate particles. Because it is, therefore, difficult to evolve specific sequences that confer escape from APOBEC3G, these findings may explain why lentiviruses evolved an activity that induces its destruction. C1 Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Rockefeller Univ, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bieniasz, PD (reprint author), Aaron Diamond AIDS Res Ctr, 455 1st Ave, New York, NY 10016 USA. EM pbienias@adarc.org NR 24 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2004 VL 78 IS 21 BP 12058 EP 12061 DI 10.1128/JVI.78.21.12058-12061.2004 PG 4 WC Virology SC Virology GA 863DM UT WOS:000224540900059 ER PT J AU Hazzard, WR AF Hazzard, WR TI Geriatrics: Specialty, subspecialty, or supraspecialty? SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Hazzard, WR (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-182-GEC, Seattle, WA 98108 USA. EM william.hazzard@med.va.gov NR 1 TC 3 Z9 3 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2004 VL 59 IS 11 BP 1161 EP 1162 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 882EH UT WOS:000225921200015 PM 15602065 ER PT J AU Kuo, HK Sorond, F Iloputaife, I Gagnon, M Milberg, W Lipsitz, LA AF Kuo, HK Sorond, F Iloputaife, I Gagnon, M Milberg, W Lipsitz, LA TI Effect of blood pressure on cognitive functions in elderly persons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID ORTHOSTATIC HYPOTENSION; HYPERTENSION; PEOPLE; RISK AB Background. Little is known about what specific cognitive functions are affected by elevated blood pressure (BP) and how orthostatic BP change is related to cognitive impairment. The aim of this study was to determine the effect of BP and its postural change on cognitive functions in otherwise healthy elders. Methods. In 70 healthy persons (mean age, 72 4 years), supine systolic BP (SBP) was assessed 3 times using a sphygmomanometer, and the average values were obtained for the analysis. After 1, 3, and 5 minutes of standing, 3 BP measurements were obtained and the orthostatic SBP changes were determined by subtracting these values from the supine average. Neuropsychological tests were administered to assess short-term and long-term verbal and visual memory, visuospatial skills, and frontal-executive functions. Participants were considered impaired in the specific cognitive performance if their scores fell below the 25th percentile of the study population. Multiple logistic regression models were used to evaluate the relation of SBP and the magnitude of orthostatic SBP decline to risk for impairment in each of the cognitive tests. Results. Controlling for potential confounders, each 10 mmHg increase in supine SBP was associated with a 2.31-fold increase (95% confidence interval, 1.14 to 4.66) in risk for impairment in psychomotor speed and set shifting as measured using the Trailmaking Pan-B test. There was no significant association between cognitive functions and orthostatic SBP decline at 1, 3, and 5 minutes of standing. Conclusion. Elevation of BP is associated with a selective impairment in executive function in otherwise healthy community-dwelling elders. C1 Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare, New England GRECC, Boston, MA USA. Harvard Univ, Sch Med, Div Aging, Boston, MA USA. Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan. RP Lipsitz, LA (reprint author), Hebrew Rehabil Ctr Aged, 1200 Ctr St, Boston, MA 02131 USA. EM lipsitz@mail.hrca.harvard.edu FU NCATS NIH HHS [KL2 TR000063]; NIA NIH HHS [K12 AG000294, P30 AG028718, P60 AG008812, P60 AG008812-10, P60 AG008812-11A10002, P60 AG008812-120002, R01 AG026091, T32 AG000251] NR 15 TC 62 Z9 62 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2004 VL 59 IS 11 BP 1191 EP 1194 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 882EH UT WOS:000225921200027 PM 15602074 ER PT J AU Ness, J Ahmed, A Aronow, WS AF Ness, J Ahmed, A Aronow, WS TI Demographics and payment characteristics of nursing home residents in the United States: A 23-year trend SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LONG-TERM-CARE AB Background. With the aging of our population, an increased number of older Americans are expected to reside in nursing homes. Our objective is to determine the national trend in nursing home residence for older Americans. Methods. Using the Beyond 20/20 software, we analyzed publicly available data from National Nursing Home Surveys 1977-1999 to determine the trend in the demographics, marital status, and source of payments for older Americans residing in nursing homes. Results. The absolute number of persons aged 65 years and older residing in nursing homes increased from 1, 126,000 to 1,469,500 during the 23-year study period, with those aged 85 years and older, women, and African Americans being at a higher risk for nursing home placement. The rate of residence per 1000 civilian population actually declined from 58 to 43. Decline was most notable for persons aged 85 years and older, female, and white residents. The proportion of widowed persons among residents declined during the study period as well. Overall, Medicaid and private sources were the most common sources of payment. In 1999, Medicaid use was particularly prevalent among residents who were aged 65-74 years old, women, and/or African Americans. Conclusions. Older Americans at high risk for placement in nursing home facilities are aged 85 years and older, women, and African Americans, who are also more likely to rely on Medicaid as their primary source of payment. Preventive programs to keep older adults in the community should focus on this group of high-risk older adults. C1 New York Med Coll, Cardiol Div, Valhalla, NY 10595 USA. Univ Iowa Hlth Care, Dept Internal Med, Div Gen Internal Med, Iowa City, IA USA. Univ Alabama, Geriatr Heart Failure Clin, Birmingham, AL USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Ctr Aging, Sch Publ Hlth,Dept Epidemiol, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Birmingham, AL USA. Birmingham VA Med Ctr, Sect Geriatr, Birmingham, AL USA. Birmingham VA Med Ctr, Geriatr Heart Failure Clin, Birmingham, AL USA. Alabama Qual Assurance Fdn, Heart Failure Project, Birmingham, W Midlands, England. New York Med Coll, Dept Med, Sect Cardiol, Valhalla, NY USA. New York Med Coll, Dept Med, Sect Geriatr, Valhalla, NY USA. Mt Sinai Sch Med, New York, NY USA. RP Aronow, WS (reprint author), New York Med Coll, Cardiol Div, Macy Pavil,Room 138, Valhalla, NY 10595 USA. EM wsaronow@aol.com NR 16 TC 24 Z9 24 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2004 VL 59 IS 11 BP 1213 EP 1217 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 882EH UT WOS:000225921200031 PM 15602078 ER PT J AU McArdle, JJ Hamgami, F Jones, K Jolesz, F Kikinis, R Spiro, A Albert, MS AF McArdle, JJ Hamgami, F Jones, K Jolesz, F Kikinis, R Spiro, A Albert, MS TI Structural modeling of dynamic changes in memory and brain structure using longitudinal data from the normative aging study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID LIFE-SPAN; AGE; DECLINE; COGNITION; VOLUMES; GROWTH AB This is an application of new longitudinal structural equation modeling techniques to time-dependent associations of memory and brain structure measurements. There were 225 participants aged 30-80 years at baseline who were measured again after a 7-year interval on both the lateral ventricular size and Wechsler memory score. Multiple regression analyses show nonlinear associations with age but no relationships among longitudinal changes. Mixed-effects latent growth curve analyses and analyses based on latent difference scores indicate that longitudinal changes in both variables are reasonably well described by an exponential or dual change model. Bivariate dynamic structural equation modeling analyses indicate age-lagged changes operate in a coupled-over-time fashion, with the brain measure (lateral ventricular size) as a leading indicator in time of memory (Wechsler memory score) declines. C1 Univ Virginia, Dept Psychol, Charlottesville, VA 22906 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Vet Affairs, Boston, MA USA. RP McArdle, JJ (reprint author), Univ Virginia, Dept Psychol, POB 400400, Charlottesville, VA 22906 USA. EM jjm@virginia.edu FU NIA NIH HHS [P01-AG04953, AG-007137] NR 44 TC 32 Z9 32 U1 1 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 2004 VL 59 IS 6 BP P294 EP P304 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 877JK UT WOS:000225564500005 PM 15576857 ER PT J AU Kestenbaum, B Andress, DL Schwartz, SM Gillen, DL Seliger, SL Jadav, PR Sherrard, DJ Stehman-Breen, C AF Kestenbaum, B Andress, DL Schwartz, SM Gillen, DL Seliger, SL Jadav, PR Sherrard, DJ Stehman-Breen, C TI Survival following parathyroidectomy among United States dialysis patients SO KIDNEY INTERNATIONAL LA English DT Article DE parathyroidectomy; parathyroid hormone; hyperparathyroidism; mortality; dialysis ID STAGE RENAL-DISEASE; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS; SUBTOTAL PARATHYROIDECTOMY; CARDIOVASCULAR-DISEASE; CALCIUM HOMEOSTASIS; MORTALITY RISK; BLOOD-PRESSURE; BONE-DISEASE; SHORT-TERM AB Background. Secondary hyperparathyroidism (SHPTH) is highly prevalent among persons with end-stage renal disease (ESRD). SHPTH has been linked to uremic bone disease, vascular calcification, and a higher risk of death. Parathyroidectomy (PTX) can dramatically reduce parathyroid hormone (PTH) and phosphate levels; however, the relationship between PTX and survival is not known. Methods. We conducted an observational matched cohort study utilizing data from the United States Renal Database System (USRDS) in which 4558 patients undergoing a first PTX while on hemodialysis or peritoneal dialysis were individually matched by age, race, gender, cause of ESRD, dialysis duration, prior transplantation status, and dialysis modality to 4558 control patients who did not undergo PTX. Patients were followed from the date of PTX until they died or were lost to follow-up. Results. The 30-day postoperative mortality rate following PTX was 3.1%. Long-term relative risks of death among patients undergoing PTX were estimated to be 10% to 15% lower than those of matched control patients not undergoing surgery. Survival curves between the 2 groups crossed 587 days following PTX. Median survival was 53.4 months (95% CI: 51.2-56.4) in the PTX group, and 46.8 months (95% CI: 44.7-48.9) in the control group. Conclusion. PTX was associated with higher short-term, and lower long-term, mortality rates among U. S. patients receiving chronic dialysis. Measures to attenuate SHPTH may play an important role in reducing mortality among patients with end-stage renal disease. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98108 USA. Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL USA. Univ Washington, Div Nephrol, Seattle, WA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Kestenbaum, B (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Mail Stop 111A,1660 S Columbian Way, Seattle, WA 98108 USA. EM brk@u.washington.edu NR 28 TC 108 Z9 110 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2004 VL 66 IS 5 BP 2010 EP 2016 DI 10.1111/j.1523-1755.2004.00972.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 862CS UT WOS:000224467900030 PM 15496173 ER PT J AU Fox, CS Larson, MG Keyes, MJ Levy, D Clouse, ME Culleton, B O'Donnell, CJ AF Fox, CS Larson, MG Keyes, MJ Levy, D Clouse, ME Culleton, B O'Donnell, CJ TI Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: The Framingham Heart Study SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FL SP Amer Heart Assoc DE coronary calcification; kidney disease; risk factor ID STAGE RENAL-DISEASE; BEAM COMPUTED-TOMOGRAPHY; GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; YOUNG-ADULTS; RISK-FACTOR; PREDICTION; COMMUNITY; OUTCOMES; FAILURE AB Background. Among patients with end-stage renal disease (ESRD), the risk of cardiovascular disease is 10 to 20 times higher than the general population. Adults with ESRD have increased coronary-artery calcification (CAC) detected by electron-beam computed tomography (EBCT). Because the risk of coronary heart disease is increased even at moderate declines in kidney function, we sought to test whether high CAC scores are seen among those with mild reductions in kidney function. Methods. Men and women free of symptomatic cardiovascular disease underwent EBCT. Coronary calcium was quantified using the method described by Agatston. Renal function was estimated by glomerular filtration rate (GFR). Spearman correlation coefficients were used to test the association between GFR and CAC. Results. Three hundred nineteen subjects (162 men/157 women), mean age 60, were included. Mean GFR was 86+/-23 mL/min/ 1.73 m(2) (range 31-169; 10% with GFR <60 mL/min/1.73 m(2)). The median CAC scores by quartile of GFR were 85.9, 48.1, 7.9, and 2.7. Overall, the unadjusted correlation of GFR and CAC was -0.28 (P<.0001). This remained significant after adjustment for age and sex (-0.11, P<0.05), and additionally after adjustment for body mass index (-0.11, P<0.05), hypertension (-0.11, P<0.05), or total cholesterol (-0.12, P=0.04). A similar correlation was noted after multivariable adjustment (-0.10, P<0.08). Conclusion. Mild declines in kidney function are associated with subclinical coronary artery calcification in a sample of subjects free of clinically apparent cardiovascular disease. This might help explain the increased risk of cardiovascular disease among individuals with renal dysfunction. Larger ongoing studies are needed to better quantify this finding. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Brigham & Womens Hosp, Dept Endocrinol Diabetes & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Beth Israel Deaconess Hosp, Dept Radiol, Boston, MA USA. Univ Calgary, Foothills Hosp, Calgary, AB, Canada. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), MPH, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov NR 32 TC 51 Z9 53 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2004 VL 66 IS 5 BP 2017 EP 2021 DI 10.1111/j.1523-1755.2004.00973.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 862CS UT WOS:000224467900031 PM 15496174 ER PT J AU Russo, LM Comper, WD Osicka, TM AF Russo, LM Comper, WD Osicka, TM TI Mechanism of albuminuria associated with cardiovascular disease and kidney disease SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT International Symposium on Albuminuria CY MAY 16-18, 2004 CL New York, NY SP Natl Kidney Fdn DE lysosome; albumin degradation; albumm-derived fragments ID HYPERTENSION AB The major underlying factors associated with tissue damage and fibrosis in cardiovascular and kidney disease are the up-regulation and action of growth factors such as transforming growth factor-beta (TGF-Pbeta) and cytokines produced in response to changes in systemic factors, particularly blood pressure or hyperalycemia. This study identifies the relationship of elevated levels of TGF-beta to increased levels of intact albumin in the urine (micro- and macroalbuminuria). This mechanism may be directly linked to the effect of TGF-beta on albumin uptake and the lysosomal breakdown of filtered albumin by proximal tubular cells prior to excretion. C1 AusAm Biotechnol Inc, New York, NY 10022 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Program Membrane Biol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3168, Australia. RP Comper, WD (reprint author), AusAm Biotechnol Inc, 645 Madison Ave, New York, NY 10022 USA. EM wcomper@ausambiotech.com NR 6 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2004 VL 66 SU 92 BP S67 EP S68 DI 10.1111/j.1523-1755.2004.09218.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 866CP UT WOS:000224751000019 ER PT J AU Sullivan, CA Jaklitsch, MT Haddad, R Goguen, LA Gagne, A Wirth, LJ Posner, MR Tishler, RB Norris, CM AF Sullivan, CA Jaklitsch, MT Haddad, R Goguen, LA Gagne, A Wirth, LJ Posner, MR Tishler, RB Norris, CM TI Endoscopic management of hypopharyngeal stenosis after organ sparing therapy for head and neck cancer SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Southern Section of the Triological-Society CY JAN 09, 2004 CL Marco Isl, FL SP Triol Soc, SO Sect ID BALLOON DILATATION; RADIATION-THERAPY; STRICTURE; RECONSTRUCTION; CHEMOTHERAPY; RADIOTHERAPY; ANTEGRADE; DILATION AB Objectives: The objective of this study was to describe and evaluate the efficacy of an endoscopic technique for the management of postchemoradiation hypopharyngeal stenosis in head and neck cancer patients. Study Design: Retrospective review. Methods. Patients with postchemoradiation hypopharyngeal stenoses were identified from the Dana Farber Cancer Institute head and neck database. Patients who had undergone extirpative surgery and reconstruction were excluded. All patients underwent either anterograde dilatation (AD) by the lead author (C.A.S.) or transgastric retrograde esophagoscopy with anterograde dilatation (TREAD) (CAS., M.T.J.). Chemoradiation records, clinic notes, operative reports, and swallowing test data were reviewed. Removal of the gastric feeding tube was considered the endpoint of rehabilitation. Results: Seventeen patients had postcricoid stenoses identified by modified barium swallow. Endoscopy confirmed 15 postcricoid stenoses and 2 proximal esophageal stenoses. Nine (53%) patients had partial stenoses, and eight (47%) had complete stenoses. Eight partial stenosis patients underwent 10 AD procedures and 3 TREAD procedures. Eight complete stenosis patients underwent 9 TREAD procedures and 26 subsequent AD procedures. Fifteen of 16 (93%) patients resumed swallowing after dilatation. Thirteen (81%) patients maintained their weight on an oral diet and had their gastric feeding tubes removed. Complications included hypopharyngeal perforation (13%), abdominal wall infection (6%), stomach wall dehiscence (6%, and chondroradionecrosis of the cricoid cartilage (6%). Conclusions: Postcricoid hypopharyngeal stenosis may be partial or complete after organ sparing chemoradiation for head and neck cancer. Using the TREAD technique, successful rehabilitation of swallowing can be achieved with a low incidence of complications. C1 Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Head & Neck Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Speech & Swallowing Therapy, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Thorac Surg, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sullivan, CA (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Dana Farber Canc Inst, 333 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM casullivan@partners.org NR 15 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2004 VL 114 IS 11 BP 1924 EP 1931 DI 10.1097/01.mlg.0000147921.74110.ee PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 871DU UT WOS:000225110300008 PM 15510015 ER PT J AU Christie, MA Hersch, SM AF Christie, MA Hersch, SM TI Demonstration of nondeclarative sequence learning in mice: Development of an animal analog of the human serial reaction time task SO LEARNING & MEMORY LA English DT Article ID MULTIPLE MEMORY-SYSTEMS; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; CAUDATE-NUCLEUS; TRANSGENIC MICE; BASAL GANGLIA; KNOCKOUT MICE; MOTOR; HIPPOCAMPUS; LESIONS AB In this paper, we demonstrate nondeclarative sequence learning in mice using an animal analog of the human serial reaction time task (SRT) that uses a within-group comparison of behavior in response to a repeating sequence versus a random sequence. Ten female B6CBA mice performed eleven 96-trial sessions containing 24 repetitions of a 4-trial sequence. During the 12th session, the repeating sequence was replaced with the random sequence halfway through the session. Reaction time (RT) to respond to an illuminated nose-poke was recorded, and performance was compared at the halfway point in each session to test for any change in behavior. For learning effect, RTs decreased over the no-switch repeating-sequence sessions. For interference effect, behavior did not change appreciably at the halfway point during the last repeating-sequence session. However, RTs deteriorated significantly after the switch from repeating to random sequences halfway through session 12. The mice demonstrated a robust interference effect when switched from repeating to random sequences. This pattern of behavior in humans performing the SRT is interpreted as evidence of nondeclarative sequence learning. The similarity between the human and mouse SRTs will enable more direct comparisons of mouse-human nondeclarative memory behavior and will provide a useful behavioral end-point in mouse-models of basal ganglia dysfunction. C1 Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Hersch, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. EM hersch@helix.mgh.harvard.edu FU NCCIH NIH HHS [AT00613]; NINDS NIH HHS [NS045242, NS35255, NS045806] NR 43 TC 15 Z9 15 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD NOV-DEC PY 2004 VL 11 IS 6 BP 720 EP 723 DI 10.1101/lm.85404 PG 4 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 876KU UT WOS:000225496500010 PM 15537741 ER PT J AU Attar, EC Scadden, DT AF Attar, EC Scadden, DT TI Regulation of hematopoietic stem cell growth SO LEUKEMIA LA English DT Review DE hematopoietic stem cell; expansion; regulation; microenvironment ID CREB-BINDING-PROTEIN; ACUTE MYELOGENOUS LEUKEMIA; CYCLIN-DEPENDENT KINASES; COLONY-FORMING CELLS; EX-VIVO EXPANSION; SELF-RENEWAL; IN-VITRO; CAENORHABDITIS-ELEGANS; SONIC HEDGEHOG; CDK INHIBITORS AB Hematopoietic stem cells (HSC) must balance self-renewal and differentiation to provide sufficient primitive cells to sustain hematopoiesis, while generating more mature cells with specialized capabilities. The enhanced self-renewal capacity of primitive HSCs enables their ability to sustain hematopoiesis throughout decades of life and their ability to repopulate a host when used therapeutically in bone marrow transplantation. However, hematopoietic cell perturbations resulting in unchecked self-renewal participate in leukemogenesis. While mechanisms governing self-renewal are still being uncovered, they are thought to bear relationship to the malignant process in a variety of tumor types and may therefore provide useful therapeutic targets in putative cancer stem cells. This review discusses molecular mechanisms recently defined to participate in HSC governance and highlights features of stem cell interactions with the microenvironment that may help guide therapies directed at HSCs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, 149 13th St,Room 5212D, Boston, MA 02129 USA. EM scadden.david@mgh.harvard.edu NR 101 TC 58 Z9 65 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2004 VL 18 IS 11 BP 1760 EP 1768 DI 10.1038/sj.leu.2403515 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 865VR UT WOS:000224732800003 PM 15457182 ER PT J AU Chan, C Berthiaume, F Nath, BD Tilles, AW Toner, M Yarmush, ML AF Chan, C Berthiaume, F Nath, BD Tilles, AW Toner, M Yarmush, ML TI Hepatic tissue engineering for adjunct and temporary liver support: Critical technologies SO LIVER TRANSPLANTATION LA English DT Review ID IMMORTALIZED HUMAN HEPATOCYTES; AMC-BIOARTIFICIAL LIVER; METABOLIC FLUX ANALYSIS; OXYGEN-UPTAKE RATES; I CLINICAL-TRIAL; BONE-MARROW; PHASE-I; CULTURED-HEPATOCYTES; CELL-INTERACTIONS; ASSIST DEVICE AB The severe donor liver shortage, high cost, and complexity of orthotopic liver transplantation have prompted the search for alternative treatment strategies for end-stage liver disease, which would require less donor material, be cheaper, and less invasive. Hepatic tissue engineering encompasses several approaches to develop adjunct internal liver support methods, such as hepatocyte transplantation and implantable hepatocyte-based devices, as well as temporary extracorporeal liver support techniques, such as bioartificial liver assist devices. Many tissue engineered liver support systems have passed the "proof of principle" test in preclinical and clinical studies; however, they have not yet been found sufficiently reliably effective for routine clinical use. In this review we describe, from an engineering perspective, the progress and remaining challenges that must be resolved in order to develop the next generation of implantable and extracorporeal devices for adjunct or temporary liver assist. (Liver Transpl2004"10:1331-1342.) C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Engn Med, Massachusetts Gen Hosp,Surg Serv, Cambridge, MA 02138 USA. Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [R01 DK37743] NR 104 TC 71 Z9 76 U1 1 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2004 VL 10 IS 11 BP 1331 EP 1342 DI 10.1002/lt.20229 PG 12 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 866BM UT WOS:000224747900001 PM 15497161 ER PT J AU Leung, JY Zhu, AX Gordon, FD Pratt, DS Mithoefer, A Garrigan, K Terella, A Hertl, M Cosimi, AB Chung, RT AF Leung, JY Zhu, AX Gordon, FD Pratt, DS Mithoefer, A Garrigan, K Terella, A Hertl, M Cosimi, AB Chung, RT TI Liver transplantation outcomes for early-stage hepatocellular carcinoma: Results of a multicenter study SO LIVER TRANSPLANTATION LA English DT Article ID UNITED-STATES; TUMOR CHARACTERISTICS; CIRRHOSIS; SURVIVAL; IMPACT; HEPATITIS AB The incidence of hepatocellular carcinoma (HCC), a frequent and incurable complication of cirrhosis, continues to rise. Orthotopic liver transplantation (OLT) has been proposed as a treatment for unresectable, intrahepatic HCC limited in extent to the Milan criteria adopted by the United Network of Organ Sharing (UNOS) in 1998. More recently, somewhat less restrictive University of California, San Francisco (UCSF)(10), criteria were proposed. To examine the long-term outcomes of OLT for HCC patients and to assess the UNOS policy of assigning weighted allocation points to patients with HCC, we retrospectively analyzed 144 patients (113 after 1998) with HCC who underwent OLT over an 11-year period at 3 institutions from UNOS Region 1. We compared their outcomes with 525 patients (272 after 1998) who underwent OLT for nonmalignant liver disease. The 1- and 5-year survival rates were 80.3% and 46.7%, respectively, for patients with HCC and 81.5% and 70.6%, respectively, for patients without HCC (P =.020). However, there was no difference in survival between HCC and non-HCC patients after implementation of disease-specific allocation for HCC in 1998. A higher proportion of the HCC cohort was older and male and had chronic HCV infection and alcoholic liver disease. In univariate analysis, having alpha-fetoprotein (AFP) levels of 10 ng/mL or less and meeting clinical and pathologic UCSF criteria were each significant predictors of improved survival (P =.005, P =.02, and P =.03, respectively). AFP greater than 10 ng/mL and exceeding pathologic UCSF criteria were also significant predictors of recurrence (P =.003 and P =.02, respectively). In conclusion, taken together, our data suggest that OLT is an acceptable option for patients with early HCC and that UCSF criteria predict outcome better than Milan or UNOS criteria. Regardless of which criteria are adopted to define eligibility, strict adherence to the criteria is important to achieve acceptable outcomes. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Lahey Clin Fdn, Burlington, MA 01805 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU NIDDK NIH HHS [DK57857] NR 16 TC 96 Z9 105 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2004 VL 10 IS 11 BP 1343 EP 1354 DI 10.1002/lt.20311 PG 12 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 866BM UT WOS:000224747900002 PM 15497158 ER PT J AU Chen, JW Pham, W Weissleder, R Bogdanov, A AF Chen, JW Pham, W Weissleder, R Bogdanov, A TI Human myeloperoxidase: A potential target for molecular MR imaging in atherosclerosis SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE atherosclerosis; magnetic resonance imaging; inflammation ID HYPOCHLORITE-MODIFIED PROTEINS; RISK-ASSESSMENT STRATEGIES; ACUTE CORONARY SYNDROMES; VULNERABLE PATIENT; OXIDATION; LESIONS; PLAQUE; DEFINITIONS; SYSTEM; ACID AB Plaque rupture in atherosclerotic disease is the major cause of morbidity and correlates well with myeloperoxidase (MPO) secretion by activated neutrophils and macrophages in humans. We hypothesized that paramagnetic electron donor compounds that rapidly oxidize and polymerize in the presence of MPO could be designed to enable imaging of local MPO activity levels in arterial segments at risk. Several potential substrates for MPO were synthesized and tested. One lead compound consisting of a covalent conjugate of GdDOTA and serotonin (3-(2-aminoethyl)-5-hydroxyindole) was efficiently polymerized in the presence of human neutrophil MPO resulting in a 70-100% increase in proton relaxivity. As a result, we were able to demonstrate MPO activity in enzyme solutions and in a model tissue-like system. These studies suggest that activatable paramagnetic MR imaging agents can be used to directly image MPO activity. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,5420 13th St, Charlestown, MA 02129 USA. EM abogdanov@helix.mgh.harvard.edu FU NIBIB NIH HHS [1R01EB00858] NR 23 TC 83 Z9 88 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD NOV PY 2004 VL 52 IS 5 BP 1021 EP 1028 DI 10.1002/mrm.20270 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 868YI UT WOS:000224948700007 PM 15508166 ER PT J AU Sitara, D Razzaque, MS Hesse, M Yoganathan, S Taguchi, T Erben, RG Juppner, H Lanske, B AF Sitara, D Razzaque, MS Hesse, M Yoganathan, S Taguchi, T Erben, RG Juppner, H Lanske, B TI Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice SO MATRIX BIOLOGY LA English DT Article DE Fgf-23 null; Hyp; phosphate; mineralization; bone ID X-LINKED HYPOPHOSPHATEMIA; TUMOR-INDUCED OSTEOMALACIA; CHRONIC-RENAL-FAILURE; PARATHYROID-HORMONE; ONCOGENIC OSTEOMALACIA; PHOSPHATE HOMEOSTASIS; PEX GENE; HEMODIALYSIS-PATIENTS; CALCIUM-CARBONATE; SERUM PHOSPHORUS AB Fibroblast growth factor-23 (FGF-23), a recently identified molecule that is mutated in patients with autosomal dominant hypophosphatemic rickets (ADHR), appears to be involved in the regulation of phosphate homeostasis. Although increased levels of circulating FGF-23 were detected in patients with different phosphate-wasting disorders such as oncogenic osteomalacia (OOM) and X-linked hypophosphatemia (XLH), it is not yet clear whether FGF-23 is directly responsible for the abnormal regulation of mineral ion homeostasis and consequently bone development. To address some of these unresolved questions, we generated a mouse model, in which the entire Fgf-23 gene was replaced with the lacZ gene. Fgf-23 null (Fgf-23(-/-)) mice showed signs of growth retardation by day 17, developed severe hyperphosphatemia with elevated serum 1,25(OH)(2)D-3 levels, and died by 13 weeks of age. Hyperphosphatemia in Fgf-23(-/-) mice was accompanied by skeletal abnormalities, as demonstrated by histological, molecular, and various other morphometric analyses. Fgf-23(-/-) mice had increased total-body bone mineral content (BMC) but decreased bone mineral density (BMD) of the limbs. Overall, Fgf-23(-/-) mice exhibited increased mineralization, but also accumulation of unmineralized osteoid leading to marked limb deformities. Moreover, Fgf-23(-/-) mice showed excessive mineralization in soft tissues, including heart and kidney. To further expand our understanding regarding the role of Fgf-23 in phosphate homeostasis and skeletal mineralization, we crossed Fgf-23(-/-) animals with Hyp mice, the murine equivalent of XLH. Interestingly, Hip males lacking both Fgf-23 alleles were indistinguishable from Fgf-23(-/-) mice, both in terms of serum phosphate levels and skeletal changes, suggesting that Fgf-23 is upstream of the phosphate regulating gene with homologies to endopeptidases on the X chromosome (Phex) and that the increased plasma Fgf-23 levels in Hip mice (and in XLH patients) may be at least partially responsible for the phosphate imbalance in this disorder. (C) 2004 Elsevier B.V./International Society of Matrix Biology. All rights reserved. C1 Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. Univ Munich, Inst Physiol Physiol Chem & Anim Nutr, Munich, Germany. Forsyth Inst, Anim Facil, Boston, MA USA. Nagasaki Univ, Grad Sch Med Sci, Dept Pathol, Nagasaki 852, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. RP Lanske, B (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. OI SITARA, DESPINA/0000-0002-4836-5039 FU NIDDK NIH HHS [R01 DK073944, R01 DK073944-01A2] NR 60 TC 293 Z9 301 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2004 VL 23 IS 7 BP 421 EP 432 DI 10.1016/j.matbio.2004.09.007 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 885QD UT WOS:000226171100002 PM 15579309 ER PT J AU Peabody, JW Luck, J Jain, S Bertenthal, D Glassman, P AF Peabody, JW Luck, J Jain, S Bertenthal, D Glassman, P TI Assessing the accuracy of administrative data in health information systems SO MEDICAL CARE LA English DT Article DE administrative data; medical informatics; quality of care; standardized patients; diagnostic errors; medical records/standards ID MEDICAL-RECORDS; VETERANS-AFFAIRS; PATIENT RECORDS; CARE; QUALITY; DATABASES; OUTCOMES; STROKE; PHYSICIAN; PATTERNS AB Background: Administrative data play a central role in health care. Inaccuracies in such data are costly to health systems, they obscure health research, and they affect the quality of patient care. Objectives: We sought to prospectively determine the accuracy of the primary and secondary diagnoses recorded in administrative data sets. Research Design: Between March and July 2002, standardized patients (SPs) completed unannounced visits at 3 sites. We abstracted the 348 medical records from these visits to obtain the written diagnoses made by physicians. We also examined the patient files to identify the diagnoses recorded on the administrative encounter forms and extracted data from the computerized administrative databases. Because the correct diagnosis was defined by the SP visit, we could determine whether the final diagnosis in the administrative data set was correct and, if not, whether it was caused by physician diagnostic error, missing encounter forms, or incorrectly filled out forms. Subjects: General internal medicine outpatient clinics at 2 Veterans Administration facilities and a large, private medical center participated in this study. Measures: A total of 45 trained SPs presented to physicians with 4 common outpatient conditions. Results: The correct primary diagnosis was recorded for 57% of visits. Thirteen percent of errors were caused by physician diagnostic error, 8% to missing encounter forms, and 22% to incorrectly entered data. Findings varied by condition and site but not by level of training. Accuracy of secondary diagnosis data (27%) was even poorer. Conclusions: Although more research is needed to evaluate the cause of inaccuracies and the relative contributions of patient, provider, and system level effects, it appears that significant inaccuracies in administrative data are common. Interventions aimed at correcting these errors appear feasible. C1 Univ Calif San Francisco, Inst Global Hlth, San Francisco, CA 94105 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RAND, Santa Monica, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. RP Peabody, JW (reprint author), Univ Calif San Francisco, Inst Global Hlth, 74 New Montgomery,Suite 508, San Francisco, CA 94105 USA. EM peabody@psg.ucsf.edu NR 49 TC 129 Z9 130 U1 1 U2 5 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 NOV PY 2004 VL 42 IS 11 BP 1066 EP 1072 DI 10.1097/00005650-200411000-00005 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 864RU UT WOS:000224651400005 PM 15586833 ER PT J AU Wolf, EJ Cooper, MSRA DiGiovine, CP Boninger, ML Guo, SF AF Wolf, EJ Cooper, MSRA DiGiovine, CP Boninger, ML Guo, SF TI Using the absorbed power method to evaluate effectiveness of vibration absorption of selected seat cushions during manual wheelchair propulsion SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE wheelchair; vibration; seat cushions ID WHOLE-BODY VIBRATION; DISCOMFORT; SUSPENSION; PREDICTION; EXPOSURE AB Although wheelchair users are frequently subjected to oscillatory and shock vibrations, little research has been conducted to assess the whole-body vibration exposure of wheelchair users. The purpose of this study was to determine if selected wheelchair cushions alter potentially harmful whole-body vibrations transferred to wheelchair users. Thirty-two participants, who use wheelchairs as their primary mode of mobility, contributed to this study. Four of the most commonly prescribed wheelchair cushions were selected. Participants were asked to propel their wheelchair over a simulated activities of daily living (ADL) course while acceleration and force data were recorded. A repeated measures ANOVA showed no significant differences between the different cushions for the total averaged absorbed power (p = 0.190), the 50 mm curb drop (p = 0.234), or the rumble strip (p = 0.143). A repeated measure ANOVA for the peak curb drop absorbed power revealed a significant difference in the cushions = 0.043). The cushions that were most effective in this testing appear to be the Invacare Pindot and the Varilite Solo. Not only did those cushions appear to have the lowest values much of the time but also they did not display the highest values. When comparing results from a similar study, absorbed power appears to be as effective in determining vibration effects in the time domain as the methods in the ISO 2631 Standard. (C) 2004 Published by Elsevier Ltd on behalf of IPEM. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, Vet Affairs Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol & Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Assist Technol Unit, Chicago, IL USA. Univ Illinois, Dept Disabil & Human Dev, Chicago, IL USA. RP Cooper, MSRA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, Vet Affairs Rehabil Res & Dev Ctr, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI DiGiovine, Carmen/E-2982-2011; OI Wolf, Erik/0000-0002-6353-7978; Boninger, Michael/0000-0001-6966-919X NR 23 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD NOV PY 2004 VL 26 IS 9 BP 799 EP 806 DI 10.1016/j.medengphy.2004.06.005 PG 8 WC Engineering, Biomedical SC Engineering GA 879WJ UT WOS:000225749600012 PM 15564117 ER PT J AU Brown, EB Boucher, Y Nasser, S Jain, RK AF Brown, EB Boucher, Y Nasser, S Jain, RK TI Measurement of macromolecular diffusion coefficients in human tumors (vol 67, pg 231, 2004) SO MICROVASCULAR RESEARCH LA English DT Correction C1 Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Brown, EB (reprint author), Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. EM edbrown@steele.mgh.harvard.edu NR 1 TC 1 Z9 1 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 2004 VL 68 IS 3 BP 313 EP 314 DI 10.1016/j.mvr.2004.08.004 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 868JN UT WOS:000224910000019 ER PT J AU Kishi, N Macklis, JD AF Kishi, N Macklis, JD TI MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID CPG-BINDING PROTEIN-2; NEURAL STEM-CELLS; MICROTUBULE-ASSOCIATED PROTEIN; CENTRAL-NERVOUS-SYSTEM; RETT-SYNDROME; DNA METHYLATION; ADULT NEUROGENESIS; SODIUM-CHANNEL; BRAIN; MICE AB Rett syndrome is a neurodevelopmental disorder and one of the causes of mental retardation and autistic behavior in girls, as well as in a small group of boys. It was recently discovered that mutation of the methyl-CpG-binding protein 2 (MECP2) gene encoding a transcriptional repressor on the X chromosome causes Rett syndrome. Although it is evident that phenotypes of MECP2 mutant mice that resemble those of Rent syndrome are attributable to lack of the MECP2 gene in the central nervous system (CNS), there is little understanding of the neuropathological abnormalities in the CNS of MECP2-null mice. Here, we investigated the developmental regulation and specific cellular expression of MECP2 during neural development both in vitro and in vivo. MECP2 is expressed in mature neurons, but not in astroglia or oligodendroglia, and is increasingly expressed during development of the mouse neocortex. In addition, in vitro culture studies suggest that MECP2 is expressed in more differentiated neurons rather than in less differentiated neuroblasts. Under in vitro conditions using neural precursor cultures, we find that MECP2 mutant neural precursors differentiate into morphologically mature neurons and glia, and no significant differences in differentiation are detected between cells from wild-type and MECP2 mutant mice, suggesting that MECP2 may play a different role in mice than it does in Xenopus embryos. In agreement with this hypothesis, neocortical projection layers in MECP2 -/y mice are thinner than those in wild-type mice, and pyramidal neurons in layer II/III in MECP2 -/y mice are smaller and less complex than those in wild-type mice. Taken together, our results indicate that MECP2 is involved in the maturation and maintenance of neurons, including dendritic arborization, rather than in cell fate decisions. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair,Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Program, Boston, MA 02114 USA. RP Macklis, JD (reprint author), MGH HMS Ctr Nervous Syst Repair, Edwards 410,50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu RI Kishi, Noriyuki/L-1379-2013 FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS41590, NS45523] NR 75 TC 242 Z9 249 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD NOV PY 2004 VL 27 IS 3 BP 306 EP 321 DI 10.1016/j.mcn.2004.07.006 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 868YU UT WOS:000224950000009 PM 15519245 ER PT J AU Gupta, ML Roof, DM Pellman, D AF Gupta, ML Roof, DM Pellman, D TI Function of the kinesin Kip3 during Kar9-dependent spindle positioning in budding yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Cytokinet Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 187 BP 34A EP 34A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800188 ER PT J AU Krause, M Leslie, JD Stewart, M Lafuente, EM Valderrama, F Jagannathan, R Strasser, GA Rubinson, DA Liu, H Way, M Yaffe, MB Boussiotis, VA Gertler, FB AF Krause, M Leslie, JD Stewart, M Lafuente, EM Valderrama, F Jagannathan, R Strasser, GA Rubinson, DA Liu, H Way, M Yaffe, MB Boussiotis, VA Gertler, FB TI Lamellipodin, a novel Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Canc Res UK, Cell Motil Grp, Lincolns Inn Fields Labs, London, England. MIT, Ctr Canc, Cambridge, MA 02139 USA. RI Valderrama, Ferran/E-8017-2011; Lafuente, Esther M/K-5684-2014 OI Lafuente, Esther M/0000-0001-8466-1022 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 225 BP 41A EP 41A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800226 ER PT J AU McCarthy, KM Yu, AL Francis, SA McCormack, JM Lynch, RD Schneeberger, EE AF McCarthy, KM Yu, AL Francis, SA McCormack, JM Lynch, RD Schneeberger, EE TI Knock down of occludin expression leads to diverse phenotypic alterations in epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Charlestown, MA USA. USC, Keck Sch Med, Los Angeles, CA USA. Univ Massachusetts, Lowell, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 366 BP 66A EP 66A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800367 ER PT J AU Casas, E Barren, CA Schneeberger, EE Lynch, RD AF Casas, E Barren, CA Schneeberger, EE Lynch, RD TI The tight junction (TJ) protein, occludin, is degraded and the products released preferentially from the basolateral (BL) surface of MDCK cells during incubation with methyl beta cyclodextrin (MBCD) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Massachusetts, Lowell, MA USA. Massachusetts Gen Hosp, Pathol Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 373 BP 68A EP 68A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800374 ER PT J AU Sever, S Gilmore, T McKee, M AF Sever, S Gilmore, T McKee, M TI Co-chaperone auxilin plays a direct role in formation of clathrin-coated vesicles at the plasma membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 438 BP 79A EP 79A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800439 ER PT J AU Garrido-Lecca, A Shimamura, A Huang, J AF Garrido-Lecca, A Shimamura, A Huang, J TI Characterization of SD01, the budding yeast ortholog of the Shwachman-Diamond gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Baylor Coll Med, Houston, TX 77030 USA. Texas Childrens Canc Ctr, Houston, TX USA. Hematol Serv, Houston, TX USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 520 BP 94A EP 94A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800521 ER PT J AU Fossale, E Wolf, P Espinola, J Lubicz-Nawrocka, T Teed, AM Gao, H Rigamonti, D Cattaneo, E MacDonald, ME Cotman, SL AF Fossale, E Wolf, P Espinola, J Lubicz-Nawrocka, T Teed, AM Gao, H Rigamonti, D Cattaneo, E MacDonald, ME Cotman, SL TI Impaired intracellular membrane trafficking and energy deficits in homozygous CbCln3(Delta ex7/8) neuronal precursor cells, an accurate model of JNCL SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Charlestown, MA USA. Univ Milan, Dept Pharmacol Sci, Milan, Italy. Univ Milan, Ctr Excellence Neurodegenerat Dis, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 640 BP 116A EP 116A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800641 ER PT J AU Sieburth, D Ch'ng, Q Dybbs, M Tavazoie, M Kennedy, S Wang, D Dupuy, D Rual, J Hill, D Vidal, M Ruvkun, G Kaplan, JM AF Sieburth, D Ch'ng, Q Dybbs, M Tavazoie, M Kennedy, S Wang, D Dupuy, D Rual, J Hill, D Vidal, M Ruvkun, G Kaplan, JM TI A systematic RNAi screen identifies 150 genes required for neurotransmitter secretion in C elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RI Ch'ng, QueeLim/C-5348-2009; Hill, David/B-6617-2011; Dupuy, Denis/M-7299-2014 OI Ch'ng, QueeLim/0000-0003-1941-3828; NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 650 BP 117A EP 118A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800651 ER PT J AU Sloan, K Eustace, B Stewart, J Zehetmeier, C Torella, C Simeone, M Roy, J Unger, C Louis, D Ilag, L Jay, D AF Sloan, K Eustace, B Stewart, J Zehetmeier, C Torella, C Simeone, M Roy, J Unger, C Louis, D Ilag, L Jay, D TI CD155/PVR plays a key role in cell motility during tumor cell invasion and migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. Xer Pharmaceut AG, Munich, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 982 BP 177A EP 177A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801327 ER PT J AU Rhee, J Xu, G Zukerberg, LR Balsamo, J Lilien, J AF Rhee, J Xu, G Zukerberg, LR Balsamo, J Lilien, J TI Cables links the repulsive axon guidance receptor ROBO to the cell-cell adhesion molecule N-cadherin through the tyrosine kinase Abl and the serine/threonine kinase cdk5 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Iowa, Iowa City, IA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 1002 BP 181A EP 181A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801347 ER PT J AU Yoshida, S Pellman, D AF Yoshida, S Pellman, D TI Regulation of budding yeast formin Bni1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 1472 BP 266A EP 266A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802196 ER PT J AU Holmes, G Romanova, LY Chay, K Mushinski, J AF Holmes, G Romanova, LY Chay, K Mushinski, J TI Phosphorylation of paxillin affects B-lymphocytic polarization and migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Genet Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 1594 BP 288A EP 288A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802318 ER PT J AU van Oudenaarden, AL Dotto, P Snapper, SB AF van Oudenaarden, AL Dotto, P Snapper, SB TI Gene targeting in skin reveals critical role for N-WASP in keratinocyte function SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 1607 BP 290A EP 290A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802331 ER PT J AU Gangopadhyay, SS Takizawa, N Gallant, C Barber, AL Je, H Smith, TC Luna, EJ Morgan, KG AF Gangopadhyay, SS Takizawa, N Gallant, C Barber, AL Je, H Smith, TC Luna, EJ Morgan, KG TI Smooth muscle archvillin: A novel regulator of signaling and Contractility in vascular smooth muscle SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 BBRI, Watertown, MA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Harvard Univ, Sch Med, Dept Med, BIDMC, Boston, MA USA. RI Luna, Elizabeth/B-4364-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 1611 BP 291A EP 291A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802335 ER PT J AU Yu, MC AF Yu, MC TI An arginine methyltransferase affects mRNP dynamics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 1834 BP 331A EP 331A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802558 ER PT J AU Conboy, IM Conboy, MJ Wagers, AJ Weissman, IL Rando, TA AF Conboy, IM Conboy, MJ Wagers, AJ Weissman, IL Rando, TA TI Understanding and reversing stem cell aging SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Stanford Univ, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S BP 361A EP 361A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803066 ER PT J AU Jagani, Z Ghaffari, S Song, K Kitidis, C Lodish, H Khosravi-Far, R AF Jagani, Z Ghaffari, S Song, K Kitidis, C Lodish, H Khosravi-Far, R TI Bcr-Abl-induced evasion from apoptosis: A mechanism for tumorigenicity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Mt Sinai Sch Med, Carl C Icahn Inst Gene Therapy & Mol Med, New York, NY USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 2071 BP 375A EP 375A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803141 ER PT J AU Alexander, A Subramanian, N Buxbaum, JN Jacobson, DR AF Alexander, A Subramanian, N Buxbaum, JN Jacobson, DR TI Drop-in, drop-out allele-specific PCR - A highly sensitive, single-tube method SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE allele-specific PCR; nested PCR; drop-in, drop-out PCR; mutation frequency; allele frequency; transthyretin ID POLYMERASE CHAIN-REACTION; NESTED PCR; AMERICANS; FREQUENCY AB Allelotyping large numbers of samples by allele-specific polymerase chain reaction (PCR) can be problematic if the DNA samples to be tested are of highly variable concentration. On the one hand, analysis of dilute DNA samples often requires nested PCR to produce a product of sufficient yield to be detectable on ethidium bromide-stained agarose gels. Such two-step assays require additional reagents, are labor-intensive, and have a higher risk of contamination. On the other hand, the specificity of allele-specific PCR assays can be lost at high input DNA concentrations. Large population-based genetic studies using DNA from varied sources would benefit from one-tube nested allele-specific PCR-based assay, in which the input DNA concentration has little effect on the assay's yield or specificity. An assay using this method is highly sensitive and specific, and was used to type several thousand DNA samples, obtained from various sources, for a G to A transition at human transthyretin codon 122. Similar assays could be readily adapted to any high-throughput allelotype assay where input DNA is of highly variable concentration. C1 Harbor Healthcare Syst, Dept Vet Affairs, Res Serv 151, New York, NY 10010 USA. VA Boston Healthcare Syst, Med Serv, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. RP Jacobson, DR (reprint author), Harbor Healthcare Syst, Dept Vet Affairs, Res Serv 151, New York Campus,423 E 23 St, New York, NY 10010 USA. EM daniel.jacobson@med.va.gov FU NIA NIH HHS [R01 AG15916] NR 7 TC 5 Z9 6 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD NOV PY 2004 VL 28 IS 3 BP 171 EP 174 DI 10.1385/MB:28:3:171 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 876KZ UT WOS:000225497000001 PM 15542916 ER PT J AU El-Shewy, HM Kelly, FL Barki-Harrington, L Luttrell, LM AF El-Shewy, HM Kelly, FL Barki-Harrington, L Luttrell, LM TI Ectodomain shedding-dependent transactivation of epidermal growth factor receptors in response to insulin-like growth factor type I SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; EGF RECEPTOR; TYROSINE KINASE; SIGNAL-TRANSDUCTION; GLUCOSE-TRANSPORT; ACTIVATION; CELLS; PHOSPHORYLATION; ADHESION; PATHWAYS AB Diverse extracellular stimuli activate the ERK1/2 MAPK cascade by transactivating epidermal growth factor (EGF) receptors. Here, we have examined the role of EGF receptors in IGF-I-stimulated ERK1/2 activation in several cultured cell lines. In human embryonic kidney 293 cells, IGF-I triggered proteolysis of heparin binding (HB)-EGF, increased tyrosine autophosphorylation of EGF receptors, stimulated EGF receptor inhibitor (AG1478)-sensitive ERK1/2 phosphorylation, and promoted EGF receptor endocytosis. In a mixed culture system that employed IGF-I receptor null murine embryo fibroblasts (MEFs) (R- cells) to detect paracrine signals produced by MEFs expressing the human IGF-I receptor (R+ cells), stimulation of R+ cells provoked rapid activation of green fluorescent protein-tagged ERK2 in cocultured R- cells. The R- cell response was abolished by either the broad-spectrum matrix metalloprotease inhibitor batimastat or by AG1478, indicating that it resulted from the proteolytic generation of an EGF receptor ligand from adjacent R+ cells. These data suggest that the paracrine production of EGF receptor ligands leading to EGF receptor transactivation is a general property of IGF-I receptor signaling. In contrast, the contribution of transactivated EGF receptors to IGF-I-stimulated downstream events, such as ERK1/2 activation, varies in a cell type-dependent manner. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,816 Clin Sci Bldg,POB 250624, Charleston, SC 29425 USA. EM luttrell@musc.edu FU NIDDK NIH HHS [DK58283] NR 53 TC 38 Z9 39 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 2004 VL 18 IS 11 BP 2727 EP 2739 DI 10.1210/me.2004-0174 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865VP UT WOS:000224732600010 PM 15272055 ER PT J AU Loeffler, JS AF Loeffler, Jay S. TI Can combined whole brain radiation therapy and radiosurgery improve the treatment of single brain metastases? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE brain metastases; Karnofsky Performance Status; stereotactic radiosurgery; whole brain radiation therapy C1 Harvard Univ, Sch Med, Boston, MA USA. RP Loeffler, JS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM jloeffler@partners.org NR 6 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2004 VL 1 IS 1 BP 12 EP 13 DI 10.1038/ncponc0008 PG 2 WC Oncology SC Oncology GA V43JJ UT WOS:000202931100004 PM 16264789 ER PT J AU Gerull, B Heuser, A Wichter, T Paul, M Basson, CT McDermott, DA Lerman, BB Markowitz, SM Ellinor, PT MacRae, CA Peters, S Grossmann, KS Michely, B Sasse-Klaassen, S Birchmeier, W Dietz, R Breithardt, G Schulze-Bahr, E Thierfelder, L AF Gerull, B Heuser, A Wichter, T Paul, M Basson, CT McDermott, DA Lerman, BB Markowitz, SM Ellinor, PT MacRae, CA Peters, S Grossmann, KS Michely, B Sasse-Klaassen, S Birchmeier, W Dietz, R Breithardt, G Schulze-Bahr, E Thierfelder, L TI Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy SO NATURE GENETICS LA English DT Article ID DYSPLASIA; CADHERINS; PLAQUE AB Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations. C1 Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. Humboldt Univ, Dept Clin & Mol Cardiol, Franz Volhard Clin, HELIOS Clin GmbH,Charite, D-13125 Berlin, Germany. Univ Hosp Munster, Dept Cardiol & Angiol, D-48149 Munster, Germany. Univ Munster, Inst Arteriosclerosis Res, D-48149 Munster, Germany. Cornell Univ, Greenberg Cardiol Div, Dept Med, Weill Med Coll, New York, NY 10021 USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Klinikum Quedlinburg, Dept Cardiol, D-06484 Quedlinburg, Germany. RP Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. EM lthier@mdc-berlin.de OI Heuser, Arnd/0000-0002-3334-960X FU NHLBI NIH HHS [R01 HL075431] NR 15 TC 417 Z9 431 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2004 VL 36 IS 11 BP 1162 EP 1164 DI 10.1038/ng1461 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 867HI UT WOS:000224832800018 PM 15489853 ER PT J AU Barrett, PL Fleming, JT Gobel, V AF Barrett, PL Fleming, JT Gobel, V TI Targeted gene alteration in Caenorhabditis elegans by gene conversion SO NATURE GENETICS LA English DT Article ID SEQUENCE-TAGGED SITES; INDUCED GAP REPAIR; DROSOPHILA-MELANOGASTER; GERM-LINE; DNA TRANSFORMATION; REVERSE GENETICS; C-ELEGANS; TRANSPOSON; ELEMENT; TC1 AB Now that some genomes have been completely sequenced, the ability to direct specific mutations into genomes is particularly desirable. Here we present a method to create mutations in the Caenorhabditis elegans genome efficiently through transgene-directed, transposon-mediated gene conversion. Engineered deletions targeted into two genes show that the frequency of obtaining the desired mutation was higher using this approach than using standard transposon insertion-deletion approaches. We also targeted an engineered green fluorescent protein insertion-replacement cassette to one of these genes, thereby confirming that custom alleles of different types can be created in vitro to make the corresponding mutations in vivo. This approach should also be applicable to heterologous transposons in C elegans and other organisms, including vertebrates. C1 Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Gobel, V (reprint author), Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. NR 37 TC 19 Z9 20 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2004 VL 36 IS 11 BP 1231 EP 1237 DI 10.1038/ng1459 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 867HI UT WOS:000224832800029 PM 15502826 ER PT J AU Stock, P Akbari, O Berry, G Freeman, GJ DeKruyff, RH Umetsu, DT AF Stock, P Akbari, O Berry, G Freeman, GJ DeKruyff, RH Umetsu, DT TI Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hyper-reactivity SO NATURE IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; ALLERGEN-SPECIFIC TH1; HEAT-KILLED LISTERIA; DENDRITIC CELLS; IN-VIVO; INTERFERON-GAMMA; IMMUNE-RESPONSES; TRANSCRIPTION FACTOR; MOLECULE ICOS; DYING CELLS AB The range of regulatory T cell (T-R cell) types that control immune responses is poorly understood. We describe here a population of T-R cells that developed in vivo from naive CD4(+)CD25(-) T cells during a T helper type 1 (T(H)1)-polarized response, distinct from CD25(+) T-R cells. These antigen-specific T-R cells were induced by CD8alpha(+) DCs, produced both interleukin 10 and interferon-gamma, and potently inhibited the development of airway hyper-reactivity. These T-R cells expressed the transcription factors Foxp3 and T-bet, indicating that these T-R cells are related to T(H)1 cells. Thus, adaptive T-R cells are heterogeneous and comprise T(H)1-like T-R cells as well as previously described T(H)2-like T-R cells, which express Foxp3 and are induced during the development of respiratory tolerance by CD8alpha(-) DCs. C1 Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Umetsu, DT (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Immunol, Karp Res Bldg, Boston, MA 02115 USA. EM umetsu@stanford.edu FU NCI NIH HHS [CA84500]; NHLBI NIH HHS [HL62348, HL69507]; NIAID NIH HHS [AI39671, AI26322] NR 58 TC 230 Z9 244 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2004 VL 5 IS 11 BP 1149 EP 1156 DI 10.1038/ni1122 PG 8 WC Immunology SC Immunology GA 865HG UT WOS:000224692700012 PM 15448689 ER PT J AU Schacter, DL Dobbins, IG Schnyer, DM AF Schacter, DL Dobbins, IG Schnyer, DM TI Specificity of priming: A cognitive neuroscience perspective SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID INFERIOR PREFRONTAL CORTEX; RIGHT CEREBRAL HEMISPHERE; EVENT-RELATED FMRI; POSITRON-EMISSION-TOMOGRAPHY; WORD STEM COMPLETION; MEDIAL TEMPORAL-LOBE; IMPLICIT MEMORY; AMNESIC SUBJECTS; EXPLICIT MEMORY; GLOBAL AMNESIA AB Priming is a nonconscious form of memory that involves a change in a person's ability to identify, produce or classify an item as a result of a previous encounter with that item or a related item. One important question relates to the specificity of priming - the extent to which priming reflects the influence of abstract representations or the retention of specific features of a previous episode. Cognitive neuroscience analyses provide evidence for three types of specificity: stimulus, associative and response. We consider empirical, methodological and conceptual issues that relate to each type of specificity, and suggest a theoretical perspective to help in guiding future research. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Duke Univ, Durham, NC 27708 USA. Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02130 USA. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM dls@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 NR 106 TC 158 Z9 161 U1 10 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD NOV PY 2004 VL 5 IS 11 BP 853 EP 862 DI 10.1038/nrn1534 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 866PN UT WOS:000224785500015 PM 15496863 ER PT J AU McMillan, PJ Peskind, E Raskind, MA Leverenz, JB AF McMillan, PJ Peskind, E Raskind, MA Leverenz, JB TI Increased galanin receptor occupancy in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; galanin; GTP; slice-binding assay; receptor occupancy ID VITRO AUTORADIOGRAPHIC ANALYSIS; RAT VENTRAL HIPPOCAMPUS; CENTRAL-NERVOUS-SYSTEM; HUMAN BASAL FOREBRAIN; BINDING-SITES; MESSENGER-RNA; NUCLEUS BASALIS; NEUROENDOCRINE PEPTIDE; ACETYLCHOLINE-RELEASE; PARKINSONS-DISEASE AB Increased galanin (GAL) may be associated with the cognitive deficits characteristic of Alzheimer's disease (AD). However, both increased and decreased GAL receptor density has been reported in AD brain. Previous studies indicate pre-treatment with guanine nucleotides displaces endogenous GAL from GAL receptors (GALR), providing an indirect measurement of GALR occupancy. In addition, pre-treatment with guanine nucleotides may provide a more accurate measurement of GALR density since it would avoid the masking of GALRs by residual binding of endogenous GAL. Thus, in the present study, we examined the influence of pre-treatment with guanine nucleotides on 125I-GAL binding in multiple regions of normal and AD brain. Our results indicate that GTP pre-treatment enhances GAL binding in specific regions in normal and AD brain. In addition, our results suggest an increase in the number of GALRs occupied by endogenous GAL in the deep layers of the frontal cortex and the lateral hypothalamus of AD subjects compared to normal subjects. The regional differences in GALR density and receptor occupancy between normal and AD subjects may play a role in the cognitive disturbances associated with the disease. (C) 2004 Elsevier Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci & Neurol, Seattle, WA 98195 USA. RP Leverenz, JB (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. EM leverenz@u.washington.edu NR 45 TC 16 Z9 16 U1 0 U2 0 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 NOV-DEC PY 2004 VL 25 IS 10 BP 1309 EP 1314 DI 10.1016/j.neurobiolaging.2004.01.004 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 864UY UT WOS:000224659600007 PM 15465628 ER PT J AU Norflus, F Nanje, A Gutekunst, CA Shi, GM Cohen, J Bejarano, M Fox, J Ferrante, RJ Hersch, SM AF Norflus, F Nanje, A Gutekunst, CA Shi, GM Cohen, J Bejarano, M Fox, J Ferrante, RJ Hersch, SM TI Anti-inflammatory treatment with acetylsalicylate or rofecoxib is not neuroprotective in Huntington's disease transgenic mice SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's disease; therapeutics; anti-inflammatory; neurodegeneration; acetylsalicylate; rofecoxib; COX2 inhibition ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOUSE MODEL; CELL-DEATH; AGGREGATE FORMATION; MOTOR DEFICITS; CYCLOOXYGENASE-2; INHIBITION; EXPRESSION; CHAPERONE; CREATINE AB Inflammatory mechanisms have been implicated in the pathogenesis of Huntington's disease (HD). Possible benefits of anti-inflammatory treatments include improved folding of mutant huntingtin mediated through chaperones, reduction of destructive cellular and Immoral inflammatory pathways, and reduction of proapoptotic signaling mediated by NF-kappaB or other transcription factors. This study was performed to investigate the therapeutic potential of anti-inflammatory drugs as treatments for Huntington's disease by examining whether two compounds in widespread human use can ameliorate the phenotype of HD transgenic mouse models. We examined the effectiveness of acetylsalicylate and rofecoxib as treatments for the R6/2 and N171-82Q transgenic mouse models of Huntington's disease. Both drugs were administered from weaning. To monitor the effectiveness of the treatment, we analyzed the mice for weight loss, behavioral changes, and gross cerebral and striatal atrophy. The studies showed that neither drug benefited the animals at doses comparable to those tolerated by humans. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Massgen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Bedford VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. RP Hersch, SM (reprint author), MassGen Inst Neurodegenerat Dis, MGH E Bldg 114-2001,114 16th St, Charlestown, MA 02129 USA. EM Hersch@helix.mgh.harvard.edu FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG12992, AG13846]; NINDS NIH HHS [NS045806, NS045242, NS35255] NR 34 TC 21 Z9 21 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2004 VL 17 IS 2 BP 319 EP 325 DI 10.1016/j.nbd.2004.07.011 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 866EV UT WOS:000224757500020 PM 15474369 ER PT J AU Yiannoutsos, CT Ernst, T Chang, L Lee, PL Richards, T Marra, CM Meyerhoff, DJ Jarvik, JG Kolson, D Schifitto, G Ellis, RJ Swindells, S Simpson, DM Miller, EN Gonzalez, RG Navia, BA AF Yiannoutsos, CT Ernst, T Chang, L Lee, PL Richards, T Marra, CM Meyerhoff, DJ Jarvik, JG Kolson, D Schifitto, G Ellis, RJ Swindells, S Simpson, DM Miller, EN Gonzalez, RG Navia, BA TI Regional patterns of brain metabolites in AIDS dementia complex SO NEUROIMAGE LA English DT Article DE MRS; factor analysis; AIDS; brain metabolism; HIV dementia ID MAGNETIC-RESONANCE-SPECTROSCOPY; IMMUNODEFICIENCY-VIRUS-INFECTION; HIV-RELATED ENCEPHALOPATHY; PROTON MR SPECTROSCOPY; SEROPOSITIVE INDIVIDUALS; MICROGLIAL ACTIVATION; NEOCORTICAL DAMAGE; POSITIVE PATIENTS; FRONTAL-LOBE; ABNORMALITIES AB The relationship of the cellular changes in the HIV-infected brain to the onset and progression of AIDS dementia complex (ADC) remains uncertain. We undertook an in vivo proton magnetic resonance spectroscopy (MRS) study and used factor analysis to identify specific cellular and regional brain changes that may serve as metabolic markers of ADC. The ratio of N-acetyl aspartate (NAA), choline (Cho), and myoinositol (MI) over creatine (Cr), markers of neuronal and glial cell metabolism, were measured in the basal ganglia, centrum semiovale, and parietal cortex from 100 subjects with and without ADC. Three metabolic patterns were identified, which we termed "inflammatory" (mainly MI/Cr elevations in all three regions plus Cho/Cr increases in the centrum semiovale and parietal cortex), "basal ganglia"(mostly NAA/Cr and Cho/Cr elevations in the basal ganglia), and "neuronal" (primarily NAA/Cr reductions in the centrum serniovale and the parietal cortex). Logistic regression analysis revealed that, adjusted for age, basal ganglia and neuronal pattern scores were strongly associated with ADC but inflammatory levels were not. We conclude that by using factor analysis, we are able to combine multiple metabolites across brain regions in a biologically plausible manner and construct a predictive model of ADC adjusting for relevant factors such as age. (C) 2004 Elsevier Inc. All rights reserved. C1 Indiana Univ, Sch Med, Div Biostat, Indianapolis, IN 46202 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif San Francisco, Ctr Med, San Francisco, CA 94143 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Rochester, Rochester, NY 14627 USA. Univ Calif San Diego, San Diego Med Ctr, San Diego, CA 92103 USA. Univ Nebraska, Med Ctr, Omaha, NE 68198 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Tufts Univ, New England Med Ctr, Dept Neurol, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. RP Yiannoutsos, CT (reprint author), Indiana Univ, Sch Med, Div Biostat, 1050 Wishard Blvd,RG 4101, Indianapolis, IN 46202 USA. EM cyiannou@iupui.edu RI Ellis, Ronald/K-3543-2015 OI Ellis, Ronald/0000-0003-4931-752X FU NCRR NIH HHS [R01RR13213, RR-00071]; NIAID NIH HHS [AI-38855]; NIMH NIH HHS [R01MH64409]; NINDS NIH HHS [R01NS36524, R01NS34626, R01NS38834] NR 45 TC 54 Z9 59 U1 1 U2 2 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 NOV PY 2004 VL 23 IS 3 BP 928 EP 935 DI 10.1016/j.neuroimage.2004.07.033 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 873BP UT WOS:000225254100015 PM 15528093 ER PT J AU Scott, JA AF Scott, JA TI The lung scan and the abnormal chest X-ray: difficult diagnoses SO NUCLEAR MEDICINE COMMUNICATIONS LA English DT Article DE ventilation-perfusion imaging; pulmonary embolism; artificial neural networks ID ARTIFICIAL NEURAL-NETWORK; ACUTE PULMONARY-EMBOLISM; VENTILATION-PERFUSION SCINTIGRAPHY; CRITERIA AB Purpose The ventilation-perfusion lung scan is evolving into an alternative diagnostic test for patients who cannot tolerate contrast computed tomography studies. It is likely that this shift in patient population will result in a larger proportion of patients with abnormal chest radiographs. The purpose of this study was to determine whether a computer based scan analysis could assist clinical interpretation in this diagnostically difficult population. Methods Radionuclide ventilation-perfusion (V-P) images were obtained from 118 patients with normal chest radiographs and 144 patients with abnormal radiographs who underwent pulmonary angiography within 3 days of the radionuclide study. Artificial neural networks (ANNs) were created using only objective image-derived inputs to diagnose the presence of pulmonary embolism. The ANN predictions were compared with clinical scan interpretations and with the results of angiography. Results In both patients with normal and with abnormal chest radiographs, the ANN based method performed comparably to the clinical interpretation of record. An average of the clinical and ANN estimates of the likelihood of embolism was more accurate than was either method alone. Conclusions Computer-based V-P scan analysis performs comparably to clinical interpretation for patients with abnormal chest radiographs. The different analytical perspective of the digital method improves test performance when used in conjunction with standard clinical interpretation. This can improve the chances of reaching a diagnosis for patients who lack diagnostic alternatives to the V-P scan. Nucl Med Commun 25:1137-1141 (C) 2004 Lippincott Williams Wilkins. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Scott, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 55 Fruit St, Boston, MA 02114 USA. EM scott@helix.mgh.harvard.edu NR 11 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0143-3636 J9 NUCL MED COMMUN JI Nucl. Med. Commun. PD NOV PY 2004 VL 25 IS 11 BP 1137 EP 1141 DI 10.1097/00006231-200411000-00012 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 871PV UT WOS:000225146600012 PM 15577594 ER PT J AU Peller, AJ Westgate, MN Holmes, LB AF Peller, AJ Westgate, MN Holmes, LB TI Trends in congenital malformations, 1974-1999: Effect of prenatal diagnosis and elective termination SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Teratology-Society CY JUN 19-23, 2003 CL Philadelphia, PA SP Teratol Soc ID NEURAL-TUBE DEFECTS; BIRTH STATUS; PREVALENCE; DECISION; IMPACT; PREGNANCIES; ANOMALIES AB OBJECTIVE To examine trends in congenital malformations, elective terminations for malformations and correlates for the decision to terminate a pregnancy with a malformation. METHODS: All malformed liveborn and stillborn infants and elective terminations for malformations were identified in a large urban tertiary center and general hospital for the years 1974 1979, 1984, 1989, 1994, and 1999. Nine hundred and fifty-Four women with malformed infants, who had always planned to deliver at the hospital, were identified. Prenatal screening by ultrasonography or amniocentesis before 24 weeks of gestation, severity rating of the malformation, parity, marital status, race, level of education, insurance status, and pregnancy history were determined RESULTS: In each of these 6 years, about 2% of newborn infants had a major malformation. The rate of prenatal screening by ultrasonography and amniocentesis before 24 weeks increased from 7% in the years 1974 and 1979 to 61% in the years 1984 and 1989 to 89% in the years 1994 and 1999. Elective termination increased from less than 1% in the years 1974 and 1979 to 18% to 20% in the years 1984, 1989, 1994, and 1999. Pregnancies with fatal and severe conditions were much more likely to be terminated electively than pregnancies with moderate or mild conditions (odds ratio 53.3; 95% confidence interval 22.7-124.7). CONCLUSION: The introduction of routine prenatal screening and the subsequent increase in elective termination for malformed fetuses means that the inclusion of terminated pregnancies in malformation surveillance programs is necessary to study prevalence and risk factors in the epidemiology, of malformations. (C) 2004 by The American College of Obstetricians and Gynecologists. C1 Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. RP Peller, AJ (reprint author), Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. EM apeller@partners.org FU ODCDC CDC HHS [U50/CCU1132247-03] NR 16 TC 47 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2004 VL 104 IS 5 BP 957 EP 964 DI 10.1097/01.AOG.0000142718.53380.8f PN 1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 875JH UT WOS:000225415900012 PM 15516385 ER PT J AU Seixas, NS Kujawa, SG Norton, S Sheppard, L Neitzel, R Slee, A AF Seixas, NS Kujawa, SG Norton, S Sheppard, L Neitzel, R Slee, A TI Predictors of hearing threshold levels and distortion product otoacoustic emissions among noise exposed young adults SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SUSCEPTIBILITY; EXPOSURES; WORKERS AB Aim: To examine the relations between noise exposure and other risk factors with hearing function as measured by audiometric thresholds and distortion product otoacoustic emissions. Methods: A total of 456 subjects were studied (393 apprentices in construction trades and 63 graduate students). Hearing and peripheral auditory function were quantified using standard, automated threshold audiometry, tympanometry, and distortion product otoacoustic emissions (DPOAEs). The analysis addressed relations of noise exposure history and other risk factors with hearing threshold levels (HTLs) and DPOAEs at the baseline test for the cohort. Results: The cohort had a mean age of 27 (7) years. The construction apprentices reported more noise exposure than students in both their occupational and non-occupational exposure histories. A strong effect of age and years of work in construction was observed at 4, 6, and 8 kHz for both HTLs and DPOAEs. Each year of construction work reported prior to baseline was associated with a 0.7 dB increase in HTL or 0.2 dB decrease DPOAE amplitude. Overall, there was a very similar pattern of effects between the HTLs and DPOAEs. Conclusions: This analysis shows a relatively good correspondence between the associations of noise exposures and other risk factors with DPOAEs and the associations observed with pure-tone audiometric thresholds in a young adult working population. The results provide further evidence that DPOAEs can be used to assess damage to hearing from a variety of exposures including noise. Clarifying advantages of DPOAEs or HTLs in terms of sensitivity to early manifestations of noise insults, or their utility in predicting future loss in hearing will require longitudinal follow up. C1 Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. RP Seixas, NS (reprint author), Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. EM nseixas@u.washington.edu RI Neitzel, Richard/P-7733-2015 OI Neitzel, Richard/0000-0001-5500-2589 FU NIOSH CDC HHS [5 R01 OH03912] NR 33 TC 30 Z9 32 U1 0 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD NOV PY 2004 VL 61 IS 11 BP 899 EP 907 DI 10.1136/oem.2003.009209 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 861HX UT WOS:000224408300005 PM 15477283 ER PT J AU Hawkins, BS AF Hawkins, BS CA Submacular Surg Trials Res Grp TI Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: Ophthalmic findings - SST report no. 11 SO OPHTHALMOLOGY LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; KRYPTON LASER PHOTOCOAGULATION; PHOTODYNAMIC THERAPY; RECURRENT NEOVASCULARIZATION; CONTRAST SENSITIVITY; SUBMACULAR SURGERY; VISUAL-ACUITY; LESIONS; SECONDARY; VERTEPORFIN AB Purpose: To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). Design: Randomized clinical trial. Participants: Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for <50% of the total area occupied by the subfoveal lesion (maximum size, 9.0 disc areas [22.9 mm(2)]). Methods: Randomization was stratified by VA and by clinical center. All patients were scheduled for study examinations at 3, 6, 12, and 24 months after enrollment for assessment of study outcomes. Main Outcome Measure: A successful outcome was defined a priori to be either improvement of BCVA or VA no more than 1 line (7 letters) worse than baseline at the 24-month examination. Results: Of 454 patients enrolled, 228 study eyes were assigned to observation and 226 to surgery. The percentages of eyes that had successful outcomes were similar in the 2 arms: 44% assigned to observation and 41% assigned to surgery. Median VA losses from baseline to the 24-month examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines (10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to 20/400 at 24 months in both arms. No subgroup of patients was identified in which submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142 initially phakic eyes had cataract surgery by the 24-month examination, compared with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment occurred in 12 surgery eyes (5%) and 1 observation eye. Conclusions: Submacular surgery, as performed in this clinical trial, did not improve or preserve VA for 24 months in more eyes than observation and is not recommended for patients with similar lesions. (C) 2004 by the American Academy of Ophthalmology. C1 Wilmer Clin Trials & Biometry, SST Coordinating Ctr, Baltimore, MD 21205 USA. Emory Univ, Ctr Eye, Atlanta, GA 30322 USA. Wilmer Ophthalmol Inst, Baltimore, MD USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Illinois Retina Associates, Chicago, IL USA. Northwestern Univ, Sch Med, Chicago, IL USA. Cole Eye Inst, Cleveland, OH USA. Retina Associates Cleveland, Cleveland, OH USA. Ohio State Univ, Columbus, OH 43210 USA. Texas Retina Associates, Dallas, TX USA. Duke Univ, Ctr Eye, Durham, NC 27706 USA. Retina Associates Hawaii, Honolulu, HI USA. Mid Amer Retina Consultants, Kansas City, MO USA. SE Retina Associates, Knoxville, TN USA. Retina & Vitreous Associates Kentucky, Lexington, KY USA. Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Calif vitreoretinal Associates, Menlo Pk, CA USA. Vitreoretinal Surg, OA, Minneapolis, MN USA. McGee Eye Inst, Oklahoma City, OK USA. Retinal Consultants Arizona, Phoenix, AZ USA. Retina Vitreous Consultants, Pittsburgh, PA USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Associated Retinal Consultants, Royal Oak, MI USA. Barnes Retina Inst, St Louis, MO USA. W Coast Retina Med Grp Inc, San Francisco, CA USA. St Vincent Mercy Med Ctr, Retina Vitreous Associates, Toledo, OH USA. Wilmer Ophthalmol Inst, Retinal Vasc Ctr, Chairmans Off, Baltimore, MD USA. Wilmer Ophthalmol Inst, Wilmer Photog Reading Ctr, Baltimore, MD USA. RP Hawkins, BS (reprint author), Wilmer Clin Trials & Biometry, SST Coordinating Ctr, 550 N Broadway,9th Floor, Baltimore, MD 21205 USA. EM bhawkins@jhmi.edu FU NEI NIH HHS [EY11558, U10 EY011547, U10 EY011547-07, U10 EY011557, U10 EY011557-08, EY11557, U10 EY011558, U10 EY011558-07, U10 EY11547] NR 46 TC 98 Z9 102 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2004 VL 111 IS 11 BP 1967 EP 1980 DI 10.1016/j.ophtha.2004.07.021 PG 14 WC Ophthalmology SC Ophthalmology GA 866JZ UT WOS:000224771100002 PM 15522362 ER PT J AU Popescu, G Deflores, LP Vaughan, JC Badizadegan, K Iwai, H Dasari, RR Feld, MS AF Popescu, G Deflores, LP Vaughan, JC Badizadegan, K Iwai, H Dasari, RR Feld, MS TI Fourier phase microscopy for investigation of biological structures and dynamics SO OPTICS LETTERS LA English DT Article ID DIGITAL HOLOGRAPHY; INTERFEROMETER; MODULATOR; CONTRAST; LIGHT AB By use of the Fourier decomposition of a low-coherence optical image field into two spatial components that can be controllably shifted in phase with respect to each other, a new high-transverse-resolution quantitative-phase microscope has been developed. The technique transforms a typical optical microscope into a quantitative-phase microscope, with high accuracy and a path-length sensitivity of lambda/5500, which is stable over several hours. The results obtained on epithelial and red blood cells demonstrate the potential of this instrument for quantitative investigation of the structure and dynamics associated with biological systems without sample preparation. (C) 2004 Optical Society of America. C1 MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Popescu, G (reprint author), MIT, George R Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM gpopescu@mit.edu FU NCRR NIH HHS [P41 RR 02594] NR 12 TC 248 Z9 258 U1 7 U2 36 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 NOV 1 PY 2004 VL 29 IS 21 BP 2503 EP 2505 DI 10.1364/OL.29.002503 PG 3 WC Optics SC Optics GA 863YR UT WOS:000224600000015 PM 15584275 ER PT J AU Park, BH Pierce, MC Cense, B de Boer, JF AF Park, BH Pierce, MC Cense, B de Boer, JF TI Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components SO OPTICS LETTERS LA English DT Article ID RESOLVED MUELLER MATRIX; BIOLOGICAL TISSUE; BIREFRINGENCE; PARAMETERS; LIGHT AB We present an analysis for polarization-sensitive optical coherence tomography that facilitates the unrestricted use of fiber and fiber-optic components throughout an interferometer and yields sample birefringence, diattenuation, and relative optic axis orientation. We use a novel Jones matrix approach that compares the polarization states of light reflected from the sample surface with those reflected from within a biological sample for pairs of depth scans. The incident polarization alternated between two states that are perpendicular in a Poincare sphere representation to ensure proper detection of tissue birefringence regardless of optical fiber contributions. The method was validated by comparing the calculated diattenuation of a polarizing sheet, chicken tendon, and muscle with that obtained by independent measurement. The relative importance of diattenuation versus birefringence to angular displacement of Stokes vectors on a Poincare sphere was quantified. (C) 2004 Optical Society of America. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Park, BH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St,BAR 7, Boston, MA 02114 USA. EM hylepark@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCRR NIH HHS [R01 RR019768-01]; PHS HHS [R01 212039] NR 20 TC 103 Z9 103 U1 1 U2 10 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 NOV 1 PY 2004 VL 29 IS 21 BP 2512 EP 2514 PG 3 WC Optics SC Optics GA 863YR UT WOS:000224600000018 PM 15584278 ER PT J AU Studer, RK AF Studer, RK TI Nitric oxide decreases IGF-1 receptor function in vitro; glutathione depletion enhances this effect in vivo SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE insulin-like growth factor receptor; nitric oxide; IGF-1 resistance; arthritis ID GROWTH-FACTOR RECEPTOR; ARTICULAR CHONDROCYTES; INHIBITION; CARTILAGE; OSTEOARTHRITIS; NITROSYLATION; INFLAMMATION; EXPRESSION; APOPTOSIS; SYNTHASE AB Insulin-like growth factor-1 (IGF) helps maintain healthy articular cartilage; however, arthritic cartilage becomes less responsive to the anabolic actions of IGF. We previously showed that high concentrations of nitric oxide (NO) decrease IGF receptor tyrosine phosphorylation and response to IGF in intact chondrocytes. The current studies evaluate direct effects of NO on IGF receptor kinase (IGF-RK) in vitro. NO from Snitroso-N-acetyl-D,L-penicillamine (SNAP) or 1-hydroxy-2-oxo-3-(N-3-methyl-aminopropyl)-3-methyl-1-triazene (NOC-7) inhibits IGF-RK auto-and substrate phosphorylation in a dose and time dependent manner. There is a linear correlation between inhibition of auto- and substrate phosphorylation (r(2) = 0.98). Increasing either dithiothreitol or reduced glutathione (GSH) content of the phosphorylation buffer to protect thiol groups blocks NO inhibition of IGF-RK substrate phosphorylation. Increased S-nitrosylation of cysteines in IGF-RK after exposure to SNAP suggests that NO may react with sulfhydryl groups, form S-nitrosothiols, which may result in functional modifications. NO blockade of IGF-1 stimulated proteoglycan synthesis in intact cells is enhanced when chondrocyte glutathione is depleted. The in vitro system shows that there can be direct effects of NO on IGF-RK that modify receptor function; the intact cell studies suggest that the mechanisms identified in vitro may be important in intact chondrocyte insensitivity to IGF-1 in cells exposed to NO. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, VA Med Ctr,Ferguson Lab,VA Pittsburgh Healthcare, Pittsburgh, PA 15240 USA. RP Studer, RK (reprint author), Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, VA Med Ctr,Ferguson Lab,VA Pittsburgh Healthcare, 151-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM rstuder@pitt.edu NR 30 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD NOV PY 2004 VL 12 IS 11 BP 863 EP 869 DI 10.1016/j.joca.2004.07.005 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 871FX UT WOS:000225116300002 PM 15501401 ER PT J AU Yeoh, KH Wang, DY Gordon, BR AF Yeoh, KH Wang, DY Gordon, BR TI Safety and efficacy of radioallergosorbent test-based allergen immunotherapy in treatment of perennial allergic rhinitis and asthma SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the American-Academy-of-Otolaryngic-Allergy CY SEP 19-21, 2002 CL SAN DIEGO, CA SP Amer Acad Otolaryng Allergy ID PREVALENCE; MITE AB OBJECTIVE. This study was undertaken to demonstrate the safety and efficacy of in vitro, radioallergosorbent test (RAST)-based inhalant allergen immunotherapy. STUDY DESIGN AND SETTING: Prospective 22 year single site clinical study, with outcome evaluations of 480 perennial allergic rhinitis patients, including 96 with concomitant asthma. RESULTS. Rhinitis symptom control after 2 years of immunotherapy was excellent in 32.5% of patients, good in 45.6%, and fair in 14.2%. There was no improvement in 7.7%. For patients with asthma, 81% had good or excellent pulmonary symptom improvement, and no patient failed to improve. No severe reactions occurred, but there were 5 limited systemic reactions, or 0.008% of injections, during a 2.5-year mean immunotherapy treatment course. CONCLUSION: RAST-based immunotherapy is safe and effective for patients with perennial allergic rhinitis, with or without concomitant asthma. SIGNIFICANCE: This is the first large, multiyear study of safety and efficacy of RAST-based immunotherapy for treatment of perennial allergic rhinitis and asthma. EBM rating: C. C1 Natl Univ Singapore, Dept Otolaryngol, Singapore 117548, Singapore. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02115 USA. Cape Cod Hosp, Div Otolaryngol, Boston, MA USA. RP Gordon, BR (reprint author), Cape Cod ENT Specialist, 65 Cedar St, Hyannis, MA 02601 USA. EM doebruce@comcast.net NR 22 TC 4 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2004 VL 131 IS 5 BP 673 EP 678 DI 10.1016/j.otohns.2004.04.020 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 870HC UT WOS:000225047200021 PM 15523447 ER PT J AU Ramsey, MJ Merchant, SN McKenna, MJ AF Ramsey, MJ Merchant, SN McKenna, MJ TI Postauricular periosteal-pericranial flap for mastoid obliteration and canal wall down tympanomastoidectomy SO OTOLOGY & NEUROTOLOGY LA English DT Article DE bone pate; canal wall-down; chronic otitis media; obliteration; periosteal flap; tympanomastoidectomy ID TYMPANOPLASTY STAPES COLUMELLA; MIDDLE-EAR MECHANICS; CHRONIC OTITIS-MEDIA; SURGERY AB Objective: To describe an effective technique for mastoid cavity obliteration in canal wall down tvinpanomastoidectomy for chronic otitis media and review its efficacy in producing a dry, low-maintenance, small mastoid cavity. Design: Retrospective clinical study of a consecutive series of procedures from 1995 to 2000. Setting: Tertiary referral center and institutional academic practice in otology and neurotology. Patients: Sixty consecutive procedures for active chronic otitis media with a minimum follow-up of 12 months (mean, 31 mo; range, 12-80 mo). Intervention: All patients had canal wall down mastoidectomy with simultaneous tympanoplasty including split-thickness skin grafting. An inferiorly pedicled, periosteal-pericranial flap was used in conjunction with autologous bone pate to obliterate the mastoid cavity. The additional length provided by the pericranial extension of the flap permitted it to reach superior to the lateral canal and into the sinodural angle, with improved coverage of bone pate and better reduction of cavity size. Outcome Measures: The primary outcome measure was control of suppuration and creation of a dry, low-maintenance mastoid cavity, which was assessed using a previously developed serniquantitative scale. This scale includes a temporal dimension to assess control of infection. Secondary outcome measures included postoperative complications (i.e., hematoma, infection, flap necrosis, and meatal stenosis) and incidence of recurrent or residual cholesteatoma. Results: Forty-nine ears (82%) maintained a small, dry, healthy mastoid cavity. Five ears (8%) had intermittent otorrhea easily controlled by topical treatment. Six ears (10%) had suboptimal control of otorrhea, of which four had meatal stenosis. There were no residual or recurrent cholesteatomas. Outcomes remained stable over progressively longer follow-up, up to 80 months. Conclusion: Obliteration of a canal wall down mastoid cavity by a postauricular periosteal-pericranial flap with autologous bone pate is a reliable and effective technique that results in a dry, trouble-free mastoid cavity in 90% of patients with active chronic otitis media. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 29 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD NOV PY 2004 VL 25 IS 6 BP 873 EP 878 DI 10.1097/00129492-200411000-00004 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 870HR UT WOS:000225048700004 PM 15547414 ER PT J AU Rauch, SD Silveira, MB Zhou, GW Kujawa, JG Wall, C Guinan, TJ Herrmann, BS AF Rauch, SD Silveira, MB Zhou, GW Kujawa, JG Wall, C Guinan, TJ Herrmann, BS TI Vestibular evoked myogenic potentials versus vestibular test battery in patients with Meniere's disease SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Meniere's disease; caloric test; vestibular function testing; vestibular evoked myogenic potential AB Objective: The present study was undertaken to assess the sensitivity of vestibular evoked myogenic potentials testing to side-of-disease in Meniere's disease patients and to test the hypothesis that information supplied by vestibular evoked myogenic potentials is complementary to that provided by a conventional vestibular test battery. Study Design: Prospective cohort study. Setting: Large specialty hospital, department of otolaryngology. Subjects: Twenty consenting adults (9 men and 11 women) with unilateral Meniere's disease by American Academy of Otolaryngology-Head and Neck Surgery diagnostic criteria. Interventions: All subjects underwent bilateral vestibular evoked myogenic potentials testing using ipsilateral broadband click and short-toneburst stimuli at 250. 500, and 1,000 Hz. All subjects also underwent electronystagmography and sinusoidal vertical axis rotation testing. Main Outcome Measures: Accuracy of side-of-disease assignment by vestibular evoked myogenic potentials, caloric asymmetry, and multivariate analysis. Results: Side-of-disease assignment was most accurate using caloric asymmetry with a 5% interaural difference criterion, achieving 85% correct assignment. The next best method was vestibular evoked myogenic potentials using 250-Hz toneburst stimuli, achieving 80% correct assignment. The least accurate method was caloric asymmetry using a traditional 30% interaural difference limen, achieving 55% correct assignment. Comparison of 5% interaural difference criterion and vestibular evoked myogenic potentials using 250-Hz toneburst stimuli showed discordant results, but in no case did both 5% interaural difference criterion and vestibular evoked myogenic potentials using 250-Hz toneburst stimuli make an incorrect assignment. Conclusion: Vestibular evoked myogenic potentials threshold was shown to be highly sensitive to side-of-disease in unilateral Meniere's disease. We observed instances of discordance in side-of-disease assignment by caloric asymmetry and vestibular evoked myogenic potential methods but no case in which both methods were incorrect. This supports the hypothesis that vestibular evoked myogenic potentials supplies information complementary to that provided by other components of the vestibular test battery. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Boston Univ, Med Ctr, Dept Otorhinolaryngol, Boston, MA USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM sdr@epl.meei.harverd.edu FU NIDCD NIH HHS [R01-DC04425] NR 8 TC 26 Z9 28 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD NOV PY 2004 VL 25 IS 6 BP 981 EP 986 DI 10.1097/00129492-200411000-00020 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 870HR UT WOS:000225048700020 PM 15547430 ER PT J AU Kaphingst, KA Rudd, RE Dejong, W Daltroy, LH AF Kaphingst, KA Rudd, RE Dejong, W Daltroy, LH TI Literacy demands of product information intended to supplement television direct-to-consumer prescription drug advertisements SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE literacy; readability; suitability; direct-to-consumer advertising; United States Food and Drug Administration ID READABILITY FORMULAS; PROMOTION AB The US Food and Drug Administration (FDA) allows television direct-to-consumer (DTC) prescription drug advertisements that do not fully disclose drug risks if the ads include "adequate provision" for dissemination of the drug's approved labeling. This requirement can be met in part by referring consumers to multiple text sources of product labeling. This study was designed to assess the materials to which consumers were referred in 23 DTC television advertisements. SMOG assessments showed that the average reading grade levels were in the high school range for the main body sections of the materials and college-level range for the brief summary sections. The Suitability Assessment of Materials (SAM) instrument identified specific difficulties with the materials, including content, graphics, layout, and typography features. Stronger plain language requirements are recommended. Health care providers should be aware that patients who ask about an advertised drug might not have the full information required to make an informed decision. (C) 2003 Published by Elsevier Ireland Ltd. C1 Harvard Univ, Sch Med, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02118 USA. Brigham & Womens Hosp, RBB Arthritis Res Ctr, Boston, MA 02115 USA. RP Kaphingst, KA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kimberly-kaphingst@dfci.harvard.edu OI DeJong, William/0000-0003-4964-0466 FU NIAMS NIH HHS [P60AR47782] NR 30 TC 25 Z9 25 U1 2 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD NOV PY 2004 VL 55 IS 2 BP 293 EP 300 DI 10.1016/j.pec.2003.11.003 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 874VR UT WOS:000225378900019 PM 15530767 ER PT J AU Chiral, M Grongnet, JF Plumier, JC David, JC AF Chiral, M Grongnet, JF Plumier, JC David, JC TI Effects of hypoxia on stress proteins in the piglet brain at birth SO PEDIATRIC RESEARCH LA English DT Article ID NITRIC-OXIDE SYNTHASE; HEAT-SHOCK PROTEINS; INDUCIBLE FACTOR-I; RAT-BRAIN; FOCAL ISCHEMIA; GLUTAMATE TRANSPORTERS; CEREBRAL-CORTEX; GENE-EXPRESSION; CELL-DEATH; INJURY AB Newborn piglets were submitted to normobaric hypoxia (5% O-2, 95% N-2) for either 1 or 4 h. The effects of hypoxia on the neonatal brain were characterized through a time-course analysis of levels of various proteins such as heat shock proteins (HSP27, 70, and 90), hypoxia inducible factor-1alpha (HIF-1alpha), neuronal nitric oxide synthase (nNOS), hemeoxygenase-2 (HO-2), and caspase-3. The expression of these proteins was determined at different stages of recovery up to 72 h in cerebellum, cortex, and hippocampus by Western blot analysis in hypoxic maintained animals that were made hypoxic at either 20 or 37degreesC. In all regions of the brain, HIF-1alpha and HSP27 expression were strongly increased until 22 h of recovery. No significant changes were observed for HSP70, HSP90, and HO-2. A small elevation of expression of nNOS was observed at early stages in the cerebellum and the cortex with no change in the hippocampus. Expression of caspase 3 was strongly increased in the cortex 24 and 48 h after hypoxia but unchanged in the hippocampus. These results are presented in terms of the porcine model of nonischemic hypoxia and its delayed neuronal effects on the cerebral outcome. Because of their recently established biochemical and functional interactions, the expression of the main HSPs, HIF-1alpha, OS, and caspase-3 after hypoxia are delineated. C1 Agrocampus, F-35042 Rennes, France. Univ Liege, Dept Sci Vie, Liege, Belgium. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP David, JC (reprint author), Agrocampus, 65 Rue St Brieuc,CS 84215, F-35042 Rennes, France. EM David@roazhon.inra.fr NR 63 TC 13 Z9 13 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2004 VL 56 IS 5 BP 775 EP 782 DI 10.1203/01.PDR.0000142732.09325.61 PG 8 WC Pediatrics SC Pediatrics GA 864WD UT WOS:000224662800018 PM 15371567 ER PT J AU Kaufmann, DE Lichterfeld, M Altfeld, M Addo, MM Johnston, MN Lee, PK Wagner, BS Kalife, ET Strick, D Rosenberg, ES Walker, BD AF Kaufmann, DE Lichterfeld, M Altfeld, M Addo, MM Johnston, MN Lee, PK Wagner, BS Kalife, ET Strick, D Rosenberg, ES Walker, BD TI Limited durability of viral control following treated acute HIV infection SO PLOS MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; STRUCTURED TREATMENT INTERRUPTIONS; SUCCESSFUL ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; TYPE-1 INFECTION; PROLONGED DISCONTINUATION; HIV-1-INFECTED SUBJECTS; PROSPECTIVE TRIAL; AUTOLOGOUS VIRUS AB Early treatment of acute HIV infection with highly active antiretroviral therapy, followed by supervised treatment interruption (STI), has been associated with at least transient control of viremia. However, the durability of such control remains unclear. Here we present longitudinal follow-up of a single-arm, open-label study assessing the impact of STI in the setting of acute HIV-1 infection. Methods and Findings Fourteen patients were treated during acute HIV-1 infection and subsequently subjected to an STI protocol that required retreatment if viral load exceeded 50,000 RNA copies/ml plasma or remained above 5,000 copies/ml for more than three consecutive weeks. Eleven of 14 (79%) patients were able to achieve viral loads of less than 5,000 RNA copies/ml for at least 90 d following one, two, or three interruptions of treatment. However, a gradual increase in viremia and decline in CD4+ T cell counts was observed in most individuals. By an intention-to-treat analysis, eight (57%), six (43%), and three (21%) of 14 patients achieved a maximal period of control of 180, 360, and 720 d, respectively, despite augmentation of HIV-specific CD4+ and CD8+ T cell responses. The magnitude of HIV-1-specific cellular immune responses before treatment interruption did not predict duration of viremia control. The small sample size and lack of concurrent untreated controls preclude assessment of possible clinical benefit despite failure to control viremia by study criteria. Conclusions These data indicate that despite initial control of viremia, durable viral control to less than 5,000 RNA copies/ml plasma in patients following treated acute HIV-1 infection occurs infrequently. Determination of whether early treatment leads to overall clinical benefit will require a larger and randomized clinical trial. These data may be relevant to current efforts to develop an HIV-1 vaccine designed to retard disease progression rather than prevent infection since they indicate that durable maintenance of low-level viremia may be difficult to achieve. C1 Harvard Univ, Sch Med, Partners AIDS Res Ctr,Infect Dis Unit, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Div Aids, Boston, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp, Boston, MA USA. RP Walker, BD (reprint author), Harvard Univ, Sch Med, Partners AIDS Res Ctr,Infect Dis Unit, Massachusetts Gen Hosp, Boston, MA USA. EM bwalker@partners.org FU NCRR NIH HHS [5-M01-RR-00052, M01 RR000052]; NIAID NIH HHS [U01 AI035043, R01 AI 29568, R01 AI 44656, R01 AI044656, R01 AI050429, U01 AI035039, U01 AI035040, U01 AI035041, U01 AI035042, U01 AI037613, U01 AI037984, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, UO1-AI-35042, UO1-AI-35043, UO1-AI-37613, UO1-AI-37984] NR 64 TC 122 Z9 124 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD NOV PY 2004 VL 1 IS 2 BP 137 EP 148 AR e36 DI 10.1371/journal.pmed.0010036 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 902TG UT WOS:000227378800014 PM 15526059 ER PT J AU Scirica, BM Morrow, DA AF Scirica, BM Morrow, DA TI Troponins in acute coronary syndromes SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID ELEVATION MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; C-REACTIVE PROTEIN; REFRACTORY UNSTABLE ANGINA; RAPID BEDSIDE ASSAY; RISK STRATIFICATION; PROGNOSTIC VALUE; NATRIURETIC-PEPTIDE; ARTERY-DISEASE; T LEVELS C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 69 TC 33 Z9 39 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD NOV-DEC PY 2004 VL 47 IS 3 BP 177 EP 188 DI 10.1016/j.pcad.2004.07.004 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 886ZJ UT WOS:000226271500002 PM 15736583 ER PT J AU Ahmed, M Zein, G Khawaja, F Foster, CS AF Ahmed, M Zein, G Khawaja, F Foster, CS TI Ocular cicatricial pemphigoid: pathogenesis, diagnosis and treatment SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article ID INTRAVENOUS IMMUNOGLOBULIN THERAPY; CORNEAL SURFACE RECONSTRUCTION; STEVENS-JOHNSON-SYNDROME; HUMAN AMNIOTIC MEMBRANE; IMMUNOSUPPRESSIVE THERAPY; LIMBAL TRANSPLANTATION; SYSTEMIC CHEMOTHERAPY; BASEMENT-MEMBRANE; SKIN DISEASES; MITOMYCIN-C AB Understanding of ocular cicatricial pemphigoid (OCP) has changed dramatically over the last three decades. Progress in basic science research in mucous membrane pemphigoid has been instrumental in outlining the key immune processes that participate in the autoimmune response. Immunomodulatory therapy has provided an avenue for preserving vision and preventing potentially fatal consequences of systemic pemphigoid. In this chapter we focus attention on the immunologic basis for disease and treatment strategies. We propose an algorithmic approach to diagnosis and management of OCP. (C) 2004 Published by Elsevier Ltd. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Ahmadi Hosp, Kuwait, Kuwait. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org NR 94 TC 40 Z9 42 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD NOV PY 2004 VL 23 IS 6 BP 579 EP 592 DI 10.1016/j.preteyeres.2004.05.005 PG 14 WC Ophthalmology SC Ophthalmology GA 864XR UT WOS:000224666900001 PM 15388075 ER PT J AU McDermott, SP AF McDermott, SP TI Treating anxiety disorders using cognitive therapy techniques SO PSYCHIATRIC ANNALS LA English DT Article ID PANIC DISORDER; DEPRESSION; INVENTORY; CARE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cognit Therapy & Res Program,Cognit Therapy Inst, Boston, MA 02114 USA. RP McDermott, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cognit Therapy & Res Program,Cognit Therapy Inst, WACC 812,Fruit St, Boston, MA 02114 USA. NR 18 TC 0 Z9 0 U1 3 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2004 VL 34 IS 11 BP 858 EP 872 PG 15 WC Psychiatry SC Psychiatry GA 871GR UT WOS:000225118400010 ER PT J AU Rosenfeld, B Roth, AJ Gandhi, S Penson, D AF Rosenfeld, B Roth, AJ Gandhi, S Penson, D TI Differences in health-related quality of life of prostate cancer patients based on stage of cancer SO PSYCHO-ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; FUNCTIONAL ASSESSMENT; HOSPITAL ANXIETY; DEPRESSION SCALE; MEN; VALIDATION; RADIATION; OUTCOMES; BOTHER AB Background: Understanding medical factors that influence quality of life for men with prostate cancer is an important goal. This study analysed the relationship between cancer stage and quality of life, including measures of physical and psychological well-being. Method: A secondary analysis of data from 341 ambulatory men with prostate cancer. The Functional Assessment of Cancer Therapy (FACT)-Prostate version, Urinary Function Subscale of UCLA Prostate Cancer Index, and Hospital Anxiety and Depression Scale (HADS), were administered during their clinic visit. Stage of disease and treatment history was obtained from clinic records. Patients were categorized into localised (T1-T2, N0, M0, n = 186), locally advanced (T3-T4, N0, M0, n = 92), and metastatic (T3-T4, N1-3 or Ma-c, n = 63) disease. Differences in quality of life based on stage were examined using multivariate analyses controlling for age, treatment type, time since diagnosis, co-morbidities, and urinary function. Results: Stage of prostate cancer was significantly associated with most FACT scales (Physical, Functioning, Social) and summary scores (Treatment Outcomes Index, FACT total score). However, no significant associations were observed between stage of cancer and psychological symptoms of depression or anxiety. This association remained significant even after controlling for the influence of illness co-morbidity, urinary functioning, time since diagnosis, age, and type of treatment. Conclusions: Higher cancer stage appears to be associated with poorer quality of life in prostate cancer and this association does not appear to be simply a function of the symptoms and disability that accompany advanced disease. These results have implications for understanding the impact of progression of prostate cancer on patients' health-related quality of life. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY USA. AstraZeneca, Hlth Econ & Outcomes Res, Wilmington, DE USA. VA Puget Sound HCS, Urol Sect, Seattle, WA USA. Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. RP Rosenfeld, B (reprint author), Fordham Univ, Dept Psychol, 441 E Fordham Rd, Bronx, NY 10458 USA. EM Rosenfeld@fordham.edu NR 24 TC 42 Z9 42 U1 0 U2 5 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 NOV PY 2004 VL 13 IS 11 BP 800 EP 807 DI 10.1002/pon.797 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 874JZ UT WOS:000225348000005 PM 15386638 ER PT J AU Ciesielski, KT Harris, RJ Cofer, LF AF Ciesielski, KT Harris, RJ Cofer, LF TI Posterior brain ERP patterns related to the go/no-go task in children SO PSYCHOPHYSIOLOGY LA English DT Review DE neural basis of inhibitory control; event-related brain potentials; no-go related N2; brain development; task strategies ID FUNCTIONAL MAGNETIC-RESONANCE; EVENT-RELATED POTENTIALS; POSITRON EMISSION TOMOGRAPHY; SPATIAL WORKING-MEMORY; AGE-RELATED-CHANGES; PREFRONTAL CORTEX; RESPONSE-INHIBITION; SELECTIVE-ATTENTION; HAND-MOVEMENT; FRONTAL-LOBE AB Event-related potentials (ERPs) and performance correlates of inhibition of responses to no-go stimuli were investigated in 6-12-year-old children and young adults. The percent of correct responses to go stimuli was high and similar in both groups-, the percent of false alarm errors to no-go was significantly higher in children. Effective inhibition of responses to no-go stimuli was elucidated by a negative component of ERPs, the frontal-central N2, with peak latency 230-430 ms after stimulus onset. In adults, N2 was larger to no-go than to go stimuli, regardless of stimulus frequency. This effect was more prominent in tasks with high (25% no-gos and 75% gos), than with low (75% no-gos and 25% gos) inhibitory demand. In children, the parietal N2 was generally larger to rare than to frequent stimuli, and it was more specifically related to inhibition. The analysis of the relationship of no-go N2 to the inhibitory content of stimuli, probability of stimuli, and the contextual task difficulty suggests that child/adult differences in behavioral responses and ERPs may be related to both the immaturity of the fronto-parietal cortical-cortical network and to different task strategies. C1 Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. RP Ciesielski, KT (reprint author), Univ New Mexico, Dept Psychol, Logan Hall, Albuquerque, NM 87131 USA. EM ciesiels@unm.edu NR 130 TC 24 Z9 29 U1 2 U2 11 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2004 VL 41 IS 6 BP 882 EP 892 DI 10.1111/j.1469-8986.2004.00250.x PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 876NF UT WOS:000225503100008 PM 15563341 ER PT J AU Glass, TA Berkman, LF Hiltunen, EF Furie, K Glymour, MM Fay, ME Ware, J AF Glass, TA Berkman, LF Hiltunen, EF Furie, K Glymour, MM Fay, ME Ware, J TI The Families In Recovery from Stroke Trial (FIRST): Primary study results SO PSYCHOSOMATIC MEDICINE LA English DT Article DE cerebrovascular disease; randomized clinical trial; social factors; social support; outcome study ID RANDOMIZED CONTROLLED TRIAL; LATE-LIFE FUNCTION; QUALITY-OF-LIFE; SOCIAL SUPPORT; DISABILITY INSTRUMENT; DEPRESSION SCALE; TREATMENT TOAST; VOLUNTEER BIAS; ORG 10172; INTERVENTION AB Objective: Social support and family ties are strong predictors of functional recovery after stroke;, however, development of successful psychosocial intervention programs has been difficult. This study examined whether a family-systems intervention designed to influence social support and self-efficacy affects functional outcome in older stroke patients. Methods: Two hundred ninety-one community-residing survivors of ischemic stroke or nontraumatic cerebral hemorrhage from eight acute-care hospitals and rehabilitation centers were randomized to either psychosocial intervention (PSI) or usual care (UC). PSI involved up to 16 sessions conducted in the home by a mental health worker. Functional recovery (measured by the Barthel Index [BI] at 6 months postrandomization, inability to assess functioning because of illness or death) was the primary end point. Results: Functional recovery did not differ between UC and PSI in intention-to-treat analyses. In adjusted logistic regression, the odds of being functionally independent at 6 months was 60% higher in the intervention group, but this difference was not statistically significant (p = .31). Subgroup analyses revealed that PSI may be more effective in subjects with better psychologic and cognitive functioning and who required less inpatient rehabilitation. Conclusion: This study does not provide evidence for the efficacy of psychosocial intervention to improve functional recovery in stroke. Although PSI showed greater improvement than UC, the differences were not statistically significant. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Glass, TA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM tglass@jhsph.edu OI Glass, Thomas/0000-0003-4399-612X FU NIA NIH HHS [AG00158, T32 AG000158]; NINDS NIH HHS [R01 NS32324-07, R01 NS/AG32324-01A1] NR 49 TC 33 Z9 34 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2004 VL 66 IS 6 BP 889 EP 897 DI 10.1097/01.psy.0000146326.01642.ca PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 874JY UT WOS:000225347900014 PM 15564354 ER PT J AU Saini, S AF Saini, S TI Multi-detector row CT: Principles and practice for abdominal applications SO RADIOLOGY LA English DT Article DE abdomen; computed tomography (CT), multi-detector row; computed tomography (CT), technology; radiology and radiologists, How I Do It ID MULTISLICE HELICAL CT; CONTRAST-MEDIA; LIVER; ANGIOGRAPHY; NEOPLASMS AB Abdominal imaging with multi-detector row computed tomography (CT) can be performed during short breath holds. On 16-channel multi-detector row CT scanners, the effective detector row thickness, depending on the manufacturer, is typically 1.0-1.5 mm, which results in a beam collimation of 16-24 mm. At a gantry rotation speed of 0.5 second and a pitch of 1, the table travel speed will be 32-48 mm/sec. At a smaller effective detector row thickness and a narrower beam collimation, a slightly higher pitch may be needed to obtain short-breath-hold CT scans. Typically, transverse scans are viewed at a reconstructed section thickness of 3-5 mm, with thinner sections used for CT angiography and whenever off-axial reformations are obtained. The radiologic technique should be optimized according to the transverse section thickness used for interpretation, and the contrast material administration protocol should be optimized according to the clinical problem, with the scanning triggered for enhancement of a target organ. (C) RSNA, 2004. C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Saini, S (reprint author), Harvard Univ, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM ssaini@portners.org NR 19 TC 31 Z9 34 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 NOV PY 2004 VL 233 IS 2 BP 323 EP 327 DI 10.1148/radiol.2332030994 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 864RK UT WOS:000224650400005 PM 15459326 ER PT J AU Sahani, DV Kalva, SP Farrell, J Maher, MM Saini, S Mueller, PR Lauwers, GY Fernandez, CD Warshaw, AL Simeone, JF AF Sahani, DV Kalva, SP Farrell, J Maher, MM Saini, S Mueller, PR Lauwers, GY Fernandez, CD Warshaw, AL Simeone, JF TI Autoimmune pancreatitis: Imaging features SO RADIOLOGY LA English DT Article DE magnetic resonance (MR), cholangiopancreatography; pancreas, CT; pancreas, MR; pancreas; pancreatitis ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; SJOGRENS-SYNDROME; DUCT; CHOLANGITIS; CARCINOMA; CT AB PURPOSE: To retrospectively determine imaging findings in patients with autoimmune pancreatitis. MATERIALS AND METHODS: Twenty-nine patients (25 male and four female; mean age, 56 years; range, 15-82 years) with histopathologic diagnosis of autoimmune pancreatitis were examined. Data were reviewed by two radiologists in consensus. Imaging findings for review included those from helical computed tomography (CT), 25 patients; magnetic resonance (MR) imaging with MR cholangiopancreatography (MRCP), four patients; endoscopic ultrasonography (US), 21 patients; endoscopic retrograde cholangiopancreatography (ERCP), 19 patients; and percutaneous transhepatic cholangiography, one patient. Images were analyzed for appearances of pancreas, biliary and pancreatic ducts, and other findings, such as peripancreatic inflammation, encasement of vessels, mass effect, pancreatic calcification, peripancreatic nodes, and peripancreatic fluid collection. Follow-up images were available in nine patients. Serologic markers such as serum immunoglobulin G (IgG) and antinuclear antibody levels were available in 12 patients. RESULTS: CT showed diffuse (n = 14) and focal (n = 7) enlargement of pancreas. Seven patients had minimal peripancreatic stranding, with lack of vascular encasement, calcification, or peripancreatic fluid collection. Nine patients had enlarged peripancreatic lymph nodes. MR imaging showed focal (n = 2) and diffuse (n = 2) enlargement with rimlike enhancement in one. MRCP revealed pancreatic duct strictures in two and sclerosing cholangitis-like appearance in one. Endoscopic US showed diffuse enlargement of pancreas with altered echotexture in 13 patients and focal mass in the head in six. ERCP showed stricture of distal common bile duct in 12 patients, irregular narrowing of intrahepatic ducts in six, diffuse irregular narrowing of pancreatic duct in nine, and focal stricture of proximal pancreatic duct in six. Serologic markers showed increased IgG and antinuclear antibody levels in seven of 12 patients. At follow-up, CT abnormalities and common bile duct strictures resolved after steroid therapy in three patients. CONCLUSION: Features that suggest autoimmune pancreatitis include focal or diffuse pancreatic enlargement, with minimal peripancreatic inflammation and absence of vascular encasement or calcification at CT and endoscopic US, and diffuse irregular narrowing of main pancreatic duct, with associated multiple biliary strictures at ERCP. (C) RSNA, 2004. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Endoscopy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, White Bldg 270F,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 23 TC 210 Z9 235 U1 1 U2 6 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 NOV PY 2004 VL 233 IS 2 BP 345 EP 352 DI 10.1148/radiol.2332031436 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 864RK UT WOS:000224650400008 PM 15459324 ER PT J AU Deserno, WMLLG Harisinghani, MG Taupitz, M Jager, GJ Witjes, JA Mulders, PF van de Kaa, CAH Kaufmann, D Barentsz, JO AF Deserno, WMLLG Harisinghani, MG Taupitz, M Jager, GJ Witjes, JA Mulders, PF van de Kaa, CAH Kaufmann, D Barentsz, JO TI Urinary bladder cancer: Preoperative nodal staging with ferumoxtran-10-enhanced MR imaging SO RADIOLOGY LA English DT Article DE bladder neoplasms, metastases; blader neoplasms, (MR); iron; magnetic resonance (MR), contrast media ID SUPERPARAMAGNETIC IRON-OXIDE; POSITRON-EMISSION-TOMOGRAPHY; INITIAL CLINICAL-EXPERIENCE; LYMPH-NODES; RADICAL CYSTECTOMY; PELVIC LYMPHADENECTOMY; PROSTATE-CANCER; CERVICAL-CANCER; CONTRAST AGENT; METASTASES AB PURPOSE: To prospectively evaluate ferumoxtran-10-enhanced magnetic resonance (MR) imaging for nodal staging in patients with urinary bladder cancer. MATERIALS AND METHODS: Fifty-eight patients with proved bladder cancer were enrolled. Results of MR imaging performed before and after injection of ferumoxtran-10 were compared with histopathologic results in surgically removed lymph nodes. High-spatial-resolution three-dimensional T1-weighted magnetization-prepared rapid acquisition gradient-echo (voxel size, 1.4 x 1.4 x 1.4 mm) and T2*-weighted gradient-echo (voxel size, 0.8 x 0.8 x 3.0 mm) sequences were performed before and 24 hours after injection of ferumoxtran-10 (2.6 mg iron per kilogram of body weight). On precontrast images, lymph nodes were defined as malignant by using size and shape criteria (round node, >8 mm; oval, >10 mm axial diameter). On postcontrast images, nodes were considered benign if there was homogeneous decrease in signal intensity and malignant if decrease was absent or heterogeneous. Qualitative evaluation was performed on a node-to-node basis. Sensitivity, specificity, predictive values, and accuracy were evaluated with logistic regression analysis. RESULTS: In 58 patients, 172 nodes imaged with use of ferumoxtran-10 were matched and correlated with results of node dissection. Of these, 122 were benign and 50 were malignant. With nodal size and shape criteria, accuracy, sensitivity, specificity, and positive and negative predictive values on precontrast images were 92%, 76%, 99%, 97%, and 91%, respectively; corresponding values on postcontrast images were 95%, 96%, 95%, 89%, and 98%. In the depiction of pelvic metastases, sensitivity and negative predictive value improved significantly at postcontrast compared with those at precontrast imaging, from 76% to 96% (P < .001) and from 91% to 98% (P < .01), respectively. At postcontrast imaging, metastases (4-9 mm) were prospectively found in 10 of 12 normal-sized nodes (<10 mm); these metastases were not detected on precontrast images. Postcontrast images also showed lymph nodes that were missed at pelvic node dissection in two patients. CONCLUSION: Ferumoxtran-10-enhanced MR imaging significantly improves nodal staging in patients with bladder cancer by depicting metastases even in normal-sized lymph nodes. (C) RSNA, 2004. C1 Univ Med St Radboud, Dept Radiol, NL-6500 HB Nijmegen, Netherlands. Univ Med St Radboud, Dept Pathol, NL-6500 HB Nijmegen, Netherlands. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Oncol, Boston, MA USA. Charite Hosp, Dept Radiol, Berlin, Germany. RP Deserno, WMLLG (reprint author), Univ Med St Radboud, Dept Radiol, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM w.desemo@rad.umcn.nl RI Barentsz, Jelle/D-3515-2009; Mulders, Peter/H-8076-2014; Witjes, Fred/N-9665-2013; Hulsbergen-van de Kaa, C.A./L-4399-2015 NR 32 TC 131 Z9 134 U1 0 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 NOV PY 2004 VL 233 IS 2 BP 449 EP 456 DI 10.1148/radiol.2332031111 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 864RK UT WOS:000224650400020 PM 15375228 ER PT J AU Connolly, SA Jaramillo, D Hong, JK Shapiro, F AF Connolly, SA Jaramillo, D Hong, JK Shapiro, F TI Skeletal development in fetal pig specimens: MR imaging of femur with histologic SO RADIOLOGY LA English DT Article DE animals; experimental study; femur, MR; fetus, growth and development; fetus, skeletal system ID AGE; CARTILAGE; EPIPHYSIS; PIGLETS; LENGTH; PLATE; KNEE AB PURPOSE To evaluate the magnetic resonance (MR) imaging features of the developing femur in fetal pig specimens. MATERIALS AND METHODS: MR images of 15 fetal pig femurs, which were categorized into three groups of specimens representing each third of the gestational period, were used to compare increasing femoral length (as an indication of gestational age) with epiphyseal growth in multiple dimensions by using Pearson product moment correlation. Physeal-epiphyseal demarcation, visibility of the secondary ossification center and its physis, prominence of the perichondrial structures (ie, groove of Ranvier and bone bark), metaphyseal undulation, and corticomedulary differences were evaluated qualitatively. These features were also evaluated on histologic sections. RESULTS: With femoral length measurements used as indications of gestational age, there were three, five, and seven fetal pig specimens in each gestation group. During fetal development, the cartilaginous epiphysis of the clistal femur transformed from an oval to a bicondylar structure, with most of the growth occurring sagittally (P <.001). Physeal-epiphyseal demarcation, visibility of the secondary ossification center and its physis, and metaphyseal undulation increased later in gestation. Detection of perichondrial structures, however, was greatest during the middle third of gestation and decreased thereafter. During the fetal period, the perichondrial groove of Ranvier and the bone bark were easily identifiable at MR imaging. Marrow cavitation increased with gestation. CONCLUSION: MR imaging depicts fetal pig skeletal features that can be confirmed histologically and that may prove to be useful at human prenatal skeletal imaging. (C) RSNA, 2004. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Orthopaed Surg Orthopaed Res Lab, Boston, MA 02115 USA. RP Connolly, SA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. EM susan.connolly@childrens.harvard.edu NR 21 TC 28 Z9 28 U1 1 U2 3 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 NOV PY 2004 VL 233 IS 2 BP 505 EP 514 DI 10.1148/radiol.2332030131 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 864RK UT WOS:000224650400028 PM 15375230 ER PT J AU Yu, E Dar, R Rodrigues, GB Stitt, L Videtic, GMM Truong, P Tomiak, A Ash, R Brecevic, E Inculet, R Malthaner, R Vincent, M Craig, I Kocha, W Lefcoe, M AF Yu, E Dar, R Rodrigues, GB Stitt, L Videtic, GMM Truong, P Tomiak, A Ash, R Brecevic, E Inculet, R Malthaner, R Vincent, M Craig, I Kocha, W Lefcoe, M TI Is extended volume external beam radiation therapy covering the anastomotic site beneficial in post-esophagectomy high risk patients? SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE cancer; esophagus; anastomosis; relapse; irradiation ID SQUAMOUS-CELL CARCINOMA; TRANSTHORACIC RESECTION; ESOPHAGUS; RADIOTHERAPY; RECURRENCE; SURGERY; CANCER; ADENOCARCINOMA; CHEMOTHERAPY; SURVIVAL AB Background and purpose: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients. Patients and methods: This is a retrospective study of high risk (T-3,T-4, nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment fields tailored to the pathologic findings and location of the anastomosis. CT planning was used in all patients to design spinal cord sparing beam arrangements. First relapse rate (first incidence of an event), disease specific survival and overall survival were calculated by Chi-Square, Log-Rank, and Kaplan-Meier (K-M) methods. Results: During the study period, 72 patients had underwent esophagectomy and were considered for adjuvant chemoradiation therapy. Three patients were excluded due to disease progression prior to therapy. The 69 remaining patients formed the study cohort for the present analysis. The median age of the study group was 60 years (range 35-82 years). Pathologic stage distribution (AJCC 1997 staging) was T-2,T-3 N-1 in 94% patients. 65% of the cases were adenocarcinoma and had undergone transhiatal esophagectomy (86%) with positive/close margins in 34 (49%) patients. Median follow-up was 30.5 months (range 3.4-116.3 months). Two- and 5-year actuarial overall survivals rates were 50 and 31 %. respectively. First relapse rate after adjuvant therapy was 63.7% (n = 44) and median time to relapse was 27.2 months. Anastomosis recurrence rates were 29% with small volume and 0% with extended volume RT (P = 0.041). Local and regional relapse occurred in 74.2% of patients treated with small volume RT compared to 15.4% in patients treated with extended volume RT (P < 0.001). After adjusting for resection margin status, the local control benefit of extended volume RT remained significant (P = 0.003). Treatment interruptions and late gastrointestinal toxicity were not significantly increased with the use of extended volume RT. Conclusions: A significant decrease in local and regional relapse without added late toxicity was achieved with the use of extended volume RT encompassing the anastomotic site post-operatively in high risk esophageal cancer patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 London Reg Canc Ctr, Dept Radiat Oncol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Biostat, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Surg Oncol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Pathol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Radiol, London, ON N6A 4L6, Canada. Kingston Reg Canc Ctr, Dept Med Oncol, Kingston, ON, Canada. Vancouver Isl Ctr, Dept Radiat Therapy, BC Canc Agcy, Victoria, BC, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Yu, E (reprint author), London Reg Canc Ctr, Dept Radiat Oncol, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. NR 29 TC 10 Z9 14 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD NOV PY 2004 VL 73 IS 2 BP 141 EP 148 DI 10.1016/j.radonc.2004.08.024 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 878EU UT WOS:000225630200004 PM 15542160 ER PT J AU Hughes, RB Robinson-Whelen, S Taylor, HB Swedlund, N Nosek, MA AF Hughes, RB Robinson-Whelen, S Taylor, HB Swedlund, N Nosek, MA TI Enhancing self-esteem in women with physical disabilities SO REHABILITATION PSYCHOLOGY LA English DT Article ID DEPRESSIVE SYMPTOMS; SOCIAL CONNECTEDNESS; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; CHRONIC ILLNESS; HEALTH-STATUS; OLDER ADULTS; SHORT-FORM; MEDIATOR; SUPPORT AB Objective: To determine the efficacy of a 6-week self-esteem group intervention for women with disabilities. Design: Random assignment to either center for independent living (CIL) services or CIL. services plus a self-esteem intervention, with pre- and-posttest. Participants: Women with physical disabilities (N 102, 51 per group). Setting: Five CILs-in 5 different states. Outcome measures: Self-esteem, self-efficacy, social connectedness, and depression. Results: Participants in the intervention group showed significantly greater improvement on self-esteem (effect sizes [ES] =.88 and.81),. self-efficacy (ES.60), and depression (ES =.59). Groups did not differ significantly on social, connectedness (ES =.32). Conclusion: Women with physical disabilities may benefit from a self-esteem group intervention., C1 Baylor Coll Med, Ctr Res Women Disabil, Dept Phys Med & Rehabil, Houston, TX 77046 USA. Houston Vet Affairs Med Ctr, Rehabil Res & Dev Serv, Houston, TX USA. RP Hughes, RB (reprint author), Baylor Coll Med, Ctr Res Women Disabil, Dept Phys Med & Rehabil, 3440 Richmond Ave,Suite B, Houston, TX 77046 USA. EM rhughes@bcm.tmc.edu NR 51 TC 14 Z9 16 U1 1 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD NOV PY 2004 VL 49 IS 4 BP 295 EP 302 DI 10.1037/0090-5550.49.4.295 PG 8 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 874OR UT WOS:000225360200004 ER PT J AU Choi, HK AF Choi, HK TI Preface - Outcomes research in rheumatology SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Rheumatol Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Dept Med, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2004 VL 30 IS 4 BP XI EP XII DI 10.1016/j.rdc.2004.08.003 PG 2 WC Rheumatology SC Rheumatology GA 868JP UT WOS:000224910200001 ER PT J AU Choi, HK Seeger, JD AF Choi, HK Seeger, JD TI Observational research in rheumatic disorders SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MARGINAL STRUCTURAL MODELS; GIANT-CELL ARTERITIS; NATURAL-HISTORY; GASTROINTESTINAL TOXICITY; DUPLEX ULTRASONOGRAPHY; PSORIATIC-ARTHRITIS; KNEE OSTEOARTHRITIS; UNITED-STATES; MORTALITY AB Observational research plays an important role in science. Much of human knowledge, including health knowledge, comes from observations, not experiments. Within medicine, observational studies cover a wide scope that ranges from case reports and case series, to descriptive studies, to analytic observational studies for causal questions. These studies often are complementary; each provides a piece of information that can be synthesized into a description and analysis of a health problem in a way that tests hypotheses and advances medical science and has the potential to lead to interventions that can improve health and quality of life. This article reviews the scope of observational studies, principles of causal inference in observational studies, and various types of observational studies with a focus of their applications in rheumatic disorders. C1 Massachusetts Gen Hosp, Dept Med, Rheumatol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Ingenix Epidemiol, Newton, MA USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Dept Med, Rheumatol Unit, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org NR 50 TC 2 Z9 2 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2004 VL 30 IS 4 BP 685 EP + DI 10.1016/j.rdc.2004.07.004 PG 16 WC Rheumatology SC Rheumatology GA 868JP UT WOS:000224910200002 PM 15488688 ER PT J AU Choi, HK Curhan, G AF Choi, HK Curhan, G TI Prospective cohorts and rheumatic disease research SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FOOD FREQUENCY QUESTIONNAIRE; BONE-MINERAL DENSITY; IOWA WOMENS HEALTH; RADIOGRAPHIC KNEE OSTEOARTHRITIS; POSTMENOPAUSAL ESTROGEN THERAPY; CONNECTIVE-TISSUE DISEASES; SILICONE BREAST IMPLANTS; BODY-MASS INDEX AB Many large, prospective cohort studies originally were established to study common major medical conditions, including heart disease and cancer. These cohorts have provided important health information for decades (eg, the link between smoking and lung cancer). More recently, some of these cohorts also have provided excellent vehicles for addressing important study questions of common rheumatic disorders. An increasing number of important observational studies has been published or are being conducted based on these cohorts; the role of these data sources in rheumatic disease research are likely to grow in the future. This article intends to put these prospective cohort studies together to enhance the understanding of their usefulness in studying rheumatic disorders among investigators and readers. We summarize those cohorts with their published examples of rheumatic disease research. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Rheumatol Unit,Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Renal Div,Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Choi, HK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Rheumatol Unit,Dept Med, Bulfinch 135,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org NR 72 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2004 VL 30 IS 4 BP 799 EP + DI 10.1016/j.rdc.2004.07.008 PG 20 WC Rheumatology SC Rheumatology GA 868JP UT WOS:000224910200008 PM 15488694 ER PT J AU Mohr, PE Cheng, CM Claxton, K Conley, RR Feldman, JJ Hargreaves, WA Lehman, AF Lenert, LA Mahmoud, R Marder, SR Neumann, PJ AF Mohr, PE Cheng, CM Claxton, K Conley, RR Feldman, JJ Hargreaves, WA Lehman, AF Lenert, LA Mahmoud, R Marder, SR Neumann, PJ TI The heterogeneity of schizophrenia in disease states SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; outcome assessment; prognosis; treatment costs ID POSITIVE-NEGATIVE DICHOTOMY; HEALTH STATES; SYMPTOMS; MODEL; RISPERIDONE; PREFERENCES; DEPRESSION; OUTCOMES; SCALE AB Previous presentation: Some of the contents of this paper have been previously presented at the 16th Annual Meeting of the International Society for Technology Assessment in Health Care June 20, 2000 in the Hague, Netherlands and at the 21st Annual Meeting of the Society for Medical Decision Making as a poster on October 3, 1999 in Reno, NV. Background: Studies of schizophrenia treatment often oversimplify the array of health outcomes among patients. Our objective was to derive a set of disease states for schizophrenia using the Positive and Negative Symptom Assessment Scale (PANSS) that captured the heterogeneity of symptom responses. Methods: Using data from a 1-year clinical trial that collected PANSS scores and costs on schizophrenic patients (N = 663), we conducted a k-means cluster analyses on PANSS scores for items in five factor domains. Results of the cluster analysis were compared with a conceptual framework of disease states developed by an expert panel. Final disease states were defined by combining our conceptual framework with the empirical results. We tested its utility by examining the influence of disease state on treatment costs and prognosis. Results: Analyses led to an eight-state framework with varying levels of positive, negative, and cognitive impairment. The extent of hostile/aggressive symptoms and mood disorders correlated with severity of disease states. Direct treatment costs for schizophrenia vary significantly across disease states (F = 27.47, df = 7, p<0.0001), and disease state at baseline was among the most important predictors of treatment outcomes. Conclusion: The disease states we describe offer a useful paradigm for understanding the links between symptom profiles and outcomes. (C) 2003 Elsevier B.V. All rights reserved. C1 Ctr Medicare, ORDI, REG, DBR, Baltimore, MD 21244 USA. PacifiCare, Med Informat, Cypress, CA 90630 USA. Univ York, Dept Econ, York YO10 5DD, N Yorkshire, England. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Univ Calif San Diego, Sch Med, Hlth Serv Res & Dev, San Diego, CA 92103 USA. Janssen Pharmaceut Prod LP, Med Dev, Titusville, NJ USA. VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Ctr Medicaid Serv, ORDI, REG, DBR, Baltimore, MD 21244 USA. RP Mohr, PE (reprint author), Ctr Medicare, ORDI, REG, DBR, Mail Stop C3-19-07 7500,Secur Blvd, Baltimore, MD 21244 USA. EM pmohr@cms.hhs.gov NR 29 TC 27 Z9 32 U1 1 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 NOV 1 PY 2004 VL 71 IS 1 BP 83 EP 95 DI 10.1016/j.schres.2003.11.008 PG 13 WC Psychiatry SC Psychiatry GA 859BW UT WOS:000224238100010 PM 15374576 ER PT J AU Carrion-Baralt, JR Fuentes-Rivera, Z Schmeidler, J Silverman, JM AF Carrion-Baralt, JR Fuentes-Rivera, Z Schmeidler, J Silverman, JM TI A case-control study of the seasonality effects on schizophrenic births on a tropical island SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; seasonality; etiology; risk factors; Puerto Rico ID BIPOLAR DISORDER AB A substantial body of evidence from dozens of studies in many different countries suggests an excess number of individuals with schizophrenia are born in winter months. The presence of a seasonality effect in regions with year-round warm climate, however, has rarely been examined. The major purpose of this project was to better understand if the seasonality effect on schizophrenic births that has been reported in other, mostly cold regions of the Northern Hemisphere, also can be detected in a warm, tropical climate. We set out to study birth months as risk factors, quantifying the risk for being born with schizophrenia for every month of the winter season in terms of incidence rate ratios (IRRs) in the central region of Puerto Rico. We also analyzed climatic data in order to determine if there was any correlation between the rate of schizophrenic births (n = 7 10) to births in the general population (n = 101,248) and average rainfall and temperature for every month of the year in our period of study (January 1932-December 1967). Our results suggest that the risk of developing schizophrenia is 36.5% higher for people born in February than for people born in the other months of the year (95% C.I. = 6.6-74.8%). We also found correlations between the rate of schizophrenic to control births for any given month, and rainfall 4 months earlier (r = 0.66, p = 0.010), and temperature 5 months earlier (r = 0.64, p = 0.013) that remained significant after correcting for multiple comparisons. (C) 2003 Elsevier B.V. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Mental Hlth Ctr, Cayey, PR 00736 USA. Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Silverman, JM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM jeremy.silverman@mssm.edu NR 14 TC 3 Z9 5 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 1 PY 2004 VL 71 IS 1 BP 145 EP 153 DI 10.1016/j.schres.2003.11.004 PG 9 WC Psychiatry SC Psychiatry GA 859BW UT WOS:000224238100016 PM 15374582 ER PT J AU Kaplan, LM AF Kaplan, LM TI Obesity and the liver SO SEMINARS IN LIVER DISEASE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD NOV PY 2004 VL 24 IS 4 BP 333 EP 334 DI 10.1055/s-2004-837862 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882WR UT WOS:000225971600001 ER PT J AU Hoppin, AG AF Hoppin, AG TI Obesity and the liver: Developmental perspectives SO SEMINARS IN LIVER DISEASE LA English DT Review DE development; obesity; fatty liver steatohepatitis ID TOTAL PARENTERAL-NUTRITION; NONALCOHOLIC FATTY LIVER; URSODEOXYCHOLIC ACID; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE; HEPATIC STEATOSIS; FOLLOW-UP; CHILDREN; STEATOHEPATITIS; ADOLESCENTS AB Obesity now affects 15% of children and adolescents in the United States. Many of the complications of obesity are seen in children, including fatty liver disease, gallstones, hyperlipidemia, insulin resistance, and type 2 diabetes. Infants and children also have unique susceptibilities to and manifestations of liver disease caused by total parenteral nutrition. In addition to genetic and environmental influences on obesity, there is increasing evidence supporting the idea of "metabolic programming," in which environmental influences at critical periods during development have permanent effects on an individual's predisposition to obesity and metabolic disease. Understanding the role the liver plays in the development and expression of the metabolic program will provide important insight into the pathogenesis and treatment of fatty liver disease, and of obesity itself. C1 Harvard Univ, Sch Med, Serv Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. RP Hoppin, AG (reprint author), Massachusetts Gen Hosp, Weight Ctr, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM ahoppin@partners.org NR 55 TC 6 Z9 6 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD NOV PY 2004 VL 24 IS 4 BP 381 EP 387 DI 10.1055/s-2004-860867 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882WR UT WOS:000225971600006 PM 15605306 ER PT J AU Pittman, SD MacDonald, MM Fogel, RB Malhotra, A Todros, K Levy, B Geva, AB White, DP AF Pittman, SD MacDonald, MM Fogel, RB Malhotra, A Todros, K Levy, B Geva, AB White, DP TI Assessment of automated scoring of polysomnographic recordings in a population with suspected sleep-disordered breathing SO SLEEP LA English DT Article DE automated scoring; obstructive sleep apnea; sleep apnea; sleep-disordered breathing arousal; periodic limb movement; polysomnography ID AGREEMENT; AROUSAL; CLASSIFICATION; DEFINITION; HYPOPNEA; ADULTS; STAGE AB Study Objectives: To assess the accuracy of an automated system (Morpheus I Sleep Scoring System) for analyzing and, quantifying polysomnographic data from a population with sleep-disordered breathing. Setting: Sleep laboratory affiliated with a tertiary care academic medical center. Measurements and Results: 31 diagnostic polysomnograms were blindly analyzed prospectively with the investigational automated system and manually by 2 registered polysomnography technologists (M1 & M2) from the same laboratory. Sleep stages, arousals, periodic limb movements, and respiratory events (apneas and hypopneas) were scored by all 3. Agreement, Cohen kappa, and intraclass correlation coefficients were tabulated for each variable and compared between scoring pairs (A-M1, A-M2, M1-M2). The 26,876 epochs (224 hours of recording time) were analyzed. For sleep staging, agreement/kappa were A-M1: 78%/0.67, A-M2: 73%/0.61, and M1-M2: 82%/0.73. The mean respiratory disturbance indexes were M1: 20.6 +/- 23.0, M2: 22.5 +/- 24.5, and A: 23.7 +/- 23.4 events per hour of sleep. The respiratory disturbance index concordance between each scoring pair was, excellent (intraclass correlation coefficients greater than or equal to 0.95 for all pairs), although there was disagreement in the classification of moderate sleep-disordered breathing (percentage of positive agreement: A-M1, 37.5% and A-M2, 44.4%) defined as a respiratory disturbance index between 15 and 30 events per hour of sleep. For respiratory-event detection, agreement/kappa were A-M1 and A-M2: 90%/0.66 and M1-M2: 95%/0.82. The agreement and kappa for limb movement detection were A-M1: 93%/0.68, A-M2: 92%/0.66, and M1-M2: 96%/0.77. The scoring of arousals was less reliable (agreement range: 76%-84%, kappa range: 0.28-0.57) for all pairs. Conclusions: Agreement between manual scorers in a population with moderate sleep-disordered breathing was close to the,average pairwise agreement of 87% reported in the Sleep Heart Health Study. The automated classification of sleep stages was also close to this standard. The automated scoring system holds promise as a rapid method to score polysomnographic records, but expert verification of the automated scoring is required. C1 Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. WideMED Ltd, Omer, Israel. RP White, DP (reprint author), Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Div Sleep Med, 75 Francis St, Boston, MA 02115 USA. EM dpwhite@rics.bwh.harvard.edu NR 23 TC 34 Z9 34 U1 1 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 2004 VL 27 IS 7 BP 1394 EP 1403 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 870XV UT WOS:000225093100019 PM 15586793 ER PT J AU Yang, YG AF Yang, YG TI Application of xenogeneic stem cells for induction of transplantation tolerance: present state and future directions SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article DE bone marrow; chimerism; pig; rejection; xenograft ID HUMAN HEMATOPOIETIC-CELLS; BONE-MARROW-CELLS; PORCINE ENDOTHELIAL-CELLS; IMMUNE-DEFICIENT MICE; HUMAN NK CELLS; MIXED CHIMERISM; T-CELL; SCID MICE; IMMUNODEFICIENT MICE; XENOGRAFT REJECTION AB Xenotransplantation using pig organs provides a possible solution to the severe shortage of allogeneic organ donors, one of the major limiting factors in clinical transplantation. However, because of the greater antigenic differences that exist between different species than within a species, the immune response to xenografts is much more vigorous than to allografts. Thus, tolerance induction is essential to the success of clinical xenotransplantation. Tolerance induced by mixed hematopoietic chimerism across the MHC barrier is remarkably robust, but its ability to induce tolerance across highly disparate xenogeneic barriers remains poorly studied. None of the current available regimens of host conditioning, which permit hematopoietic stem cell engraftment and chimerism induction in allogeneic or closely related ( concordant) xenogeneic combinations, has been demonstrated to be effective in establishing porcine hematopoietic chimerism in a discordant xenogeneic species. Unlike bone marrow transplantation within the same species, the innate immune system and the species specificity of cytokines and adhesion molecules essential to hematopoiesis pose formidable obstacles to the establishment of donor hematopoiesis across discordant xenogeneic barriers. The genetic incompatibility between species may also impede xenograft tolerance induction by mixed chimerism. While we remain far from achieving tolerance in clinical xenotransplantation, recent studies using a transgenic mouse model have proven the principle that mixed hematopoietic chimerism may induce mouse and human T cell tolerance to porcine xenografts. This review article focuses on the barriers to porcine hematopoietic engraftment in highly disparate xenogeneic species and the possible application of mixed hematopoietic chimerism to xenograft tolerance induction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Yang, YG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu NR 80 TC 16 Z9 16 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD NOV PY 2004 VL 26 IS 1-2 BP 187 EP 200 DI 10.1007/s00281-004-0159-1 PG 14 WC Immunology; Pathology SC Immunology; Pathology GA 869QX UT WOS:000225000200013 PM 15378269 ER PT J AU Coutts, SB Lev, MH Eliasziw, M Roccatagliata, L Hill, MD Schwamm, LH Pexman, JHW Koroshetz, WJ Hudon, ME Buchan, AM Gonzalez, RG Demchuk, AM AF Coutts, SB Lev, MH Eliasziw, M Roccatagliata, L Hill, MD Schwamm, LH Pexman, JHW Koroshetz, WJ Hudon, ME Buchan, AM Gonzalez, RG Demchuk, AM TI ASPECTS on CTA source images versus unenhanced CT - Added value in predicting final infarct extent and clinical outcome SO STROKE LA English DT Article DE computed tomography; stroke, acute; thrombolysis ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC-STROKE; COMPUTED-TOMOGRAPHY; THROMBOLYTIC THERAPY; CEREBRAL INFARCTS; INTRAARTERIAL THROMBOLYSIS; HYPERACUTE STROKE; ANGIOGRAPHY; PERFUSION; SELECTION AB Background and Purpose-The Alberta Stroke Program Early CT Score (ASPECTS) is a grading system to assess ischemic changes on CT in acute ischemic stroke. CT angiography-source images (CTA-SI) predict final infarct volume. We examined whether the final infarct ASPECTS and clinical outcome were more related to acute CTA-SI ASPECTS than to the acute noncontrast CT (NCCT) ASPECTS. Methods-ASPECTS was assigned by 2 raters on the acute NCCT, CTA-SI, and follow-up imaging. The mean baseline ASPECTS of acute NCCT and CTA-SI was compared with the follow-up ASPECTS. Rate ratios (RRs) were used to quantify the relationship between the dichotomized baseline ASPECTS (categorized as 0 to 7 versus 8 to 10) and favorable patient outcome. Results-Thirty-nine patients were recruited. Proximal occlusion (internal carotid artery or middle cerebral artery) was seen in 62%, M2 occlusion in 18%, and no occlusion was seen in 20% of patients. The median time between symptom onset and imaging was 1.9 (1.2 to 2.5) hours. There was a significantly larger difference of 1.4 between the mean baseline NCCT and CTA-SI ASPECTS in patients who had more ischemic changes (follow-up ASPECTS=0 to 3) than a difference of 0.6 in patients who had near-to-normal CT scans (follow-up ASPECTS=8 to 10). The rate of favorable outcome for acute NCCT ASPECTS of 8 to 10 was 51.8% versus 25.0% for 0 to 7 (RR, 2.1, 95% CI: 0.7 to 5.9, P=0.12). For acute CTA-SI ASPECTS of 8 to 10, the rate of favorable outcome was 58.8% versus 31.8% for 0 to 7 (RR, 1.8, 95% CI: 0.9 to 3.8, P=0.09). Conclusions-CTA-SI ASPECTS provides added information in the prediction of final infarct size. C1 Calgary Hlth Reg, Foothills Med Ctr, Seaman Family MR Res Ctr, Calgary, AB, Canada. Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Med & Community Hlth Sci, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Radiol, Calgary, AB T2N 1N4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Coutts, SB (reprint author), Foothills Prov Gen Hosp, Seaman Family MR Ctr, 1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM shelagh.coutts@calgaryhealthregion.ca RI Buchan, Alastair/B-9095-2009; Demchuk, Andrew/E-1103-2012; OI Buchan, Alastair/0000-0002-2918-5200; Demchuk, Andrew/0000-0002-4930-7789; Schwamm, Lee/0000-0003-0592-9145; Hill, Michael/0000-0002-6269-1543 NR 26 TC 91 Z9 95 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2004 VL 35 IS 11 BP 2472 EP 2476 DI 10.1161/01.STR.0000145330.14928.2a PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 866LM UT WOS:000224775000020 PM 15486327 ER PT J AU Greenberg, SA Gurol, ME Rosand, J Smith, EE AF Greenberg, SA Gurol, ME Rosand, J Smith, EE TI Amyloid angiopathy-related vascular cognitive impairment SO STROKE LA English DT Article; Proceedings Paper CT 24th Princeton Conference on Cerebrovascular Disease CY APR 02-04, 2004 CL Baltimore, MD SP Amer Heart Assoc, Amer Stroke Assoc, Stroke Council, Astra Zeneca Pharmaceut, Centocor Inc, Janssen Ortho McNeil Johnson & Johnson, Mitsubishi Pharma, NINDS, Bristol Myers Squibb, Sanofi Synthelabo DE amyloid; angiopathy; vascular dementia ID WHITE-MATTER LESIONS; PRECURSOR PROTEIN; ALZHEIMER-DISEASE; FUNCTIONAL HYPEREMIA; LOBAR HEMORRHAGE; TRANSGENIC MICE; MOUSE MODEL; DEMENTIA; DYSFUNCTION; REACTIVITY AB We review accumulating evidence that cerebrovascular amyloid deposition (cerebral amyloid angiopathy [CAA]) is an independent risk factor for cognitive dysfunction. The two population-based autopsy studies that have analyzed cognitive status during life as a function of CAA have each suggested deleterious effects of CAA on cognition even after controlling for age and Alzheimer disease pathology. We also review data from patients with CAA-related intracerebral hemorrhage (the one form of CAA that can be noninvasively recognized) suggesting associations of CAA with radiographic white matter abnormalities and cognitive impairment. These data highlight the importance of elucidating the effects of vascular amyloid on cerebrovascular function and of developing therapeutic strategies for this potentially widespread form of microvascular cognitive impairment. C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, SA (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Wang ACC 836, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Smith, Eric/C-5443-2012; Gurol, Edip/J-2279-2014 OI Smith, Eric/0000-0003-3956-1668; Gurol, Edip/0000-0002-2169-4457 FU NIA NIH HHS [AG21084]; NINDS NIH HHS [NS41409, NS42147, NS42695, NS46327] NR 38 TC 163 Z9 168 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 NOV PY 2004 VL 35 IS 11 SU 1 BP 2616 EP 2619 DI 10.1161/01.str.0000143224.36527.44 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 867PP UT WOS:000224854800003 PM 15459438 ER PT J AU Weinstein, PR Hong, S Sharp, FR AF Weinstein, PR Hong, S Sharp, FR TI Molecular identification of the ischemic penumbra SO STROKE LA English DT Article; Proceedings Paper CT 24th Princeton Conference on Cerebrovascular Disease CY APR 02-04, 2004 CL Baltimore, MD SP Amer Heart Assoc, Amer Stroke Assoc, Stroke Council, Astra Zeneca Pharmaceut, Centocor Inc, Janssen Ortho McNeil Johnson & Johnson, Mitsubishi Pharma, NINDS, Bristol Myers Squibb, Sanofi Synthelabo DE brain edema; blood flow; energy metabolism; magnetic resonance imaging; protein synthesis; stroke, ischemic ID CEREBRAL-ARTERY OCCLUSION; APPARENT DIFFUSION-COEFFICIENT; HSP70 MESSENGER-RNA; MAGNETIC-RESONANCE SPECTROSCOPY; TRANSIENT FOCAL ISCHEMIA; IN-SITU HYBRIDIZATION; HEAT-SHOCK-PROTEIN; C-FOS; RAT HEAT-SHOCK-PROTEIN-70; BLOOD-FLOW AB Review of results of experimental and clinical studies indicates that the penumbra of physiologically impaired but potentially salvageable tissue surrounding the central core of focal cerebral ischemia that develops shortly after onset of major conducting vessel occlusion is complex and dynamic with severity and duration thresholds for hypoxic stress and injury that are specific to tissue site, cell type, molecular pathway or gene expression investigated and efficiency of collateral or residual flow and reperfusion. Imaging methods that have been utilized in vivo to identify penumbra and predict response to reperfusion and other protective therapies include magnetic resonance spectroscopy, diffusion- and perfusion-MRI as well as positron emission tomography. However, resolution of focal lesions characterized by lactic acidosis or cellular edema does not predict tissue survival, and imaging thresholds for resuscitation after reperfusion have not been determined experimentally. HSP-70 stress protein induction represents an endogenous protective mechanism that occurs in penumbra but not core neurones. A robust protective effect has been demonstrated during focal ischemia in transgenic mice overexpressing HSP-70 perhaps by suppressing early cytochrome c release. Delayed manganese mediated striatal neurodegeneration can be detected with T I MRI after brief episodes of transient focal ischemia. Future studies may define endogenous cytotoxic and cytoprotective molecular penumbras that can be exploited to improve outcome after temporary focal ischemia. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Dept Neurol Surg, San Francisco, CA USA. Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. RP Weinstein, PR (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,M 779, San Francisco, CA 94143 USA. EM weinsteinp@neurosurg.ucsf.edu NR 31 TC 65 Z9 72 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2004 VL 35 IS 11 SU 1 BP 2666 EP 2670 DI 10.1161/01.STR.0000144052.10644.ed PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 867PP UT WOS:000224854800016 PM 15486332 ER PT J AU Wang, XY Tsuji, K Lee, SR Ning, MM Furie, KL Buchan, AM Lo, EH AF Wang, XY Tsuji, K Lee, SR Ning, MM Furie, KL Buchan, AM Lo, EH TI Mechanisms of hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke SO STROKE LA English DT Article; Proceedings Paper CT 24th Princeton Conference on Cerebrovascular Disease CY APR 02-04, 2004 CL Baltimore, MD SP Amer Heart Assoc, Amer Stroke Assoc, Stroke Council, Astra Zeneca Pharmaceut, Centocor Inc, Janssen Ortho McNeil Johnson & Johnson, Mitsubishi Pharma, NINDS, Bristol Myers Squibb, Sanofi Synthelabo DE blood-brain barrier; cerebral ischemia; hemorrhage; neuroprotection ID LONG-TERM POTENTIATION; BLOOD-BRAIN-BARRIER; FOCAL CEREBRAL-ISCHEMIA; SCIATIC-NERVE CRUSH; GENE KNOCK-OUT; MATRIX-METALLOPROTEINASE; MICE LACKING; NEURONAL DAMAGE; TPA; MATRIX-METALLOPROTEINASE-9 AB Reperfusion therapy with tissue plasminogen activator (tPA) is a rational therapy for acute ischemic stroke. Properly titrated use of tPA improves clinical outcomes. However, there is also an associated risk of hemorrhagic transformation after tPA therapy. Emerging data now suggest that some of these potentially neurotoxic side effects of tPA may be due to its signaling actions in the neurovascular unit. Besides its intended role in clot lysis, tPA is also an extracellular protease and signaling molecule in brain. tPA mediates matrix remodeling during brain development and plasticity. By interacting with the NMDA-type glutamate receptor, tPA may amplify potentially excitotoxic calcium currents. At selected concentrations, tPA may be vasoactive. Finally, by augmenting matrix metalloproteinase (NIMP) dysregulation after stroke, tPA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood-brain barrier leakage, edema, and hemorrhage. Understanding these pleiotropic actions of tPA may reveal new therapeutic opportunities for combination stroke therapy. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. Univ Calgary, Stroke Program, Calgary Brain Inst, Calgary, AB T2N 1N4, Canada. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu RI Buchan, Alastair/B-9095-2009 OI Buchan, Alastair/0000-0002-2918-5200 FU NINDS NIH HHS [R01-NS37074, P50-NS10828, R01-NS38731, R01-NS40529] NR 50 TC 140 Z9 148 U1 1 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 NOV PY 2004 VL 35 IS 11 SU 1 BP 2726 EP 2730 DI 10.1161/01.STR.0000143219.16695.af PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 867PP UT WOS:000224854800033 PM 15459442 ER PT J AU Grillo, HC AF Grillo, HC TI Edward D. Churchill and the "rectangular" surgical residency SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 22 Z9 23 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2004 VL 136 IS 5 BP 947 EP 952 DI 10.1016/j.surg.2004.09.002 PG 6 WC Surgery SC Surgery GA 871JA UT WOS:000225125800001 PM 15523385 ER PT J AU Mori, K Nakao, Y Yamamoto, T Maeda, M AF Mori, K Nakao, Y Yamamoto, T Maeda, M TI Early external decompressive craniectomy with duroplasty improves functional recovery in patients with massive hemispheric embolic infarction - Timing and indication of decompressive surgery for malignant cerebral infarction SO SURGICAL NEUROLOGY LA English DT Article DE cerebral infarction; decompressive surgery; quality of life ID ARTERY TERRITORY INFARCTION; MODERATE HYPOTHERMIA; ISCHEMIC-STROKE; CLINICAL COURSE; BRAIN EDEMA; HEAD-INJURY; HEMICRANIECTOMY; PRESSURE; DETERIORATION; REPERFUSION AB BACKGROUND Extensive cerebral hemispheric infarction associated with massive brain swelling is known as malignant infarction because of the rapid clinical deterioration and mortality as high as 80% unless appropriate treatment is performed. Decompressive craniectomy is an effective treatment, but patient selection, timing, functional recovery, and complications remain unclear. METHODS Seventy-one patients with massive embolic hemispheric infarctions (infarct volume >200 cm(3)) associated with brain swelling were retrospectively divided into 3 groups according to the therapeutic modalities: 21 patients were treated conservatively (conservative group); 50 patients were treated by external decompressive craniectomy with duroplasty in 2 groups; 29 patients treated after the appearance of clinical and radiologic findings of brain herniation (late surgery group); and 21 patients treated before the onset of brain herniation (early surgery group). RESULTS The mortality at 1 and 6 months in the conservative group were 61.9% and 71.4%, respectively. The mortality at 1 and 6 months in the late surgery group were significantly improved to 17.2% and 27.6%, respectively, (p < 0.01) and in the early surgery group were further improved to 4.8% and 19.1%, respectively. The functional recovery of the patients was estimated by the Glasgow Outcome Scale (GOS) and Barthel Index (BI) at 6 months after the ictus. The GOS scores of the early surgery group were significantly better than that of the late surgery group (p < 0.05). The mean BI score of the survivors in the late surgery group (26.9 +/- 30.4) was not significantly different from that of the conservative group (28.3 +/- 42.2), but was significantly improved in the early surgery group (52.9 +/- 34.2) compared with the late surgery group (p < 0.05). CONCLUSIONS Early decompressive craniectomy with duroplasty before the onset of brain herniation should be performed to achieve satisfactory functional recovery if the infarct volume of the hemispheric cerebral infarction is more than 200 cm(3) and computed tomography on the second day after the ictus shows mass effect. (C) 2004 Elsevier Inc. All rights reserved. C1 Juntendo Univ, Dept Neurosurg, Izunagaoka Hosp, Shizuoka 4102295, Japan. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Mori, K (reprint author), Juntendo Univ, Dept Neurosurg, Izunagaoka Hosp, 1129 Nagaoka, Shizuoka 4102295, Japan. EM KMORI1919@hkg.odn.ne.jp NR 38 TC 64 Z9 69 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD NOV PY 2004 VL 62 IS 5 BP 420 EP 430 DI 10.1016/j.surneu.2003.12.017 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 867CP UT WOS:000224820000011 PM 15518850 ER PT J AU Taneri, S Zieske, JD Azar, DT AF Taneri, S Zieske, JD Azar, DT TI Evolution, techniques, clinical outcomes, and pathophysiology of LASEK: Review of the literature SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE laser subepithelial keratomileusis (LASEK); laser in situ keratomileusis (LASIK) photorefractive keratectomy (PRK) ID IN-SITU KERATOMILEUSIS; DIFFUSE LAMELLAR KERATITIS; ASSISTED SUBEPITHELIAL KERATECTOMY; TOPICAL MITOMYCIN-C; SMOOTH MUSCLE ACTIN; MECHANICAL EPITHELIAL DEBRIDEMENT; KERATAN SULFATE PROTEOGLYCAN; REFRACTIVE CORNEAL SURGERY; WOUND-HEALING RESPONSE; PHOTOREFRACTIVE KERATECTOMY AB Laser subepithelial keratomileusis (LASEK) is a relatively new laser surgical procedure that combines certain elements of both laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) to improve the risk/benefit ratio. Diluted alcohol is used to loosen the epithelial adhesion to the corneal stroma. The loosened epithelium is moved aside from the treatment zone as a hinged sheet. Laser ablation of the subepithelial stroma is performed before the epithelial sheet is returned to its original position. We reviewed the literature regarding modifications of the technique, indications, outcomes, and complications, as well as wound healing after LASEK surgery. This literature review of 1,421 LASEK-treated eyes provided many findings: 1) The long-term stable results in the absence of serious complications, such as infections, recurrent erosions, scars, or late-onset corneal haze formation in patients re-examined up to 5 years after LASEK; 2) Epithelial closure with recovery of functional vision was completed at days 4 to 7 in most cases; 3) A tendency toward overcorrection with PRK nomograms; 4) We hypothesize that this tendency may be due to the decreased wound healing response, which may lead to myopic regression in PRK; and 5) Postoperative discomfort and prolonged visual recovery until the epithelium closes remain the biggest disadvantages of LASEK compared to LASIK. LASEK surgery is especially valuable in patients with thin corneas who would not qualify for LASIK surgery. However, a potential superiority of LASEK to LASIK in wavefront guided ablations still remains speculative. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, Boston, MA 02114 USA. Zentrum Refrakt Chirurg, Munster, Germany. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. OI Taneri, Suphi/0000-0003-0593-6847 FU NEI NIH HHS [EY 10101] NR 154 TC 65 Z9 71 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD NOV-DEC PY 2004 VL 49 IS 6 BP 576 EP 602 DI 10.1016/j.survophthal.2004.08.003 PG 27 WC Ophthalmology SC Ophthalmology GA 873SR UT WOS:000225301800003 PM 15530945 ER PT J AU Vidal-Trecan, GM Stahl, JE Eckman, MH AF Vidal-Trecan, GM Stahl, JE Eckman, MH TI Radioiodine or surgery for toxic thyroid adenoma: Dissecting an important decision - A cost-effectiveness analysis SO THYROID LA English DT Article ID OCCULT PAPILLARY CARCINOMA; QUALITY-OF-LIFE; SURGICAL-TREATMENT; RADIOACTIVE IODINE; I-131 THERAPY; FOLLOW-UP; INDUCED AGRANULOCYTOSIS; TREATMENT GUIDELINES; AUTONOMOUS NODULE; PERSONAL-COMPUTER AB Objective: To examine the cost effectiveness of therapeutic strategies for toxic thyroid adenoma. Design: Markov state transition decision analytic model. Setting: Ambulatory and inpatient. Patients: Hypothetical cohort of 40-year-old women with toxic thyroid adenomas. Patient age was varied in sensitivity analyses. Data on the prevalence of coincident thyroid cancer, complications, and treatment efficacies were derived from a systematic review of the literature. Interventions: Thyroid lobectomy after a 3 month-course of antithyroid drugs (ATDs), high-dose (>555 MBq) radioactive iodine (RAI), low-dose (<555 MBq) RAI, and lifelong ATDs. Measurements and main results: Outcomes were measured in quality-adjusted life years (QALYs). Costs were estimated from the health care system perspective. Future costs and effectiveness were discounted at 3% per year. For a 40-year-old woman, surgery was the most effective, while low-dose RAI. was the least costly. The marginal cost-effectiveness of surgery versus low-dose RAI was $13,183 per QALY. Surgery was less costly and more effective than lifelong ATDs. RAI was more effective than surgery if surgical mortality exceeded 0.90% (base-case 0.001%). Surgery provided relatively inexpensive gains (<$50,000 per QALY) in quality-adjusted life expectancy in patients less than 74 years of age. Conclusions: For most patients less than 60 years of age, surgery is an effective strategy with a reasonable cost. However, for any given patient, surgical mortality, therapeutic costs and preference must be considered in choosing an appropriate therapy. C1 Univ Paris 05, Assistance Publ Hop Paris, CHU Cochin Port Royal, Dept Sante Publ, Paris, France. Massachusetts Gen Hosp, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA. Univ Cincinnati, Med Ctr, Div Gen Internal Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Ctr Clin Effectiveness, Cincinnati, OH 45267 USA. RP Vidal-Trecan, GM (reprint author), CHU Cochin Port Royal, Dept Sante Publ, 24 Rue Faubourg St Jacques, F-75014 Paris, France. EM gwenaelle.Vidal-Trecan@univ-paris5.fr OI Vidal-Trecan, Gwenaelle/0000-0002-2010-0207 NR 92 TC 23 Z9 23 U1 1 U2 5 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 2004 VL 14 IS 11 BP 933 EP 945 DI 10.1089/thy.2004.14.933 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 878MO UT WOS:000225651100009 PM 15671772 ER PT J AU Alexander, EK Marqusee, E Orcutt, J Benson, CB Frates, MC Doubilet, PM Cibas, ES Atri, A AF Alexander, EK Marqusee, E Orcutt, J Benson, CB Frates, MC Doubilet, PM Cibas, ES Atri, A TI Thyroid nodule shape and prediction of malignancy SO THYROID LA English DT Article ID NEEDLE-ASPIRATION BIOPSY; ULTRASOUND; TUMORS; ULTRASONOGRAPHY; SONOGRAPHY; MANAGEMENT; BENIGN; COLD; REARRANGEMENT; CANCER AB Background: Thyroid nodules are common; the vast majority benign. Preoperative determination of malignancy remains imprecise, despite fine-needle aspiration (FNA). Numerous risk factors have been proposed for predicting malignancy, though few have been found useful. Oxygen delivery is a crucial component for tumor cell growth. It has been hypothesized that malignant tumors may configure their shape to maximize access to local nutrient delivery. Mathematically, surface area to volume is maximized by a spherical shape. We sought to determine if spherical shape is a predictor of malignancy. Methods: Seven hundred forty-seven consecutive patients underwent ultrasound evaluation and FNA of 993 solid thyroid nodules (< 25% cystic) between 1995 and 2000 and were retrospectively analyzed. Nodules were classified as benign or malignant based on FNA and/or surgical pathology. Spherical shape was estimated by calculating a ratio of the longest to shortest dimensions, and rate of malignancy correlated. Results: Spherical shape was independently correlated with risk of malignancy (p < 0.001). Thyroid cancer was detected in 11% of all nodules, but ranged from 18% in spherical nodules to 5% in those least spherical. Nodules found to have suspicious or intermediate cytology showed similar variation in malignant risk. A long to short axis ratio greater than 2.5 was 100% predictive of a benign process, although present in only 4% of our cohort. A prospective validation was performed and confirmed consistent results (p < 0.01). Conclusion: Spherical shape is associated with an increased rate of malignancy in solid thyroid nodules. Determination of shape may assist in clinical risk assessment of thyroid cancer. C1 Brigham & Womens Hosp, Thyroid Unit, Div Endocrinol Diabet & Hypertens, Thyroid Sect,Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, MIT Hlth Sci & Technol, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. RP Alexander, EK (reprint author), Brigham & Womens Hosp, Thyroid Unit, Div Endocrinol Diabet & Hypertens, Thyroid Sect,Dept Med, 221 Longwood Ave,2nd Floor, Boston, MA 02115 USA. EM ekalexander@partners.org OI Atri, Alireza/0000-0003-4405-6973 NR 30 TC 69 Z9 75 U1 0 U2 2 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 2004 VL 14 IS 11 BP 953 EP 958 DI 10.1089/thy.2004.14.953 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 878MO UT WOS:000225651100011 PM 15671774 ER PT J AU Li, Z Yarmush, ML Chan, C AF Li, Z Yarmush, ML Chan, C TI Insulin concentration during preconditioning mediates the regulation of urea synthesis during exposure to amino acid-supplemented plasma SO TISSUE ENGINEERING LA English DT Article ID METABOLIC FLUX ANALYSIS; CULTURED-HEPATOCYTES; CYCLE; TRANSCRIPTION; RECEPTOR; ENZYMES AB Understanding the effects of preconditioning on cellular metabolism is important in providing insight into how cells and tissues may behave when confronted with alterations in their environment. Previously, elevated accumulation of lipids and a correspondingly reduced rate of urea synthesis were found in primary heptocytes preconditioned in culture medium containing high levels of insulin and then exposed to plasma. Subsequent studies found that preconditioning primary hepatocytes in medium containing low levels of insulin before exposure to plasma supplemented with amino acids was able to confer resistance to the lipid-accumulating effect of plasma exposure and restored urea synthesis. In the current study, we investigated the effects of insulin preconditioning and amino acid supplementation on the gene expression profile of the urea cycle and fatty acid metabolism enzymes. We found that insulin preconditioning mediates the effects of amino acids in the plasma exposure period on urea synthesis. Urea synthesis is regulated by insulin and amino acids through both short-term and long-term control. Possible mechanisms of long-term control through transcriptional regulation of urea synthesis by insulin, amino acids, and enzymes and transcription factors associated with lipid metabolism are discussed. C1 Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Surg Serv, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Chan, C (reprint author), Michigan State Univ, Dept Chem Engn & Mat Sci, 1257 EB, E Lansing, MI 48824 USA. EM krischan@egr.msu.edu NR 19 TC 5 Z9 5 U1 0 U2 3 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD NOV PY 2004 VL 10 IS 11-12 BP 1737 EP 1746 DI 10.1089/ten.2004.10.1737 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 883XM UT WOS:000226049100014 PM 15684682 ER PT J AU Dieguez-Acuna, FJ Polk, WW Ellis, ME Simmonds, PL Kushleika, JV Woods, JS AF Dieguez-Acuna, FJ Polk, WW Ellis, ME Simmonds, PL Kushleika, JV Woods, JS TI Nuclear factor kappa B activity determines the sensitivity of kidney epithelial cells to apoptosis: Implications for mercury-induced renal failure SO TOXICOLOGICAL SCIENCES LA English DT Article DE nuclear factor kappa B; kidney epithelial cells; renal failure; Hg2+ toxicity; apoptosis ID TUMOR-NECROSIS-FACTOR; MITOCHONDRIAL BIOENERGETICS; INDUCED NEPHROTOXICITY; TRANSCRIPTION FACTOR; REGULATORY PROTEINS; TUBULAR CELLS; FACTOR-ALPHA; DNA-BINDING; ACTIVATION; PHOSPHORYLATION AB Nuclear factor kappa B (NF-kappaB) is a thiol-dependent transcriptional factor that promotes cell survival and protects cells from apoptotic stimuli. Numerous studies have demonstrated increased sensitivity to apoptosis associated with inhibition of NF-kappaB activation in various cell types. We have previously demonstrated that mercuric ion (Hg2+), one of the strongest thiol-binding agents known, impairs NF-kappaB activation and DNA binding at low muM concentrations in kidney epithelial cells. In the present studies we investigated the hypothesis that inhibition of NF-kappaB activation by Hg2+ and other selective NF-kappaB inhibitors would increase the sensitivity of kidney epithelial (NRK52E) cells to apoptogenic agents to which these cells are normally resistant. Fewer than 10% of untreated cells in culture were found to be apoptotic when evaluated by DNA fragmentation (TUNEL) assay. Treatment of cells with Hg2+ in concentrations up to 5 muM or with tumor necrosis factor-alpha (TNF) (300 units/ml) did not significantly increase the proportion of apoptotic cells, compared with untreated controls. However, when TNF was given following Hg2+ pretreatment (0.5 to 5 muM for 30 min), the proportion of cells undergoing apoptosis increased by 2- to 6-fold over that seen in untreated controls. Kidney cells pretreated with specific NF-kappaB inhibitors (Bay11-7082 or SN50) prior to TNF also showed a significant increase in apoptosis. Increased sensitivity to apoptotic cell death following these treatments was significantly attenuated in cells transfected with a p65 expression vector. In studies in vivo, rats pretreated by intraperitoneal injection with Hg2+ (0.75 mg/kg) 18 h prior to administration of bacterial lipopolysaccharide (LPS) (10 mg/kg) displayed impaired NF-kappaB activation and an increased mitochondrial cytochrome c release in kidney cortical cells. These findings are consistent with the view that prevention of NF-kappaB activity in vitro or in vivo enhances the sensitivity of kidney cells to apoptotic stimuli to which these cells are otherwise resistant. Since apoptosis is known to play a seminal role in the pathogenesis of renal failure caused by toxicant injury to tubular cells, the present findings suggest that inhibition of NF-kappaB activity may define a molecular mechanism underlying the pathogenesis of Hg2+ toxicity in kidney cells. C1 Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98105 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Woods, JS (reprint author), Univ Washington, Dept Environm & Occupat Hlth Sci, 4225 Roosevelt Way NE,Suite 100, Seattle, WA 98105 USA. EM jwoods@u.washington.edu FU NIEHS NIH HHS [ES 07032, P30 ES 07033, P42 ES 04696] NR 39 TC 25 Z9 26 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2004 VL 82 IS 1 BP 114 EP 123 DI 10.1093/toxsci/kfh236 PG 10 WC Toxicology SC Toxicology GA 865LL UT WOS:000224704500013 PM 15282405 ER PT J AU Fernandes, JR Duvivier-Kali, VF Keegan, M Hollister-Lock, J Omer, A Su, S Bonner-Weir, S Feng, S Lee, JS Mulligan, RC Weir, GC AF Fernandes, JR Duvivier-Kali, VF Keegan, M Hollister-Lock, J Omer, A Su, S Bonner-Weir, S Feng, S Lee, JS Mulligan, RC Weir, GC TI Transplantation of islets transduced with CTLA4-Ig and TGF beta using adenovirus and lentivirus vectors SO TRANSPLANT IMMUNOLOGY LA English DT Article DE diabetes; islet transplantation; adenovirus; lentivirus; cytotoxic T lymphocyte antigen 4; transforming growth factor beta ID GROWTH-FACTOR-BETA; MEDIATED GENE-TRANSFER; CELL LINE; T-CELLS; REJECTION; MICE; EXPRESSION; RESPONSES; SURVIVAL; RAT AB Background. A major problem facing islet transplantation is immune destruction of grafts by transplant rejection and autoimmunity. Some success in prolonging graft rejection has been obtained by transducing islets prior to transplantation with adenoviral (Ad) vectors containing CTLA4-Ig and TGFbeta. The purpose of this study was to see if lentiviral (LV) vectors would provide superior results compared with adenoviral vectors. Methods. Islets were isolated from Sprague-Dawley rats and transduced with Ad or LV vectors containing LacZ, CTLA4-Ig, TLA4, and TGFbeta1 using various MOIs. Islets transduced with LV were healthy as judged by DNA and insulin content, and insulin secretion. Using the kidney capsule transplant site, 500 transduced rat islets were transplanted into streptozotocin diabetic B6AF1 mice. Results. Maintenance of normoglycemia was prolonged in recipient mice carrying islets transduced with Ad vectors containing CTLA4-Ig, CTLA4, and TGFbeta1. Return of hyperglycemia in controls was 17-18 days while loss of function for the experimental groups occurred at 20-27 days. For the lentivirus transduced islets, rejection of controls was 20 +/- 1.6 days, for CTLA4-Ig was 42 21 days and for TGFbeta was 28 +/- 3.2 days. Conclusions. Although islets transduced with either adenovirus or lentivirus containing CTLA4-Ig, CTLA4, and TGFbeta1 could prolong graft survival in a rat to mouse transplantation model, with the conditions of this study lentivirus provided no advantage over adenovirus vectors. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02215 USA. Cominatorx Inc, Boston, MA 02118 USA. Sanofi Synthelabo, Diabet & Obes Unit, Rueil Malmaison, France. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl,Room 535, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU NIDDK NIH HHS [DK53087, DK 50657] NR 36 TC 18 Z9 20 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD NOV PY 2004 VL 13 IS 3 BP 191 EP 200 DI 10.1016/j.trim.2004.04.004 PG 10 WC Immunology; Transplantation SC Immunology; Transplantation GA 859RI UT WOS:000224285200006 PM 15381202 ER PT J AU Prodhan, P Casavant, D Medlock, MD Yager, P Kim, J Noviski, N AF Prodhan, P Casavant, D Medlock, MD Yager, P Kim, J Noviski, N TI Inhaled nitric oxide in neurogenic cardiopulmonary dysfunction: Implications for organ donation SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; PULMONARY-EDEMA; MANAGEMENT; INJURY; DONOR; RATS AB Many cadaveric organs for transplantation come from patients dying of sudden intracranial catastrophes. Cardiopulmonary dysfunction after such neurogenic insults is a well-recognized entity. The pulmonary dysfunction usually presents as florid pulmonary edema within minutes to hours after the initial intracranial insult and may occur in isolation or co-exist with overt or subclinical myocardial dysfunction. This may result in severe hypoxia, which threatens survival and outcomes in salvageable cases and organ preservation in patients who would be potential organ donors. Thus, rapid initiation of strategies aimed at ameliorating hypoxia after an acute neurogenic insult is paramount. Strategies aimed at improving acute hypoxia include maximizing ventilator support, diuretics, and volume resuscitation. Cardiac dysfunction may require use of ionotropes. We report the case of a 16-year-old female who developed catastrophic acute posterior fossa intracranial bleeding with resulting intractable hypoxia due to neurogenic cardiopulmonary dysfunction that responded dramatically to inhaled nitric oxide (INO). The patient went on to successfully donate organs following a non-heart-beating donor protocol. This therapy, to our knowledge, has never been described previously for use in patients with hypoxia secondary to neurogenic cardiopulmonary dysfunction. Conclusions: We document for the first time a dramatic response of hypoxia to INO in neurogenic cardiopulmonary dysfunction. This therapy ameliorates hypoxia, which may have vital implications in minimizing secondary brain injury in salvageable cases and optimizing organ preservation in potential organ donors with catastrophic intracranial insults. C1 Massachussets Gen Hosp Children, Div Pediat Crit Care Med, Boston, MA USA. Massachussets Gen Hosp Children, Div Pediat, Boston, MA USA. Massachussets Gen Hosp Children, Div Neurosurg, Boston, MA USA. RP Prodhan, P (reprint author), Massachusetts Gen Hosp, Ellison 317,55 Fruit St, Boston, MA 02114 USA. EM pprodhan@partners.org NR 18 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD NOV PY 2004 VL 36 IS 9 BP 2570 EP 2572 DI 10.1016/j.transproceed.2004.09.032 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 885FI UT WOS:000226142100013 PM 15621092 ER PT J AU Janakiraman, A Goldberg, MB AF Janakiraman, A Goldberg, MB TI Recent advances on the development of bacterial poles SO TRENDS IN MICROBIOLOGY LA English DT Review ID PENICILLIN-BINDING-PROTEINS; CELL-DIVISION PROTEIN; ESCHERICHIA-COLI-CELLS; ACTIN-LIKE PROTEINS; BACILLUS-SUBTILIS; CHROMOSOME SEGREGATION; NUCLEOID OCCLUSION; SHIGELLA-FLEXNERI; CAULOBACTER-CRESCENTUS; POLAR LOCALIZATION AB In rod-shaped bacteria, a surprisingly large number of proteins are localized to the cell poles. Polar positioning of proteins is crucial to many fundamental cellular processes. Formation of the pole occurs at the time of a prior cell division event and involves coordination of the cell division machinery with septal placement of newly-synthesized peptidoglycan. Development of polar peptidoglycan and outer membrane depends on the formation of the cytokinetic FtsZ ring at midcell. By contrast, positioning of at least two polar proteins depends on signals independent of both the assembly of the FtsZ ring and the synthesis of septal and polar peptidoglycan. We propose a model for distinct but interrelated developmental pathways for polar cell envelope synthesis and positional information recognized by polar proteins. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Infect Dis, Cambridge, MA 02139 USA. RP Goldberg, MB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Infect Dis, 65 Landsdowne St, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org NR 77 TC 38 Z9 39 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD NOV PY 2004 VL 12 IS 11 BP 518 EP 525 DI 10.1016/j.tim.2004.09.003 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 871QO UT WOS:000225148500010 PM 15488393 ER PT J AU Briesacher, B Orwig, D Seton, M Omar, M Kahler, K AF Briesacher, B Orwig, D Seton, M Omar, M Kahler, K TI Treatment costs and disease burden of patients with Paget's Disease SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Univ Massachusetts, Worcester, MA 01605 USA. Univ Maryland, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2004 VL 7 IS 6 SU S BP 722 EP 723 DI 10.1016/S1098-3015(10)65905-0 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 869YK UT WOS:000225020700273 ER PT J AU Siebert, U Bornschein, B Spottke, EA Dodel, R AF Siebert, U Bornschein, B Spottke, EA Dodel, R TI Effect of disease-specific complications on the prediction of utilities in Parkinson's disease SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Munich, Munich, Germany. Univ Bonn, D-5300 Bonn, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2004 VL 7 IS 6 SU S BP 794 EP 794 DI 10.1016/S1098-3015(10)66128-1 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 869YK UT WOS:000225020700496 ER PT J AU Shen, WT Kebebew, E Clark, OH Duh, QY AF Shen, WT Kebebew, E Clark, OH Duh, QY TI Reasons for conversion from laparoscopic to open or hand-assisted adrenalectomy: Review of 261 laparoscopic adrenalectomies from 1993 to 2003 SO WORLD JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the International-Association-of-Endocrine-Surgeons CY JUN 14-17, 2004 CL Uppsala, SWEDEN SP Int Assoc Endocrine Surg ID OPEN CHOLECYSTECTOMY; SURGERY AB Over the past decade, laparoscopic adrenalectomy has become the operation of choice for resecting adrenal tumors. However, few reported data exist regarding the reasons for conversion from laparoscopic to open or hand-assisted adrenalectomy. We retrospectively reviewed the records of 261 consecutive laparoscopic adrenalectomies performed by one surgeon between 1993 and 2003. Laparoscopic adrenalectomy could not be completed in 8 of the 261 patients (3%); four of the operations were converted to hand-assisted laparoscopic adrenalectomy and four to open adrenalectomy. The reasons for the conversion were as follows: In three patients the tumor was too adherent to surrounding structures to be resected laparoscopically; in three patients the tumor was found to have malignant features during laparoscopy, and the operation was converted to achieve proper resection margins; in two patients the tumors were too large (15 and 1.6 cm, respectively) to be safely removed laparoscopically. The eight resected tumors included three pheochromocytomas, one myelolipoma, one angiomyolipoma, one solitary fibrous tumor, one liposarcoma, and one metastatic hepatocellular carcinoma. There were no cases in which conversion was required emergently for bleeding or other intraoperative catastrophes. All eight of the tumors removed were at least 5 cm in size (range 5-16 cm). The mean length of hospitalization was 4.4 days (range 3-8 days). C1 San Francisco Vet Affairs Med Ctr, Surg Serv 112, San Francisco, CA 94121 USA. Univ Calif San Francisco, Mt Zion Med Ctr, Dept Surg, San Francisco, CA 94143 USA. RP Duh, QY (reprint author), San Francisco Vet Affairs Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. NR 12 TC 39 Z9 39 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD NOV PY 2004 VL 28 IS 11 BP 1176 EP 1179 DI 10.1007/s00268-004-7620-0 PG 4 WC Surgery SC Surgery GA 874TL UT WOS:000225372600021 PM 15490056 ER PT J AU Mueller, NJ Fishman, JA AF Mueller, NJ Fishman, JA TI Herpesvirus infections in xenotransplantation: pathogenesis and approaches SO XENOTRANSPLANTATION LA English DT Review DE porcine cytomegalovirus; porcine lymphotropic herpesvirus; post-transplantation lymphoproliferative disorder; transplantation; viral infection; xenotransplantation ID TO-BABOON XENOTRANSPLANTATION; HUMORAL XENOGRAFT REJECTION; PORCINE CYTOMEGALOVIRUS; LYMPHOPROLIFERATIVE DISEASE; HETEROLOGOUS IMMUNITY; MINIATURE SWINE; PIGS; TRANSPLANTATION; RISK; GAMMAHERPESVIRUSES AB Infectious risk remains an important consideration in the clinical application of xenotransplantation. Vascularized xenografts create unique immunological niches in which bidirectional transmission of pathogens between donor and recipient may occur. Enhanced replication of many pathogens is stimulated by the immune responses induced by transplantation and by the immune suppression used to prevent graft rejection. Herpesviruses are the prototype viruses that are activated during immunosuppression. Quantitative diagnostic molecular assays have been developed for the known herpesviruses causing infection in pigs. Recent data suggest that some herpesviral infections, such as porcine cytomegalovirus, may be excluded from swine used as source animals by careful breeding, while others will require novel strategies for control. This review focuses on porcine and baboon herpesviruses in pig-to-non-human primate solid organ xenotransplantation including direct effects (tissue damage), indirect effects (coagulopathy, rejection), and possible approaches to these infections. C1 Univ Zurich Hosp, Dept Med, Div Infect Dis & Hosp Epidemiol, CH-8091 Zurich, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Infect Dis Div, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. RP Mueller, NJ (reprint author), Univ Zurich Hosp, Dept Med, Div Infect Dis & Hosp Epidemiol, Ramistr 100,RAE U 74, CH-8091 Zurich, Switzerland. EM nicolas.mueller@usz.ch RI Mueller, Nicolas/B-6864-2013; Infektiologie, USZ/A-6921-2011 OI Mueller, Nicolas/0000-0002-1059-3191; FU NIAID NIH HHS [P01-AI45897, 5T32-AI07529-04] NR 33 TC 17 Z9 17 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2004 VL 11 IS 6 BP 486 EP 490 DI 10.1111/j.1399-3089.2004.00180.x PG 5 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 861QK UT WOS:000224432900001 PM 15479457 ER PT J AU Koulmanda, M Laufer, TM Auchincloss, H Smith, RN AF Koulmanda, M Laufer, TM Auchincloss, H Smith, RN TI Prolonged survival of fetal pig islet xenografts in mice lacking the capacity for an indirect response SO XENOTRANSPLANTATION LA English DT Article DE fetal pig pancreas; indirect pathway; islets; xenotransplantation ID MHC CLASS-II; T-CELL ALLORECOGNITION; ALLOGRAFT-REJECTION; KIDNEY ALLOGRAFTS; DEFICIENT MICE; IN-VITRO; RECOGNITION; GRAFTS; DONOR; XENOTRANSPLANTATION AB Background: Xenografts of islets from organ-cultured fetal pig pancreases transplanted into non-immunosuppressed mice are rejected within 10 days. Immunosuppression with anti-T cell (anti-CD4) monoclonal antibody alone delays rejection of these xenografts for about 28 days, but rejection eventually occurs despite marked depletion of T cells. To determine if the critical CD4+ T cells responsible for xenograft islet rejection function through the direct or indirect pathway, selective class II-deficient mice that express class II antigens only on their thymic epithelium (not on peripheral cells) with normal numbers of CD4+ T cells, (class II-, CD4+), were used as recipients of xenograft islets to test if rejection occurs in the absence of an indirect response. Methods: Control (C57BL/6) or class II-, CD4+ mice were transplanted under the kidney capsule with cultured fetal pig islets. Class II-, CD4+ mice have normal numbers of B cells, CD4+, gammadelta T cells, and slightly increased numbers of CD8+ T cells. Additional mice were thymectomized before receiving anti-CD4 or anti-CD8 monoclonal antibodies. Islet graft survival was determined histologically as fetal pig islets were too immature to secrete insulin. Results: Xenograft survival in control animals was 7 to 14 days. In contrast, graft survival in class II-, CD4+ mice was significantly prolonged to greater than 35 days. Depletion of CD8+ T cells in class II-, CD4+ mice prolonged graft survival to about 70 days. Depletion of CD4+ T cells from these mice further prolonged xenograft survival to about 100 days. Conclusions: These results suggest that the rejection of pig islets by mice initially depends on a CD4 dependent indirect response. The CD4 direct response also contributes to graft destruction. CD8+ T cells also participate in graft destruction, albeit weakly. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Islet Transplantat Res Lab, Boston, MA 02114 USA. Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Koulmanda, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Islet Transplantat Res Lab, WH 541,55 Fruit St, Boston, MA 02114 USA. EM koulmand@helix.mgh.harvard.edu FU NIDDK NIH HHS [P01 DK53087] NR 31 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2004 VL 11 IS 6 BP 525 EP 530 DI 10.1111/j.1399-3089.2004.00174.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 861QK UT WOS:000224432900006 PM 15479462 ER PT J AU Xu, GY Kane, DJ Faller, LD Farley, RA AF Xu, GY Kane, DJ Faller, LD Farley, RA TI The role of loop 6/7 in folding and functional performance of Na,K-ATPase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; SITE-DIRECTED MUTAGENESIS; TRANSMEMBRANE SEGMENTS 6; CYTOPLASMIC LOOP; ALPHA-SUBUNIT; RENAL NA,K-ATPASE; COORDINATING RESIDUES; GASTRIC H+,K+-ATPASE; CATION OCCLUSION; CA2+ BINDING AB Alanine substitutions were made for 15 amino acids in the cytoplasmic loop between transmembrane helices 6 and 7 (L6/7) of the human alpha(1)-subunit of Na,K-ATPase. Most mutations reduced Na,K-ATPase activity by less than 50%; however, the mutations R834A, R837A, and R848A reduced Na,K-ATPase activity by 75, 89, and 66%, respectively. Steady-state phosphoenzyme formation from ATP was reduced in mutants R834A, R837A, and R848A, and R837A also had a faster E2P-->E-2 dephosphorylation rate compared with the wild-type enzyme. Effects of L6/7 mutations on the phosphorylation domain of the protein were also demonstrated by O-18 exchange, which showed that intrinsic rate constants for P-i binding and/or reaction with the protein were altered. Although most L6/7 mutations had no effect on the interaction of Na+ or K+ with Na,K-ATPase, the E825A, E828A, R834A, and R837A mutations reduced the apparent affinity of the enzyme for both Na+ and K+ by 1.5-3-fold. 1-Bromo-2,4,6-tris(methylisothiouronium) benzene (Br-TITU3+), a competitive antagonist of Rb+ and Na+ occlusion (Hoving, S., Bar-Shimon, M., Tijmes, J.J., Goldschleger, R., Tal, D. M., and Karlish, S.J.D. (1995) J. Biol. Chem. 270, 29788-29793), was used to test whether charged residues in L6/7 are involved in binding monovalent cations and cation antagonists. Br-TITU3+ inhibited ouabain binding to wild type Na, K-ATPase with an IC50 of 30 muM. Ouabain binding to the E825A, E828A, R834A, or R837A mutants was still inhibited by Br-TITU3+, indicating that Br-TITU3+ does not bind to charged residues in L6/7. This observation makes it unlikely that L6/7 functions as a cytoplasmic cation binding site in Na,K-ATPase, and together with the effects of L6/7 mutations on phosphate interactions with the enzyme suggests that L6/7 is important in stabilizing the phosphorylation domain and its relationship to the ion binding sites of the protein. C1 Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Farley, RA (reprint author), Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, 1333 San Pablo St,MMR 250, Los Angeles, CA 90033 USA. EM rfarley@usc.edu FU NIDDK NIH HHS [DK52802]; NIGMS NIH HHS [GM28673] NR 37 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 29 PY 2004 VL 279 IS 44 BP 45594 EP 45602 DI 10.1074/jbc.M408147200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 865IC UT WOS:000224694900038 PM 15322120 ER PT J AU Yin, L Huang, L Kufe, D AF Yin, L Huang, L Kufe, D TI MUC1 oncoprotein activates the FOXO3a transcription factor in a survival response to oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; GROWTH-FACTOR RECEPTOR; BETA-CATENIN; CELL-CYCLE; C-SRC; PROTEIN; PATHWAY; DOMAIN; DF3; GENE AB The MUC1 transforming protein is aberrantly overexpressed by most human carcinomas. Recent studies demonstrated that MUC1 confers a protective function against oxidative stress-induced apoptosis; however, the mechanisms responsible for this response are not known. The present work demonstrates that MUC1 regulates FKHRL1/FOXO3a, a member of the forkhead family of transcription factors that induces oxidant scavenging and DNA repair. We show that MUC1 attenuates activation of the phosphoinositide 3-kinase --> phosphoAkt/PKB pathway in HCT116 colon carcinoma cells and thereby decreases FOXO3a phosphorylation. MUC1 is expressed as an N-terminal ectodomain that is tethered to the cell surface by a C-terminal transmembrane subunit. The results demonstrate that the MUC1 cytoplasmic domain is sufficient to induce FOXO3a activation and attenuation of oxidative stress. We also demonstrate that stable down-regulation of endogenous MUC1 in ZR75-1 breast cancer cells inactivates FOXO3a, increases intracellular oxidant levels, and sensitizes cells to H2O2-induced necrosis. These findings indicate that MUC1 regulates the FOXO3a signaling pathway in a survival response to oxidative stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA97098, CA98628] NR 30 TC 68 Z9 71 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 OCT 29 PY 2004 VL 279 IS 44 BP 45721 EP 45727 DI 10.1074/jbc.M408027200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 865IC UT WOS:000224694900054 PM 15322085 ER PT J AU Mukherjee, S AF Mukherjee, S TI Becoming a physician: A precarious exchange SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Dana Farber Partners Canc Care, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Mukherjee, S (reprint author), Dana Farber Partners Canc Care, Boston, MA 02115 USA. NR 3 TC 47 Z9 48 U1 0 U2 0 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 OCT 28 PY 2004 VL 351 IS 18 BP 1822 EP 1824 DI 10.1056/NEJMp048085 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 865SM UT WOS:000224723100003 PM 15509813 ER PT J AU Swartz, MN AF Swartz, MN TI Bacterial meningitis - A view of the past 90 years SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Swartz, MN (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 4 TC 89 Z9 94 U1 1 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 OCT 28 PY 2004 VL 351 IS 18 BP 1826 EP 1828 DI 10.1056/NEJMp048246 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 865SM UT WOS:000224723100005 PM 15509815 ER PT J AU Eskandar, EN Loeffler, JS O'Neill, AM Hunter, GJ Louis, DN Batchelor, T AF Eskandar, EN Loeffler, JS O'Neill, AM Hunter, GJ Louis, DN Batchelor, T TI A man with a seizure and a frontal-lobe brain lesion - Anaplastic oligodendroglioma with allelic loss of chromosomes 1p and 19q SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MOLECULAR-GENETIC-ANALYSIS; GROWTH-FACTOR RECEPTOR; GLIOBLASTOMA-MULTIFORME; CHEMOTHERAPY; SURVIVAL; P53; AMPLIFICATION; RADIOTHERAPY; PREDICTORS; GLIOMAS C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Eskandar, EN (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 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 OCT 28 PY 2004 VL 351 IS 18 BP 1875 EP 1882 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 865SM UT WOS:000224723100012 PM 15509821 ER PT J AU Blumenthal, D AF Blumenthal, D TI Doctors and drug companies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PHARMACEUTICAL-INDUSTRY; PHYSICIANS; GIFTS; REPRESENTATIVES; PRACTITIONERS; PERSPECTIVE; GUIDELINES; ETHICS; PIZZA; PAYS C1 Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. NR 36 TC 127 Z9 134 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 OCT 28 PY 2004 VL 351 IS 18 BP 1885 EP 1890 DI 10.1056/NEJMhpr042734 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 865SM UT WOS:000224723100014 PM 15509823 ER PT J AU Kawakubo, H Carey, JL Brachtel, E Gupta, V Green, JE Walden, PD Maheswaran, S AF Kawakubo, H Carey, JL Brachtel, E Gupta, V Green, JE Walden, PD Maheswaran, S TI Expression of the NF-kappa B-responsive gene BTG2 is aberrantly regulated in breast cancer SO ONCOGENE LA English DT Article DE BTG2; breast cancer; cell cycle; cyclin D1; NF-kappa B ID MULLERIAN-INHIBITING SUBSTANCE; CYCLIN D1 TRANSCRIPTION; NERVE GROWTH-FACTOR; CELL-GROWTH; DOWN-REGULATION; TIS21 PROTEIN; DNA-DAMAGE; IN-VIVO; CARCINOMA; PC3 AB BTG2, a p53-inducible antiproliferative gene, is stimulated in breast cancer cells by activation of nuclear factor kappa B (NF-kappaB). In rat mammary glands, BTG2 is expressed in epithelial cells and levels decreased during pregnancy and lactation but recovered during involution. Estrogen and progestin suppress BTG2 expression, suggesting that these steroids, which stimulate proliferation and lobuloalveolar development of mammary epithelial cells, may downregulate BTG2 in the mammary gland during pregnancy. Consistent with the report that BTG2 inhibits cyclin D1 expression, suppression of BTG2 mRNA in the mammary gland during gestation, and by estrogen and progestin, correlated with stimulation of cyclin D1. Ectopic expression of BTG2 inhibited breast cancer cell growth by arresting cells in the G1 phase, an effect reversed by cyclin D1. BTG2 expression was very low or undetectable in human breast cancer cell lines compared with nontumorigenic mammary epithelial cells, and nuclear expression of BTG2 was absent in 65% of human breast tumors compared with adjacent matched normal glands. Spontaneous mammary tumors arising in a mouse model with targeted expression of the early region of the SV40 large tumor Ag demonstrated loss of BTG2 protein very early during the tumorigenic process. Thus deregulation of BTG2 may be an important step in the development of mammary tumors. C1 Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NYU Med Ctr, Dept Urol, New York, NY 10016 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Jackson 904,55 Fruit St, Boston, MA 02114 USA. EM maheswaran@helix.mgh.harvard.edu FU NCI NIH HHS [CA84441, CA89138] NR 44 TC 48 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 OCT 28 PY 2004 VL 23 IS 50 BP 8310 EP 8319 DI 10.1038/sj.onc.1208008 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 866CC UT WOS:000224749500013 PM 15378000 ER PT J AU Jenkins, BG Sanchez-Pernaute, R Brownell, AL Chen, YCI Isacson, O AF Jenkins, BG Sanchez-Pernaute, R Brownell, AL Chen, YCI Isacson, O TI Mapping dopamine function in primates using pharmacologic magnetic resonance imaging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amphetamine; dopamine; MRI; macaque; Parkinson's disease; PET ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-VOLUME; PARKINSONS-DISEASE; RHESUS-MONKEYS; BASAL GANGLIA; RAT-BRAIN; MRI; AMPHETAMINE; PET; RELEASE AB Dopamine (DA) receptors play a central role in such diverse pathologies as Parkinson's disease, schizophrenia, and drug abuse. We used an amphetamine challenge combined with pharmacologic magnetic resonance imaging (phMRI) to map DA-associated circuitry in nonhuman primates with high sensitivity and spatial resolution. Seven control cynomolgous monkeys and 10 MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated parkinsonian primates were studied longitudinally using both positron emission tomography ( PET) and phMRI. Amphetamine challenge (2.5 mg/kg, i.v.) in control monkeys increased relative cerebral blood volume (rCBV) in a number of brain regions not described previously, such as parafascicular thalamus, precentral gyrus, and dentate nucleus of the cerebellum. With the high spatial resolution, we were also able to readily identify changes in rCBV in the anterior cingulate, substantia nigra, ventral tegmental area, caudate (tail and head), putamen, and nucleus accumbens. Amphetamine induced decreases in rCBV in occipital and posterior parietal cortices. Parkinsonian primates had a prominent loss of response to amphetamine, with relative sparing of the nucleus accumbens and parafascicular thalamus. There was a significant correlation between rCBV loss in the substantia nigra and both PET imaging of dopamine transporters and behavioral measures. Monkeys with partial lesions as defined by 2alpha-carbomethoxy-3beta-(4-fluorophenyl) tropane binding to dopamine transporters showed recruitment of premotor and motor cortex after amphetamine stimulus similar to what has been noted in Parkinson's patients during motor tasks. These data indicate that phMRI is a powerful tool for assessment of dynamic changes associated with normal and dysfunctional DA brain circuitry in primates. C1 Massachusetts Gen Hosp, Positron Emiss Tomog Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. McLean Hosp, Neuroregenerat Lab, Belmont, MA 02478 USA. RP Jenkins, BG (reprint author), MGH, Nucl Magnet Resonance Ctr, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bgj@nmr.mgh.harvard.edu FU NCRR NIH HHS [P51 RR000168, P51RR00168]; NIDA NIH HHS [DA-09467, DA-16187A, P01 DA009467, R01 DA016187]; NINDS NIH HHS [NS-39793, P50 NS039793, P50 NS039793-05] NR 47 TC 64 Z9 67 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 27 PY 2004 VL 24 IS 43 BP 9553 EP 9560 DI 10.1523/JNEUROSCI.1558-04.2004 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 866CD UT WOS:000224749600010 PM 15509742 ER PT J AU Cooke, DT Caffarelli, AD Robbins, RC AF Cooke, DT Caffarelli, AD Robbins, RC TI The road to clinical xenotransplantation: A worthwhile journey SO TRANSPLANTATION LA English DT Article DE xenotransplantation; ethics; transplantation; clinical research ID TRANSPLANTATION; COMMITTEE; SOCIETY; HEART AB Xenotransplantation carries numerous ethical dilemmas. In the Position Paper of the Ethics Committee of the International Xenotransplantation Association, Sykes et al. diagram important ethics issues including respect for clinical subjects characterized by proper informed consent, and beneficence to the patient and the community at large, highlighting the possible risk of porcine endogenous retroviruses and xenotourism. We propose optimizing informed consent to take into account the psychological, scientific, and ethical nuances of xenotransplantation. Moreover, regulation of xenotourism should mirror established U.S. guidelines for visitors with communicable diseases, thereby not limiting the rights of xenotransplant recipients. C1 Stanford Univ, Dept Cardiothorac Surg, Ctr Med, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Cooke, DT (reprint author), Stanford Univ, Dept Cardiothorac Surg, Ctr Med, 300 Pasteur Dr,Falk Cardiovasc Res Bldg, Stanford, CA 94305 USA. EM dcooke@partners.org NR 10 TC 3 Z9 3 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2004 VL 78 IS 8 BP 1108 EP 1109 DI 10.1097/01.TP.0000142609.97203.EC PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 871DW UT WOS:000225110500004 PM 15502703 ER PT J AU Ishiyama, M Ramabadran, RS Sekiguchi, K Sakata, Y DeFreitas, G Carabello, BA Mann, DL AF Ishiyama, M Ramabadran, RS Sekiguchi, K Sakata, Y DeFreitas, G Carabello, BA Mann, DL TI Hemodynamic overload provokes accelerated cardiac decompensation in DARE mice that lack TNF AU-rich elements SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 22 BP 7 EP 7 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500023 ER PT J AU Grazette, LP Matsui, T Rosenzweig, A AF Grazette, LP Matsui, T Rosenzweig, A TI Inhibition of erbB2 causes mitochondrial dysfunction and impaired growth response in cardiomyocytes through altered Bcl-xS/Bcl-xL signaling: Implications for herceptin-induced cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 29 BP 8 EP 8 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500030 ER PT J AU Pathak, A del Monte, F Zhao, W Carr, A Schultz, JE Hahn, H Syed, F Mareez, Y DePaoli-Roach, A Hajjar, RJ Kranias, EG AF Pathak, A del Monte, F Zhao, W Carr, A Schultz, JE Hahn, H Syed, F Mareez, Y DePaoli-Roach, A Hajjar, RJ Kranias, EG TI Therapeutic targeting of the type 1 phosphatase activity in murine models of cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Cincinnati, Cincinnati, OH USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Proctor & Gamble Pharm, Cincinnati, OH USA. Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 96 BP 22 EP 22 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500096 ER PT J AU Dewald, O Ren, GF Klemm, C Koerting, A Winkelmann, K Rollins, BJ Entman, ML Frangogiannis, NG AF Dewald, O Ren, GF Klemm, C Koerting, A Winkelmann, K Rollins, BJ Entman, ML Frangogiannis, NG TI The role of monocyte chemoattractant protein (MCP)-1 in infarct healing SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Dewald, Oliver/A-3126-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 125 BP 28 EP 28 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500124 ER PT J AU Georgescu, SP Li, JH Karas, RH Brown, M Mendelsohn, ME AF Georgescu, SP Li, JH Karas, RH Brown, M Mendelsohn, ME TI Modulator recognition factor 1 (MRF1), an ARID-family member, is a novel corepressor for estrogen receptor-alpha SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Tufts New England Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 146 BP 32 EP 32 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500145 ER PT J AU Hataishi, R Morgan, JG Rodrigues, ACT Ichinose, F Zapol, WM Picard, MH Bloch, KD Scherrer-Crosbie, M AF Hataishi, R Morgan, JG Rodrigues, ACT Ichinose, F Zapol, WM Picard, MH Bloch, KD Scherrer-Crosbie, M TI Inhaled nitric oxide limits murine ischemia-reperfusion injury SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 234 BP 50 EP 50 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500233 ER PT J AU Mani, K Nam, YJ Ashton, AW Peng, CF Krishnamurthy, B Korsmeyer, SJ Crow, MT Kitsis, RN AF Mani, K Nam, YJ Ashton, AW Peng, CF Krishnamurthy, B Korsmeyer, SJ Crow, MT Kitsis, RN TI Molecular mechanism of Bax inhibition by ARC SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, HHMI, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 261 BP 57 EP 57 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500264 ER PT J AU Deschenes, I Armoundas, AA Jones, SP Poelzing, S Tomaselli, GF AF Deschenes, I Armoundas, AA Jones, SP Poelzing, S Tomaselli, GF TI Functional link between Na channels and I-to revealed by posttranscriptional gene silencing of Na-v beta(1) in cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 283 BP 61 EP 61 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500286 ER PT J AU Colston, JT de la Rosa, SD Strader, JR Anderson, MA Freeman, GL AF Colston, JT de la Rosa, SD Strader, JR Anderson, MA Freeman, GL TI H2O2 activates Nox4 through phospholipase A(2)-dependent arachidonic acid production in adult cardiac fibroblasts SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 421 BP 89 EP 90 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500422 ER PT J AU Zhang, P Guccione, JM Nicholas, SI Walker, JC Crawford, PC Shamal, A Saloner, D Wallace, AW Ratcliffe, MB AF Zhang, P Guccione, JM Nicholas, SI Walker, JC Crawford, PC Shamal, A Saloner, D Wallace, AW Ratcliffe, MB TI Effect of Dor procedure in the left ventricle with dyskinetic anterior wall on ventricular volume, chamber stiffness, and function SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 489 BP 103 EP 104 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500490 ER PT J AU Freeman, MW Fanier, M Bays, HE Macdonell, G Davies, MJ Mitchel, Y Gumbiner, B AF Freeman, MW Fanier, M Bays, HE Macdonell, G Davies, MJ Mitchel, Y Gumbiner, B TI Efficacy and safety of coadministered fenofibrate and ezetimibe in patients with mixed hyperlipidemia SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Point Med, Dijon, France. Louisville Metab & Atherosclerosis Res Ctr, Louisville, KY USA. Merck & Co Inc, Rahway, NJ 07065 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 556 BP 117 EP 117 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500556 ER PT J AU Zhan, YM Brown, C Ho, IC Wang, H Oettgen, P AF Zhan, YM Brown, C Ho, IC Wang, H Oettgen, P TI Ets-1 is a transcriptional mediator of angiotensin II-induced vascular inflammation and remodeling SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RI Wang, Hong/H-6298-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 565 BP 119 EP 119 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500565 ER PT J AU Erwin, PA Michel, T AF Erwin, PA Michel, T TI Dynamic S-nitrosylation of endothelial nitric oxide synthase: Identification of a novel intracellular pathway for receptor-modulated regulation of NO synthase SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 575 BP 121 EP 122 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500575 ER PT J AU Yu, PB Beppu, H Kawai, N Ichinose, F Bloch, KD Li, E AF Yu, PB Beppu, H Kawai, N Ichinose, F Bloch, KD Li, E TI Pulmonary artery smooth muscle cells deficient in type II bone morphogenetic protein receptor exhibit gain of function in response to bone morphogenetic protein 7 SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Novartis Inst BioMed Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 623 BP 131 EP 131 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500623 ER PT J AU Tribble, D Farnier, M Freeman, MW Macdonell, G Perevozskaya, I Davies, MJ Gumbiner, B AF Tribble, D Farnier, M Freeman, MW Macdonell, G Perevozskaya, I Davies, MJ Gumbiner, B TI Effect of Fenofibrate and Ezetimibe on lipoprotein subclasses and LDL subclass pattern in patients with mixed hyperlipidemia SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Merck & Co Inc, Rahway, NJ 07065 USA. Point Med, Dijon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 679 BP 143 EP 144 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500679 ER PT J AU Liu, E Friedrich, EB Sinha, S St-Arnaud, R Force, T Rosenzweig, A Dedhar, S Gerszten, RE AF Liu, E Friedrich, EB Sinha, S St-Arnaud, R Force, T Rosenzweig, A Dedhar, S Gerszten, RE TI Targeted deletion of ILK reveals an essential role in vertebrate development SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Montreal, PQ, Canada. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Jack Bell Res Ctr, Vancouver, BC, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 686 BP 145 EP 145 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500686 ER PT J AU Lewis, GD Witzke, C Colon-Hernandez, P Guerrero, JL Bloch, KD Semigran, MJ AF Lewis, GD Witzke, C Colon-Hernandez, P Guerrero, JL Bloch, KD Semigran, MJ TI Sildenafil abolishes cyclic coronary occlusion in a canine model of platelet-mediated coronary occlusion after thrombolysis SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 714 BP 150 EP 150 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500713 ER PT J AU Leopold, JA Scribner, AW Dam, A Liao, RL Stanton, R Loscalzo, J AF Leopold, JA Scribner, AW Dam, A Liao, RL Stanton, R Loscalzo, J TI Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 733 BP 154 EP 154 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500732 ER PT J AU Jaffer, FA Tung, CH Wykrzykowska, JJ Ho, NH Houng, AK Reed, GL Weissleder, R AF Jaffer, FA Tung, CH Wykrzykowska, JJ Ho, NH Houng, AK Reed, GL Weissleder, R TI Molecular imaging of factor XIIIa activity in thrombosis using a novel, near infrared fluorescent contrast agent that covalently links to thrombi SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 832 BP 174 EP 174 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500829 ER PT J AU Potente, M Urbich, C Hofmann, WK Kollipara, R Depinho, RA Zeiher, AM Dimmeler, S AF Potente, M Urbich, C Hofmann, WK Kollipara, R Depinho, RA Zeiher, AM Dimmeler, S TI Forkhead transcription factors: Novel transcriptional repressors of eNOS to block endothelial migration and angiogenesis SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Frankfurt, D-6000 Frankfurt, Germany. Charite, Berlin, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 830 BP 174 EP 174 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500827 ER PT J AU Liu, E Heller, E Koehn, S Huang, P Freeman, M Tager, A Moore, K Luster, A Gerszten, R AF Liu, E Heller, E Koehn, S Huang, P Freeman, M Tager, A Moore, K Luster, A Gerszten, R TI Pleiotropic effects of leukotriene B-4 receptor BLT1 on early atheragenesis SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 842 BP 177 EP 177 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501001 ER PT J AU Arikawa, E Ma, RC He, ZH King, GL AF Arikawa, E Ma, RC He, ZH King, GL TI Fatty acid compromises cardiac glucose oxidation through attenuation of insulin-stimulated Akt phosphorylation and induction of fuel-metabolizing genes via protein kinase C (PKC) activation SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RI Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1004 BP 210 EP 210 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501163 ER PT J AU Orasanu, G Ziouzenkova, O Ahmed, W Shoelson, S Plutzky, J AF Orasanu, G Ziouzenkova, O Ahmed, W Shoelson, S Plutzky, J TI Lipoprotein metabolism and uptake direct divergent peroxisome proliferator-activated receptor alpha and hepatocyte nuclear factor 4 alpha responses SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1007 BP 211 EP 211 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501166 ER PT J AU Saam, T Takaya, N Polissar, NL Hatsukami, TS Yuan, C AF Saam, T Takaya, N Polissar, NL Hatsukami, TS Yuan, C TI Identification of early hemorrhage with magnetic resonance imaging is highly associated with markers of plaque vulnerability and patients' symptom status SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Washington, Seattle, WA 98195 USA. Mt Whisper Light Stat Consulting, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1190 BP 248 EP 248 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501348 ER PT J AU Caironi, P Ichinose, F Liu, R Jones, RC Bloch, KD Zapol, WM AF Caironi, P Ichinose, F Liu, R Jones, RC Bloch, KD Zapol, WM TI 5-lipoxygenase deficiency prevents respiratory failure and impairment of hypoxic pulmonary vasoconstriction during ventilator-induced lung injury SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1193 BP 249 EP 249 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501351 ER PT J AU Chen, HJ Michel, T AF Chen, HJ Michel, T TI Insulin signaling in vascular endothelium: A key role for heterotrimeric G proteins revealed by siRNA-mediated g beta 1 subunit knockdown SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1231 BP 258 EP 258 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501389 ER PT J AU Nagoshi, T Matsui, T Champion, HC Li, L Rosenzweig, A AF Nagoshi, T Matsui, T Champion, HC Li, L Rosenzweig, A TI Adenoviral expression of activated P13-kinase rescues detrimental effects of chronic cardiac-specific Akt activation SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 3 Z9 3 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 1364 BP 285 EP 285 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501521 ER PT J AU Wu, SM Orkin, SH AF Wu, SM Orkin, SH TI Embryonic stem cell-derived cKit positive Nkx2-5 positive cardiomyogenic stem cells are clonogenic, highly proliferative, and differentiate spontaneously into beating cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1447 BP 302 EP 303 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501603 ER PT J AU Buys, ES Sips, P Rogge, E Dewerchin, M Brouckaert, P AF Buys, ES Sips, P Rogge, E Dewerchin, M Brouckaert, P TI Gender-specific hypertension in mice deficient in the alpha(1) subunit of soluble guanylate cyclase SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Ghent Univ VIB, Ghent, Belgium. Catholic Univ Leuven VIB, Louvain, Belgium. NR 0 TC 2 Z9 2 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 1466 BP 307 EP 307 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501622 ER PT J AU Nadkarni, SK Helg, T Bouma, BE Chan, RC Minsky, MS Chau, A Motz, JT Houser, S Tearney, GJ AF Nadkarni, SK Helg, T Bouma, BE Chan, RC Minsky, MS Chau, A Motz, JT Houser, S Tearney, GJ TI Identification of vulnerable atherosclerotic plaque features by the analysis of laser speckle patterns SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1495 BP 312 EP 312 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501650 ER PT J AU Sedding, DG Ramaswamy, S Sellers, WR Braun-Dullaeus, RC AF Sedding, DG Ramaswamy, S Sellers, WR Braun-Dullaeus, RC TI The forkhead transcription factor Fox01a regulates cell cycle entry of smooth muscle cells and prevents neointima formation SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Giessen, Giessen, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dresden Univ Technol, D-8027 Dresden, Germany. RI Braun-Dullaeus, Ruediger/G-1844-2013 OI Braun-Dullaeus, Ruediger/0000-0003-3888-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1506 BP 314 EP 315 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501660 ER PT J AU Dewald, O Ren, GF Winkelmann, K Koerting, A Kraemer, D Taffet, G Rollins, BJ Entman, ML Frangogiannis, NG AF Dewald, O Ren, GF Winkelmann, K Koerting, A Kraemer, D Taffet, G Rollins, BJ Entman, ML Frangogiannis, NG TI The crucial role of monocyte chemoatractant protein-1 in the development of murine ischemic cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Clin Ctr, Bonn, Germany. Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Dewald, Oliver/A-3126-2008 NR 0 TC 1 Z9 1 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 1536 BP 320 EP 321 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501689 ER PT J AU Janssens, SP Pokreisz, P Pellens, M Vermeersch, P Jans, P Gillijns, H Schoonjans, L Van de Werf, F Collen, D Bloch, K AF Janssens, SP Pokreisz, P Pellens, M Vermeersch, P Jans, P Gillijns, H Schoonjans, L Van de Werf, F Collen, D Bloch, K TI Cardiomyocyte-specific NOS3 overexpression protects against chronic pressure overload-induced LV hypertrophy and dysfunction. SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Katholieke Univ Leuven, Louvain, Belgium. Thromb X, Louvain, Belgium. Massachusetts Gen Hosp, Cardiol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Vermeersch, Pieter/M-8352-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1599 BP 333 EP 334 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501751 ER PT J AU Ichinose, F Morgan, JG Buys, E Scherrer-Crosbie, M Janssens, S Bloch, KD AF Ichinose, F Morgan, JG Buys, E Scherrer-Crosbie, M Janssens, S Bloch, KD TI Cardiomyocyte-restricted overexpression of NOS3 prevents endotoxin-induced myocardial dysfunction in mice SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Katholieke Univ Leuven, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1600 BP 334 EP 334 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501752 ER PT J AU Nesta, F Leyne, M Simpson, C Dai, D Marshall, JE Hung, J Slaugenhaupt, SA Levine, RA AF Nesta, F Leyne, M Simpson, C Dai, D Marshall, JE Hung, J Slaugenhaupt, SA Levine, RA TI A new locus for autosomal dominant mitral valve prolapse on chromosome 13: Clinical lessons SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 1605 BP 335 EP 335 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501757 ER PT J AU Everett, BM Foo, SY Criss, D Van Cott, EM Laposata, M Jang, IK Torchiana, D Walker, JF AF Everett, BM Foo, SY Criss, D Van Cott, EM Laposata, M Jang, IK Torchiana, D Walker, JF TI The prevalence of heparin/platelet factor 4 antibody is high in patients undergoing cardiac surgery SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1710 BP 358 EP 358 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502027 ER PT J AU Zahid, M Sonel, AF Saba, S Good, CB AF Zahid, M Sonel, AF Saba, S Good, CB TI Perioperative risk of noncardiac surgery associated with aortic stenosis SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1718 BP 360 EP 360 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502035 ER PT J AU Gerull, B Heuser, A Schulze-Bahr, E MacRae, C Basson, C McDermott, D Lerman, B Markowitz, S Sasse-Klaassen, S Breithardt, G Wichter, T AF Gerull, B Heuser, A Schulze-Bahr, E MacRae, C Basson, C McDermott, D Lerman, B Markowitz, S Sasse-Klaassen, S Breithardt, G Wichter, T TI Genetic analyses idenitify common mutations of a new disease gene in patients with arrhythmogenic right ventricular cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Max Delbruck Ctr Mol Med, Berlin, Germany. Univ Hosp Munster, Munster, Germany. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1737 BP 364 EP 364 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502054 ER PT J AU Siebert, U Januzzi, JL Beinfeld, MT Cameron, R Gazelle, GS AF Siebert, U Januzzi, JL Beinfeld, MT Cameron, R Gazelle, GS TI NT-proBNP testing is cost-effective in the diagnostic assessment and management of dyspneic patients in the Emergency Department: A ProBNP investigation of dyspnea in the Emergency Department (PRIDE) substudy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1762 BP 369 EP 369 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502078 ER PT J AU Reddy, VY Malchano, ZJ Doshi, SK Holmvang, G Mikaelian, B Neuzil, P Ruskin, JN AF Reddy, VY Malchano, ZJ Doshi, SK Holmvang, G Mikaelian, B Neuzil, P Ruskin, JN TI Integration of CT/MR imaging with electroanatomical mapping to direct catheter ablation of atrial fibrillation: A strategy for rapid registration SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. Homolka Hosp, Prague, Czech Republic. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1780 BP 373 EP 373 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502096 ER PT J AU Ang, EO Neuzil, P Bergman, D Heist, K Doshi, S Ruskin, JN Reddy, VY AF Ang, EO Neuzil, P Bergman, D Heist, K Doshi, S Ruskin, JN Reddy, VY TI Intracardiac ultirsound imaging of the left atrium: Comparative study of Imaging from within the right atrium versus the left atrium SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Homolka Hosp, Prague, Czech Republic. Accuson, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1784 BP 374 EP 374 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502100 ER PT J AU Pinto, DS Kirtane, AJ Barron, HV Dumaine, R Murphy, SA Jeremias, A Morrow, DA Giugliano, RP Gibson, CM AF Pinto, DS Kirtane, AJ Barron, HV Dumaine, R Murphy, SA Jeremias, A Morrow, DA Giugliano, RP Gibson, CM TI U-shaped relationship of blood glucose with adverse outcomes among patients with ST-segment elevation myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Genentech Corp, San Francisco, CA USA. TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1850 BP 390 EP 390 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502171 ER PT J AU Cury, RC Schmidt, S Abbara, S Malchano, Z Neuzil, P Weichet, J Ruskin, JN Brady, TJ Reddy, VY AF Cury, RC Schmidt, S Abbara, S Malchano, Z Neuzil, P Weichet, J Ruskin, JN Brady, TJ Reddy, VY TI The relationship of the esophagus and aorta to the left atrium and pulmonary veins: Implications for catheter ablation of atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Na Homolce Hosp, Prague, Czech Republic. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1970 BP 417 EP 417 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502283 ER PT J AU Kirtane, AJ Martinezclark, P Rahman, A Ray, KK Karmpaliotis, D Pinto, DS Southard, M Perez-Estabrooks, L Wiviott, SD Aroesty, JM Murphy, SA Antman, EM Gibson, CM AF Kirtane, AJ Martinezclark, P Rahman, A Ray, KK Karmpaliotis, D Pinto, DS Southard, M Perez-Estabrooks, L Wiviott, SD Aroesty, JM Murphy, SA Antman, EM Gibson, CM TI Association of smoking with improved myocardial perfusion and the angiographic characterization of myocardial tissue perfusion following fibrinolytic therapy for ST-elevation myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2124 BP 451 EP 451 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502437 ER PT J AU Daimon, M Shiota, T Liddicoat, J Hayase, M Ruel, M Cohn, W Blacker, S Gillinov, AM AF Daimon, M Shiota, T Liddicoat, J Hayase, M Ruel, M Cohn, W Blacker, S Gillinov, AM TI Percutaneous mitral valve repair for chronic ischemic mitral regurgitation: Feasibility study in ovine model SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Texas Heart Inst, Houston, TX 77025 USA. Viacor Inc, Wilmington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2305 BP 489 EP 489 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502615 ER PT J AU Kumbhani, DJ Healey, NA Birjiniuk, V Crittenden, MD Treanor, PR Khuri, SF AF Kumbhani, DJ Healey, NA Birjiniuk, V Crittenden, MD Treanor, PR Khuri, SF TI Regional myocardial acidosis during aortic clamping determines adverse 30-day outcomes after cardiac surgery SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2371 BP 505 EP 505 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502690 ER PT J AU Teerlink, JR Massie, BM Cleland, JG Tzivoni, D Rainisio, M Frey, A AF Teerlink, JR Massie, BM Cleland, JG Tzivoni, D Rainisio, M Frey, A CA RITZ-1 Investigators TI The relationship between hypotension and renal dysfunction during tezosentan treatment for acute decompensated heart failure: An analysis of the randomized interventions with TeZosentan (RITZ-1) trial SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Calif San Francisco, San Francisco VAMC, San Francisco, CA 94143 USA. Univ Hull, Castle Hill Hosp, Kingston Upon Hull, Yorks, England. Shaare Zedek Med Ctr, Jerusalem, Israel. Actelion Pharm Ltd, Allschwil, Switzerland. RI Teerlink, John/D-2986-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2409 BP 514 EP 514 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502728 ER PT J AU Yoerger, DM Marcus, F Sherrill, D Calkins, H Zareba, W Towbin, JA Moss, A Picard, MH AF Yoerger, DM Marcus, F Sherrill, D Calkins, H Zareba, W Towbin, JA Moss, A Picard, MH CA Multidisciplinary Study Arrhythmog TI Quantitation of echocardiographic abnormalities in individuals meeting task force criteria for Arrhythmogenic Right Ventricular Dysplasia SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arizona, Tucson, AZ USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Rochester, Rochester, NY USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2418 BP 516 EP 516 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502737 ER PT J AU Baggish, AL Siebert, U Cameron, R Anwaruddin, S Chen, A Krauser, DG Tung, R Brown, DF Januzzi, JL AF Baggish, AL Siebert, U Cameron, R Anwaruddin, S Chen, A Krauser, DG Tung, R Brown, DF Januzzi, JL TI A clinical and biochemical risk score for the diagnosis of acute CHF: The proBNP investigation of Dyspnea in the Emergency Department (PRIDE) Acute CHF Score SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2428 BP 518 EP 518 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502747 ER PT J AU Foran-Melanson, S Sluss, P Lewandrowski, E Lewandrowski, K Januzzi, J AF Foran-Melanson, S Sluss, P Lewandrowski, E Lewandrowski, K Januzzi, J TI What are the optimal cut-points for NT-proBNP use in the emergency department? A ProBNP investigation of dyspnea in the Emergency Department (PRIDE) substudy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2429 BP 518 EP 518 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502748 ER PT J AU Januzzi, JL Sluss, P Lewandrowski, E Lewandrowski, K AF Januzzi, JL Sluss, P Lewandrowski, E Lewandrowski, K TI NT-proBNP combined with troponin T for the prediction of short-term mortality in decompensated acute CHF: A ProBNP investigation of dyspnea in the Emergency Department (PRIDE) substudy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2430 BP 518 EP 519 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502749 ER PT J AU Teerlink, JR Cleland, JG Massie, BM Tzivoni, D Frey, A AF Teerlink, JR Cleland, JG Massie, BM Tzivoni, D Frey, A CA RITZ-1 Investigators TI Treatments for acute decompensated heart failure have significant international variations: An analysis of the randomized interventions with TeZosentan (RITZ-1) trial SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Calif San Francisco, San Francisco VAMC, San Francisco, CA 94143 USA. Univ Hull, Castle Hill Hosp, Kingston Upon Hull, Yorks, England. Shaare Zedek Med Ctr, Jerusalem, Israel. Actelion Pharm Ltd, Allschwil, Switzerland. RI Teerlink, John/D-2986-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2426 BP 518 EP 518 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502745 ER PT J AU Lisauskas, JB Ferencik, M Moselewski, F Houser, S Gupta, R Chan, RC Brady, TJ AF Lisauskas, JB Ferencik, M Moselewski, F Houser, S Gupta, R Chan, RC Brady, TJ TI Morphologic measurements of ex vivo coronary arteries from high resolution SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2448 BP 522 EP 523 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502767 ER PT J AU Kawasaki, M Tearney, GJ Houser, SL Chau, A Chan, R Bressner, J Nadkarni, K MacNeill, BD Jang, IK Bouma, BE AF Kawasaki, M Tearney, GJ Houser, SL Chau, A Chan, R Bressner, J Nadkarni, K MacNeill, BD Jang, IK Bouma, BE TI Comparison between optical coherent tomography (OCT) and integrated backscatter intravascular ultrasound (IB-IVUS) images for tissue characterization of human coronary plaques SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2463 BP 526 EP 526 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502782 ER PT J AU Pinto, DS Kirtane, AJ Barron, HV Blaney, M Frederick, PD Miller, DP Nallamothu, BK Bates, ER Antman, EM Cannon, CP Gibson, CM AF Pinto, DS Kirtane, AJ Barron, HV Blaney, M Frederick, PD Miller, DP Nallamothu, BK Bates, ER Antman, EM Cannon, CP Gibson, CM TI As door-to-balloon times exceed door-to-needle times at a given hospital, mortality in STEMI rises SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Genentech Inc, San Francisco, CA 94080 USA. Ovat Res Grp, Seattle, WA USA. Ovat Res Grp, San Francisco, CA USA. Univ Michigan, Ann Arbor, MI 48109 USA. TIMI Study Grp, Boston, MA USA. NR 0 TC 1 Z9 1 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 2510 BP 538 EP 538 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502829 ER PT J AU Sebag, IA Davis, MB Handschumacher, MD Ichinose, F Morgan, JG Hataishi, R Rodrigues, ACT Guerrero, JL Bloch, KD Scherrer-Crosbie, M AF Sebag, IA Davis, MB Handschumacher, MD Ichinose, F Morgan, JG Hataishi, R Rodrigues, ACT Guerrero, JL Bloch, KD Scherrer-Crosbie, M TI Quantitative assessment of regional myocardial function in mice by tissue Doppler imaging: Comparison with hemodynamics and sonomicrometry SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Sir Mortimer B Davis Jewish Hosp, Montreal, PQ H3T 1E2, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. INSERM, U644, Rouen, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2568 BP 551 EP 551 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503022 ER PT J AU Ellinor, PT Low, AF MacRae, CA AF Ellinor, PT Low, AF MacRae, CA TI Apelin levels in lone atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2694 BP 579 EP 579 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503148 ER PT J AU Abraham, WT Trupp, RJ Mehra, MR Lawless, CE Mitchell, JE Le Jemtel, TH Smart, FW Bijou, R O'Connor, CM Yancy, CW Massie, BM Silver, MA Packer, M AF Abraham, WT Trupp, RJ Mehra, MR Lawless, CE Mitchell, JE Le Jemtel, TH Smart, FW Bijou, R O'Connor, CM Yancy, CW Massie, BM Silver, MA Packer, M TI A multivariate impedance cardiography composite scare can predict the occurrence of major heart failure events: the PREDICT study SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Ohio State Univ, Ctr Heart, Columbus, OH 43210 USA. Ochsner Clin Fdn, New Orleans, LA USA. DuPage Med Grp, Chicago, IL USA. Suny Downstate Med Ctr, New York, NY USA. Albert Einstein Hosp, New York, NY USA. Texas Heart Inst, Houston, TX 77025 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Texas, SW Med Ctr, Dallas, TX USA. San Francisco VA Med Ctr, San Francisco, CA USA. Advocate Christ Med Ctr, Chicago, IL USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. NR 0 TC 7 Z9 7 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 2775 BP 597 EP 597 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503229 ER PT J AU Lim, CC Cui, L Pimentel, DR Wang, B Hajjar, R Liao, R AF Lim, CC Cui, L Pimentel, DR Wang, B Hajjar, R Liao, R TI Functional comparison of two missense mutations in troponin C identified in a patient with idiopathic dilated cardionnyopathy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2954 BP 635 EP 635 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503405 ER PT J AU Hill, JA Shah, MR Hasselblad, V Pauly, DF Russell, SD Nohria, A Koelling, TM Adams, KF Fonarow, GC Drazner, MH Frantz, RP DiSalvo, T Heroux, A Butler, J Tonkon, MJ Johnson, MR Yancy, CW AF Hill, JA Shah, MR Hasselblad, V Pauly, DF Russell, SD Nohria, A Koelling, TM Adams, KF Fonarow, GC Drazner, MH Frantz, RP DiSalvo, T Heroux, A Butler, J Tonkon, MJ Johnson, MR Yancy, CW TI Pulmonary artery catheter use does not change the contribution of renal dysfunction to outcomes in patients with advanced heart failure: Findings from ESCAPE SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Florida, Gainesville, FL USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Brigham & Womens Hosp, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Mayo Clin, Coll Med, Rochester, MN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Apex Res Inst, Santa Ana, CA USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 2 Z9 2 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 2964 BP 638 EP 638 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503415 ER PT J AU Gohler, A Dietz, R Osterziel, KJ Siebert, U AF Gohler, A Dietz, R Osterziel, KJ Siebert, U TI Combining the evidence and explaining the heterogeneity of the efficacy of disease management programs in patients with heart failure SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Humboldt Med Sch, Charite, Berlin, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2969 BP 639 EP 639 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503420 ER PT J AU Gohler, A Osterziel, KJ Siebert, U AF Gohler, A Osterziel, KJ Siebert, U TI Long-term effectiveness and cost-effectiveness of disease management programs in congestive heart failure: A decision-analytic view SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Humboldt Med Sch, Charite, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2968 BP 639 EP 639 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503419 ER PT J AU Schmidt, EJ Hayase, M Reddy, VY Dumoulin, CL AF Schmidt, EJ Hayase, M Reddy, VY Dumoulin, CL TI Self-expanding MRI imaging and tracking catheters for high-resolution intra-cardiac and vessel-wall imaging SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 GE Healthcare, Appl Sci Lab, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. GE Global Rsch Ctr, Niskayuna, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3005 BP 647 EP 647 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503455 ER PT J AU Rankin, SH Carroll, DL Hamilton, G AF Rankin, SH Carroll, DL Hamilton, G TI Peer advisors improve physical health outcomes in elders SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Hosp, Rikshosp, Oslo, Norway. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3034 BP 653 EP 653 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503483 ER PT J AU Ton-Nu, TT Levine, RA Handschumaker, MD Fan, DL Jiang, L Hung, J AF Ton-Nu, TT Levine, RA Handschumaker, MD Fan, DL Jiang, L Hung, J TI Nonplanarity of the tricuspid valve annulus: Assessment by real-time three-dimensional echocardiography SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3045 BP 655 EP 656 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503494 ER PT J AU Meine, TJ Roe, MT Chen, AY Patel, MR Washam, JB Smith, SC Brown, DF Fintel, D Peacock, F Pollack, CV Gibler, WB Peterson, ED AF Meine, TJ Roe, MT Chen, AY Patel, MR Washam, JB Smith, SC Brown, DF Fintel, D Peacock, F Pollack, CV Gibler, WB Peterson, ED TI The association of intravenous morphine use and outcomes in acute coronary syndromes: Results from the CRUSADE quality improvement initiative SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Duke Univ, Duke Clin Res Inst, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NW Mem Hosp, Chicago, IL 60611 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3056 BP 659 EP 659 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503505 ER PT J AU Mehta, RH Manfredini, R Bossone, E Fattori, R Evangelista, A Cooper, JV Sechtem, U Isselbacher, EM Nienaber, CA Eagle, KA AF Mehta, RH Manfredini, R Bossone, E Fattori, R Evangelista, A Cooper, JV Sechtem, U Isselbacher, EM Nienaber, CA Eagle, KA CA IRAD TI The winter peak in risk of acute aortic dissection is independent of the varying climatic conditions at different geographical locations SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Duke Univ, Clin Res Inst, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Ferrara, I-44100 Ferrara, Italy. Natl Rsch Council So Italy, Brindisi, Italy. Univ Hosp S Orsola, Bologna, Italy. Hosp Gen Univ Vall Hebron, Barcelona, Spain. Univ Michigan, Hlth Syst, Ann Arbor, MI 48109 USA. Robert Bosch Krankenhaus, Stuttgart, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rostock, Rostock, Germany. NR 0 TC 1 Z9 1 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 3107 BP 670 EP 670 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503556 ER PT J AU White, JK Titus, JS Yoneyama, R Jagannath, A Agnihotri, AK Madsen, JC Torchiana, DF AF White, JK Titus, JS Yoneyama, R Jagannath, A Agnihotri, AK Madsen, JC Torchiana, DF TI The relationship between particle dislodgement from an aortic wall simulator and fluid flow patterns from various aortic perfusion cannula SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3108 BP 670 EP 671 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503557 ER PT J AU Sosnovik, DE Schellenberger, E Matsui, T Dai, G Grazette, L Novikov, M Rosenzweig, A Weissleder, R Josephson, L AF Sosnovik, DE Schellenberger, E Matsui, T Dai, G Grazette, L Novikov, M Rosenzweig, A Weissleder, R Josephson, L TI Magnetic resonance imaging of cardiomyocyte apoptosis in vivo with a novel magneto-optical nanoparticle SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S BP 687 EP 687 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503628 ER PT J AU Gibson, CM Sabatine, MS Murphy, SA Morrow, DA Wiviott, SD Smith, S McCabe, CH Cannon, CP Braunwald, E AF Gibson, CM Sabatine, MS Murphy, SA Morrow, DA Wiviott, SD Smith, S McCabe, CH Cannon, CP Braunwald, E TI Association of intensive lipid lowering with reductions in target vessel revascularization (clinical restenosis) and non-target vessel revascularization (lesion progression): A PROVE IT TIMI 22 substudy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 TIMI Study Grp, Boston, MA USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3222 BP 696 EP 696 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503671 ER PT J AU Sabatine, MS Morrow, DA McCabe, CH Smith, S Meredith, I de Ferrari, G Gibson, CM AF Sabatine, MS Morrow, DA McCabe, CH Smith, S Meredith, I de Ferrari, G Gibson, CM TI Does intensive statin therapy reduce both urgent and elective coronary revascularization? Results from PROVE-IT TIMI 22 SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. Monash Med Ctr, Melbourne, Vic, Australia. Policlin San Matteo, I-27100 Pavia, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3220 BP 696 EP 696 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503669 ER PT J AU Derumeaux, G Morgan, JG Coman, T Cuesta, JM Lee, C Rodrigues, ACT Thilbault, H Raher, MJ Hatashi, R Buys, E Bloch, KD Ichinose, F Scherrer-Crosbie, M AF Derumeaux, G Morgan, JG Coman, T Cuesta, JM Lee, C Rodrigues, ACT Thilbault, H Raher, MJ Hatashi, R Buys, E Bloch, KD Ichinose, F Scherrer-Crosbie, M TI Exercise training attenuates aging-related left ventricular systolic dysfunction in mice: A strain-rate study SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3313 BP 716 EP 716 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503761 ER PT J AU Go, AS Yang, JR Ackerson, LM Lepper, KL Massie, BM Robbins, S Shlipalk, MG AF Go, AS Yang, JR Ackerson, LM Lepper, KL Massie, BM Robbins, S Shlipalk, MG TI Chronic kidney disease is the strongest predictor of developing anemia in heart failure: The kaiser permanente CHF cohort study SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Kaiser Permanente No Calif, Oakland, CA USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Amgen Inc, Thousand Oaks, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3344 BP 722 EP 723 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503792 ER PT J AU Ferencik, M Lisauskas, JB Cury, RC Hoffmann, U Abbara, S Achenbach, S Karl, WC Brady, TJ Chan, RC AF Ferencik, M Lisauskas, JB Cury, RC Hoffmann, U Abbara, S Achenbach, S Karl, WC Brady, TJ Chan, RC TI Improved vessel morphology measurements in contrast-enhanced multidetector spiral computed tomography coronary angiography using edge-preserving noise suppression and deblurring SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Erlangen Nurnberg, Erlangen, Germany. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3386 BP 732 EP 732 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503834 ER PT J AU Mukamal, KJ Mittleman, MA Maclure, M Muller, JE AF Mukamal, KJ Mittleman, MA Maclure, M Muller, JE TI Binge drinking and mortality following acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 OCT 26 PY 2004 VL 110 IS 17 SU S MA 3438 BP 743 EP 743 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504021 ER PT J AU Yosefy, C Hung, J Vaturi, M Shahzad, K Handschumacher, MD Levine, RA AF Yosefy, C Hung, J Vaturi, M Shahzad, K Handschumacher, MD Levine, RA TI A new simplified technique to improve accuracy of mitral regurgitation quantification by real time 3D echocardiography mapping of the proximal flow convergence region SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3446 BP 745 EP 745 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504029 ER PT J AU Yosefy, C Levine, RA Vaturi, M Ton-Nu, TT Handschumacher, M Hung, J AF Yosefy, C Levine, RA Vaturi, M Ton-Nu, TT Handschumacher, M Hung, J TI Real-time 3D echo can enhance assessment of the vena contracta width: Overcoming the problem of oblique measurement in eccentric jets SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3451 BP 746 EP 746 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504034 ER PT J AU Das, SR Dries, DL Drazner, MH Reynolds, DW Yancy, CW Chae, CU AF Das, SR Dries, DL Drazner, MH Reynolds, DW Yancy, CW Chae, CU TI Lower hematocrit is associated with risk of progression from ALVD to symptomatic heart failure SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 UT SW Med Ctr, Cardiovasc Clin Res Ctr, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3474 BP 751 EP 751 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504057 ER PT J AU Fang, MC Singer, DE Chang, YC Hylek, EM Henault, LE Jensvold, NG Go, AS AF Fang, MC Singer, DE Chang, YC Hylek, EM Henault, LE Jensvold, NG Go, AS TI Women are at higher risk than men for atrial fibrillation-related thromboembolism: The AnTicoagulation and risk factors in atrial fibrillation (ATRIA) study SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente No Calif, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3519 BP 763 EP 763 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504101 ER PT J AU Murabito, JM Nam, BH D'Agostino, RB Lloyd-Jones, DM Wang, TJ Wilson, PW O'Donnell, CJ AF Murabito, JM Nam, BH D'Agostino, RB Lloyd-Jones, DM Wang, TJ Wilson, PW O'Donnell, CJ TI Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: The Framingham Offspring Study SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Northwestern Univ, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NHLBI, Bethesda, MD 20892 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3527 BP 764 EP 764 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504109 ER PT J AU Albert, CM Oh, K Whang, W Manson, JE Stampfer, MJ Wilett, WC Hu, FB AF Albert, CM Oh, K Whang, W Manson, JE Stampfer, MJ Wilett, WC Hu, FB TI alpha-linolenic acid intake and risk of sudden cardiac death and fatal CHD among women SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3604 BP 781 EP 781 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504181 ER PT J AU Baruch, L Gage, B Persson, M Zabalgoitia, M Juul-Moller, S Labrovitz, A Horrow, J AF Baruch, L Gage, B Persson, M Zabalgoitia, M Juul-Moller, S Labrovitz, A Horrow, J TI Which is the most accurate stroke prediction scheme in atrial fibrillation patients treated with anticoagulants? A comparison of 5 risk stratification schemes SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. AstraZeneca R&D Molndal, Molndal, Sweden. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Hosp, Malmo, Sweden. St Louis Univ Hosp, St Louis, MO USA. AstraZeneca, Wilmington, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3616 BP 783 EP 784 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504193 ER PT J AU Peterson, PN Safley, D Vaglio, J Masoudi, FA Reid, KJ Spertus, JA Rumsfeld, JS AF Peterson, PN Safley, D Vaglio, J Masoudi, FA Reid, KJ Spertus, JA Rumsfeld, JS TI The impact of diabetes on one-year health status outcomes following acute coronary syndromes SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Colorado, Denver, CO 80202 USA. Univ Missouri, Kansas City, MO 64110 USA. Univ Kansas, Kansas City, KS USA. UMKC, Mid Amer Heart Inst, Kansas City, KS USA. Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3619 BP 784 EP 784 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504196 ER PT J AU Kumbhani, DJ Healey, NA Nawas, S Thatte, HS Crittenden, MD Birjiniuk, V Treanor, PR Khuri, SF AF Kumbhani, DJ Healey, NA Nawas, S Thatte, HS Crittenden, MD Birjiniuk, V Treanor, PR Khuri, SF TI Diabetic patients are at greater risk for developing intraoperative myocardial acidosis/ischemia during cardiac surgery SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3635 BP 786 EP 786 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504202 ER PT J AU Deswal, A Petersen, NJ Urbauer, DL Beyth, R Debakey, ME AF Deswal, A Petersen, NJ Urbauer, DL Beyth, R Debakey, ME TI Impact of race on the quality of outpatient care for heart failure SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3691 BP 798 EP 799 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504258 ER PT J AU Lopez-Garcia, E Schulze, MB Meigs, JB Manson, JE Rifai, N Stampfer, MJ Willett, WC Hu, FB AF Lopez-Garcia, E Schulze, MB Meigs, JB Manson, JE Rifai, N Stampfer, MJ Willett, WC Hu, FB TI Consumption of trans fatty acids and plasma markers of inflammation and endothelial dysfunction SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3739 BP 810 EP 810 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504305 ER PT J AU Fox, CS Coady, S Sorlie, PD Levy, D Meigs, JB Wilson, PW Savage, PJ AF Fox, CS Coady, S Sorlie, PD Levy, D Meigs, JB Wilson, PW Savage, PJ TI Trends in cardiovascular complications of diabetes: the Framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3746 BP 811 EP 811 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504312 ER PT J AU Dhingra, R Nam, BH Benjamin, EJ D'Agostino, RB Wilson, PW O'Donnell, CJ AF Dhingra, R Nam, BH Benjamin, EJ D'Agostino, RB Wilson, PW O'Donnell, CJ TI Relations of C-reactive protein to inflammatory conditions in men and women: Implications for cardiovascular disease risk prediction SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Massachusetts Gen Hosp, Framingham Heart Study, NHLBI, Boston, MA 02114 USA. Boston Univ, Med Ctr, Boston, MA USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3761 BP 814 EP 814 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504326 ER PT J AU Aronow, H Samaha, FF Kimmel, SE Williams, M Roche, D AF Aronow, H Samaha, FF Kimmel, SE Williams, M Roche, D TI Increasing statin dose is associated with a stepwise decline in long-term all-cause mortality SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3783 BP 819 EP 819 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504348 ER PT J AU McGuire, DK Khera, A de Lemos, JA Warner, JJ Keebler, ME Rogers, WJ Canto, JG AF McGuire, DK Khera, A de Lemos, JA Warner, JJ Keebler, ME Rogers, WJ Canto, JG TI Suboptimal use of evidenced-based medications before myocardial infarction among patients with and without diabetes mellitus: Observations from the national registry of myocardial infarction (NRMI) 4 SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Alabama, Birmingham, AL USA. Watson Clin, Lakeland, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3849 BP 834 EP 834 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504414 ER PT J AU Sabatine, MS Wiviott, SD Morrow, DA McCabe, CH Cannon, CP AF Sabatine, MS Wiviott, SD Morrow, DA McCabe, CH Cannon, CP TI High-dose atorvastatin associated with worse glycemic control: A PROVE-IT TIMI 22 substudy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 49 Z9 49 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 3848 BP 834 EP 834 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783504413 ER PT J AU Hoffmann, U Moselewski, F Cury, RC Ferencik, M Jang, IK Diaz, LJ Abbara, S Brady, TJ Achenbach, S AF Hoffmann, U Moselewski, F Cury, RC Ferencik, M Jang, IK Diaz, LJ Abbara, S Brady, TJ Achenbach, S TI Predictive value of 16-slice multidetector spiral computed tomography to detect significant obstructive coronary artery disease in patients at high risk for coronary artery disease - Patient-versus segment-based analysis SO CIRCULATION LA English DT Article DE tomography; atherosclerosis; coronary disease ID CT ANGIOGRAPHY; STENOSES; RECONSTRUCTION AB Background-In this study, we investigated the diagnostic value and limitations of multidetector computed tomography (MDCT)-based noninvasive detection of significant obstructive coronary artery disease ( CAD) in a consecutive high-risk patient population with inclusion of all coronary segments. Methods and Results-In a prospective, blinded, standard cross-sectional technology assessment, a cohort of 33 consecutive patients with a positive stress test result underwent 16-slice MDCT and selective coronary angiography for the detection of significant obstructive CAD. We assessed the diagnostic accuracy of MDCT in a segment-based and a patient-based model and determined the impact of stenosis location and the presence of calcification on diagnostic accuracy in both models. Analysis of all 530 coronary segments demonstrated moderate sensitivity (63%) and excellent specificity (96%) with a moderate positive predictive value of 64% and an excellent negative predictive value (NPV) of 96% for the detection of significant coronary stenoses. Assessment restricted to either proximal coronary segments or segments with excellent image quality (83% of all segments) led to an increase in sensitivity (70% and 82%, respectively), and high specificities were maintained (94% and 93%, respectively). In a patient-based model, the NPV of MDCT for significant CAD was limited to 75%. Coronary calcification was the major cause of false-positive findings ( 94%). Conclusions-For all coronary segments included, 16-slice MDCT has moderate diagnostic value for the detection of significant obstructive coronary artery stenosis in a population with a high prevalence of CAD. The moderate NPV of patient-based detection of CAD suggests a limited impact on clinical decision-making in high-risk populations. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Internal Med 2, Erlangen, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Ste 400, Boston, MA 02114 USA. EM uhoffman@partners.org NR 14 TC 294 Z9 311 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 BP 2638 EP 2643 DI 10.1161/01.CIR.0000145614.07427.9F PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 865JT UT WOS:000224699500015 PM 15492297 ER PT J AU Goh, S Butler, W Thiele, EA AF Goh, S Butler, W Thiele, EA TI Subependymal giant cell tumors in tuberous sclerosis complex SO NEUROLOGY LA English DT Article ID CONSENSUS CONFERENCE; EARLY-DIAGNOSIS; ASTROCYTOMA; TSC1; HETEROZYGOSITY; CHILDREN AB Objectives: To describe the clinical presentations, radiologic features, and postoperative outcomes of a clinic-based population of patients with subependymal giant cell tumors (SGCT) and tuberous sclerosis complex (TSC) and to redefine and reclassify SGCT based on radiologic, clinical, and pathologic criteria. Methods: Of 134 TSC patients evaluated from December 2001 to November 2003, 11 (8.2%) had undergone resection of a pathologically confirmed SGCT. The authors reviewed the medical records of each case. Follow-up ranged from 2 months to 36 years. Results: Four were asymptomatic at the time of resection while the other seven presented subacutely with fatigue, decreased appetite, headache, increased seizure frequency, visual field deficit, cognitive decline, or behavioral problems. Poor outcomes occurred in all patients aged 11 years or older at the time of resection. Conclusions: Subependymal giant cell tumors in patients with TSC appear to be of mixed glioneuronal lineage, and, therefore, the current practice of classifying these tumors as astrocytomas merits revision. The clinical diagnosis of SGCT should be made for subependymal lesions in TSC that are associated with symptoms, papilledema, or radiologic evidence of hydrocephalus or interval growth. A diagnosis of probable SGCT should be made when a lesion has the potential to cause obstruction based on size or location. Annual screening by MRI with or without contrast is indicated until at least 21 years of age even if subependymal nodules are absent on initial imaging. A diagnosis of SGCT or probable SGCT warrants more frequent monitoring or surgical intervention. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,VBK 830, Boston, MA 02114 USA. EM ethiele@partners.org NR 26 TC 115 Z9 119 U1 1 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 OCT 26 PY 2004 VL 63 IS 8 BP 1457 EP 1461 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 865VN UT WOS:000224732400022 PM 15505165 ER PT J AU Harada, H Quearry, B Ruiz-Vela, A Korsmeyer, SJ AF Harada, H Quearry, B Ruiz-Vela, A Korsmeyer, SJ TI Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; BCL-2 family; mitogen-activated protein kinase; BH3-only ID BCL-2 FAMILY-MEMBER; APOPTOTIC PROTEIN BIM; MITOCHONDRIAL DYSFUNCTION; BH3-ONLY PROTEIN; PROMOTES; DEATH; PATHWAY; HOMEOSTASIS; DEGRADATION; MAINTENANCE AB The "BH3-only" proapoptotic BCL-2 family members initiate the intrinsic apoptotic pathway. A small interfering RNA knockdown of BIM confirms this BH3-only member is important for the cytokine-mediated homeostasis of hematopoietic cells. We show here that the phosphorylation status of BIM controls its proapoptotic activity. IL-3, a hematopoietic survival factor, induces extracellular signal-regulated kinase/mitogen-activated protein kinase-mediated phosphorylation of BIM on three serine sites (S55, S65, and S100). After IL-3 withdrawal, only nonphosphorylated BIM interacts with the multidomain proapoptotic effector BAX. phosphorylation of BIM on exposure of cells to IL-3 dramatically reduces the BIM/BAX interaction. A nonphosphorylatable BIM molecule (S55A, S65A, and S100A) demonstrates enhanced interaction with BAX and enhanced proapoptotic activity. Thus, ERK/mitogen-activated protein kinase-dependent phosphorylation of BIM in response to survival factor regulates BIM/BAX interaction and the pro-death activity of BIM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol & Med, Boston, MA 02115 USA. Virginia Commonwealth Univ, Massey Canc Ctr, Dept Internal Med, Richmond, VA 23298 USA. RP Harada, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol & Med, Boston, MA 02115 USA. EM hharada@vcu.edu OI Ruiz-Vela, Antonio/0000-0002-4410-6208 NR 30 TC 216 Z9 218 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 2004 VL 101 IS 43 BP 15313 EP 15317 DI 10.1073/pnas.0406837101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 866OI UT WOS:000224782400009 PM 15486085 ER PT J AU Xie, C Shimaoka, M Xiao, T Schwab, P Klickstein, LB Springer, TA AF Xie, C Shimaoka, M Xiao, T Schwab, P Klickstein, LB Springer, TA TI The integrin alpha-subunit leg extends at a Ca2+-dependent epitope in the thigh/genu interface upon activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; I-LIKE DOMAIN; ADHESION MOLECULE-1 ICAM-1; SITE-DIRECTED MUTAGENESIS; POLYMERASE CHAIN-REACTION; CELL-ADHESION; CONFORMATIONAL-CHANGES; EXTRACELLULAR SEGMENT; OVERLAP EXTENSION; CRYSTAL-STRUCTURE AB Two activation-dependent Abs to the integrin alpha(L)-Subunit were used to study conformational rearrangement of alpha(L)beta(2) on the cell surface. Activation lowered the concentration of Ca2+ required for maximal expression of each epitope. Each Ab requires the Ca2+- binding loop in the integrin genu and nearby species-specific residues in the thigh domain. Key thigh residues are shielded from Ab in the bent integrin conformation by the alpha-subunit calf-1 domain and the nearby bent beta leg, suggesting that extension at the genu is required for epitope exposure. Activating stimuli and alpha/beta I-like small molecule antagonists demonstrate that exposure of epitopes in the integrin alpha- and beta-subunit legs is coordinate during integrin activation. A coordinating residue donated by the calf-1 domain is as important as Ca2+ for mAb binding. Together with inspection of the alpha(v) structure, this result suggests that the genu/ calf-1 interface is maintained in integrin activation, and that extension occurs by a rearrangement at the thigh/genu interface. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Xiao, Tsan/A-8590-2010; Xiao, Tsan/I-7616-2013 OI Xiao, Tsan/0000-0001-9688-475X FU NCI NIH HHS [R01 CA031798, R37 CA031798, CA31798] NR 35 TC 37 Z9 39 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 2004 VL 101 IS 43 BP 15422 EP 15427 DI 10.1079/pnas.0406680101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 866OI UT WOS:000224782400028 PM 15494438 ER PT J AU Reddy, J Illes, Z Zhang, XM Encinas, J Pyrdol, J Nicholson, L Sobel, RA Wucherpfennig, KW Kuchroo, VK AF Reddy, J Illes, Z Zhang, XM Encinas, J Pyrdol, J Nicholson, L Sobel, RA Wucherpfennig, KW Kuchroo, VK TI Myelin proteolipid protein-specific CD4(+) CD25(+) regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; IMMUNOLOGICAL SELF-TOLERANCE; IMMUNOREGULATORY T-CELLS; THYMIC SELECTION; MICE; SUSCEPTIBILITY; PEPTIDE; TETRAMERS; IL-12 AB SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, whereas H-2 congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are associated with a high precursor frequency of PLP 139-151-specific T cells in the naive repertoire of SA mice. To understand the mechanism of EAE resistance in B10.S mice, we determined the precursor frequency of PLP 139-151-reactive T cells in both strains by using IA(s)/PLP 139-151 tetramers. SJL and B10.S mice had similar frequencies of tetra mer-reactive T cells in the naive peripheral repertoire. However, in SJL mice, the majority of PLP 139-151 tetramer-positive cells were in the CD4(+)CD25(-) population, whereas there were more tetra mer-positive cells in the CD4(+)CD25(+) population of B10.S mice. Depletion of CD4(+)CD25(+) cells in vivo facilitated the expansion of PLP 139-151-reactive cells with production of T helper 1 cytokines in EAE-resistant B10.S mice. Furthermore, anti-CD25 Ab treatment before immunization resulted in EAE induction in these otherwise resistant mice. These data indicate an important role for autoantigen-specific CD4(+)CD25(+) cells in genetic resistance to autoimmunity. C1 Brigham & Womens Hosp, Ctr Neurol Dis, HIM, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Bristol, Sch Med Sci, Bristol BS8 1TD, Avon, England. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. RP Kuchroo, VK (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, HIM, Room 786,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vkuchroo@rics.bwh.harvard.edu RI Reddy, Jay/K-7200-2014 OI Reddy, Jay/0000-0003-4082-9254 FU NIAID NIH HHS [R01 AI44880, R01 AI044880]; NINDS NIH HHS [P01 NS38037, NS 046414, R01 NS046414, P01 NS038037, R01 NS030843, R01 NS30843]; PHS HHS [P01 A145757] NR 26 TC 136 Z9 140 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 2004 VL 101 IS 43 BP 15434 EP 15439 DI 10.1073/pnas.0404444101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 866OI UT WOS:000224782400030 PM 15492218 ER PT J AU Chao, MY Komatsu, H Fukuto, HS Dionne, HM Hart, AC AF Chao, MY Komatsu, H Fukuto, HS Dionne, HM Hart, AC TI Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLR-1 GLUTAMATE-RECEPTOR; MAMMALIAN SPINAL-CORD; EGG-LAYING BEHAVIOR; C-ELEGANS; NERVOUS-SYSTEM; PROTEIN; NEURONS; SYNAPSES; OLFACTION; RESPONSES AB Serotonin (5-HT) modulates synaptic efficacy in the nervous system of vertebrates and invertebrates. In the nematode Caenorhabditis elegans, many behaviors are regulated by 5-HT levels, which are in turn regulated by the presence or absence of food. Here, we show that both food and 5-HT signaling modulate chemosensory avoidance response of octanol in C elegans, and that this modulation is both rapid and reversible. Sensitivity to octanol is decreased when animals are off food or when 5-HT levels are decreased; conversely, sensitivity is increased when animals are on food or have increased 5-HT signaling. Laser microsurgery and behavioral experiments reveal that sensory input from different subsets of octanol-sensing neurons is selectively used, depending on stimulus strength, feeding status, and 5-HT levels. 5-HT directly targets at least one pair of sensory neurons, and 5-HT signaling requires the Galpha protein GPA-11. Glutamatergic signaling is required for response to octanol, and the GLR-1 glutamate receptor plays an important role in behavioral response off food but not on food. Our results demonstrate that 5-HT modulation of neuronal activity via G protein signaling underlies behavioral plasticity by rapidly altering the functional circuitry of a chemosensory circuit. C1 Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hart, AC (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, 149-7202 13th St, Charlestown, MA 02129 USA. EM hart@helix.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM057918, R01 GM057918-05]; NINDS NIH HHS [R01 NS055813] NR 42 TC 106 Z9 113 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 2004 VL 101 IS 43 BP 15512 EP 15517 DI 10.1073/pnas.0403369101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 866OI UT WOS:000224782400043 PM 15492222 ER PT J AU Ceriello, A Hanefeld, M Leiter, L Monnier, L Moses, A Owens, D Tajima, N Tuomilehto, J AF Ceriello, A Hanefeld, M Leiter, L Monnier, L Moses, A Owens, D Tajima, N Tuomilehto, J CA Int PGR Study Grp TI Postprandial glucose regulation and diabetic complications SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID POST-CHALLENGE HYPERGLYCEMIA; FASTING PLASMA-GLUCOSE; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; DOUBLE-BLIND; GLYCEMIC CONTROL; BLOOD-GLUCOSE; RISK-FACTOR; DIAGNOSTIC-CRITERIA; HELSINKI POLICEMEN AB Atherosclerotic disease accounts for much of the increased mortality and morbidity associated with type 2 diabetes. Epidemiological studies support the potential of improved glycemic control to reduce cardiovascular complications. An association between glycosylated hemoglobin (HbA(1c)) level and the risk for cardiovascular complications has frequently been reported. Most epidemiological data implicate postprandial hyperglycemia in the development of cardiovascular disease, whereas the link between fasting glycemia and diabetic complications is inconclusive. Moreover, in many studies, postprandial glycemia is a better predictor of cardiovascular risk than HbA(1c) level. Postprandial glucose may have a direct toxic effect on the vascular endothelium, mediated by oxidative stress that is independent of other cardiovascular risk factors such as hyperlipidemia. Postprandial hyperglycemia also may exert its effects through its substantial contribution to total glycemic exposure. The present review examines the hypothesis that controlling postprandial glucose level is an important strategy in the prevention of cardiovascular complications associated with diabetes. C1 Univ Udine, Dept Pathol & Med Expt & Clin, I-33100 Udine, Italy. Dresden Univ Technol, Ctr Clin Studies, Dresden, Germany. Univ Toronto, St Michaels Hosp, Div Endocrinol & Metab, Toronto, ON, Canada. Lapeyronie Hosp, Dept Metab, Montpellier, France. Joslin Diabet Ctr, Boston, MA USA. Llandough Hosp, Diabet Res Unit Acad Ctr, Penarth, S Glam, Wales. Jikei Univ, Sch Med, Dept Internal Med, Div Diabet & Endocrinol, Tokyo, Japan. Natl Publ Hlth Inst, Diabet & Genet Epidemiol Unit, Helsinki, Finland. RP Ceriello, A (reprint author), Univ Udine, Dept Pathol & Med Expt & Clin, Ple S Maria Misericordia 1, I-33100 Udine, Italy. EM ceriello@uniud.it NR 58 TC 170 Z9 178 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 25 PY 2004 VL 164 IS 19 BP 2090 EP 2095 DI 10.1001/archinte.164.19.2090 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 865NZ UT WOS:000224711100002 PM 15505121 ER PT J AU Kowalczyk, A Filipkowski, RK Rylski, M Wilczynski, GM Konopacki, FA Jaworski, J Ciemerych, MA Sicinski, P Kaczmarek, L AF Kowalczyk, A Filipkowski, RK Rylski, M Wilczynski, GM Konopacki, FA Jaworski, J Ciemerych, MA Sicinski, P Kaczmarek, L TI The critical role of cyclin D2 in adult neurogenesis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NERVOUS-SYSTEM; ENRICHED ENVIRONMENT; SUBVENTRICULAR ZONE; MESSENGER-RNA; DENTATE GYRUS; NEURONS; CELL; PROLIFERATION; MICE; BRAIN AB Adult neurogenesis (i.e., proliferation and differentiation of neuronal precursors in the adult brain) is responsible for adding new neurons in the dentate gyrus of the hippocampus and in the olfactory bulb. We describe herein that adult mice mutated in the cell cycle regulatory gene Ccnd2, encoding cyclin D2, lack newly born neurons in both of these brain structures. In contrast, genetic ablation of cyclin D1 does not affect adult neurogenesis. Furthermore, we show that cyclin D2 is the only D-type cyclin (out of D1, D2, and D3) expressed in dividing cells derived from neuronal precursors present in the adult hippocampus. In contrast, all three cyclin D mRNAs are present in the cultures derived from 5-day-old hippocampi, when developmental neurogenesis in the dentate gyrus takes place. Thus, our results reveal the existence of molecular mechanisms discriminating adult versus developmental neurogeneses. C1 Nencki Inst, Dept Mol & Cellular Neurobiol, PL-02093 Warsaw, Poland. Mossakowski Med Res Ctr, PL-02106 Warsaw, Poland. Med Univ Warsaw, Dept Pathol, PL-02106 Warsaw, Poland. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Kaczmarek, L (reprint author), Nencki Inst, Dept Mol & Cellular Neurobiol, PL-02093 Warsaw, Poland. EM leszek@nencki.gov.pl RI Kaczmarek, Leszek/B-6171-2008 OI Kaczmarek, Leszek/0000-0002-7207-3490 NR 30 TC 104 Z9 106 U1 2 U2 10 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 OCT 25 PY 2004 VL 167 IS 2 BP 209 EP 213 DI 10.1083/jcb.200404181 PG 5 WC Cell Biology SC Cell Biology GA 866IS UT WOS:000224767800004 PM 15504908 ER PT J AU Carman, CV Springer, TA AF Carman, CV Springer, TA TI A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them SO JOURNAL OF CELL BIOLOGY LA English DT Article ID VESICULO-VACUOLAR ORGANELLES; CENTRAL-NERVOUS-SYSTEM; TRANSENDOTHELIAL MIGRATION; INFLAMMATORY RESPONSE; NEUTROPHIL MIGRATION; LYMPHOCYTE MIGRATION; VENULES; ADHESION; ICAM-1; MONOLAYERS AB T he basic route and mechanisms for leukocyte migration across the endothelium remain poorly defined. We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel "cuplike" transmigratory structure. This endothelial structure was comprised of highly intercellular adhesion molecule-1- and vascular cell adhesion molecule-1-enriched vertical microvilli-like projections that surrounded transmigrating leukocytes and drove redistribution of their integrins into linear tracks oriented parallel to the direction of diapedesis. Disruption of projections was highly correlated with inhibition of transmigration. These findings suggest a novel mechanism, the "transmigratory cup", by which the endothelium provides directional guidance to leukocytes for extravasation. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 NR 39 TC 383 Z9 399 U1 1 U2 23 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 OCT 25 PY 2004 VL 167 IS 2 BP 377 EP 388 DI 10.1083/jcb.200404129 PG 12 WC Cell Biology SC Cell Biology GA 866IS UT WOS:000224767800019 PM 15504916 ER PT J AU Koybasi, S Senkal, CE Sundararaj, K Spassieva, S Bielawski, J Osta, W Day, TA Jiang, JC Jazwinski, SM Hannun, YA Obeid, LM Ogretmen, B AF Koybasi, S Senkal, CE Sundararaj, K Spassieva, S Bielawski, J Osta, W Day, TA Jiang, JC Jazwinski, SM Hannun, YA Obeid, LM Ogretmen, B TI Defects in cell growth regulation by C-18 : 0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; TELOMERASE ACTIVITY; ENDOGENOUS CERAMIDE; INDUCED APOPTOSIS; LAG1; YEAST; INHIBITION; GENERATION; ACTIVATION; CANCER AB In this study, endogenous long chain ceramides were measured in 32 human head and neck squamous cell carcinoma (HNSCC) and 10 nonsquamous head and neck carcinoma tumor tissues, as compared with adjacent noncancerous tissues, by liquid chromatography/mass spectroscopy. Interestingly, only one specific ceramide, C-18:0-ceramide, was selectively down-regulated in the majority of HNSCC tumor tissues. On the other hand, in nonsquamous tumor tissues, this selectivity for C-18-ceramide was not detected. These data suggested the hypotheses that decreased levels of C-18-ceramide might impart a growth advantage to HNSCC cells and that increased generation of C-18-ceramide may be involved in the inhibition of growth. These roles were examined by reconstitution of C-18-ceramide at physiologically relevant concentrations in UM-SCC-22A cells ( squamous cell carcinoma of hypopharynx) via overexpression of mammalian upstream regulator of growth and differentiation factor 1 (mUOG1), a mouse homologue of longevity assurance gene 1 (mLAG1), which has been shown to specifically induce the generation of C-18-ceramide. Liquid chromatography/mass spectroscopy analysis showed that overexpression of the mLAG1/mUOG1 resulted in increased levels of only C-18:0-ceramide by similar to2-fold, i.e. concentrations similar to those of normal head and neck tissues. Importantly, increased generation of C-18-ceramide by mLAG1/mUOG1 inhibited cell growth (similar to70-80%), which mechanistically involved the modulation of telomerase activity and induction of apoptotic cell death by mitochondrial dysfunction. In conclusion, this study demonstrates, for the first time, a biological role for LAG1 and C-18-ceramide in the regulation of growth of HNSCC. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. Abant Izzet Baysal Univ, Izzet Baysal Med Fac, Dept Otolaryngol, Bolu, Turkey. RP Ogretmen, B (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM ogretmen@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA-097132, CA-88932]; NIA NIH HHS [AG-16583, AG06168] NR 34 TC 115 Z9 121 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 OCT 22 PY 2004 VL 279 IS 43 BP 44311 EP 44319 DI 10.1074/jbc.M406920200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 862QJ UT WOS:000224505600012 PM 15317812 ER PT J AU Wang, YH Hancock, WS Weber, G Eckerskorn, C Palmer-Toy, D AF Wang, YH Hancock, WS Weber, G Eckerskorn, C Palmer-Toy, D TI Free flow electrophoresis coupled with liquid chromatography-mass spectrometry for a proteomic study of the human cell line (K562/CR3) SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE proteomic; electrophoresis; liquid chromatography; mass spectrometry; prefractionation ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; PEROXISOME SUBPOPULATIONS; CEREBROSPINAL-FLUID; GROWTH-HORMONE; RAT-LIVER; PREFRACTIONATION; PROTEINS; IDENTIFICATION; STRATEGY AB The requirement for prefractionation in proteomic analysis is linked to the challenge of performing such an analysis on complex biological samples and identifying low level components in the presence of numerous abundant housekeeping and structural proteins. The employment of a preliminary fractionation step results in a reduction of complexity in an individual fraction and permits more complete liquid chromatography/mass spectrometry (LC/MS) analysis. Free flow electrophoresis (FFE), a solution-based preparative isoelectric focusing technique, fractionates and enriches protein fractions according to their charge differences and is orthogonal in selectivity to the popular reversed phase high performance liquid chromatography (HPLC) fractionation step. In this paper, we explored the advantages of a combination of FFE and liquid chromatography/mass spectrometry to extend the dynamic range of a proteomic analysis of a complex cell lysate. In this study, the whole cell lysate of a chronic myelogeneous leukemia cell line, K562/CR3, was prefractionated by FFE into 96 fractions spanning pH 3-12. Of these, 35 fractions were digested with trypsin and then analyzed by LC/MS. Depending on the algorithm used for peptide assignment from MS/MS data, at least 319 proteins were identified through database searches. The results also suggested that pI could serve as an additional criterion besides peptide fragmentation pattern for protein identification, although in some cases, a pI shift might indicate post-translational modification. In summary, this study demonstrated that free flow electrophoresis provided a useful prefractionation step for proteomic analysis and when combined with LC/MS allowed the identification of significant number of low level proteins in complex samples. (C) 2004 Elsevier B.V. All fights reserved. C1 Northeastern Univ, Barnett Inst, Dept Chem & Chem Biol, Boston, MA 02115 USA. FFEWeber GmbH, D-82152 Martinsried, Germany. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Genom, Cambridge, MA 02139 USA. RP Hancock, WS (reprint author), Northeastern Univ, Barnett Inst, Dept Chem & Chem Biol, Boston, MA 02115 USA. EM wi.hancock@neu.edu NR 30 TC 30 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD OCT 22 PY 2004 VL 1053 IS 1-2 BP 269 EP 278 DI 10.1016/j.chroma.2004.08.164 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 864XZ UT WOS:000224667900030 PM 15543993 ER PT J AU Shelkovnikov, S Gonick, HC AF Shelkovnikov, S Gonick, HC TI Peroxynitrite but not nitric oxide donors destroys epinephrine: HPLC measurement and rat aorta contractility SO LIFE SCIENCES LA English DT Article DE epinephrine; nitric oxide; peroxynitrite; rat; aorta; contraction ID ESSENTIAL-HYPERTENSION; GUANYLATE-CYCLASE; PULMONARY-ARTERY; NITROGEN-OXIDES; RELAXATION; CATECHOLAMINES; NOREPINEPHRINE; INHIBITION; ADRENALINE; NITRATION AB Nitric oxide (INTO) and peroxynitrite (ONOO) have been reported to destroy catecholamines. We compared the ability of NO donors and peroxynitrite to decompose epinephrine in both chemical and pharmacological experiments. Epinephrine (1 muM) was incubated with NO donors (SNAP and MAHMA NONOate) and ONOO at a concentration of 0.1 mM in phosphate buffer (pH 7.4; 0.1 M) or Krebs solution for 10 minutes at 37 degreesC. HPLC revealed that the concentration of epinephrine in the presence of NO donors was unaltered. In contrast, peroxynitrite decreased epinephrine concentration more than 20 fold. Similar relationships were obtained in the study of rat thoracic aorta ring contraction. The contractile activity (EC50) of epinephrine in control solutions and after incubation of NE with NO donors did not change. EC50 was measured at 8-10 nM in control solutions and after preincubation with NO donors. However when epinephrine was preincubated with peroxynitrite, no contractile effect was evoked. Therefore, under these experimental conditions peroxynitrite, but not NO donors, was capable of destroying epinephrine. (C) 2004 Elsevier Inc. All rights reserved. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Nephrol Sect, Med & Res Sect, Los Angeles, CA 90073 USA. RP Shelkovnikov, S (reprint author), Univ Calif Irvine, Dept Pharmacol, MSRII,Room 350C, Irvine, CA 92697 USA. EM shelkovnikov@pcmagic.net NR 25 TC 20 Z9 22 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 22 PY 2004 VL 75 IS 23 BP 2765 EP 2773 DI 10.1016/j.lfs.2004.04.044 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 859SE UT WOS:000224287400003 PM 15464828 ER PT J AU Hock, H Hamblen, MJ Rooke, HM Schindler, JW Saleque, S Fujiwara, Y Orkin, SH AF Hock, H Hamblen, MJ Rooke, HM Schindler, JW Saleque, S Fujiwara, Y Orkin, SH TI Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells SO NATURE LA English DT Article ID IN-VIVO; TRANSGENIC MICE; DIFFERENTIATION; EXPANSION; CAPACITY; BMI-1; MYC AB Haematopoietic stem cells (HSCs) sustain blood production throughout life. HSCs are capable of extensive proliferative expansion, as a single HSC may reconstitute lethally irradiated hosts(1). In steady-state, HSCs remain largely quiescent and self-renew at a constant low rate, forestalling their exhaustion during adult life(2,3). Whereas nuclear regulatory factors promoting proliferative programmes of HSCs in vivo and ex vivo have been identified(4-6), transcription factors restricting their cycling have remained elusive. Here we report that the zinc-finger repressor Gfi-1 (growth factor independent 1), a cooperating oncogene in lymphoid cells(7,8), unexpectedly restricts proliferation of HSCs. After loss of Gfi-1, HSCs display elevated proliferation rates as assessed by 5-bromodeoxyuridine incorporation and cell-cycle analysis. Gfi-1(-/-) HSCs are functionally compromised in competitive repopulation and serial transplantation assays, and are rapidly out-competed in the bone marrow of mouse chimaeras generated with Gfi-1(-/-) embryonic stem cells. Thus, Gfi-1 is essential to restrict HSC proliferation and to preserve HSC functional integrity. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu NR 23 TC 329 Z9 339 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 21 PY 2004 VL 431 IS 7011 BP 1002 EP 1007 DI 10.1038/nature02994 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 863TI UT WOS:000224585600048 PM 15457180 ER PT J AU Ryan, DP Titton, RL Harris, NL Fletcher, CDM Demetri, GD Colvin, RB AF Ryan, DP Titton, RL Harris, NL Fletcher, CDM Demetri, GD Colvin, RB TI Case 32-2004: A 68-year-old man with a large retroperitoneal mass - Gastrointestinal stromal tumor SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID TYROSINE KINASE INHIBITOR; SOFT-TISSUE SARCOMAS; KIT CD117; C-KIT; IMATINIB MESYLATE; MUTATIONS; DIAGNOSIS; EFFICACY; STI571; SAFETY C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ryan, DP (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. NR 22 TC 3 Z9 3 U1 0 U2 0 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 OCT 21 PY 2004 VL 351 IS 17 BP 1779 EP 1787 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 863TH UT WOS:000224585200015 PM 15496628 ER PT J AU Alexander, RB Propert, KJ Schaeffer, AJ Landis, JR Nickel, JC O'Leary, MP Pontari, MA McNaughton-Collins, M Shoskes, DA Comiter, CV Datta, NS Fowler, JE Nadler, RB Zeitlin, SI Knauss, JS Wang, YL Kusek, JW Nyberg, LM Litwin, MS AF Alexander, RB Propert, KJ Schaeffer, AJ Landis, JR Nickel, JC O'Leary, MP Pontari, MA McNaughton-Collins, M Shoskes, DA Comiter, CV Datta, NS Fowler, JE Nadler, RB Zeitlin, SI Knauss, JS Wang, YL Kusek, JW Nyberg, LM Litwin, MS CA Chronic Prostatitis Collaborative TI Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome - A randomized, double-blind trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NATIONAL-INSTITUTES; SYMPTOM INDEX; CLINICAL-TRIAL; PREVALENCE; DIAGNOSIS; COHORT; THERAPY AB Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is principally defined by pain in the pelvic region lasting more than 3 months. No cause of the disease has been established, and therapies are empirical and mostly untested. Antimicrobial agents and alpha-adrenergic receptor blockers are frequently used. Objective: To determine whether 6-week therapy with ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms in men with refractory, long-standing CP/CPPS. Design: Randomized, double-blind trial with a 2 x 2 factorial design comparing 6 weeks of therapy with ciprofloxacin, tamsulosin, both drugs, or placebo. Setting: Urology outpatient clinics at 10 tertiary care medical centers in North America. Patients: Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment. Measurements: The authors evaluated NIH-CPSI total score and subscores, patient-reported global response assessment, a generic measure of quality of life, and adverse events. Interventions: Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily; a combination of the 2 drugs; or placebo. Results: The NIH-CPSI total score decreased modestly in all treatment groups. No statistically significant difference in the primary outcome was seen for ciprofloxacin versus no ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments also did not differ significantly for any of the secondary outcomes. Limitations: Treatment lasting longer than 6 weeks was not tested. Patients who had received less pretreatment may have responded differently. Conclusion: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Penn, Philadelphia, PA 19104 USA. Temple Univ, Philadelphia, PA 19104 USA. Northwestern Univ, Chicago, IL 60611 USA. Queens Univ, Kingston, ON, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Florida, Weston, FL USA. Univ Arizona, Tucson, AZ USA. Charles Drew Univ, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Mississippi, Jackson, MS 39216 USA. Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. RP Alexander, RB (reprint author), Vet Affairs Maryland Hlth Care Syst, 10 N Greene St, Baltimore, MD 21201 USA. EM ralexander@smail.umaryland.edu RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [U01 DK53730, U01 DK53572, U01 DK53732, U01 DK53734, U01 DK53736, U01 DK53738, U01 DK53746] NR 26 TC 119 Z9 131 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 19 PY 2004 VL 141 IS 8 BP 581 EP 589 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 864SD UT WOS:000224652300001 PM 15492337 ER PT J AU Kenney, LB Yasui, Y Inskip, PD Hammond, S Neglia, JP Mertens, AC Meadows, AT Friedman, D Robison, LL Diller, L AF Kenney, LB Yasui, Y Inskip, PD Hammond, S Neglia, JP Mertens, AC Meadows, AT Friedman, D Robison, LL Diller, L TI Breast cancer after childhood cancer: A report from the childhood cancer survivor study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID 2ND MALIGNANT NEOPLASMS; LONG-TERM SURVIVORS; INVOLVED-FIELD RADIATION; HODGKINS-DISEASE; RISK-FACTORS; YOUNG-WOMEN; ADOLESCENCE; CHEMOTHERAPY; COHORT; PROBABILITIES AB Background: Survivors of childhood cancer are at risk for secondary breast cancer. Other than previous chest radiation therapy, risk factors for secondary breast cancer have not been established. Objective: To identify risk factors for breast cancer among female survivors of childhood cancer. Design: Retrospective cohort study. Setting: The Childhood Cancer Survivor Study (CCSS), a multicenter study of persons who survived more than 5 years after childhood cancer diagnosed from 1970 to 1986. Participants: Among 6068 women in the CCSS, 95 women had 111 confirmed cases of breast cancer. Measurements: Standardized incidence ratios for breast cancer were calculated by using age-specific incidence rates in the general population. Breast cancer incidence was evaluated with respect to primary cancer diagnosis and therapy, age at and time since primary diagnosis, menstrual and reproductive history, and family history of cancer. Results: Breast cancer risk was increased in survivors who were treated with chest radiation therapy (standardized incidence ratio, 24.7 [95% CI, 19.3 to 31.0]) and survivors of bone and soft-tissue sarcoma who were not treated with chest radiation therapy (standardized incidence ratios, 6.7 and 7.6, respectively). Family history of breast cancer (relative rate, 2.7 [CI, 1.3 to 5.0]) and history of thyroid disease (relative rate, 1.7 [CI, 1.1 to 2.6]) were independently associated with increased risk, and exposure to pelvic radiation was protective (relative rate, 0.6 [CI, 0.4 to 0.9]). Age at primary cancer diagnosis and menstrual and reproductive histories did not statistically significantly modify risk. Limitations: This cohort has not yet attained an age at which breast cancer risk is greatest. Conclusion: Survivors of childhood sarcomas and those who received chest radiation therapy are at risk for secondary breast cancer. When assessing a survivor's risk, clinicians should consider primary diagnosis, previous radiation therapy, family cancer history, and history of thyroid disease. C1 Dana Farber Canc Inst, Qual Life Clin, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. NCI, Bethesda, MD USA. Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Kenney, LB (reprint author), Dana Farber Canc Inst, Qual Life Clin, 44 Binney St, Boston, MA 02115 USA. EM Lisa_Kenney@DFCI.harvard.edu RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU NCI NIH HHS [CA 55727] NR 37 TC 138 Z9 142 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 19 PY 2004 VL 141 IS 8 BP 590 EP 597 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 864SD UT WOS:000224652300002 PM 15492338 ER PT J AU Bibbins-Domingo, K Lin, F Vittinghof, E Barrett-Connor, E Grady, D Shlipak, MG AF Bibbins-Domingo, K Lin, F Vittinghof, E Barrett-Connor, E Grady, D Shlipak, MG TI Renal insufficiency as an independent predictor of mortality among women with heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ESTROGEN/PROGESTIN REPLACEMENT; CREATININE CLEARANCE; SURVIVAL; DISEASE; TRIAL; DYSFUNCTION; OUTCOMES; THERAPY; RISK AB OBJECTIVES We sought to explore the association between renal insufficiency and mortality among women with heart failure (HF) and to evaluate this risk by the presence of preserved or depressed systolic function. BACKGROUND Although HF is common in older women, little is known about their risk factors for mortality. METHODS This prospective cohort study retrospectively analyzed data from the Heart and Estrogen/ progestin Replacement Study (HERS). Of the 2,763 women in HERS, 702 had HF. Renal function was categorized as creatinine clearance (CrCl) >60 ml/min, 40 to 60 ml/min, and <40 ml/min. We used proportional hazards models to evaluate the association between renal insufficiency and mortality. RESULTS Over a mean 5.8 years, 228 women with HF died (32%). Renal insufficiency was strongly associated with mortality, even after adjustment for co-morbid conditions, systolic function, and medications (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.09 to 2.16 for CrCl 40 to 60 ml/min; adjusted HR 2.40, 95% CI 1.60 to 3.62 for CrCl <40 ml/min). Preserved or depressed systolic function did not modify the association between renal insufficiency and mortality risk, but the use of angiotensin-converting enzyme (ACE) inhibitors did modify this risk (ACE users: adjusted HR = 0.9, 95% CI 0.6 to 1.6; ACE nonusers: adjusted HR 2.1, 95% CI 1.3 to 3.2; p = 0.02 for interaction). Compared with other risk factors for mortality, renal insufficiency had the highest population attributable risk (27%). CONCLUSIONS Renal insufficiency was a major predictor of mortality among women with HF and preserved or depressed systolic function. This risk was attenuated by the use of ACE inhibitors. (C) 2004 by the American College of Cardiology Foundation. C1 Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94143 USA. RP Bibbins-Domingo, K (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Box 1364, San Francisco, CA 94143 USA. EM bibbinsk@medicine.ucsf.edu NR 28 TC 45 Z9 50 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 19 PY 2004 VL 44 IS 8 BP 1593 EP 1600 DI 10.1016/j.jacc.2004.07.040 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863PJ UT WOS:000224573700009 PM 15489091 ER PT J AU Palacios, IF AF Palacios, IF TI Percutaneous valve replacement and repair - Fiction or reality SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID CALCIFIC AORTIC-STENOSIS; TRANSCATHETER IMPLANTATION; PROSTHESIS; DISEASE C1 Massachusetts Gen Hosp, Cardiac Catheterizat Labs, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Cardiac Catheterizat Labs, Dept Med, Cardiac Unit, Boston, MA 02114 USA. EM palacios.igor@mgh.harvard.edu NR 10 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 19 PY 2004 VL 44 IS 8 BP 1662 EP 1663 DI 10.1016/j.jacc.2004.07.025 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863PJ UT WOS:000224573700018 PM 15489100 ER PT J AU Beer, TM Garzotto, M Henner, WD Eilers, KM Wersinger, EM AF Beer, TM Garzotto, M Henner, WD Eilers, KM Wersinger, EM TI Multiple cycles of intermittent chemotherapy in metastatic androgen-independent prostate cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE docetaxel; calcitriol; vitamin D; prostate cancer; chemotherapy AB Recently, completed phase III studies demonstrated a survival benefit for a fixed number of cycles of docetaxel-containing chemotherapy treatment of androgen-independent prostate cancer (AIPC). Management of patients who respond well to initial chemotherapy for AIPC remains ill-defined. We previously reported that in a select group of such patients, retreatment with the same regimen was feasible and was associated with quality of life gains. Here, we report that multiple cycles of such intermittent chemotherapy are feasible. We prospectively tested intermittent chemotherapy in eight AIPC patients responding to calcitriol plus docetaxel who reached a serum prostate-specific antigen (PSA) <4 ng ml(-1) (22% of the 37 patients who were initially treated with this regimen). Chemotherapy was suspended until a rise in PSA &GE;50% and 1 ng ml(-1). The median duration of the first treatment holiday was 20 weeks (13-74 weeks) and all patients retained sensitivity to retreatment. Four patients were eligible for a second chemotherapy holiday, and the median duration was 21 weeks (17-28 weeks). Two patients elected to take a third chemotherapy holiday, which lasted 10 and 28 weeks. The median time to treatment failure was 26.5 months (95% CI 23.6-29.4 months), and the median survival is 41 months (95% CI 33.7-48.3 months). Multiple cycles of intermittent chemotherapy interrupted by clinically meaningful treatment holidays are feasible in a subset of AIPC patients treated with this docetaxel-containing regimen. Intermittent chemotherapy for AIPC is feasible and deserves further study. C1 Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97207 USA. Portland VA Med Ctr, Portland, OR 97207 USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code CR145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM beert@ohsu.edu FU NCRR NIH HHS [M01 RR000334, 3M01RR00334-33S2] NR 5 TC 36 Z9 37 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 OCT 18 PY 2004 VL 91 IS 8 BP 1425 EP 1427 DI 10.1038/sj.bjc.6602198 PG 3 WC Oncology SC Oncology GA 861JJ UT WOS:000224412500003 PM 15467765 ER PT J AU Schmahmann, JD Rosene, DL Pandya, DN AF Schmahmann, JD Rosene, DL Pandya, DN TI Motor projections to the basis Pontis in rhesus monkey SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE pons; corticopontine; precentral gyrus; supplementary motor area; anatomical; connections ID RETICULARIS TEGMENTI-PONTIS; COGNITIVE-AFFECTIVE SYNDROME; FOU RIRE PRODROMIQUE; CLUMSY HAND SYNDROME; CORTICOPONTINE PROJECTION; BRAIN-STEM; EFFERENT CONNECTIONS; MACACA-FASCICULARIS; MACAQUE MONKEY; CEREBELLAR CONTRIBUTION AB Motor corticopontine studies suggest that the pons is topographically organized, but details remain unresolved. We used physiological mapping in rhesus monkey to define subregions in precentral motor cortex (M1), injected isotope tracers into M1 and the supplementary motor area (SAM), and studied projections to the basis pontis. Labeled fibers descend in the internal capsule (SMA in anterior limb and genu; M1 in posterior limb) and traverse the midsection of the cerebral peduncle, where SMA fibers are medial, and face, arm, and leg fibers are progressively lateral. Each motor region has unique terminations in the ipsilateral basis pontis and nucleus reticularis tegmenti pontis. Projections are topographically organized, preferentially in the caudal half of the pons, situated in close proximity to traversing corticofugal fibers. In nuclei that receive multiple inputs, terminations appear to interdigitate. Projections from the SMA-face region are most medial and include the median pontine nucleus. M1-face projections are also medial but are lateral to those from SMA-face. Hand projections are in medially placed curved lamellae in mid- and caudal pons. Dorsal trunk projections are in medial and ventral locations. Ventral trunk/hip projections encircle the peduncle in the caudal pons. Foot projections are heaviest caudally in laterally placed, curved lamellae. These results have relevance for anatomical clinical correlations in the human basis pontis. Furthermore, the dichotomy of motor-predominant caudal pons projections to cerebellar anterior lobe, contrasted with associative-predominant rostral. pons projections to cerebellar posterior lobe, is consistent with new hypotheses regarding the cerebellar contribution to motor activity and cognitive processing. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Neurol VBK 915, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol VBK 915, Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org RI Rosene, Douglas/G-1973-2015; OI Rosene, Douglas/0000-0001-8719-1441 NR 86 TC 41 Z9 42 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 18 PY 2004 VL 478 IS 3 BP 248 EP 268 DI 10.1002/cne.20286 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 859HX UT WOS:000224255100004 PM 15368534 ER PT J AU Boggon, TJ Eck, MJ AF Boggon, TJ Eck, MJ TI Structure and regulation of Src family kinases SO ONCOGENE LA English DT Review DE Src regulation; modular signaling; CD4/CD8 alpha ID TYROSINE-PROTEIN-KINASE; N-TERMINAL REGION; AFFINITY PHOSPHOTYROSYL PEPTIDE; FOCAL ADHESION KINASE; CRYSTAL-STRUCTURE; SH3 DOMAIN; C-SRC; SERINE PHOSPHORYLATION; TRANSFORMING PROTEIN; SIGNAL-TRANSDUCTION AB Src family kinases are prototypical modular signaling proteins. Their conserved domain organization includes a myristoylated N-terminal segment followed by SH3, SH2, and tyrosine kinase domains, and a short C-terminal tail. Structural dissection of Src kinases has elucidated the canonical mechanisms of phosphotyrosine recognition by the SH2 domain and proline-motif recognition by the SH3 domain. Crystallographic analysis of nearly intact Src kinases in the autoinhibited state has shown that these protein interaction motifs turn inward and lock the kinase in an inactive conformation via intramolecular interactions. The autoinhibited Src kinase structures reveal a mode of domain assembly used by other tyrosine kinases outside the Src family, including Abl and likely Tec family kinases. Furthermore, they illustrate the underlying regulatory principles that have proven to be general among diverse modular signaling proteins. Although there is considerable structural information available for the autoinhibited conformation of Src kinases, how they may assemble into active signaling complexes with substrates and regulators remains largely unexplored. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, 44 Binney St, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu NR 94 TC 312 Z9 317 U1 2 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 18 PY 2004 VL 23 IS 48 BP 7918 EP 7927 DI 10.1038/sj.onc.1208081 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 863JR UT WOS:000224558300003 PM 15489910 ER PT J AU Luttrell, DK Luttrell, LM AF Luttrell, DK Luttrell, LM TI Not so strange bedfellows: G-protein-coupled receptors and Src family kinases SO ONCOGENE LA English DT Review DE G-protein-coupled receptor; focal adhesion kinase; epidermal growth factor; mitogen-activated protein kinase; receptor crosstalk ID GROWTH-FACTOR RECEPTOR; SMOOTH-MUSCLE-CELLS; FOCAL ADHESION KINASE; DEPENDENT TYROSINE KINASE; C-SRC; EGF RECEPTOR; ANGIOTENSIN-II; MAP KINASE; BETA-ARRESTIN; LYSOPHOSPHATIDIC ACID AB Src family nonreceptor tyrosine kinases are an integral component of the signal transduction apparatus employed by growth factor receptor tyrosine kinases. As such, their role in cellular growth control and malignant transformation has been the subject of intensive investigation. In contrast, classical G-protein-coupled receptor ( GPCR) signaling involves activation of second messenger-regulated serine/threonine kinases or ion channels, and is primarily involved in neurotransmission and the short-term regulation of intermediary metabolism. Over the past decade, this strictly dichotomous model of transmembrane signaling has been challenged by the discovery that GPCRs also exert control over cellular growth, proliferation, and differentiation, and do so by stimulating tyrosine phosphorylation cascades. Several mechanisms, from the direct association of Src family kinases with GPCRs or receptor-associated proteins, to the transactivation of receptor tyrosine kinases and focal adhesion complexes by G-protein-mediated signals, permit GPCRs to activate Src family kinases. Conversely, Src activity plays a central role in controlling GPCR trafficking and effects on cell proliferation and cytoskeletal rearrangement. It is now clear that GPCRs and Src family kinases do not belong to separate, exclusive clubs. Rather, these strange bedfellows are intimately involved in multilayered forms of crosstalk that influence a host of cellular processes. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,816 CSB,POB 250624, Charleston, SC 29425 USA. EM luttrell@musc.edu FU NIDDK NIH HHS [DK58283, DK55524, DK64353] NR 103 TC 134 Z9 135 U1 0 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 OCT 18 PY 2004 VL 23 IS 48 BP 7969 EP 7978 DI 10.1038/sj.onc.1208162 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 863JR UT WOS:000224558300007 PM 15489914 ER PT J AU Kovacs, TOG Lee, CQ Chiu, YL Pilmer, BL Metz, DC AF Kovacs, TOG Lee, CQ Chiu, YL Pilmer, BL Metz, DC TI Intravenous and oral lansoprazole are equivalent in suppressing stimulated acid output in patient volunteers with erosive oesophagitis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; ESOMEPRAZOLE AB Background: Some patients requiring acid suppression may be unable to take oral medications. Aim: To compare the gastric acid inhibition effects of lansoprazole 30 mg administered either intravenous or orally in erosive oesophagitis patients. Methods: The study included 87 Helicobacter pylori-negative patients with erosive oesophagitis. Each patient received 7 days of lansoprazole 30 mg orally prior to being randomized in a 3:1 fashion to intravenously lansoprazole 30 mg or intravenously placebo for 7 days. Basal acid output and pentagastrin-stimulated acid output were measured on days 8, 9 and 15. Results: Median pentagastrin-stimulated acid output was 7.2 mmol/h after 7 days of oral lansoprazole. The median pentagastrin-stimulated acid output increased to 7.6 mmol/h after 7 days of intravenous lansoprazole compared with 26.9 mmol/h after intravenous placebo (P < 0.001). Conclusions: Lansoprazole 30 mg administered intravenous was equivalent to the 30 mg oral capsule in gastric acid suppression. Intravenous proton pump inhibitor therapy represents an important treatment option for those with acid-related diseases who are unable to take oral medications. C1 VA Greater Los Angeles Healthcare Syst, Cure Digest Dis Res Ctr, CURE Clin, Los Angeles, CA 90073 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Kovacs, TOG (reprint author), VA Greater Los Angeles Healthcare Syst, Cure Digest Dis Res Ctr, CURE Clin, 11301 Wilshire Blvd,Bldg 115,Room 212, Los Angeles, CA 90073 USA. EM tkovacs@mednet.ucla.edu NR 13 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD OCT 15 PY 2004 VL 20 IS 8 BP 883 EP 889 DI 10.1111/j.1365-2036.2004.02188.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 861UO UT WOS:000224444300008 PM 15479360 ER PT J AU Yeh, GY Wood, MJ Lorell, BH Stevenson, LW Eisenberg, DM Wayne, PM Goldberger, AL Davis, RB Phillips, RS AF Yeh, GY Wood, MJ Lorell, BH Stevenson, LW Eisenberg, DM Wayne, PM Goldberger, AL Davis, RB Phillips, RS TI Effects of tai chi mind-body movement therapy on functional status and exercise capacity in patients with chronic heart failure: A randomized controlled trial SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID QUALITY-OF-LIFE; CARDIORESPIRATORY FUNCTION; DILATED CARDIOMYOPATHY; CHUAN PRACTITIONERS; NATRIURETIC PEPTIDE; EMERGENCY DIAGNOSIS; AEROBIC EXERCISE; OLDER ADULTS; STRENGTH; BALANCE AB PURPOSE: To examine the effects of a 12-week tai chi program on quality of life and exercise capacity in patients with heart failure. METHODS: Thirty patients with chronic stable heart failure and left ventricular ejection fraction less than or equal to 40% (mean [ +/- SD] age, 64 +/- 13 years; mean baseline ejection fraction, 23% +/- 7%; median New York Heart Association class, 2 [range, 1 to 4]) were randomly assigned to receive usual care (n = 15), which included pharmacologic therapy and dietary and exercise counseling, or 12 weeks of tai chi training (n = 15) in addition to usual care. Tai chi training consisted of a 1-hour class held twice weekly. Primary outcomes included quality of life and exercise capacity. Secondary outcomes included serum B-type natriuretic peptide and plasma catecholamine levels. For 3 control patients with missing data items at 12 weeks, previous values were carried forward. RESULTS: At 12 weeks, patients in the tai chi group showed improved quality-of-life scores (mean between-group difference in change, -25 points, P = 0.001), increased distance walked in 6 minutes (135 meters, P = 0.001), and decreased serum B-type natriuretic peptide levels (-138 pg/mL, P = 0.03) compared with patients in the control group. A trend towards improvement was seen in peak oxygen uptake. No differences were detected in catecholamine levels. CONCLUSION: Tai chi maybe a beneficial adjunctive treatment that enhances quality of life and functional capacity in patients with chronic heart failure who are already receiving standard medical therapy. (C) 2004 by Elsevier Inc. C1 Harvard Univ, Sch Med, Osher Inst, Div Res & Educ Complementary & Integrat Med Thera, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Program Heart Failure, Div Cardiol, Boston, MA 02115 USA. New England Sch Acupuncture, Div Res, Watertown, MA USA. RP Yeh, GY (reprint author), Harvard Univ, Sch Med, Osher Inst, Div Res & Educ Complementary & Integrat Med Thera, 401 Pk Dr,Suite 22A, Boston, MA 02215 USA. EM gyeh@caregroup.harvard.edu FU NCCIH NIH HHS [AT00051, AT00589]; NCRR NIH HHS [RR 01032, RR13622]; NIA NIH HHS [AG08812] NR 45 TC 109 Z9 116 U1 5 U2 21 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 15 PY 2004 VL 117 IS 8 BP 541 EP 548 DI 10.1016/j.amjmed.2004.04.016 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 861SQ UT WOS:000224439300001 PM 15465501 ER PT J AU Irimia, D Tompkins, RG Toner, M AF Irimia, D Tompkins, RG Toner, M TI Single-cell chemical lysis in picoliter-scale closed volumes using a microfabricated device SO ANALYTICAL CHEMISTRY LA English DT Article ID MICROFLUIDIC DEVICE; F-ACTIN; SAMPLE PREPARATION; GENE-EXPRESSION; MICROCHANNELS; MANIPULATION; CHIP; STIMULATION; EXTRACTION; TRANSPORT AB Investigating the intracellular contents of single cells is essential for understanding physiologic and pathologic processes at the cellular level. While existing protocols for cell lysis and sample preparation work well for larger samples, scaling to a single-cell level is challenging because of unavoidable analyte dilution and losses. Thus, we are proposing a microfabricated device for the controlled handling and mixing of picoliter cell suspension and lysis solution volumes. Cells and fluids are independently isolated in two microchambers of 25-pL volumes using the geometry of the microchannels and the coordinated action of four on-chip thermopneumatic actuators. Virtual walls formed by liquid-air interfaces in the hydrophobic capillary separate the two volumes, which are subsequently allowed to mix after drawing the air out of the capillary connecting the two microchambers. Following cell lysis, a limited and stable dilution of intracellular components is achieved, simplifying the requirements for subsequent analysis. Two assays at single-cell level, one for direct estimation of the intracellular concentration of a soluble dye and the other for indirect evaluation of intracellular quantities of insoluble actin, demonstrate the use of the microfabricated device for single-cell assays. C1 Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Shriners Hosp Children, Boston, MA 02114 USA. EM mtoner@sbi.org OI Irimia, Daniel/0000-0001-7347-2082 FU NIBIB NIH HHS [P41 EB002503]; NIGMS NIH HHS [U54 GM062119] NR 42 TC 74 Z9 75 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD OCT 15 PY 2004 VL 76 IS 20 BP 6137 EP 6143 DI 10.1021/ac0497508 PG 7 WC Chemistry, Analytical SC Chemistry GA 863ME UT WOS:000224565200020 PM 15481964 ER PT J AU Frost, DO Tamminga, CA Medoff, DR Caviness, V Innocenti, G Carpenter, WT AF Frost, DO Tamminga, CA Medoff, DR Caviness, V Innocenti, G Carpenter, WT TI Neuroplasticity and schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; plasticity; neurodevelopmental; course of illness; glutamate; BDNF ID SEVERE MENTAL-ILLNESS; CEREBRAL BLOOD-FLOW; ABNORMAL EXPRESSION; NEUROTROPHIC FACTOR; PREFRONTAL CORTEX; GENE-EXPRESSION; VERBAL FLUENCY; MESSENGER-RNA; SYMPTOMS; HIPPOCAMPAL AB This article's title is also the name of a workshop sponsored by the International Congress on Schizophrenia Research that was focused on an appraisal of the potential role of neuroplastic processes in the etiology or course of schizophrenia. The workshop brought together clinical investigators of schizophrenia and basic scientists who study various aspects of neuroplasticity, including central nervous system (CNS) development, learning and memory, and drug action. The goal was to identify special opportunities to advance knowledge and understanding of schizophrenia pathology, treatment, or prevention by applying neuroplasticity concepts as a framework to theories of the illness. Although the focus of this workshop was schizophrenia, the phenomena considered are pertinent to other disorders, such as depression and drug abuse. C1 Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Pediat Neurol Serv, Boston, MA 02114 USA. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Tamminga, CA (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. NR 56 TC 23 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2004 VL 56 IS 8 BP 540 EP 543 DI 10.1016/j.biopsych.2004.01.020 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 863CT UT WOS:000224538800002 PM 15476682 ER PT J AU Chauhan, D Li, GL Podar, K Hideshima, T Mitsiades, C Schlossman, R Munshi, N Richardson, P Cotter, FE Anderson, KC AF Chauhan, D Li, GL Podar, K Hideshima, T Mitsiades, C Schlossman, R Munshi, N Richardson, P Cotter, FE Anderson, KC TI Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells SO BLOOD LA English DT Article ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; NF-KAPPA-B; DRUG-RESISTANCE; INDUCED APOPTOSIS; CYTOCHROME-C; THERAPEUTIC IMPLICATIONS; MULTIDRUG-RESISTANCE; INDUCE APOPTOSIS; LEUKEMIA-CELLS; INTERLEUKIN-6 AB Bortezomib (PS-341), a selective inhibitor of proteasomes, induces apoptosis in multiple myeloma (MM) cells; however, prolonged drug exposure may result in cumulative toxicity and the development of chemoresistance. Here we show that combining PK-11195 (PK), an antagonist to mitochondrial peripheral benzodiazepine receptors (PBRs), with bortezomib triggers synergistic anti-MM activity even in doxorubicin-, melphalan-, thalidomide-, dexamethasone-, and bortezomib-resistant MM cells. No significant cytotoxicity was noted in normal lymphocytes. Lowdose combined PK and bortezomib treatment overcomes the growth, survival, and drug resistance conferred by interleukin-6 or insulin growth factor within the MM bone marrow milieu. The mechanism of PK + bortezomib-induced apoptosis includes: loss of mitochondrial membrane potential; superoxide generation; release of mitochondrial proteins cytochrome-c (cyto-c) and Smac; and activation of caspases-8/-9/-3. Furthermore, PK + bortezomib activates c-Jun NH2 terminal kinase (JNK), which translocates to mitochondria, thereby facilitating release of cyto-c and Smac from mitochondria to cytosol. Blocking JNK, by either dominant-negative mutant (DN-JNK) or cotreatment with a specific JNK inhibitor SP600125, abrogates both PK + bortezomib-induced release of cyto-c/Smac and induction of apoptosis. Together, these preclinical studies suggest that combining bortezomib with PK may enhance its clinical efficacy, reduce attendant toxicity, and overcome conventional and bortezomib resistance in patients with relapsed refractory MM. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Royal London Sch Med, Dept Expt Haematol, London, England. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [P01 CA078378-06, IP50 CA100707-01, CA 78373]; PHS HHS [50947] NR 56 TC 57 Z9 59 U1 1 U2 3 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 OCT 15 PY 2004 VL 104 IS 8 BP 2458 EP 2466 DI 10.1182/blood-2004-02-0547 PG 9 WC Hematology SC Hematology GA 860XU UT WOS:000224378300043 PM 15217830 ER PT J AU Widhopf, GF Rassenti, LZ Toy, TL Gribben, JG Wierda, WG Kipps, TJ AF Widhopf, GF Rassenti, LZ Toy, TL Gribben, JG Wierda, WG Kipps, TJ TI Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins SO BLOOD LA English DT Article ID CHAIN VARIABLE REGION; CROSS-REACTIVE IDIOTYPES; V-H GENES; HEAVY-CHAIN; CD38 EXPRESSION; MUTATION STATUS; NATURAL AUTOANTIBODIES; SOMATIC HYPERMUTATION; GENOMIC ABERRATIONS; RHEUMATOID FACTORS AB We examined the immunoglobulin (Ig) heavy chain variable region genes (V-H genes) used by leukemia cells of 1220 unrelated patients with chronic lymphocytic leukemia (CLL). We found 1188 (97%) expressed Ig encoded by a single 19 V-H subgroup, the most common of Which was V(H)3 (571 or 48.1%), followed by V(H)1 (319 or 26.8%) and V(H)4 (241 or 20.2%). Using allele-specific primers, we found 13.8% of all samples (n = 164) used one major V(H)1-69 allele, designated 51p1, 163 of which were not somatically mutated. For these cases, there was marked restriction in the structure of the Ig third complementarity determining regions (CDR3s), which were encoded by a small number of unmutated D and J(H) gene segments. Strikingly, 15 of the 163 cases had virtually identical CDR3s encoded by the second reading frame of D3-16 and J(H)3. Further analysis revealed that each of these 15 samples used the same unmutated Ig kappa light-chain gene, namely A27. These data reveal that approximately 1.3% (15/1220) of all patients had leukemia cells that expressed virtually identical Ig. This finding provides compelling evidence that the Ig expressed by CLL B cells are highly selected and not representative of the Ig expressed by naive B cells. (C) 2004 by The American Society of Hematology. C1 Univ Calif San Diego, Sch Med, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA. Univ Calif San Diego, CLL Res Consortium, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. RP Kipps, TJ (reprint author), Univ Calif San Diego, Sch Med, Dept Med, Div Hematol Oncol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM tkipps@ucsd.edu FU NCI NIH HHS [P01-CA81534, R37-CA49870] NR 45 TC 157 Z9 162 U1 0 U2 4 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 OCT 15 PY 2004 VL 104 IS 8 BP 2499 EP 2504 DI 10.1182/blood-2004-03-0818 PG 6 WC Hematology SC Hematology GA 860XU UT WOS:000224378300048 PM 15217828 ER PT J AU Earle, CC Neville, BA AF Earle, CC Neville, BA TI Under use of necessary care among cancer survivors SO CANCER LA English DT Editorial Material DE acute care indicators; cancer survivors; chronic comorbidities; colorectal carcinoma; quality of care ID COLORECTAL-CANCER; HEALTH-CARE; SURVEILLANCE; VALIDATION; ONCOLOGY; QUALITY; BREAST C1 Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Ctr, Ctr Outcomes & Policy Res, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu NR 23 TC 211 Z9 217 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2004 VL 101 IS 8 BP 1712 EP 1719 DI 10.1002/cncr.20560 PG 8 WC Oncology SC Oncology GA 860TR UT WOS:000224366700002 PM 15386307 ER PT J AU Colbert, JA Kaine, EM Bigby, J Smith, DN Moore, RH Rafferty, E Georgian-Smith, D D'Alessandro, HA Yeh, E Kopans, DB Halpern, EF Hughes, K Smith, BL Tanabe, KK Michaelson, JS AF Colbert, JA Kaine, EM Bigby, J Smith, DN Moore, RH Rafferty, E Georgian-Smith, D D'Alessandro, HA Yeh, E Kopans, DB Halpern, EF Hughes, K Smith, BL Tanabe, KK Michaelson, JS TI The age at which women begin mammographic screening SO CANCER LA English DT Article DE breast carcinoma; mammography; screening; disparity ID BREAST-CANCER; HISPANIC WOMEN; UNITED-STATES; HEALTH; CARCINOMA; RECOMMENDATION; ASSOCIATION; GUIDELINES; PATTERNS; COVERAGE AB BACKGROUND. The American Cancer Society recommends yearly mammographic screening for women starting at the age of 40 years. The authors examined the age at which women began screening at a large tertiary care center. METHODS. Utilization of mammography was assessed in a population of 72,417 women who received 254,818 screening mammograms at the Massachusetts General Hospital Avon Comprehensive Breast Center from January 1, 1985 to February 19, 2002, of which 940 received their first mammogram between January 16, 2000 and February 19, 2002. RESULTS. The median age at first mammogram for women in the population as a whole was 40.4 years. Sixty percent of women had their first mammogram by the end of their 40th year, and almost 90% had begun screening by age 50 years. However, these reassuring findings were not seen in several specific subpopulations of women. Black women began screening at a median age of 41.0 years, 0.7 years later than white women. Hispanic women began screening at a median age of 41.4 years, 1.1 years later than non-Hispanic women. Obese women began screening at a median age of 41.2 years, 1.6 years later than thin women. Women without a primary care physician began screening at a median age of 42.1 years, 1.8years later than women with a primary care physician. Women without private health insurance began screening at a median age of 46.6 years, 6.3 years later than women with private health coverage. Women who did not speak English began screening at a median age of 49.3 years, 9.0 years later than women for whom English was the primary language. Women who both lacked private health insurance and spoke a language other than English began screening at a median age of 55.3 years, 15.2 years later than women without these characteristics. CONCLUSIONS. The analysis presented in the current study provided one of the most detailed descriptions of the age at screening initiation to be performed to date. Most women in the study population began screening by the end of their 40th year. This contrasted with the widespread failure of women to return promptly for subsequent annual examinations. However, specific subpopulations of women were at risk for not beginning screening on time, including women without private insurance, women without a primary care physician, and women who did not speak English. These findings suggest that there is little to be gained from populationwide efforts to encourage entry into the screening process, and that public health efforts should be focused on those subpopulations of women at highest risk for not using screening. These results also indicate that public health efforts to encourage women to start screening may be less critical than interventions to improve prompt return once they have entered the screening system. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Michaelson, JS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. EM michaelj@helix.mgh.harvard.edu OI Hughes, Kevin/0000-0003-4084-6484 NR 33 TC 16 Z9 17 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2004 VL 101 IS 8 BP 1850 EP 1859 DI 10.1002/cncr.20583 PG 10 WC Oncology SC Oncology GA 860TR UT WOS:000224366700017 PM 15386333 ER PT J AU Tracy, S Mukohara, T Hansen, M Meyerson, M Johnson, BE Janne, PA AF Tracy, S Mukohara, T Hansen, M Meyerson, M Johnson, BE Janne, PA TI Gefitinib induces apoptosis in the EGFR(L858R) non-small-cell lung cancer cell line H3255 SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; ZD1839 IRESSA; BREAST-CANCER; MUTATIONS; TRIAL; MESOTHELIOMA; CHEMOTHERAPY; SENSITIVITY; PACLITAXEL AB Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) have recently been described in patients with non-small-cell lung cancer (NSCLC) who achieve radiographic regressions to the EGFR inhibitor gefitinib. One of these mutations, L858R (Leu-->Arg), is also found in NSCLC cell line H3255, which is very sensitive to gefitinib treatment. We characterized nine NSCLC cell lines (three isolated from patients with bronchioloalveolar carcinoma and six isolated from patients with adenocarcinoma) for their in vitro sensitivity to gefitinib. Of these, only H3255 (EGFR(L858R)) and H1666 (EGFR(WT)) are sensitive to gefitinib with IC50 values of 40 nmol/L and 2 mumol/L, respectively. We examined the effects of gefitinib on H3255 and cell lines containing wild-type EGFR that are either sensitive (111666) or resistant (A549 and H441) to gefitinib exposure in vitro. Gefitinib treatment (1 mumol/L) leads to significant apoptosis accompanied by increased poly(ADP-ribose) polymerase cleavage only in the H3255 cell line, leads to G(1)-S arrest in H1666, and has no effects in the A549 and H441 cell lines. Although EGFR and AKT are constitutively phosphorylated in H3255, H1666, and H441 cell lines, AKT is completely inhibited by gefitinib treatment only in the H3255 cell line. These findings further characterize a mechanism by which gefitinib treatment of NSCLC harboring EGFR(L858R) leads to a dramatic response to gefitinib. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, McCormack Adv Mol Diagnost Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D1234,44 Binney St, Boston, MA 02115 USA. EM bejohnson@partners.org RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [1K12CA87723-01, P20CA90578-02] NR 22 TC 259 Z9 265 U1 2 U2 20 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2004 VL 64 IS 20 BP 7241 EP 7244 DI 10.1158/0008-5472.CAN-04-1905 PG 4 WC Oncology SC Oncology GA 862WO UT WOS:000224522200012 PM 15492241 ER PT J AU Hong, WY Kutok, JL Lee, NH Hui, YP Fletcher, CDM Kanki, JP Look, AT AF Hong, WY Kutok, JL Lee, NH Hui, YP Fletcher, CDM Kanki, JP Look, AT TI Targeted expression of human MYCN selectively causes pancreatic neuroendocrine tumors in transgenic zebrafish SO CANCER RESEARCH LA English DT Article ID DIFFERENT DEVELOPMENTAL-STAGES; N-MYC; DANIO-RERIO; C-MYC; EXPOSURE ROUTES; AMPLIFICATION; GENE; DISEASE; MODEL; MYOD AB The zebrafish model organism has been used extensively for studies of genetic pathways in development, indicating its potential applicability to cancer. Here we show that targeted expression of MYCN in cells of the pancreatic islet induces neuroendocrine carcinoma. Four transgenic fish developed abdominal tumors between 4 and 6 months of age, and histologic analysis revealed lobulated arrangements of neoplastic cells with expression of the MYCN transgene. The tumors also expressed insulin mRNA, and pancreatic exocrine cells and ducts were identified within the neoplasms, indicating a pancreatic origin for the tumor. Transmission electron microscopy revealed cytoplasmic, endocrine-dense core granules, analogous to those found in human neuroendocrine tumors. Our studies establish a zebrafish transgenic model of pancreatic neuroendocrine carcinoma, setting the stage to evaluate molecular pathways downstream of MYCN in this vertebrate forward genetic model system. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 630, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu NR 44 TC 0 Z9 0 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2004 VL 64 IS 20 BP 7256 EP 7262 PG 7 WC Oncology SC Oncology GA 862WO UT WOS:000224522200015 ER PT J AU Podar, K Shringarpure, R Tai, YT Simoncini, M Sattler, M Ishitsuka, K Richardson, PG Hideshima, T Chauhan, D Anderson, KC AF Podar, K Shringarpure, R Tai, YT Simoncini, M Sattler, M Ishitsuka, K Richardson, PG Hideshima, T Chauhan, D Anderson, KC TI Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib SO CANCER RESEARCH LA English DT Article ID PLASMA-MEMBRANE CHOLESTEROL; PROTEASOME INHIBITOR PS-341; SMOOTH-MUSCLE CELLS; TYROSINE PHOSPHORYLATION; IN-VIVO; OLIGONUCLEOTIDE ARRAYS; SIGNAL-TRANSDUCTION; INSULIN-RECEPTOR; BETA(1) INTEGRIN; V-SRC AB We recently demonstrated that caveolae, vesicular flask-shaped invaginations of the plasma membrane, represent novel therapeutic targets in multiple myeloma. In the present study, we demonstrate that vascular endothelial growth factor (VEGF) triggers Sre-dependent phosphorylation of caveolin-1, which is required for p130(Cas) phosphorylation and multiple myeloma cell migration. Conversely, depletion of caveolin-1 by antisense methodology abrogates p130(Cas) phosphorylation and VEGF-triggered multiple myeloma cell migration. The proteasome inhibitor bortezomib both inhibited VEGF-triggered caveolin-1 phosphorylation and markedly decreased caveolin-1 expression. Consequently, bortezomib inhibited VEGF-induced multiple myeloma cell migration. Bortezomib also decreased VEGF secretion in the bone marrow microenvironment and inhibited VEGF-triggered tyrosine phosphorylation of caveolin-1, migration, and survival in human umbilical vascular endothelial cells. Taken together, these studies demonstrate the requirement of caveolae for VEGF-triggered multiple myeloma cell migration and identify caveolin-1 in multiple myeloma cells and human umbilical vascular endothelial cells as a molecular target of bortezomib. C1 Harvard Univ, Dana Farber Canc Inst,Med Sch, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Dana Farber Canc Inst,Med Sch, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM Kenneth_Anderson@dfci.harvard.edu FU PHS HHS [P0-1 78378, R0 50947] NR 50 TC 61 Z9 68 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2004 VL 64 IS 20 BP 7500 EP 7506 DI 10.1158/0008-5472.CAN-04-0124 PG 7 WC Oncology SC Oncology GA 862WO UT WOS:000224522200047 PM 15492276 ER PT J AU Spiegelman, BM Heinrich, R AF Spiegelman, BM Heinrich, R TI Biological control through regulated transcriptional coactivators SO CELL LA English DT Review ID STEROID-RECEPTOR COACTIVATOR-1; MESSENGER-RNA EXPRESSION; MUSCLE GENE-EXPRESSION; SERUM RESPONSE FACTOR; MITOCHONDRIAL BIOGENESIS; NUCLEAR RECEPTORS; OCA-B; PROTEIN METHYLTRANSFERASE; HISTONE ACETYLTRANSFERASE; HEPATIC GLUCONEOGENESIS AB Gene activation in higher eukaryotes requires the concerted action of transcription factors and coactivator proteins. Coactivators exist in multiprotein complexes that dock on transcription factors and modify chromatin, allowing effective transcription to take place. While biological control focused at the level of the transcription factor is very common, it is now quite clear that a substantial component of gene control is directed at the expression of coactivators, involving pathways as diverse as B-cell development, smooth muscle differentiation, and hepatic gluconeogenesis. Quantitative control of coactivators allows the functional integration of multiple transcription factors and facilitates the formation of distinct biological programs. This coordination and acceleration of different steps in linked pathways has important kinetic considerations, enabling outputs of particular pathways to be increased far more than would otherwise be possible. These kinetic aspects suggest opportunities and concerns as coactivators become targets of therapeutic intervention. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Humboldt Univ, Sect Theoret Biophys, Inst Biol, D-10115 Berlin, Germany. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [DK54477, DK61562] NR 84 TC 219 Z9 224 U1 6 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 15 PY 2004 VL 119 IS 2 BP 157 EP 167 DI 10.1016/j.cell.2004.09.037 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 863QQ UT WOS:000224577200005 PM 15479634 ER PT J AU Korenjak, M Taylor-Harding, B Binne, UK Satterlee, JS Stevaux, O Aasland, R White-Cooper, H Dyson, N Brehm, A AF Korenjak, M Taylor-Harding, B Binne, UK Satterlee, JS Stevaux, O Aasland, R White-Cooper, H Dyson, N Brehm, A TI Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes SO CELL LA English DT Article ID DROSOPHILA FOLLICLE CELLS; DNA-REPLICATION; C-ELEGANS; RETINOBLASTOMA PROTEIN; DISTINCT MECHANISMS; NEGATIVE REGULATOR; VULVAL DEVELOPMENT; CYCLE CONTROL; RB; CHROMATIN AB The retinoblastoma tumor suppressor protein (pRb) regulates gene transcription by binding E2F transcription factors. pRb can recruit several repressor complexes to E2F bound promoters; however, native pRb repressor complexes have not been isolated. We have purified E2F/RBF repressor complexes from Drosophila embryo extracts and characterized their roles in E2F regulation. These complexes contain RBF, E2F and Myb-interacting proteins that have previously been shown to control developmentally regulated patterns of DNA replication in follicle cells. The complexes localize to transcriptionally silent sites on polytene chromosomes and mediate stable repression of a specific set of E2F targets that have sex- and differentiation-specific expression patterns. Strikingly, seven of eight complex subunits are structurally and functionally related to C. elegans synMuv class B genes, which cooperate to control vulval differentiation in the worm. These results reveal an extensive evolutionary conservation of specific pRb repressor complexes that physically combine subunits with established roles in the regulation of transcription, DNA replication, and chromatin structure. C1 Univ Munich, Adolf Butenandt Inst, Lehrstuhl Mol Biol, Munich, Germany. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Univ Bergen, Dept Mol Biol, Bergen, Norway. Univ Bergen, Computat Biol Unit, Bergen, Norway. Univ Oxford, Dept Zool, Oxford OX1 3PS, England. RP Brehm, A (reprint author), Univ Munich, Adolf Butenandt Inst, Lehrstuhl Mol Biol, Munich, Germany. EM abrehm@lmu.de RI White-Cooper, Helen/A-4633-2010 OI White-Cooper, Helen/0000-0002-3373-8023 FU NCI NIH HHS [CA95281, CA64402, P01 CA95281]; NIGMS NIH HHS [GM53203] NR 46 TC 187 Z9 197 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 15 PY 2004 VL 119 IS 2 BP 181 EP 193 DI 10.1016/j.cell.2004.09.034 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 863QQ UT WOS:000224577200007 PM 15479636 ER PT J AU Cai, DS Frantz, JD Tawa, NE Melendez, PA Oh, BC Lidov, HGW Hasselgren, PO Frontera, WR Lee, J Glass, DJ Shoelson, SE AF Cai, DS Frantz, JD Tawa, NE Melendez, PA Oh, BC Lidov, HGW Hasselgren, PO Frontera, WR Lee, J Glass, DJ Shoelson, SE TI IKK beta/NF-kappa B activation causes severe muscle wasting in mice SO CELL LA English DT Article ID UBIQUITIN-PROTEASOME PATHWAY; FOXO TRANSCRIPTION FACTORS; TUMOR NECROSIS FACTOR; SKELETAL-MUSCLE; TNF-ALPHA; PROTEIN BREAKDOWN; ATROPHY; KINASE; CACHEXIA; EXPRESSION AB Muscle wasting,accompanies aging and pathological conditions ranging from cancer, cachexia, and diabetes to denervation and immobilization. We show that activation of NF-kappaB, through muscle-specific transgenic expression of activated IkappaB kinase beta (MIKK), causes profound muscle wasting that resembles clinical cachexia. In contrast, no overt phenotype was seen upon muscle-specific inhibition of NF-kappaB through expression of IkappaBalpha superrepressor (MISR). Muscle loss was due to accelerated protein breakdown through ubiquitin-dependent proteolysis. Expression of the E3 ligase MuRF1, a mediator of muscle atrophy, was increased in MIKK mice. Pharmacological or genetic inhibition of the IKKbeta/NF-kappaB/MuRF1 pathway reversed muscle atrophy. Denervation- and tumor-induced muscle loss were substantially reduced and survival rates improved by NF-kappaB inhibition in MISR mice, consistent with a critical role for NF-kappaB in the pathology of muscle wasting and establishing it as an important clinical target for the treatment of muscle atrophy. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Regeneron Pharmaceut Inc, Muscle Program, Tarrytown, NY 10591 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. RP Shoelson, SE (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM steven.shoelson@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK045943-08, DK36836, DK45943, DK51729, R01 DK045943-07, R01 DK051729-07, R01 DK051729-08, R01 DK051729-09] NR 45 TC 688 Z9 722 U1 6 U2 36 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 15 PY 2004 VL 119 IS 2 BP 285 EP 298 DI 10.1016/j.cell.2004.09.027 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 863QQ UT WOS:000224577200015 PM 15479644 ER PT J AU Kwiatkowski, BA Ragoczy, T Ehly, J Schubach, WH AF Kwiatkowski, BA Ragoczy, T Ehly, J Schubach, WH TI Identification and cloning of a novel chromatin-associated protein partner of Epstein-Barr nuclear protein 2 SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Epstein-Barr virus; EBNA2; Parallel Sister Chromatids Protein; wings apart-like ID VIRUS NUCLEAR ANTIGEN-2; BINDING-PROTEIN; DROSOPHILA-MELANOGASTER; ACIDIC DOMAIN; COMPLEX; TRANSCRIPTION; ORGANIZATION; LOCALIZATION; ARCHITECTURE; ACTIVATION AB In a screen for binding partners of the Epstein-Barr virus transformation-related protein EBNA2, we cloned a novel, evolutionarily conserved protein showing similarity to the Drosophila Parallel Sister Chromatids Protein (PASC). We have named this protein "Friend of EBNA2" (FOE). Human FOE encodes a protein of 1227 amino acids with a functional bipartite nuclear localization signal, an arginine-rich motif, a putative nuclear export signal as well as with three highly acidic regions and a predicted coiled-coil domain. FOE and EBNA2 coimmunoprecipitate from lymphocyte nuclear extracts. RNA and protein blots show that FOE is expressed in all human tissues. FOE is a nuclear protein with the bulk of the protein associated with the insoluble nuclear fraction biochemically defined as the nuclear matrix. Indirect immunofluorescence and dynamic imaging studies suggest that FOE associates with transcriptionally active nuclear subregions in interphase cells and concentrates at the ends of formed chromosomes during mitosis. (C) 2004 Elsevier Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Dept Med, Div Oncol, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Schubach, WH (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Oncol, S-111-ONC,1660 S Columbian Way, Seattle, WA 98108 USA. EM wschu@u.washington.edu FU NCI NIH HHS [CA82459] NR 33 TC 7 Z9 9 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 15 PY 2004 VL 300 IS 1 BP 223 EP 233 DI 10.1016/j.yexcr.2004.06.028 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 858YH UT WOS:000224228200021 PM 15383329 ER PT J AU Freedman, ML Penney, KL Stram, DO Le Marchand, L Hirschhorn, JN Kolonel, LN Altshuler, D Henderson, BE Haiman, CA AF Freedman, ML Penney, KL Stram, DO Le Marchand, L Hirschhorn, JN Kolonel, LN Altshuler, D Henderson, BE Haiman, CA TI Common variation in BRCA2 and breast cancer risk: a haplotype-based analysis in the Multiethnic Cohort SO HUMAN MOLECULAR GENETICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; LOS-ANGELES; SUSCEPTIBILITY; POPULATION; IDENTIFICATION; DIVERSITY; DISEASE; BLOCKS; HAWAII; HUMANS AB It is well established that rare mutations in BRCA2 predispose to familial breast cancer, but whether common variants at this locus contribute more modest risk to sporadic breast cancer has not been thoroughly investigated. We performed a haplotype-based study of BRCA2 among women in the Multiethnic Cohort Study (MEC), genotyping 50 SNPs spanning 109.4 kb of the BRCA2 gene. Twenty-one haplotype-tagging SNPs (including seven missense SNPs) were selected to predict the common BRCA2 haplotypes and were genotyped in a breast cancer case-control study nested in the MEC (cases, n=1715; controls, n=2502). Compared to non-carriers, we observed nominally significant positive associations for homozygous carriers of specific haplotypes in blocks 2 (haplotype 2c: OR=1.50; 95% CI, 1.08-2.09) and 3 (haplotype 3d: OR=1.50; 95% CI, 1.01-2.24). These results could be explained on the basis of a single marker in intron 24 (SNP 42: rs206340) that was correlated with these haplotypes and the homozygous state was associated with a significantly increased risk of breast cancer (AA versus GG genotypes: OR=1.59, 95% CI, 1.18-2.16; nominal P=0.005). This association was modestly stronger among women with advanced disease (OR=2.00, 95% CI, 1.30-3.08; P=0.002). In this exploratory analysis, we found little indication that common variation in BRCA2 dramatically impacts sporadic breast cancer risk. However, a significant elevation in risk was observed among similar to6% of women who carried a specific haplotype pattern and may harbor a susceptibility allele at the BRCA2 locus. C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ Hawaii, Canc Res Ctr Hawaii, Etiol Program, Honolulu, HI 96813 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Haiman, CA (reprint author), Univ So Calif, USC Norris Comprehens canc ctr, Dept Prevent Med, 1441 Eastlake Ave,Rm 4441, Los Angeles, CA 90089 USA. EM haiman@usc.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 30 TC 39 Z9 40 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2004 VL 13 IS 20 BP 2431 EP 2441 DI 10.1093/hmg/ddh270 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 856YA UT WOS:000224080800010 PM 15317758 ER PT J AU Loftis, JM Hauser, P AF Loftis, JM Hauser, P TI The phenomenology and treatment of interferon-induced depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE hepatitis C; multiple sclerosis; cancer; interferon; depression; cytokines ID CHRONIC HEPATITIS-C; CHRONIC VIRAL-HEPATITIS; MULTIPLE-SCLEROSIS; ALPHA-INTERFERON; PSYCHIATRIC-SYMPTOMS; ANXIETY SYMPTOMS; ALFA-INTERFERON; CANCER-PATIENTS; PHASE-III; IFN-ALPHA AB Interferon (IFN)-alpha, IFN-beta, and IFN-gamma are currently available for the treatment of malignancies, viral infections (e.g., hepatitis C virus), multiple sclerosis (MS), and skin conditions. In addition to their therapeutic effects, IFNs commonly cause various side effects. Most common among the side effects of IFN are "flu-like" symptoms such as chills, fever, and muscle soreness. However, IFN can also cause significant neuropsychiatric side effects, particularly symptoms of depression. A literature search was conducted in order to summarize current information on (1) the frequency, characteristics, and risk factors of IFN-induced depression, (2) possible biochemical mechanisms associated with IFN-induced depression, and (3) the treatment strategies for IFN-induced depression. Review of the literature suggests that symptoms of depression induced by IFN therapy, in particular IFN-alpha therapy, are common and can limit the treatment utility, often necessitating discontinuation of TFN therapy or the use of psychopharmacologic agents. Depression is also a suspected side effect of therapy with IFN-beta and IFN-gamma; however, the association has not been as convincingly confirmed. Importantly, IFNs affect neurochemical pathways putatively involved in the etiology of depression. While these depressive side effects usually resolve after the completion of IFN therapy, they can persist or reappear with dose escalations. It is recommended that health care providers, patients and their families be informed about the potential risk of the psychiatric disturbances that can occur with IFN-a therapy. Screening and monitoring, ideally using symptom rating scales for depression, and early antidepressant treatment intervention appear necessary to optimize IFN therapy for the majority of patients. (C) 2004 Elsevier B.V. All rights reserved. C1 Portland VA Med Ctr P3MHAdm, NW Hepatitis C Resources Ctr, Psychiat Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR USA. Portland VA Med Ctr, JENS Lab, Portland, OR USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR USA. RP Hauser, P (reprint author), Portland VA Med Ctr P3MHAdm, NW Hepatitis C Resources Ctr, Psychiat Behav Hlth & Clin Neurosci Div, 3710 SW US Veterans Hosp Rd, Portland, OR 97239 USA. EM loftisj@ohsu.edu; peter.hauser2@med.va.gov NR 74 TC 123 Z9 127 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT 15 PY 2004 VL 82 IS 2 BP 175 EP 190 DI 10.1016/j.jad.2004.04.002 PG 16 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 870IQ UT WOS:000225051200002 PM 15488246 ER PT J AU Biederman, J Monuteaux, MC Faraone, SV Hirshfeld-Becker, DR Henin, A Gilbert, J Rosenbaum, JF AF Biederman, J Monuteaux, MC Faraone, SV Hirshfeld-Becker, DR Henin, A Gilbert, J Rosenbaum, JF TI Does referral bias impact findings in high-risk offspring for anxiety disorders? A controlled study of high-risk children of non-referred parents with panic disorder/agoraphobia and major depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE panic disorder; depression; children; comorbidity; high-risk ID DEFICIT HYPERACTIVITY DISORDER; PROSPECTIVE-LONGITUDINAL-COMMUNITY; PSYCHIATRIC-DISORDERS; BEHAVIORAL-INHIBITION; PSYCHOPATHOLOGY; FAMILY; PROBANDS; RELATIVES; COMORBIDITY; ADOLESCENTS AB Background: Previous findings in referred samples documented significant diagnostic specificity in patterns of transmission between parents with panic disorder (PD) and parents with major depression (MD) and their offspring. This study evaluated whether these patterns of transmission between parents and high-risk offspring are moderated by referral bias. Methods: Parental PD/agoraphobia (AG) and parental MD were used to predict rates of offspring psychiatric disorders and functional outcomes using data from an opportunistic sample of parents (n = 991) and offspring (n = 734) ascertained from case-control family genetic studies of youth with and without attention-deficit hyperactivity disorder. Subjects were comprehensively assessed with structured diagnostic interview methodology to evaluate psychiatric disorders in parents and offspring. Results: Parental PD/AG increased the risk for anxiety disorders in offspring, independently of parental MD while parental MD increased the risk for mood and disruptive behavior disorders in offspring, independently of parental PD/AG. Parental psychopathology was also associated with functional impairment in offspring. Limitations: The use of a sample ascertained by ADHD and control probands, and parent psychiatric diagnostic reports for children under 12. Conclusions: These results extend to non-referred samples previous findings from referred samples documenting diagnostic specificity in the familial transmission of PD/AG and MD from parents to offspring, suggesting that these patterns of transmission are not due to referral bias. These results could inform and enhance community programs aimed at screening for and treating pediatric psychopathology. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharm Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharm Program, Warren 705,15 Parkman St, Boston, MA 02114 USA. EM Jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD-36317]; NIMH NIH HHS [5R01MH50657-11A1] NR 32 TC 16 Z9 16 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT 15 PY 2004 VL 82 IS 2 BP 209 EP 216 DI 10.1016/j.jad.2003.12.015 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 870IQ UT WOS:000225051200005 PM 15488249 ER PT J AU von Arnim, CAF Tangredi, MM Peltan, ID Lee, BM Irizarry, MC Kinoshita, A Hyman, BT AF von Arnim, CAF Tangredi, MM Peltan, ID Lee, BM Irizarry, MC Kinoshita, A Hyman, BT TI Demonstration of BACE (beta-secretase) phosphorylation and its interaction with GGA1 in cells by fluorescence-lifetime imaging microscopy SO JOURNAL OF CELL SCIENCE LA English DT Article DE BACE; GGA; Alzheimer's disease; phosphorylation ID AMYLOID PRECURSOR PROTEIN; MANNOSE 6-PHOSPHATE RECEPTORS; ALZHEIMERS-DISEASE; VHS DOMAINS; A-BETA; ENDOCYTIC PATHWAY; ASPARTYL PROTEASE; CYTOSOLIC DOMAIN; SORTING SIGNAL; GAMMA-ADAPTIN AB beta-Secretase (BACE) carries out the first of two proteolysis steps to generate the amyloid-beta peptides that accumulate in the senile plaques in Alzheimer's disease (AD). Because most BACE activity occurs in endosomes, signals regulating its trafficking to these compartments are important to an understanding of AD pathogenesis. A DISLL sequence near the BACE C-terminus mediates binding of BACE to the VHS domains of Golgi-localized gamma-ear-containing ARF-binding (GGA) proteins, which are involved in the sorting of proteins to endosomes. Phosphorylation of the motif's serine residue regulates BACE recycling back to the cell surface from early endosomes and enhances the interaction of BACE with GGA proteins in isolated protein assays. We found that BACE phosphorylation influences BACE-GGA interactions in cells using a new fluorescence-resonance- energy-transfer-based assay of protein proximity, fluorescence lifetime imaging. Although serine-phosphorylated BACE was distributed throughout the cell, interaction of GGA1 with the wild-type protein occurred in juxtanuclear compartments. Pseudo-phosphorylated and non-phosphorylated BACE mutants remained localized with GGA1 in the Golgi body, but the latter mutation diminished the two proteins' FRET signal. Because BACE phosphorylated at serine residues can be identified in human brain, these data suggest that serine phosphorylation of BACE is a physiologically relevant post-translational modification that regulates trafficking in the juxtanuclear compartment by interaction with GGA1. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Dis Res Lab, Boston, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Dis Res Lab, 114 16th St, Boston, MA 02129 USA. EM bhyman@partners.org OI Peltan, Ithan/0000-0003-1730-234X NR 40 TC 81 Z9 81 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 15 PY 2004 VL 117 IS 22 BP 5437 EP 5445 DI 10.1242/jcs.01422 PG 9 WC Cell Biology SC Cell Biology GA 875IQ UT WOS:000225414100024 PM 15466887 ER PT J AU Yao, JK Cheng, P AF Yao, JK Cheng, P TI Determination of multiple redox-active compounds by high-performance liquid chromatography with coulometric multi-electrode array system SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Coulometric multi-electrode array system; redox-active compounds ID DEPENDENT METABOLIC SEROTYPES; RATS; FEMALE AB Studies of the antioxidant defense system and the related metabolic pathways are often complicated by cumbersome analytical methods, which require separate and multi-step extraction and chemical reaction procedures. Further, assaying multiple parameters is limited because of the usual small sample amounts. High-performance liquid chromatography coupled with a coulometric multi-electrode array system provides us high specificity and sensitivity to measure electrochemically oxidizable compounds in biological samples. In contrast to previously reported methods with two columns in series and a complex gradient elution profile, we have developed an automated procedure to simultaneously measure multiple redox-active low-molecular weight compounds that utilizes a single column with a simplified binary gradient profile. No other chemical reactions are necessary. In order to reduce the running time and yet achieve a reproducible retention time by the auto sampler injection, our gradient elution profile was modified to produce a shorter equilibration time, stable retention time, and a reduced cost per test. (C) 2004 Elsevier B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU NIMH NIH HHS [MH 58141] NR 13 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD OCT 15 PY 2004 VL 810 IS 1 BP 93 EP 100 DI 10.1016/j.jchromb.2004.07.021 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 855YE UT WOS:000224010000012 PM 15358312 ER PT J AU Skates, SJ Horick, N Yu, YH Xu, FJ Berchuck, A Havrilesky, LJ de Bruijn, HWA van der Zee, AGJ Woolas, RP Jacobs, IJ Zhang, Z Bast, RC AF Skates, SJ Horick, N Yu, YH Xu, FJ Berchuck, A Havrilesky, LJ de Bruijn, HWA van der Zee, AGJ Woolas, RP Jacobs, IJ Zhang, Z Bast, RC TI Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MULTIPLE SERUM MARKERS; TUMOR-MARKERS; STATISTICS; CISPLATIN; CARCINOMA; WOMEN; TESTS AB Purpose In CA-125-based ovarian cancer screening trials, overall specificity and screening sensitivity of ultrasound after an elevated CA-125 exceeded 99.6% and 70%, respectively, thereby yielding a positive predictive value (PPV) exceeding 10%. However, sensitivity for early-stage disease was only 40%. This study aims to increase preoperative sensitivity for early-stage ovarian cancer while maintaining the annual referral rate to ultrasound at 2% by combining information across CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor (M-CSF). For direct comparisons between marker panels, all sensitivity results correspond to a 98% fixed first-line specificity (referral rate 2%). Patients and Methods Logistic regression, classification tree, and mixture discriminant analysis (MDA) models were fit to a training data set of preoperative serum measurements (63 patients, 126 healthy controls) from one center. Estimates from the training set applied to an independent validation set (60 stage I to II patients, 98 healthy controls) from two other centers provided unbiased estimates of sensitivity. Results Preoperative sensitivities for early-stage disease of the optimal panels were 45% for CA-125II; 67% for CA-125II and CA72-4; 70% for CA-125II, CA72-4, and M-CSF; and 68% for all four markers (latter two results using MDA). Conclusion Efficiently combining information on CA-125II, CA 72-4, and M-CSF significantly increased preoperative early-stage sensitivity from 45% with CA-125II alone to 70%, while maintaining 98% first-line specificity. Screening trials with these markers using MDA followed by referral to ultrasound may maintain previously high levels of specificity and PPV, while significantly increasing early-stage screening sensitivity. MDA is a useful, biologically justified method for combining biomarkers. (C) 2004 by American Society of Clinical Oncology C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Med Ctr, Durham, NC USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Groningen Hosp, Groningen, Netherlands. St Bartholomews Hosp, London, England. RP Skates, SJ (reprint author), Massachusetts Gen Hosp, 50 Stanford St,Suite 560, Boston, MA 02114 USA. EM sskates@partners.org RI Bast, Robert/E-6585-2011; Jacobs, Ian/F-1743-2013 OI Bast, Robert/0000-0003-4621-8462; Jacobs, Ian/0000-0002-8112-4624 FU NCI NIH HHS [1P50 CA83639] NR 30 TC 94 Z9 98 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 OCT 15 PY 2004 VL 22 IS 20 BP 4059 EP 4066 DI 10.1200/JCO.2004.03.091 PG 8 WC Oncology SC Oncology GA 863PG UT WOS:000224573400006 PM 15381683 ER PT J AU Ballen, KK Becker, PS Yeap, BY Matthews, B Henry, DH Ford, PA AF Ballen, KK Becker, PS Yeap, BY Matthews, B Henry, DH Ford, PA TI Autologous stem-cell transplantation can be performed safely without the use of blood-product support SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; RECOMBINANT-HUMAN-ERYTHROPOIETIN; EPSILON-AMINOCAPROIC ACID; HIGH-DOSE THERAPY; JEHOVAH-WITNESS; TRANSFUSION REQUIREMENTS; MULTIPLE-MYELOMA; CANCER-PATIENTS; HEMATOLOGIC MALIGNANCY; MYELOABLATIVE THERAPY AB Purpose Autologous stem-cell transplantation has been shown to be a curative procedure for a variety of leukemias and lymphomas. Most transplants require RBC and platelet support. We report the ability to perform autologous transplantation without blood-product support. Subjects and Methods In this study, we treated 26 patients with religious objection to blood products with autologous stem-cell support without the use of any blood products. Patients received a combination of granulocyte colony-stimulating factor (G-CSF), erythropoietin, and interleukin-11 or G-CSF alone to mobilize stem cells. Post-transplant patients received intravenous iron, erythropoietin, G-CSF, and epsilon aminocaproic acid. Results There were two major bleeding complications (8%), with two treatment-related deaths (8%). There were three minor bleeding complications (12%). The median fall in hemoglobin level was 4.7 g/dL; the median hemoglobin level 30 days after transplantation was 9.2 g/dL. The median total number of days with platelet count less than 10 X 10(9)/L was 4 days; the median days to platelet recovery greater than 20 X 10 (9)/L was 12 days. Conclusion Autologous stem-cell transplantation can be performed safely without the use of any blood products. (C) 2004 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Univ Massachusetts Mem Hlth Care, Worcester, MA 01605 USA. Penn Hosp, Philadelphia, PA 19107 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM kballen@partners.org NR 52 TC 20 Z9 22 U1 1 U2 2 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 OCT 15 PY 2004 VL 22 IS 20 BP 4087 EP 4094 DI 10.1200/JCO.2004.01.144 PG 8 WC Oncology SC Oncology GA 863PG UT WOS:000224573400009 PM 15353543 ER PT J AU French, CA Kutok, JL Faquin, WC Toretsky, JA Antonescu, CR Griffin, CA Nose, V Vargas, SO Vargas, SO Moschovi, M Tzortzatou-Stathopoulou, F Miyoshi, I Pcrez-Atayde, AR Aster, JC Fletcher, JA AF French, CA Kutok, JL Faquin, WC Toretsky, JA Antonescu, CR Griffin, CA Nose, V Vargas, SO Vargas, SO Moschovi, M Tzortzatou-Stathopoulou, F Miyoshi, I Pcrez-Atayde, AR Aster, JC Fletcher, JA TI Midline carcinoma of children and young adults with NUT rearrangement SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AGGRESSIVE CARCINOMA; BROMODOMAIN PROTEIN; THYMIC CARCINOMA; TRANSLOCATION; CELLS; CD34 AB Purpose A balanced chromosomal translocation, t(15;19), resulting in the BRD4-NUT oncogene, has been identified in a lethal carcinoma of young people, a disease described primarily in case reports. We sought to amass a more definitive series of tumors with NUT and/or BRD4 gene rearrangements and to determine distinct clinicopathologic features. Patients and Methods Carcinomas (N = 98) in young individuals (median age, 32.5 years) were screened for NUT and BRD4 rearrangements using dual-color fluorescence in situ hybridization. Four published carcinomas with BRD4 and NUT rearrangements were also evaluated. Immunophenotypic analyses were performed. Results Eleven tumors had NUT gene rearrangements, including eight with BRD4-NUT fusions and three with novel rearrangements, which were designated as NUT variant. All NUT-rearranged carcinomas (NRCs) arose from midline epithelial structures, including the first example arising below the diaphragm. Patients were young (median age, 17.6 years). Squamous differentiation (seen in 82% of NRCs) was particularly striking in NUT-variant cases. In this first description of NUT-variant carcinomas, the average survival (96 weeks, n = 3) was longer than for BRD4-NUT carcinomas (28 weeks, n = 8). Strong CD34 expression was found in six of 11 NRCs but in zero of 45 NUT wild-type carcinomas. Conclusion NRCs arise from midline structures in young people, and NRCs with BRD4-NUT are highly lethal, despite intensive therapies. NUT-variant carcinomas might have a less fulminant clinical course than those with BRD4-NUT fusions. CD34 expression is characteristic in NRCs and, therefore, holds promise as a diagnostic test for this distinctive clinicopathologic entity. (C) 2004 by American Society of Clinical Oncology. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Dept Pediat, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Univ Athens, Aghi Sofia Childrens Hosp, Dept Pediat Hematol Oncol, Athens, Greece. Kochi Med Sch, Dept Med, Kochi 783, Japan. RP French, CA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM Cfrench@partners.org FU NCI NIH HHS [K08 CA92158-01, R01 CA088004, R01 CA088004-08] NR 14 TC 122 Z9 127 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 15 PY 2004 VL 22 IS 20 BP 4135 EP 4139 DI 10.1200/JCO.2004.02.107 PG 5 WC Oncology SC Oncology GA 863PG UT WOS:000224573400015 PM 15483023 ER PT J AU Partridge, AH Gelber, S Peppercorn, J Sampson, E Knudsen, K Laufer, M Rosenberg, R Przypyszn, M Rein, A Winer, EP AF Partridge, AH Gelber, S Peppercorn, J Sampson, E Knudsen, K Laufer, M Rosenberg, R Przypyszn, M Rein, A Winer, EP TI Web-based survey of fertility issues in young women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; AGE-RELATED DIFFERENCES; BONE-MINERAL DENSITY; ADJUVANT CHEMOTHERAPY; PREGNANCY; CARCINOMA; SURVIVORS; DIAGNOSIS; MENOPAUSE; CHILDBEARING AB Purpose \Young women with breast cancer often seek advice about whether treatment will affect their fertility. We sought to gain a better understanding of women's attitudes about fertility and how these concerns affect decision making. Patients and Methods We developed a survey about fertility issues for young women with a history of early-stage breast cancer. The survey was e-mailed to all registered Young Survival Coalition survivor members (N = 1,702). E-mail reminders were used. Results Six hundred fifty-seven eligible respondents completed the survey. Mean age at breast cancer diagnosis was 32.9 years; mean current age was 35.8 years. Ninety percent of women were white; 62% were married; 76% were college graduates. Stages at diagnosis were as follows: 0, 10%; I, 27%; Il, 47%; III, 13%. Sixty-two percent of women were within 2 years of diagnosis. Fifty-seven percent recalled substantial concern at diagnosis about becoming infertile with treatment. In multivariate logistic regression, greater concern about infertility was associated with wish for children/more children (odds ratio [OR], 120; P < .0001), number of prior pregnancies (OR, 0.78; P = .01), and prior difficulty conceiving (OR, 1.86; P = .08). Twenty-nine percent of women reported that infertility concerns influenced treatment decisions. Seventy-two percent of women reported discussing fertility concerns with their doctors; 51 % felt their concerns were addressed adequately. Women seemed to overestimate their risk of becoming postmenopausal with treatment. Conclusion Fertility after treatment is a major concern for young women with breast cancer. There is a need to communicate with and educate young patients regarding fertility issues at diagnosis and a need for future research directed at preserving fertility for young breast cancer survivors. (C) 2004 by American Society of Clinical Oncology. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Young Survival Coalit, New York, NY USA. RP Partridge, AH (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St,D1210, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 56 TC 340 Z9 350 U1 2 U2 11 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 OCT 15 PY 2004 VL 22 IS 20 BP 4174 EP 4183 DI 10.1200/jco.2004.01.159 PG 10 WC Oncology SC Oncology GA 863PG UT WOS:000224573400020 PM 15483028 ER PT J AU Figueroa, BE Brown, JR Nascimento, A Fisher, DC Tuli, S AF Figueroa, BE Brown, JR Nascimento, A Fisher, DC Tuli, S TI Unusual sites of Hodgkin's lymphoma - Case 2. Hodgkin's lymphoma of the CNS masquerading as meningioma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DISEASE; PATIENT C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Brookline, MA USA. RP Figueroa, BE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Brookline, MA USA. NR 7 TC 18 Z9 19 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 OCT 15 PY 2004 VL 22 IS 20 BP 4228 EP 4230 DI 10.1200/jco.2004.01.163 PG 3 WC Oncology SC Oncology GA 863PG UT WOS:000224573400027 PM 15483035 ER PT J AU Giri, S Rattan, R Singh, AK Singh, I AF Giri, S Rattan, R Singh, AK Singh, I TI The 15-deoxy-delta 12,14-prostaglandin J(2) inhibits the inflammatory response in primary rat astrocytes via down-regulating multiple steps in phosphatidylinositol 3-kinase-Akt-NF-kappa B-p300 pathway independent of peroxisome proliferator-activated receptor gamma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; PPAR-GAMMA; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); CYCLOPENTENONE PROSTAGLANDINS; PROINFLAMMATORY CYTOKINES; NEGATIVE REGULATION; PROTEIN-KINASE; BETA-SUBUNIT; GLIAL-CELLS AB Ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), such as 15-deoxy-12,14-PGJ(2) (15d-PGJ(2)), have been proposed as a new class of anti-inflammatory compounds because 15d-PGJ(2) was able to inhibit the induction of inflammatory response genes such as inducible NO synthase (MOS) and TNF (TNF-alpha) in a PPAR-dependent manner in various cell types. In primary astrocytes, the anti-inflammatory effects (inhibition of TNF-alpha, IL-1beta, IL-6, and iNOS gene expression) of 15d-PGJ(2) are observed to be independent of PPARgamma. Overexpression (wild-type and dominant-negative forms) of PPARgamma and its antagonist (GW9662) did not alter the 15d-PGJ(2)-induced inhibition of LPS/IFN-gamma-mediated iNOS and NF-kappaB activation. The 15d-PGJ(2) inhibited the inflammatory response by inhibiting IkappaB kinase activity, which leads to the inhibition of degradation of IkappaB and nuclear translocation of p65, thereby regulating the NF-kappaB pathway. Moreover, 15d-PGJ2 also inhibited the LPS/IFN-gamma-induced PI3K-Akt pathway. The 15d-PGJ2 inhibited the recruitment of p300 by NF-kappaB (p65) and down-regulated the p300-mediated induction of iNOS and NF-kappaB luciferase reporter activity. Coexpression of constitutive active Akt and PI3K (p110) reversed the 15d-PGJ(2)-mediated inhibition of p300-induced iNOS and NF-kappaB luciferase activity. This study demonstrates that 15d-PGJ(2) suppresses inflammatory response by inhibiting NF-kappaB signaling at multiple steps as well as by inhibiting the PI3K/Akt pathway independent of dPPARgamma in primary astrocytes. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 316 Clin Sci Bldg, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-37766, NS-22576, NS-34741, NS-40144, NS-40810] NR 60 TC 102 Z9 106 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2004 VL 173 IS 8 BP 5196 EP 5208 PG 13 WC Immunology SC Immunology GA 861BX UT WOS:000224392200051 PM 15470065 ER PT J AU Alter, G Malenfant, JM Delabre, RM Burgett, NC Yu, XG Lichterfeld, M Zaunders, J Altfeld, M AF Alter, G Malenfant, JM Delabre, RM Burgett, NC Yu, XG Lichterfeld, M Zaunders, J Altfeld, M TI Increased natural killer cell activity in viremic HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE IMMUNITY; ANTIRETROVIRAL THERAPY; SELECTIVE DEPLETION; VIRUS-INFECTION; I MOLECULES; NEF PROTEIN; NK CELLS; RECEPTORS; IMMUNODEFICIENCY; ACTIVATION AB NK cells are a subset of granular lymphocytes that are critical in the innate immune response to infection. These cells are capable of killing infected cells and secreting integral cytokines and chemokines. The role that this subset of cytolytic cells plays in HIV infection is not well understood. In this study, we dissected the function of NK cells in viremic and aviremic HIV-1-infected subjects, as well as HIV-1-negative control individuals. Despite reduced NK cell numbers in subjects with ongoing viral replication, these cells were significantly more active in secreting both IFN-gamma and TNF-alpha than NK cells from aviremic subjects or HIV-1-negative controls. In addition, NK cells in subjects with detectable viral loads expressed significantly higher levels of CD107a, a marker of lysosomal granule exocytosis. The expression of CD107a correlated with NK cell-mediated cytokine secretion and cytolytic activity as well as with the level of viral replication, suggesting that CD107a represents a good marker for the functional activity of NK cells. Finally, killer Ig-related receptor(+) NK cells were stable or elevated in viremic subjects, while the numbers of CD3(-)/CD56(+)/CD94(+) and CD3(-)/CD56(+)/CD161(+) NK cells were reduced. Taken together, these data demonstrate that viremic HIV-1 infection is associated with a reduction in NK cell numbers and a perturbation of NK cell subsets, but increased overall NK cell activity. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA. St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia. Univ New S Wales, Sydney, NSW, Australia. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. EM maltfeld@partners.org RI Zaunders, John/J-6553-2012 OI Zaunders, John/0000-0002-5912-5989 NR 31 TC 71 Z9 75 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2004 VL 173 IS 8 BP 5305 EP 5311 PG 7 WC Immunology SC Immunology GA 861BX UT WOS:000224392200063 PM 15470077 ER PT J AU Schneyer, A Sidis, Y Xia, Y Saito, S del Re, E Lin, HY Keutmann, H AF Schneyer, A Sidis, Y Xia, Y Saito, S del Re, E Lin, HY Keutmann, H TI Differential actions of follistatin and follistatin-like 3 SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Inhibins, Activins and Follistatins CY JUL 03-04, 2003 CL Siena, ITALY DE follistatin; follistatin-like 3; FLRG; FSRP; activin; structure; activity ID ACTIVIN; BINDING; PROTEIN; INHIBIN; GENE; NEUTRALIZATION; LOCALIZATION; BETAGLYCAN; MYOSTATIN; DEFECTS AB Follistatin (FS) is an important physiological regulator of activin and other TGFbeta superfamily members. The recently discovered follistatinlike 3 (FSTL3; a.k.a. FLRG; FSRP) shares significant structural and functional homology with FS, but also has some interesting differences, including a prominent nuclear localization. The existence of these two related proteins allows detailed molecular and biochemical comparisons of the biologic roles of their individual structural elements. Current studies indicate that the heparin binding sequence is essential for the ability of FS to inhibit autocrine activin but is not sufficient to confer this activity on FSTL3. Preliminary analysis of FSTL3 transgenic mice suggests that FSTL3 regulates gonadal development and function through inhibition of the paracrine activity of activin and/or other related factors. These studies have identified important structural elements necessary for biological activity of FS and FSTL3 and potential roles for FSTL3 in vivo. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Schneyer, A (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5, Boston, MA 02114 USA. EM Schneyer.alan@mgh.harvard.edu NR 19 TC 30 Z9 33 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD OCT 15 PY 2004 VL 225 IS 1-2 BP 25 EP 28 DI 10.1016/j.mce.2004.02.009 PG 4 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 864HC UT WOS:000224623600005 PM 15451564 ER PT J AU Lambert-Messerlian, GM Pinar, H Laprade, E Tantravahi, U Schneyer, A Canick, JA AF Lambert-Messerlian, GM Pinar, H Laprade, E Tantravahi, U Schneyer, A Canick, JA TI Inhibins and activins in human fetal abnormalities SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Inhibins, Activins and Follistatins CY JUL 03-04, 2003 CL Siena, ITALY DE inhibin; activin; Down syndrome; fetus; palate; cleft ID MATERNAL SERUM INHIBIN; PRO-ALPHA-C; MESSENGER RIBONUCLEIC-ACIDS; DOWNS-SYNDROME PREGNANCIES; 2ND TRIMESTER LEVELS; LIVING HUMAN FETUSES; PLASMA-PROTEIN-A; AMNIOTIC-FLUID; DIMERIC INHIBINS; MOLECULAR CHARACTERISTICS AB To date, the only routine clinical application of inhibin or activin measurement in testing for fetal abnormalities has been the use of inhibin A in prenatal screening for trisomy 21 (Down syndrome). Second trimester maternal serum levels of inhibin A are, on average, two-fold higher in Down syndrome than in unaffected pregnancies. Although the biology of altered second trimester maternal serum analyte levels in Down syndrome pregnancy cannot yet be explained, it seems that fetal products tend to be decreased, while placental products tend to be increased. This pattern holds true for inhibin A because maternal serum levels appear to be derived from placental rather than fetal sources. Therefore, the measurement of inhibins and activins in maternal fluids, although clinically useful and relatively easy to obtain, may not be helpful in studying their role in human fetal development. Studies in transgenic mice indicate a role for activin, follistatin, and activin receptor type IIA in development of the palate and craniofacial region. Cleft palate is a common birth defect and is associated with serious feeding and respiratory complications in newborns. We have begun to investigate the potential role of activin in human craniofacial development by examining the spatial and temporal expression of inhibin/activin subunits, follistatin and the activin receptors in the fetal palate. Palate tissues were collected at autopsy from fetuses ranging in gestational age from 9 to 42 weeks, and 8 week embryonic tissues were also examined. Tissues were either stored in paraffin for immunocytochemistry or were frozen for RT-PCR examination of the expression of inhibin/activin proteins or mRNAs, respectively. To date, betaA subunit, follistatin, and activin receptor, but not alpha and betaB subunit, mRNAs are present in palate tissues and inhibin/activin betaA immunoreactivity has been consistently observed in developing bone. Expression of the activin A subunit and its receptors in the human fetal palate are consistent with a developmental role. Studies are ongoing to determine whether altered activin biosynthesis is associated with cleft palate. Future studies of fetal tissues may help to elucidate other roles for the TGF-beta family in human development. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Women & Infants Hosp Rhode Isl, Div Prenatal & Special Testing, Dept Pathol & Lab Med, Providence, RI 02903 USA. Brown Univ, Women & Infants Hosp, Sch Med, Div Perinatal & Pediat Pathol, Providence, RI 02905 USA. Brown Univ, Women & Infants Hosp, Sch Med, Div Genet, Providence, RI 02905 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Lambert-Messerlian, GM (reprint author), Women & Infants Hosp Rhode Isl, Div Prenatal & Special Testing, Dept Pathol & Lab Med, 70 Elm St,2nd Floor, Providence, RI 02903 USA. EM gmesserl@wihri.org OI Messerlian, Geralyn/0000-0002-9440-3411 FU NIDCR NIH HHS [R03 DE14002] NR 56 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD OCT 15 PY 2004 VL 225 IS 1-2 BP 101 EP 108 DI 10.1016/j.mce.2004.02.019 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 864HC UT WOS:000224623600015 PM 15451574 ER PT J AU Yelin, D Bouma, BE Yun, SH Tearney, GJ AF Yelin, D Bouma, BE Yun, SH Tearney, GJ TI Double-clad fiber for endoscopy SO OPTICS LETTERS LA English DT Article ID CONFOCAL MICROSCOPE AB Endoscopes employing a single optical fiber may have advantages over conventional fiber-bundle or CCD array imaging techniques, including the potential for greater flexibility and miniaturization. Although single-mode fibers can provide superior resolution compared with multimode fibers, they are prone to increased speckle noise and suffer from limited optical throughput and reduced depth of field. We demonstrate the use of a double-clad fiber for single-mode illumination and multimode detection to achieve high-resolution, reduced-speckle imaging with high optical throughput and a large depth of field. (C) 2004 Optical Society of America. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Yelin, D (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 55 Fruit St,BAR 703, Boston, MA 02114 USA. EM dyelin@partners.org NR 10 TC 44 Z9 44 U1 2 U2 5 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 OCT 15 PY 2004 VL 29 IS 20 BP 2408 EP 2410 DI 10.1364/OL.29.002408 PG 3 WC Optics SC Optics GA 860PO UT WOS:000224355700026 PM 15532282 ER EF