FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Levine, DA Saag, KG Casebeer, LL Colon-Emeric, C Lyles, KW Shewchuk, RM AF Levine, Deborah A. Saag, Kenneth G. Casebeer, Linda L. Colon-Emeric, Cathleen Lyles, Kenneth W. Shewchuk, Richard M. TI Using a modified nominal group technique to elicit director of nursing input for an osteoporosis intervention SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE osteoporosis; nominal group technique; intervention; quality improvement ID CONTINUING MEDICAL-EDUCATION; BONE-MINERAL DENSITY; HIP FRACTURE; HOME RESIDENTS; OLDER-PEOPLE; MANAGEMENT; HEALTH; OPPORTUNITY; PHYSICIANS; OUTCOMES AB Background. Barriers prevent osteoporosis care in nursing homes. Successful interventions designed to circumvent these barriers benefit from target recipient input during development. Objective: To elicit suggestions for an osteoporosis quality improvement intervention designed for use by nursing home health care professionals. Design: Modified nominal group technique Setting: Convenience sample of Alabama nursing home directors. Participants: Fifteen Alabama nursing home directors of nursing were recruited by mailing. Sixty percent of respondents participated (n = 9). Measurements: In the first phase conducted via teleconference, an experienced moderator used a preformulated question and elicited 41 suggestions to improve osteoporosis care in nursing homes. Substantively similar suggestions were combined and idiosyncratic suggestions were discarded resulting in the retention of 20 suggestions. In the second phase conducted by mail, the same participants rated the 20 suggestions based on perceived practicality and helpfulness. Elements were grouped into tertiles based on the ranking of the mean ratings of the 2 attributes and then cross-tabulated. Results: All director of nursing (n = 9) participants completed both phases. The most practical, most helpful suggestions were information on fall prevention program implementation, osteoporosis treatment protocols, and osteoporosis medication information. Conclusions: A modified nominal group technique provided useful information from nursing home directors of nursing for an osteoporosis intervention. The technique proved efficient and facile to perform. C1 Univ Alabama, Div Gen Internal Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, HSR&D REAP, Deep S Ctr Effectiveness Res, Birmingham, AL USA. Univ Alabama, Dept Med, Ctr Educ & Res Therapeut Musculoskeletal Disorder, Birmingham, AL 35294 USA. Duke Univ, Med Ctr, Durham, NC USA. Durham VA Med Ctr, Durham, NC USA. Univ Alabama, Dept Hlth Adm, Birmingham, AL USA. RP Levine, DA (reprint author), Univ Alabama, Div Gen Internal Med, 1530 3rd Ave S,FOT 720, Birmingham, AL 35294 USA. EM dlevine@uab.edu FU NIA NIH HHS [K23 AG024787] NR 47 TC 12 Z9 13 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2006 VL 7 IS 7 BP 420 EP 425 DI 10.1016/j.jamda.2006.05.004 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 090CX UT WOS:000240929300004 PM 16979085 ER PT J AU Bagby, SP AF Bagby, Susan P. TI Developmental origins of hypertension: Biology meets statistics SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID BLOOD-PRESSURE; BIRTH-WEIGHT; FETAL ORIGINS; CHILDHOOD GROWTH; ADULT LIFE; INSULIN-RESISTANCE; DISEASE; OBESITY; SIZE; ASSOCIATION C1 Oregon Hlth Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Bagby, SP (reprint author), Oregon Hlth Sci Univ, Div Nephrol & Hypertens, 3314 SW US Vet Hosp Rd,Suite PP 262, Portland, OR 97239 USA. EM bagbys@ohsu.edu NR 32 TC 2 Z9 2 U1 0 U2 2 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 SEP PY 2006 VL 17 IS 9 BP 2356 EP 2358 DI 10.1681/ASN.2006070744 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 078OP UT WOS:000240113400004 PM 16899513 ER PT J AU Liebschutz, JM Darko, GO Finley, EP Cawse, JM Bharel, M Orlander, JD AF Liebschutz, Jane M. Darko, Godwin O. Finley, Erin P. Cawse, Jeanne M. Bharel, Monica Orlander, Jay D. TI In the minority: Black, physicians in residency and their experiences SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE racism; grounded theory; residency ID MEDICAL-STUDENTS PERCEPTIONS; UNDERREPRESENTED MINORITIES; SCHOOLS; DISCRIMINATION; ABUSE; MISTREATMENT; ENVIRONMENT; EDUCATION C1 Boston Univ, Sch Med, Boston Med Ctr, Gen Internal Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston Med Ctr, Gen Internal Med Sect, Boston, MA 02118 USA. VA Boston HealthCare Syst, Boston, MA USA. Washington Hosp Ctr, Washington, DC 20010 USA. Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RP Liebschutz, JM (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Gen Internal Med Sect, Boston, MA 02118 USA. EM jliebs@bu.edu OI Finley, Erin/0000-0003-4497-7721 NR 28 TC 11 Z9 11 U1 0 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD SEP PY 2006 VL 98 IS 9 BP 1441 EP 1448 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 087BK UT WOS:000240717000007 PM 17019911 ER PT J AU Edwards, CL Primm, A Johnson, S Feliu, M O'Garo, K Bennett, GG Robinson, E McDougald, C Byrd, G Harrison, O Whitfield, K Killough, AL AF Edwards, Christopher L. Primm, Annelle Johnson, Stephanie Feliu, Miriam O'Garo, Keisha Bennett, Gary G. Robinson, Elwood McDougald, Camela Byrd, Goldie Harrison, Ojinga Whitfield, Keith Killough, Alvin L. TI Reconsideration of the training of psychiatrists and mental health professionals: Helping to make soup SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Editorial Material DE education; diversity; mental health training; pathology; psychiatry ID HENRYISM,JOHN AB For many years, we have known of deficits in our system of training mental health professionals, particularly in recognizing and integrating diversity. Recently, we have begun to understand that our literature must more authentically reflect the experiences of all people that we serve. The current paper suggests that a comprehensive biopsychosocial conceptualization of normal and abnormal behavior for all individuals is necessary to truly begin to reduce mental health disparities. The authors argue that factors such as racial, ethnic and cultural differences must be integrated into research before the literature will begin to change in a fashion that is beneficial to the mental health training process. C1 Duke Univ, Med Ctr, Div Med Psychol, Dept Psychiat, Durham, NC USA. Duke Univ, Med Ctr, Div Hematol, Dept Med,Pain & Palliat Care Ctr, Durham, NC USA. Amer Psychiat Assoc, Off Minor & Natl Affairs, Baltimore, MD USA. Bloomberg John Hopkins Sch Publ Hlth, John Hopkins Sch Med, Dept Psychiat, Dept Hlth Policy & Management, Baltimore, MD USA. Amer Psychol Assoc, Off Sci Directorate, Washington, DC 20036 USA. Yale Univ, Sch Med, New Haven, CT USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. N Carolina Cent Univ, Dept Psychol, Durham, NC USA. N Carolina Agr & Tech State Univ, Dept Biol, Greensboro, NC USA. Duke Univ, Dept Psychol, Durham, NC USA. Cultural Ecol Syst, Durham, NC USA. RP Edwards, CL (reprint author), Duke Univ, Med Ctr, Biofeedback & Pediat Neuropsychol Serv, Chron Pain Management Program, 932 Morreene Rd,Room 170, Durham, NC 27705 USA. EM christopher.edwards@duke.edu NR 8 TC 1 Z9 1 U1 1 U2 1 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD SEP PY 2006 VL 98 IS 9 BP 1498 EP 1500 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 087BK UT WOS:000240717000014 PM 17019918 ER PT J AU Gordon, GJ Deters, LA Nitz, MD Lieberman, BC Yeap, BY Bueno, R AF Gordon, Gavin J. Deters, Levi A. Nitz, Matthew D. Lieberman, Barry C. Yeap, Beow Y. Bueno, Raphael TI Differential diagnosis of solitary lung nodules with gene expression ratios SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID FINE-NEEDLE-ASPIRATION; CANCER ACTION PROJECT; PROFILING DATA; BREAST-CANCER; ADENOCARCINOMA; MESOTHELIOMA; CLASSIFICATION; CARCINOMAS; SIGNATURES; TESTS AB Objective: We have developed a new technique that uses the ratios of select gene expression levels to translate complex genomic data into simple clinically relevant tests for the diagnosis and prognosis of cancer. We determined whether select gene pair ratio combinations can be used to detect and diagnose lung cancer with high accuracy and sensitivity. Methods: We used gene expression profiling data to train a ratio-based predictor model to discriminate among a set of samples (n = 145 total) composed of normal lung, small cell lung cancer, adenocarcinoma, squamous cell carcinoma, and pulmonary carcinoid (the training set). We then examined the optimal test in an independent set of samples (the test set, n = 122). Finally, we used one aspect of the test to determine whether the gene ratio technique was capable of detecting cancer in specimens from fine-needle aspirations performed ex vivo with normal lung (n = 14) and suspected tumor nodules (n = 15) acquired at our institution. Results: We found that a ratio-based test with 23 genes could be used to classify training set samples with 90% accuracy. This same test was similarly accurate (88%) when applied to the test set of samples. We also found that this test was 87% and 100% accurate at detecting cancer in normal and tumorous fine-needle aspiration specimens, respectively. Conclusion: The gene expression ratio diagnostic technique is likely to aid in the differential diagnosis of solitary lung nodules in patients with suspected cancer and may also prove useful in developing lung cancer screening strategies that incorporate analysis of fine-needle aspiration specimens. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Thorac Surg Oncol Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gordon, GJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM ggordon@partners.org; rbueno@partners.org FU NCI NIH HHS [R01 CA120528, CA098501, R03 CA105249-01, R03 CA105249, R01 CA120528-01, R03 CA105249-02, CA105249, R33 CA100315, L30 CA109938-01, R21 CA098501-02, R33 CA100315-02, R21 CA098501, L30 CA109938-02, R21 CA100315-01A1, R21 CA098501-01A1, R21 CA100315] NR 26 TC 4 Z9 4 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 SEP PY 2006 VL 132 IS 3 BP 621 EP 627 DI 10.1016/j.jtcvs.2006.03.046 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 077NY UT WOS:000240037700030 PM 16935118 ER PT J AU Masters, GA Li, SG Dowlati, A Madajewicz, S Langer, C Schiller, J Johnson, D AF Masters, Gregory A. Li, Sigui Dowlati, Afshin Madajewicz, Stefan Langer, Corey Schiller, Joan Johnson, David TI A phase II trial of carboplatin and gemcitabine with exisulind (IND #65,056) in patients with advanced non-small cell lung cancer: An Eastern Cooperative Oncology Group Study (E1501) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE non-small cell lung cancer; phase II trial; gemcitabine; carboplatin; novel agent; exisulind ID CHEMOTHERAPY; PACLITAXEL; INDUCTION AB Background: Carboplatin and gemcitabine are one standard regimen for patients with advanced non-small cell lung cancer (NSCLC). The oral proapoptotic agent exisulind is a cyclic guanosine monophosphate phosphodiesterase that increases apoptosis in vitro. We performed a phase II trial of carboplatin and gemcitabine with exisulind in patients with advanced NSCLC. Methods: Gemcitabine (1000 mg/m(2) days 1 and 8) and carboplatin (AUC = 5 day 1) were administered every 21 days, with exisulind orally at 250 mg orally twice daily continuously, starting day 1. The primary objective was to evaluate the 18-month survival. Secondary objectives included response rate, progression-free survival, and toxicities. Eligibility included stage IIIB (pleural effusion) or stage IV NSCLC. no previous chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1. Results: Of 57 eligible patients treated, 34 patients were male and 23 female. 42 had stage IV, six stage IIIB, and nine had recurrent disease. The median age was 63 years (range, 37-83). Twenty-six patients had an ECOG PS of 0 and 31 had a PS of 1. The majority of grade 3-4 toxicities were hematologic. Grade 3-4 nonhematologic toxicity seen in >5% of patients included nausea/vomiting in 16% and fatigue in 23% of patients. The overall response rate was 19.3%. Median progression-free survival was 4.7 months. Median overall survival was 9.0 months. Eighteen-month overall survival was 30%. Conclusion: The chemotherapy combination of gemcitabine and carboplatin with the oral proapoptotic agent exisulind is generally well tolerated with principally hematologic toxicity. The statistical endpoint of 17 patients alive at 18 months was met, but given ongoing developments in advanced NSCLC, ECOG will not be pursuing additional trials of exisulind in NSCLC. C1 Christiana Care CCOP, Newark, DE USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Hosp SUNY, Stony Brook, NY USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Wisconsin, Madison, WI USA. Vanderbilt Univ, Nashville, TN USA. RP Masters, GA (reprint author), Med Oncol Hematol Consultants, Helen F Graham Canc Ctr, 4701 Ogletown Stanton Rd,Suite 2200, Newark, DE 19713 USA. EM gmasters@cbg.org NR 28 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2006 VL 1 IS 7 BP 673 EP 678 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 086HP UT WOS:000240664700012 PM 17409935 ER PT J AU Sequist, LV Dziadziuszko, R AF Sequist, Lecia V. Dziadziuszko, Rafal TI Update on epidermal growth factor receptor inhibitor development in lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT 6th Annual Targeted Therapies for the Treatment of Lung Cancer Conference CY JAN 27-28, 2006 CL Los Angeles, CA DE non-small cell lung cancer; epidermal growth factor; receptor; gefitinib; erlotinib; cetuximab; panitumumab; matuzumab ID METASTATIC COLORECTAL-CANCER; PHASE-III TRIAL; EGF RECEPTOR; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; PROLONGED SURVIVAL; PLUS IRINOTECAN; KINASE DOMAIN; GEFITINIB; ERLOTINIB AB Therapeutic strategies targeting the epidermal growth factor receptor (EGFR) are being evaluated in a number of ongoing clinical studies in non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are currently used worldwide to treat advanced refractory NSCLC, whereas the efficacy of anti-EGFR monoclonal antibodies remains to be established. Using molecular profiling to select patients to receive earlier EGFR targeted therapy as first-line treatment or in the adjuvant setting is an area of active research. Based on preclinical data, combining EGFR TKIs with other treatment modalities has promise, and clinical validation is underway. A new generation of irreversibly bound EGFR TKIs is being developed, and insights into the molecular biology of NSCLC should help to better define the patients who are most likely to benefit from these compounds. We summarize updates on EGFR targeted therapies that were presented during the sixth annual Targeted Therapies for the Treatment of Lung Cancer Conference in Los Angeles, CA; January 27-28, 2006. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. Univ Colorado, Ctr Canc, Div Med Oncol, Aurora, CO USA. Med Univ Gdansk, Dept Radiotherapy & Oncol, Gdansk, Poland. RP Sequist, LV (reprint author), MGH Canc Ctr, 32 Fruit St,Yawley Suite 7B, Boston, MA 02114 USA. EM lvsequist@partners.org NR 41 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2006 VL 1 IS 7 BP 740 EP 743 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 086HP UT WOS:000240664700029 PM 17409951 ER PT J AU Hatton, MP Chen, SH Bernardino, CR Rubin, PAD D'Amico, DJ Eskandar, E AF Hatton, Mark P. Chen, Sherleen H. Bernardino, Carlo R. Rubin, Peter A. D. D'Amico, Donald J. Eskandar, Emad TI Trans-orbital foreign body with intracranial extension SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID NAIL-GUN INJURIES; PENETRATING OCULAR INJURIES C1 Massachusetts Eye & Ear Infirm, Trauma Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Hatton, MP (reprint author), Massachusetts Eye & Ear Infirm, Trauma Serv, 243 Charles St, Boston, MA 02114 USA. EM Mark_Hatton@meei.harvard.edu NR 8 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD SEP PY 2006 VL 61 IS 3 BP 752 EP 754 DI 10.1097/01.ta.0000236548.62006.71 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 084YL UT WOS:000240570200052 PM 16967021 ER PT J AU Rousseau, CM Birditt, BA Mckay, AR Stoddard, JN Lee, TC McLaughlin, S Moore, SW Shindo, N Learn, GH Korber, BT Brander, C Goulder, PJR Kiepiela, P Walker, BD Mullins, JI AF Rousseau, Christine M. Birditt, Brian A. McKay, Angela R. Stoddard, Julia N. Lee, Tsan Chun McLaughlin, Sherry Moore, Sarah W. Shindo, Nice Learn, Gerald H. Korber, Bette T. Brander, Christian Goulder, Philip J. R. Kiepiela, Photini Walker, Bruce D. Mullins, James I. TI Large-scale amplification, cloning and sequencing of near full-length HIV-1 subtype C genomes SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1; subtype C; large-scale; molecular epidemiology; South Africa ID INFECTIOUS MOLECULAR CLONE; BIOLOGICAL CHARACTERIZATION; VIRUS; RECOMBINATION; CONSTRUCTION; AFRICA; PCR; ISOLATE; PLASMA; RNA AB Full-length HIV-1 genome sequencing provides important data needed to address several vaccine design, molecular epidemiologic and pathogenesis questions. A protocol is presented for obtaining near full-length genomes (NFLGs) from subjects infected with HIV-1 subtype C. This protocol was used to amplify NFLGs from 244 of 366 (67%) samples collected at two clinics in Durban, South Africa (SK and PS). Viral load was directly associated with frequency of successful NFLG amplification for both cohorts (PS; p = 0.005 and SK; p < 0.001). Seventeen of 38 initially NFLG-negative SK samples had variation within the PCR primer binding sites, however only 3 of these were successfully re-amplified using re-designed primers homologous to the target viruses. NFLGs were obtained from 7 of 24 PBMC samples processed from subjects whose plasma did not yield a NFLG. Stable plasmid clones were obtained from all 244 NFLG-positive PCR products, and both strands of each genome were sequenced, using a primary set of 46 primers. These methods thus allow the large-scale collection of HIV-1 NFLGs from populations infected primarily with subtype C. The methods are readily adaptable to other HIV-1 subtypes, and provide materials for viral functional analyses and population-based molecular epidemiology studies that include analysis of viral genome chimerization. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Univ Oxford, Dept Pediat, Nuffield Dept Med, Oxford OX1 3SY, England. Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4015 Durban, South Africa. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Rousseau, CM (reprint author), Univ Washington, Dept Microbiol, Box 358070,1959 NE Pacific St, Seattle, WA 98195 USA. EM cmr@u.washington.edu OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [AI27757]; PHS HHS [N01-A1-15422] NR 35 TC 63 Z9 66 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 2006 VL 136 IS 1-2 BP 118 EP 125 DI 10.1016/j.jviromet.2006.04.009 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 073IC UT WOS:000239735200016 PM 16701907 ER PT J AU Song, RJ Chenine, AL Rasmussen, RA Ruprecht, CR Mirshahidi, S Grisson, RD Xu, W Whitney, JB Goins, LM Ong, H Li, PL Shai-Kobiler, E Wang, T McCann, CM Zhang, H Wood, C Kankasa, C Secor, WE McClure, HM Strobert, E Else, JG Ruprecht, RM AF Song, R. J. Chenine, A. -L. Rasmussen, R. A. Ruprecht, C. R. Mirshahidi, S. Grisson, R. D. Xu, W. Whitney, J. B. Goins, L. M. Ong, H. Li, P. -L. Shai-Kobiler, E. Wang, T. McCann, C. M. Zhang, H. Wood, C. Kankasa, C. Secor, W. E. McClure, H. M. Strobert, E. Else, J. G. Ruprecht, R. M. TI Molecularly cloned SHIV-1157ipd3N4: a highly replication-competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C env SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; TYPE-1 SUBTYPE-C; TUMOR-NECROSIS-FACTOR; PIG-TAILED MACAQUES; CD4(+) T-CELLS; RHESUS-MONKEYS; KAPPA-B; DISEASE PROGRESSION; ANTIBODY 2G12; IN-VIVO AB Human immunodeficiency virus type 1 (HIV-1) clade C causes > 50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4(+) T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naive animal induced memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In parallel, genomic DNA from the blood donor was amplified to generate the late proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV1157ipd3, an extra NF-kappa B binding site was engineered into its 3' long terminal repeat, giving rise to SHIV-1157ipd3N4. This virus was exclusively R5 tropic and replicated more potently in rhesus peripheral blood mononuclear cells than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus macaques of Indian and Chinese origin were next inoculated intrarectally with SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally transmissible R5 SHIV that represents a valuable tool to test candidate AIDS vaccines targeting HIV-1 clade C Env. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA. Univ Lusaka, Teaching Hosp, Lusaka, Zambia. Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA 30341 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St,JFB809, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu FU NCRR NIH HHS [P20 RR015635, RR00165, RR15635, P51 RR000165]; NIAID NIH HHS [P01 AI48240, R37 AI34266, P01 AI048240, R37 AI034266]; NICHD NIH HHS [HD39620, R01 HD039620]; NIDCR NIH HHS [R01 DE0160354, R01 DE12937, R01 DE012937] NR 59 TC 86 Z9 86 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2006 VL 80 IS 17 BP 8729 EP 8738 DI 10.1128/JVI.00558-06 PG 10 WC Virology SC Virology GA 076CL UT WOS:000239934500040 PM 16912320 ER PT J AU Lin, WY Kim, SS Yeung, E Kamegaya, Y Blackard, JT Kim, KA Holtzman, MJ Chung, RT AF Lin, Wenyu Kim, Sun Suk Yeung, Elaine Kamegaya, Yoshitaka Blackard, Jason T. Kim, Kyung Ah Holtzman, Michael J. Chung, Raymond T. TI Hepatitis C virus core protein blocks interferon signaling by interaction with the STAT1 SH2 domain SO JOURNAL OF VIROLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; INHIBITS INTERFERON; TRANSGENIC MICE; ACTIVATES ERK; V-PROTEIN; IFN-ALPHA; EXPRESSION; DEGRADATION; PATHWAY; IDENTIFICATION AB Emerging data have indicated that hepatitis C virus (HCV) subverts the host antiviral response to ensure its persistence. We previously demonstrated that HCV protein expression suppresses type I interferon (IFN) signaling by leading to the reduction of phosphorylated STAT1 (P-STAT1). We also demonstrated that HCV core protein directly bound to STAT1. However, the detailed mechanisms by which HCV core protein impacts IFN signaling components have not been fully clarified. In this report, we show that the STAT1 interaction domain resides in the N-terminal portion of HCV core (amino acids [aa] 1 to 23). This domain is also required to produce P-STAT1 reduction and inhibit IFN signaling transduction. Conversely, the C-terminal region of STAT1, specifically the SH2 domain (aa 577 to 684), is required for the interaction of HCV core with STAT1. The STAT1 SH2 domain is critical for STAT1 hetero- or homodimerization. We propose a model by which the binding of HCV core to STAT1 results in decreased P-STAT, blocked STAT1 heterodimerization to STAT2, and, therefore, reduced IFN-stimulated gene factor-3 binding to DNA and disrupted IFN-stimulated gene transcription. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. Washington Univ, Sch Med, Dept Med & Cell Biol, St Louis, MO 63110 USA. RP Chung, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org NR 43 TC 111 Z9 119 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2006 VL 80 IS 18 BP 9226 EP 9235 DI 10.1128/JVI.00459-06 PG 10 WC Virology SC Virology GA 082KF UT WOS:000240384800038 PM 16940534 ER PT J AU Matloff, ET Moyer, A Shannon, KM Niendorf, KB Col, NF AF Matloff, Ellen T. Moyer, Anne Shannon, Kristen M. Niendorf, Kristin B. Col, Nananda F. TI Healthy women with a family history of breast cancer: Impact of a tailored genetic counseling intervention on risk perception, knowledge, and menopausal therapy decision making SO JOURNAL OF WOMENS HEALTH LA English DT Article ID HORMONE REPLACEMENT THERAPY; SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; POSTMENOPAUSAL WOMEN; OVARIAN-CANCER; PSYCHOLOGICAL DISTRESS; ESTROGEN DEFICIENCY; PRIMARY PREVENTION; PATIENTS BELIEFS; TAMOXIFEN AB Background: Women with a family history of breast cancer have several menopausal therapy options, including tamoxifen, hormone therapy (HT), alternative medications, or no treatment. This complex decision should be based on each woman's risk to develop breast cancer, menopausal symptoms, preferences, and risks for other conditions. The authors determined the effects of a personalized risk assessment and genetic counseling intervention on knowledge, risk perception, and decision making in a group of healthy women who had a first-degree relative with breast cancer. Methods: Forty-eight cancer-free menopausal women age >= 40 years who had at least one first-degree relative with breast cancer were randomized to a genetic counseling intervention or control. Intervention participants were given a personalized risk assessment for breast cancer, heart disease, osteoporosis, and uterine cancer based on family history and personal health data. Knowledge, risk perception, and medication usage were measured at baseline, 1 month, and 6 months. Results: Knowledge was higher in the intervention group at both follow-up time points postintervention. Perceived risk for developing breast cancer was significantly lower and more accurate in the intervention group at 1 and 6 months postintervention than at baseline, as was perceived risk of developing heart disease. Although the counseling intervention did affect both knowledge and risk perception, overall, both groups were reluctant to take any form of menopausal therapy. Conclusions: A personalized risk assessment and genetic counseling intervention improves patient knowledge and risk perception; however, it is unclear that the intervention influenced menopausal treatment decisions. C1 Yale Univ, Sch Med, Canc Genet Consulting, Ctr Canc, New Haven, CT 06520 USA. SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Rhode Isl Hosp, Providence, RI 02903 USA. RP Matloff, ET (reprint author), Yale Univ, Sch Med, Canc Genet Consulting, Ctr Canc, 55 Church St,Suite 402, New Haven, CT 06520 USA. EM Ellen.Matloff@yale.edu NR 52 TC 25 Z9 25 U1 4 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD SEP PY 2006 VL 15 IS 7 BP 843 EP 856 DI 10.1089/jwh.2006.15.843 PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 101NB UT WOS:000241746400007 PM 16999640 ER PT J AU Schutzer, WE Hong, X Reed, JF Mader, SL AF Schutzer, William E. Hong Xue Reed, John F. Mader, Scott L. TI Effect of age on vascular beta(2)-adrenergic receptor desensitization is not mediated by the receptor coupling to G alpha i proteins SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BETA-ADRENERGIC-RECEPTORS; SENSITIVE G-PROTEINS; SMOOTH-MUSCLE; RAT AORTA; KINASE-A; RESPONSES; ISOPROTERENOL; SYSTEM; PHOSPHORYLATION; EXPRESSION AB Beta-adrenergic receptor (beta-AR)-mediated vasorelaxation declines with age. In the vasculature, beta(2)-AR undergoes protein kinase A-mediated desensitization that causes a switch in the G protein coupled to beta(2)-AR; God links instead of G alpha s. We exposed Fischer 344 rat aortae of increasing age to a desensitizing dose of isoproterenol, and determined its effect on beta(2)-AR-mediated vasorelaxation. Desensitization decreased beta(2)-AR-mediated vasorelaxation in young aortae only. Subsequently, we used pertussis toxin to block God to determine whether changes in beta(2)-AR/G protein coupling occurred. God inhibition did not reverse desensitization or the age-related change, but there appears to be a population of beta(2)-AR linked to G alpha i, as pertussis toxin treatment improved beta(2)-AR-mediated vasorelaxation in aortae from animals of all ages. These findings suggest aortic beta(2)-AR in older animals may be maximally desensitized, which would explain impaired vasorelaxation. Our results also imply that protein kinase A-mediated beta(2)-AR desensitization may not be responsible for the age-related decline. C1 Portland VA Med Ctr, Res Serv, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Sch Med, Portland, OR USA. RP Mader, SL (reprint author), Portland VA Med Ctr, Res Serv, R&D 26,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM scott.mader@med.va.gov NR 48 TC 6 Z9 8 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2006 VL 61 IS 9 BP 899 EP 906 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 085CP UT WOS:000240581100003 PM 16960020 ER PT J AU Calvert, JF Hollander-Rodriguez, J Kaye, J Leahy, M AF Calvert, James F., Jr. Hollander-Rodriguez, Joyce Kaye, Jeffrey Leahy, Marjorie TI Dementia-free survival among centenarians: An evidence-based review SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Review ID OLDEST-OLD; EXTREME LONGEVITY; EXCEPTIONAL LONGEVITY; DANISH CENTENARIANS; ALZHEIMER-DISEASE; FUNCTIONAL STATUS; PREVALENCE; AGE; HEALTH; MORBIDITY AB Background. The 2000 U.S. census identified 50,454 Americans older than 100 years (18 per 100,000). Increased longevity is only of benefit if accompanied by the maintenance of physical, social, and cognitive function into advanced age. The goal of this review was to identify research describing centenarians to find the prevalence of dementia-free survival. Methods. We reviewed 650 publications to find studies that described the prevalence of dementia in centenarians, were community-based, had data that were specific to persons older than 100 years, and were published in peer-reviewed journals. For each study, we identified the prevalence of dementia, the completeness of the sample, the number of study participants, the method used to diagnose dementia, and the duration of the study. Results. We identified 20 research groups from 14 countries with publications meeting our search criteria. The studies showed substantial variation in methods of assessing cognitive status, assuring a complete cohort, and sample size. Few studies reported longitudinal data or attempted diagnosis of the cause of dementia. The prevalence of dementia-free survival past 100 years of age varied between 0 and 50 percent. Conclusions. The methodology used in studies regarding dementia prevalence among centenarians is sufficiently varied that combination of existing studies into a meta-analysis is not possible. Suggestions for assuring quality in future centenarian research are presented. C1 Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Merle W Ctr Med Res, Klamath Falls, OR USA. RP Calvert, JF (reprint author), 1453 Esplanade, Klamath Falls, OR 97601 USA. EM calvertj@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG08017] NR 59 TC 10 Z9 10 U1 1 U2 5 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2006 VL 61 IS 9 BP 951 EP 956 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 085CP UT WOS:000240581100009 PM 16960026 ER PT J AU Holden, A Hill, A Jaff, MR Pilmore, H AF Holden, A. Hill, A. Jaff, M. R. Pilmore, H. TI Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy SO KIDNEY INTERNATIONAL LA English DT Article DE renal artery stenosis; ischemic nephropathy; atheromatous embolization ID ATHEROSCLEROTIC RENOVASCULAR DISEASE; BALLOON ANGIOPLASTY; RANDOMIZED-TRIAL; HYPERTENSIVE PATIENTS; VASCULAR-DISEASE; NATURAL-HISTORY; MEDICAL THERAPY; CONTRAST-AGENT; FOLLOW-UP; EX-VIVO AB A prospective analysis of renal artery stent revascularization with distal embolic protection in a high-risk patient population with ischemic nephropathy is presented. A total of 63 patients (median age 70.2 years, range 54-86 years) had significant atherosclerotic stenosis of 83 renal arteries documented on pre-procedural imaging. All patients had baseline chronic renal insufficiency with a documented deterioration in renal function in the 6 months before revascularization. The endovascular technique used in all patients involved primary passage of an embolic filter into the distal main renal artery followed by primary stent deployment with a balloon expandable stainless steel stent. The filter baskets were recaptured and contents submitted for pathological analysis. At 6 months post-intervention, 97% of patients demonstrated stabilization or improvement in renal function. Only 3% of patients had an inexorable decline in renal function, unchanged by the intervention. After a mean follow up of 16.0 months (6-27), 94% of patients demonstrated stabilization or improvement in renal function. One patient suffered an acute post-procedural deterioration in renal function. In total, 60% of the filter baskets contained embolic material. This study confirms the technical feasibility of renal artery stent deployment with adjuvant embolic protection. The excellent results for renal preservation at 6 months post-intervention also suggest that a distal embolic protection device may improve the impact of percutaneous renal revascularization on progressive deterioration in renal function. The postulated mechanism is through the prevention of atheromatous embolization and the embolic yield from the distal filters supports this hypothesis. Patients most likely to receive the greatest benefit are those with mild baseline chronic renal insufficiency and a recent decline in renal function. C1 Auckland City Hosp, Dept Radiol, Auckland, New Zealand. Massachusetts Gen Hosp, Dept Vasc Med, Boston, MA 02114 USA. Auckland City Hosp, Dept Renal Med, Auckland, New Zealand. RP Holden, A (reprint author), Auckland City Hosp, Dept Radiol, Park Rd, Auckland, New Zealand. EM andrewh@adhb.govt.nz NR 60 TC 78 Z9 81 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2006 VL 70 IS 5 BP 948 EP 955 DI 10.1038/sj.ki.5001671 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 081XO UT WOS:000240351100024 PM 16837918 ER PT J AU Lum, G Solarz, DE Farney, L AF Lum, Gifford Solarz, David E. Farney, Linda TI False positive cardiac troponin results in patients without acute myocardial infarction SO LABMEDICINE LA English DT Review ID I ASSAYS; HETEROPHILIC ANTIBODIES; 2-SITE IMMUNOASSAYS; RHEUMATOID FACTORS; INTERFERENCE; SERUM; RECOMMENDATIONS; DEGRADATION; SPECIFICITY; PERFORMANCE AB Cardiac troponin I (cTnI) and T (cTnI) are highly sensitive and specific biochemical markers for myocardial necrosis and are generally not elevated in cases other than acute myocardial infarction (AMI) and acute coronary syndrome (ACS). However, if the patient's clinical picture for AMI or ACS do not match an elevated troponin result, the laboratory should suspect a false positive troponin value caused by analytical interferences with this assay. These analytic interferences include fibrin clots, microparticles in sample, heterophile and human anti-animal antibodies, rheumatoid factor, interference by bilirubin, hemolysis lipemia, elevated alkaline phosphatase activity, macro immunocomplex formation, and analyzer malfunction. In general, analytical interferences resulting in false positive troponin results are associated with a specific manufacturer's troponin assay and are not encountered in all troponin assays. This review discusses steps which the laboratory should consider taking in the investigation of suspected analytical interference with the troponin assay. Awareness of the possibility of a false positive troponin result may assist the physician in the management of the patient without AMI or ACS and may spare the patient additional diagnostic procedures especially if the troponin result is not consistent with these diagnoses. A false positive troponin result is a reminder that although troponin plays an important role in the diagnosis of AMI and ACS, it should not ne the only criterion for establishing these diagnoses. C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Med Ctr, Boston, MA 02118 USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 34 TC 26 Z9 27 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD SEP PY 2006 VL 37 IS 9 BP 546 EP 550 DI 10.1309/T94UUXTJ3TX5Y9W2 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 076QN UT WOS:000239972900020 ER PT J AU Mowry, SE Ho, A LoTempio, MM Sadeghi, A Blackwell, KE Wang, MB AF Mowry, Sarah E. Ho, Allen LoTempio, Maria M. Sadeghi, Ahmad Blackwell, Keith E. Wang, Marilene B. TI Quality of life in advanced oropharyngeal carcinoma after chemoradiation versus surgery and radiation SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 109th Annual Meeting of the Triological-Society CY MAY, 2006 CL Chicago, IL SP Triol Soc DE quality of life; oropharyngeal carcinoma ID NECK-CANCER; HEAD; CHEMOTHERAPY; RADIOTHERAPY AB Objective: The objective of this cohort study from a tertiary academic university practice was to identify differences in patients' perceived quality of life after either chemoradiation or surgery and radiation for advanced-stage oropharyngeal carcinoma. Methods: From institutional databases, thirty-five patients were identified who had undergone either primary chemoradiation or primary surgery and postoperative radiation for advanced oropharyngeal cancer (stage II-IV). Patients voluntarily responded by mail using the University of Washington quality-of-life instrument version 4 (UW-QOL). Data were analyzed using chi(2) and Wilcogon tests. Results: There were 17 patients who underwent chemoradiation and 18 patients who underwent surgery and postoperative radiation. All surgical patients had undergone free-flap reconstruction. Patients completed the UW-QOL an average of 25 months after treatment. There was no statistically significant difference between the two groups with regard to any specific domain, including pain, appearance, swallowing, chewing, speech, saliva, or mood. There was a trend toward significance for taste (P =.07) with chemoradiation patients reporting poorer taste function. The lack of difference in the patients' perception of appearance and swallowing was rather surprising given the vastly different treatment modalities. Respondents reported equivalent overall quality of life in response to global quality-of-life questions. Conclusion: Most patients with advanced oropharyngeal carcinoma report good quality of life after treatment, regardless of treatment modality. Although the short-term side effects of treatment may be different between the groups, long-term quality of life is remarkably similar whether the patients choose primary chemoradiation or surgery with postoperative radiation. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Radiat Oncol, Los Angeles, CA USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, 10833 Le Conte Ave,CHS 62-132, Los Angeles, CA 90095 USA. EM mbwang@ucla.edu NR 13 TC 50 Z9 51 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2006 VL 116 IS 9 BP 1589 EP 1593 DI 10.1097/01.mlg.0000233244.18901.44 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 081OD UT WOS:000240326000012 PM 16954985 ER PT J AU Pletcher, SD Sindwani, R Metson, R AF Pletcher, Steven D. Sindwani, Raj Metson, Ralph TI The agger nasi punch-out procedure (POP): Maximizing exposure of the frontal recess SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Annual Meeting of the Eastern Section of the Triological-Society CY JAN 21, 2006 CL Toronto, CANADA SP Triol Soc DE frontal sinus; frontal recess; sinus surgery ID ENDOSCOPIC SINUS SURGERY; FAILURE C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. St Louis Univ, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63103 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Metson, R (reprint author), 0 Emerson Pl,Suite 2D, Boston, MA 02115 USA. EM ralph_metson@meei.harvard.edu NR 10 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2006 VL 116 IS 9 BP 1710 EP 1712 DI 10.1097/01.mlg.0000231743.74993.0b PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 081OD UT WOS:000240326000038 PM 16955011 ER PT J AU Durie, BGM Harousseau, JL Miguel, JS Blade, J Barlogie, B Anderson, K Gertz, M Dimopoulos, M Westin, J Sonneveld, P Ludwig, H Gahrton, G Beksac, M Crowley, J Belch, A Boccadaro, M Turesson, I Joshua, D Vesole, D Kyle, R Alexanian, R Tricot, G Attal, M Merlini, G Powles, R Richardson, P Shimizu, K Tosi, P Morgan, G Rajkumar, SV AF Durie, B. G. M. Harousseau, J-L Miguel, J. S. Blade, J. Barlogie, B. Anderson, K. Gertz, M. Dimopoulos, M. Westin, J. Sonneveld, P. Ludwig, H. Gahrton, G. Beksac, M. Crowley, J. Belch, A. Boccadaro, M. Turesson, I. Joshua, D. Vesole, D. Kyle, R. Alexanian, R. Tricot, G. Attal, M. Merlini, G. Powles, R. Richardson, P. Shimizu, K. Tosi, P. Morgan, G. Rajkumar, S. V. CA Internatl Myeloma Working Grp TI International uniform response criteria for multiple myeloma SO LEUKEMIA LA English DT Article DE myeloma; response criteria; staging; survival duration; uniform criteria; clinical outcomes ID CELL TRANSPLANTATION; CHEMOTHERAPY; THERAPY; DEXAMETHASONE; THALIDOMIDE; REMISSION; PROGRESSION; DOXORUBICIN; BORTEZOMIB; IMPACT AB New uniform response criteria are required to adequately assess clinical outcomes in myeloma. The European Group for Blood and Bone Marrow Transplant/International Bone Marrow Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system. Categories for stringent complete response and very good partial response are added. The serum free light-chain assay is included to allow evaluation of patients with oligo-secretory disease. Inconsistencies in prior criteria are clarified making confirmation of response and disease progression easier to perform. Emphasis is placed upon time to event and duration of response as critical end points. The requirements necessary to use overall survival duration as the ultimate end point are discussed. It is anticipated that the International Response Criteria for multiple myeloma will be widely used in future clinical trials of myeloma. C1 Aptium Oncol Inc, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA 90048 USA. Inst Biol, Nantes, France. Univ Salamanca, E-37008 Salamanca, Spain. Hosp Clin Barcelona, Barcelona, Spain. MIRT UAMS, Little Rock, AR USA. DFCI, Boston, MA USA. Mayo Clin, Rochester, MN USA. Alexandra Hosp, Athens, Greece. Gothenburg Univ, S-41124 Gothenburg, Sweden. Univ Gothenburg, Rotterdam, Netherlands. Wilhelminenspital Stat Wien, Vienna, Austria. Karolinska Inst, S-10401 Stockholm, Sweden. Ankara Univ, TR-06100 Ankara, Turkey. Canc Res & Biostat, Seattle, WA USA. Univ Turin, I-10124 Turin, Italy. Univ Malmo, Malmo, Sweden. Royal Prince Alfred Hosp, Sydney, NSW, Australia. St Vincents Comprehens Canc Ctr, New York, NY USA. MD Anderson, Houston, TX USA. Purpan Hosp, Toulouse, France. Univ Pavia, I-27100 Pavia, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Nagoya City Midori Gen Hosp, Nagoya, Aichi, Japan. Univ Bologna, I-40126 Bologna, Italy. Royal Marsden Hosp, London SW3 6JJ, England. RP Durie, BGM (reprint author), Aptium Oncol Inc, Cedars Sinai Outpatient Canc Ctr, 8201 Beverly Blvd, Los Angeles, CA 90048 USA. EM bdurie@aptiumoncology.com; rajkumar.vincent@mayo.edu RI Merlini, Giampaolo/A-3817-2008; Beksac, Meral/D-6411-2013; Karabulut, Erman/G-6679-2011; OI Merlini, Giampaolo/0000-0001-7680-3254; Rajkumar, S. Vincent/0000-0002-5862-1833 NR 28 TC 1175 Z9 1289 U1 7 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2006 VL 20 IS 9 BP 1467 EP 1473 DI 10.1038/sj.leu.2404284 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 077GB UT WOS:000240015800001 PM 16855634 ER PT J AU Walters, DK Goss, VL Stoffregen, EP Gu, TL Lee, K Nardone, J McGreevey, L Heinrich, MC Deininger, MW Polakiewicz, R Druker, BJ AF Walters, Denise K. Goss, Valerie L. Stoffregen, Eric P. Gu, Ting-Lei Lee, Kimberly Nardone, Julie McGreevey, Laura Heinrich, Michael C. Deininger, Michael W. Polakiewicz, Roberto Druker, Brian J. TI Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes SO LEUKEMIA RESEARCH LA English DT Article DE AML; phosphopeptide; tyrosine kinases; leukemia ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; CONSTITUTIVE ACTIVATION; MYELOGENOUS LEUKEMIA; PHOSPHORYLATION; MUTATION; INHIBITOR; GROWTH; STAT5 AB STAT5 is constitutively phosphorylated in leukemic cells in approximately 70% of acute myeloid leukemia (AML) patients. To identify kinase candidates potentially responsible for STAT5 phosphorylation, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry to detect phosphoproteins in AML cell lines. We established TEL-ARG and BCR-ABL fusion proteins as the mechanism underlying STAT5 phosphorylation in HT-93 and KBM-3 cells, respectively. In addition, we identified a JAK2 pseudokinase domain mutation in HEL cells and using siRNA downregulation, established JAK2 as the kinase responsible for phosphorylating STAT5. This study illustrates the benefit of LC-MS/MS mass spectrometry and siRNA for the identification of novel targets and mutations. (c) 2006 Elsevier Ltd. All rights reserved. C1 Oregon Hlth Sci Univ, Inst Canc, Howard Hughes Med Inst, Dept Hematol & Oncol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Cell Signaling Technol Inc, Beverly, MA 01915 USA. RP Walters, DK (reprint author), Oregon Hlth Sci Univ, Inst Canc, Howard Hughes Med Inst, Dept Hematol & Oncol, 3181 Sam Jackson Pk Rd, Portland, OR 97239 USA. EM waltersd@ohsu.edu NR 26 TC 42 Z9 44 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2006 VL 30 IS 9 BP 1097 EP 1104 DI 10.1016/j.leukres.2006.01.001 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 071RV UT WOS:000239620500010 PM 16464493 ER PT J AU Litman, HJ Horton, NJ Murphy, JM Laird, NM AF Litman, Heather J. Horton, Nicholas J. Murphy, Jane M. Laird, Nan M. TI Marginal regression models with a time to event outcome and discrete multiple source predictors SO LIFETIME DATA ANALYSIS LA English DT Article DE multiple informants; censored survival data; maximum likelihood; generalized estimating equations; inverse probability weights ID MAXIMUM-LIKELIHOOD ANALYSIS; GENERALIZED LINEAR-MODELS; CENSORED SURVIVAL-DATA; PSYCHIATRIC-DISORDERS; INCOMPLETE DATA; COVARIATE DATA; MISSING DATA; MORTALITY; INFORMATION AB Information from multiple informants is frequently used to assess psychopathology. We consider marginal regression models with multiple informants as discrete predictors and a time to event outcome. We fit these models to data from the Stirling County Study; specifically, the models predict mortality from self report of psychiatric disorders and also predict mortality from physician report of psychiatric disorders. Previously, Horton et al. found little relationship between self and physician reports of psychopathology, but that the relationship of self report of psychopathology with mortality was similar to that of physician report of psychopathology with mortality. Generalized estimating equations (GEE) have been used to fit marginal models with multiple informant covariates; here we develop a maximum likelihood (ML) approach and show how it relates to the GEE approach. In a simple setting using a saturated model, the ML approach can be constructed to provide estimates that match those found using GEE. We extend the ML technique to consider multiple informant predictors with missingness and compare the method to using inverse probability weighted (IPW) GEE. Our simulation study illustrates that IPW GEE loses little efficiency compared with ML in the presence of monotone missingness. Our example data has non-monotone missingness; in this case, ML offers a modest decrease in variance compared with IPW GEE, particularly for estimating covariates in the marginal models. In more general settings, e.g., categorical predictors and piecewise exponential models, the likelihood parameters from the ML technique do not have the same interpretation as the GEE. Thus, the GEE is recommended to fit marginal models for its flexibility, ease of interpretation and comparable efficiency to ML in the presence of missing data. C1 New England Res Inst, Watertown, MA 02472 USA. Smith Coll, Dept Math & Stat, Northampton, MA 01063 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Litman, HJ (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM hlitman@neriscience.com RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 FU NIMH NIH HHS [R01 MH054693, MH54693, R01 MH039576, R01-MH39576, T32 MH017119, T32-MH017119] NR 30 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD SEP PY 2006 VL 12 IS 3 BP 249 EP 265 DI 10.1007/s10985-006-9013-1 PG 17 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 104JE UT WOS:000241953900001 PM 17021951 ER PT J AU Zhou, W Heist, RS Liu, G Park, S Neuberg, DS Asomaning, K Wain, JC Lynch, TJ Christiani, DC AF Zhou, Wei Heist, Rebecca Suk Liu, Geoffrey Park, Sohee Neuberg, Donna S. Asomaning, Kofi Wain, John C. Lynch, Thomas J. Christiani, David C. TI Smoking cessation before diagnosis and survival in early stage non-small cell lung cancer patients SO LUNG CANCER LA English DT Article DE smoking; smoking cessation; survival; non-small cell lung cancer; gender ID TOBACCO SMOKING; MORTALITY; WOMEN; CARCINOMA; MUTATIONS; SMOKERS; LONG AB Smoking cessation decreases the risk of lung cancer. However, little is known about how smoking cessation affects lung cancer survival. We examined the association between smoking cessation and overall survival (OS) and recurrence-free survival (RFS) in 543 early stage non-small cell lung cancer (NSCLC) patients. The data were analyzed using log-rank test and Cox proportional hazard models, adjusting for age, gender, stage, and smoking intensity. The median follow-up time was 57 months (range 0.2-140 months). There were 191 recurrences and 285 deaths. The 5-year OS rates were 50% (95% confidence interval (CI), 43-58%) for current smokers, 54% (44-65%) for ex-smokers who quit 1-8 years, 59% (49-70%) for ex-smokers who quit 9-17 years, 58% (47-69%) for ex-smokers who quit >= 18 years prior to diagnosis, and 76% (63-90%) for never smokers (P=0.09, log-rank test). The adjusted hazard ratios for ex-smokers who quit 1-8, 9-17, >= 18 years, and never smokers were 0.82 (95% CI, 0.59-1.13), 0.69 (0.49-0.97), 0.66 (0.45-0.95), and 0.54 (0.29-0.996), respectively, when compared with current smokers (P-trend =0.004). Similar associations were found among ever smokers-only, when smoking cessation time was treated as a continuous variable, and for RFS. The significantly beneficial effects of smoking cessation on OS and RFS were observed among women only, while not among men (P=0.01 for interactions between gender and smoking cessation). In conclusion, smoking cessation is associated with improved survival in early stage NSCLC patients. The longer the time since cessation of smoking, the better the survival outcome. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA USA. RP Zhou, W (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM wzhou@hohp.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA090578, CA074386, 5T32CA071345, CA092824]; NIEHS NIH HHS [ES00002] NR 18 TC 38 Z9 39 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD SEP PY 2006 VL 53 IS 3 BP 375 EP 380 DI 10.1016/j.lungcan.2006.05.017 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 082YG UT WOS:000240422500015 PM 16814423 ER PT J AU Cragan, JD Friedman, JM Holmes, LB Uhl, K Green, NS Riley, L AF Cragan, Janet D. Friedman, J. M. Holmes, Lewis B. Uhl, Kathleen Green, Nancy S. Riley, Laura TI Ensuring the safe and effective use of medications during pregnancy: Planning and prevention through preconception care SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE preconception care; medications; pregnancy; anticonvulsants; asthma; isotretinoin ID SPINA-BIFIDA; WOMEN; GASTROSCHISIS; MALFORMATIONS; VALPROATE; CHILDREN; ASTHMA; RISK; PHARMACOKINETICS; TERATOGENICITY C1 Ctr Dis Control & Prevent, Natl Ctr Birht DDefects & Dev Disabil, Atlanta, GA 30333 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1W5, Canada. MassGen Hosp Children, Genet & Teratol Unit, Boston, MA USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. March Dimes Birth Defects Fsn, White Plains, NY USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Cragan, JD (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birht DDefects & Dev Disabil, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM jcragan@cdc.gov OI Green, Nancy/0000-0002-9877-1561 NR 53 TC 15 Z9 16 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD SEP PY 2006 VL 10 IS 5 SU S BP S129 EP S135 DI 10.1007/s10995-006-0102-2 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 093KM UT WOS:000241167200018 PM 16850277 ER PT J AU Pietz, K Byrne, MM Petersen, LA AF Pietz, Kenneth Byrne, Margaret M. Petersen, Laura A. TI A decision-theoretic approach to identifying future high-cost patients SO MEDICAL CARE LA English DT Article DE risk adjustment; logistic regression; decision theory; cost; diagnostic cost groups ID HEALTH PLANS; MEDICAL-CARE; OUTCOMES; USERS AB Objective: The objective of this study was to develop and evaluate a method of allocating funding for very-high-cost (VHC) patients among hospitals. Research Design: Diagnostic cost groups (DCGs) were used for risk adjustment. The patient population consisted of 253,013 veterans who used Department of Veterans Affairs (VA) medical care services in fiscal year (FY) 2003 (October 1, 2002-September 30, 2003) in a network of 8 VA hospitals. We defined VHC as greater than $75,000 (0.81%). The upper fifth percentile was also used for comparison. Methods: A Bayesian decision rule for classifying patients as VHC/not VHC using DCGs was developed and evaluated. The method uses FY 2003 DCGs to allocate VHC funds for FY 2004. We also used FY 2002 DCGs to allocate VHC funds for FY 2003 for comparison. The resulting allocation was compared with using the allocation of VHC patients among the hospitals in the previous year. Results: The decision rule identified DCG 17 as the optimal cutoff for identifying VHC patients for the next year. The previous year's allocation came closest to the actual distribution of VHC patients. Conclusions: The decision-theoretic approach may provide insight into the economic consequences of classifying a patient as VHC or not VHC. More research is needed into methods of identifying future VHC patients so that capitation plans can fairly reimburse healthcare systems for appropriately treating these patients. C1 Houston Vet Affairs Med Ctr, Div Hlth Policy & Qual, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33152 USA. RP Pietz, K (reprint author), Houston Vet Affairs Med Ctr, Div Hlth Policy & Qual, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Ctr Excellence, Hlth Serv Res & Dev 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM kpietz@bcm.tmc.edu NR 19 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2006 VL 44 IS 9 BP 842 EP 849 DI 10.1097/01.mlr.0000220680.19667.da PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 080PV UT WOS:000240260900007 PM 16932136 ER PT J AU Garcia, AD Thomas, DR AF Garcia, Aimee Dinorah Thomas, David R. TI Assessment and management of chronic pressure ulcers in the elderly SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID RISK-ASSESSMENT SCALES; PROVISIONAL MATRIX; DECUBITUS ULCERS; SORE PREVENTION; NURSING-HOME; HUMAN SKIN; FIBRONECTIN; NUTRITION; PATHOPHYSIOLOGY; MALNUTRITION AB The aging population is increasing the number of individuals at risk for pressure ulcer formation. Risk factors, such as immobility, poor nutrition, comorbidities, and aging skin, make the elderly more susceptible to pressure ulcer formation. The key to management is prevention, but once pressure ulcers occur, it is important to understand the principles of wound healing including debridement, bacterial management, moist wound healing, pressure relief, and nutritional support. C1 Baylor Coll Med, VA Med Ctr, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. St Louis Univ, Div Geriatr Med, St Louis, MO 63104 USA. RP Garcia, AD (reprint author), Baylor Coll Med, VA Med Ctr, Michael E DeBakey VA Med Ctr, 2002 Holcombe ECL 110, Houston, TX 77030 USA. EM aimeeg@bcm.tmc.edu NR 103 TC 27 Z9 27 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2006 VL 90 IS 5 BP 925 EP + DI 10.1016/j.mcna.2006.05.018 PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA 089MV UT WOS:000240885600011 PM 16962850 ER PT J AU McMahon, PM Zaslavsky, AM Weinstein, MC Kuntz, KM Weeks, JC Gazelle, GS AF McMahon, Pamela M. Zaslavsky, Alan M. Weinstein, Milton C. Kuntz, Karen M. Weeks, Jane C. Gazelle, G. Scott TI Estimation of mortality rates for disease simulation models using Bayesian evidence synthesis SO MEDICAL DECISION MAKING LA English DT Article DE mortality rates; Bayesian evidence synthesis; simulation; disease ID MARGINAL STRUCTURAL MODELS; COMPETING RISKS; LUNG-CANCER; SMOKING-CESSATION; FAILURE TIMES; UNITED-STATES; CHAIN; IDENTIFIABILITY; EPIDEMIOLOGY; CONVERGENCE AB Purpose. The authors propose a Bayesian approach for estimating competing risks for inputs to disease simulation models. This approach is suggested when modeling a disease that causes a large proportion of all-cause mortality, particularly when mortality from the disease of interest and other-cause mortality are both affected by the same risk factor. Methods. The authors demonstrate a Bayesian evidence synthesis by estimating other-cause mortality, stratified by smoking status, for use in a simulation model of lung cancer. National (US) survey data linked to death registries (National Health Interview Survey [NHIS]-Multiple Cause of Death files) were used to fit cause-specific hazard models for 3 causes of death (lung cancer, heart disease, and all other causes), controlling for age, sex, race, and smoking status. Synthesis of NHIS data with national vital statistics data on numbers and causes of deaths was performed in WinBUGS (version 1.4.1, MRC Biostatistics Unit, UK). Correction for inconsistencies between the NHIS and vital statistics data is described. A published cohort study was a source of prior information for smoking-related mortality. Results. Marginal posterior densities of annual mortality rates for lung cancer and other-cause death (further divided into heart disease and all other causes), stratified by 5-year age interval, race (white and black), gender, and smoking status (current, former, never), were estimated, specific to a time period (1987-1995). Overall, black current smokers experienced the highest mortality rates. Conclusions. Bayesian evidence synthesis is an effective method for estimation of cause-specific mortality rates, stratified by demographic factors. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP McMahon, PM (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pamela@mgh-ita.org NR 62 TC 11 Z9 11 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2006 VL 26 IS 5 BP 497 EP 511 DI 10.1177/0272989X06291326 PG 15 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 089QW UT WOS:000240896700007 PM 16997927 ER PT J AU Craft, DL Halabi, TF Shih, HA Bortfeld, TR AF Craft, David L. Halabi, Tarek F. Shih, Helen A. Bortfeld, Thomas R. TI Approximating convex Pareto surfaces in multiobjective radiotherapy planning SO MEDICAL PHYSICS LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; DOSE-VOLUME CONSTRAINTS; MULTIPLE LOCAL MINIMA; OPTIMIZATION AB Radiotherapy planning involves inherent tradeoffs: the primary mission, to treat the tumor with a high, uniform dose, is in conflict with normal tissue sparing. We seek to understand these tradeoffs on a case-to-case basis, by computing for each patient a database of Pareto optimal plans. A treatment plan is Pareto optimal if there does not exist another plan which is better in every measurable dimension. The set of all such plans is called the Pareto optimal surface. This article presents an algorithm for computing well distributed points on the (convex) Pareto optimal surface of a multiobjective programming problem. The algorithm is applied to intensity-modulated radiation therapy inverse planning problems, and results of a prostate case and a skull base case are presented, in three and four dimensions, investigating tradeoffs between tumor coverage and critical organ sparing. (c) 2006 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Craft, DL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dcraft@partners.org FU NCI NIH HHS [1 R01 CA103904-01A1] NR 28 TC 87 Z9 88 U1 0 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2006 VL 33 IS 9 BP 3399 EP 3407 DI 10.1118/1.2335486 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086SX UT WOS:000240694400038 PM 17022236 ER PT J AU Stefano, GB Fricchione, GL Esch, T AF Stefano, George B. Fricchione, Gregory L. Esch, Tobias TI Relaxation: Molecular and physiological significance SO MEDICAL SCIENCE MONITOR LA English DT Review DE relaxation response; nitric oxide; belief; limbic system; norepinephrine; morphine; dopamine ID NITRIC-OXIDE RELEASE; INTRACELLULAR CALCIUM TRANSIENTS; NITROXIDERGIC NERVE FUNCTION; MONKEY CEREBRAL-ARTERIES; MU(3) OPIATE RECEPTOR; RAT MEDIAN-EMINENCE; ENDOGENOUS MORPHINE; INVERTEBRATE IMMUNOCYTES; ENDOTHELIAL-CELLS; DEPENDENT MECHANISM AB There appears to be a molecular process for relaxation. Given this, we attempt to demonstrate this phenomenon based on established molecular and physiological processes in light of our current understanding of central and peripheral nervous system mechanisms. Central to our hypothesis is the significance of norepinephrine, nitric oxide, dopamine and morphine signaling both in the central and peripheral nervous system. We find that nitric oxide and morphine control catecholamine processes on many levels, including synthesis, release and actions. We conclude that enough scientific information exists to support these phenomena as actual physical processes that can be harnessed to provide better patient care. C1 SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Coburg Univ Appl Sci, Div Integrat Hlth Promot, Coburg, Germany. RP Stefano, GB (reprint author), SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. EM gstefano@sunynri.org RI Esch, Tobias/J-3812-2013 OI Esch, Tobias/0000-0001-5176-4367 FU NIDA NIH HHS [DA 09010]; NIMH NIH HHS [MH 47392] NR 145 TC 22 Z9 22 U1 0 U2 1 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD SEP PY 2006 VL 12 IS 9 BP HY21 EP HY31 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 085YX UT WOS:000240641400001 PM 16940938 ER PT J AU Shifren, JL Davis, SR Moreau, M Waldbaum, A Bouchard, C DeRogatis, L Derzko, C Bearnson, P Kakos, N O'Neill, S Levine, S Wekselman, K Buch, A Rodenberg, C Kroll, R AF Shifren, Jan L. Davis, Susan R. Moreau, Michele Waldbaum, Arthur Bouchard, Celme DeRogatis, Leonard Derzko, Christine Bearnson, Patricia Kakos, Norman O'Neill, Sheila Levine, Stephen Wekselman, Kathryn Buch, Akshay Rodenberg, Cynthia Kroll, Robin TI Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE transdermal testosterone; hypoactive sexual desire; natural menopause; postmenopausal women; libido ID PLACEBO-CONTROLLED TRIAL; POSTMENOPAUSAL WOMEN; OOPHORECTOMIZED WOMEN; ESTERIFIED ESTROGENS; ANDROGEN; REPLACEMENT; ESTRADIOL; SYMPTOMS; IMPLANTS; EFFICACY AB Objective: To evaluate the efficacy and safety of a testosterone patch for the treatment of women with hypoactive sexual desire disorder after natural menopause. Design: A multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in naturally menopausal women with hypoactive sexual desire disorder receiving a stable dose of oral estrogen with or without progestin (N = 549). Women were randomized to receive testosterone 300 mu g/day or placebo patches twice weekly for 24 weeks. The primary efficacy measure was change from baseline in frequency of total satisfying sexual activity over a 4-week period (weeks 21-24). Results: A total of 483 women (88%) were included in the primary analysis population (those with baseline sex hormone binding globulin levels <= 160 nmol/L). The change from baseline in number of total satisfying sexual episodes was significantly greater for testosterone compared with placebo (participants with baseline sex hormone binding globulin levels : 160 nmol/L, mean change of 2.1 +/- 0.28 versus 0.5 +/- 0.23 episodes/4 weeks; P < 0.0001; intent-to-treat population, mean change from baseline of 1.9 +/- 0.26 versus 0.5 +/- 0.21 episodes/4 weeks, P < 0.0001). Testosterone also produced statistically significant improvements compared with placebo in all secondary efficacy measures, including sexual desire and personal distress. The testosterone patch was well tolerated. Conclusions: Testosterone patch treatment increased the frequency of satisfying sexual activity and sexual desire, decreased personal distress, and was well tolerated in naturally menopausal women with hypoactive sexual desire disorder. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Monash Univ, Dept Med CECS, Melbourne, Vic 3004, Australia. Montreal Clin Study Ctr, Montreal, PQ, Canada. Downtown Womens Hlth Care, Denver, CO USA. Clin RSF Inc, Quebec City, PQ, Canada. Johns Hopkins Ctr Sexual Hlth & Med, Lutherville Timonium, MD USA. St Michaels Hosp, Ctr Hlth, Toronto, ON M5B 1W8, Canada. Phase II Ctr Womens Hlth, Salt Lake City, UT USA. QUEST Res Inst, Southfield, MI USA. Royal Brisbane & Womens Hosp, Betty Byrne Henderson Womens Hlth Res Ctr, Brisbane, Qld, Australia. Ctr Martial & Sexual Hlth Inc, Beachwood, OH USA. Procter & Gamble Pharmaceut, Mason, OH USA. Womens Clin Res, Seattle, WA USA. RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Mem Obstet & Gynecol Serv, 55 Fruit St,Yawkey 10A, Boston, MA 02114 USA. EM jshifren@partners.org RI Davis, Susan/A-3111-2009; OI Davis, Susan R/0000-0002-2955-0415 NR 30 TC 149 Z9 153 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP-OCT PY 2006 VL 13 IS 5 BP 770 EP 779 DI 10.1097/01.gme.0000227400.60816.52 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 086QY UT WOS:000240689300011 PM 16932240 ER PT J AU Soares, CN Arsenio, H Joffe, H Bankier, B Cassano, P Petrillo, LF Cohen, LS AF Soares, Claudio N. Arsenio, Helga Joffe, Hadine Bankier, Bettina Cassano, Paolo Petrillo, Laura F. Cohen, Lee S. TI Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep, and quality of life SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE depression; menopause; escitalopram; estradiol; hot flashes ID RANDOMIZED CONTROLLED-TRIAL; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; HORMONE REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; HOT FLASHES; MENOPAUSAL TRANSITION; CLINICAL-PRACTICE; DOUBLE-BLIND; DSM-IV; EFFICACY AB Objective: To examine the efficacy and tolerability of escitalopram (ESCIT) compared to estrogen and progestogen therapy (EPT) for the treatment of symptomatic peri- and postmenopausal women. Design: Forty women (aged 40-60 years) with depressive disorders and menopause-related symptoms were randomly assigned to an 8-week open trial with ESCIT (flexible dose, 10-20 mg/ day; fixed dose, 10 mg/day for the first 4 weeks) or estrogen plus progestogen therapy (ethinyl estradiol 5 mu g/day plus norethindrone acetate I mg/day). Primary outcome measures included Montgomery-Asberg Depression Rating Scale and the Greene Climacteric Scale at week 8. Secondary outcome measures included the Clinical Global Impressions as well as sleep and quality of life assessments. Results: Thirty-two women (16 on EPT, 16 on ESCIT) were included in the analyses. Full remission of depression (score of < 10 on the Montgomery-Asberg Depression Rating Scale) was observed in 75% (12/16) of subjects treated with ESCIT, compared to 25% (4/16) treated with EPT (P = 0.01, Fisher's exact tests). Remission of menopause-related symptoms (>50% decrease in Greene Climacteric Scale scores) was noted in 56% (9/16) of women treated with ESCIT compared to 31.2% (5/16) on EPT (P = 0.03, Pearson's chi(2) tests). Improvement in sleep, hot flashes, and quality of life was observed with both treatments. Conclusions: ESCIT is more efficacious than EPT for the treatment of depression and has a positive impact on other menopause-related symptoms. ESCIT may constitute a treatment option for symptomatic menopausal women who are unable or unwilling to use hormone therapy. C1 McMaster Univ, Womens Hlth Concerns Clin, St Josephs Healthcare, Dept Psychiat & Behav Neurosci, Hamilton, ON L8P 3B6, Canada. Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Soares, CN (reprint author), McMaster Univ, Womens Hlth Concerns Clin, St Josephs Healthcare, Dept Psychiat & Behav Neurosci, 301 James St S,FB 638, Hamilton, ON L8P 3B6, Canada. EM csoares@mcmaster.ca RI Cassano, Paolo/I-6959-2012 NR 46 TC 64 Z9 70 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP-OCT PY 2006 VL 13 IS 5 BP 780 EP 786 DI 10.1097/01.gme.0000240633.46300.fa PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 086QY UT WOS:000240689300012 PM 16894334 ER PT J AU Ollero, M Laposata, M Zaman, MM Blanco, PG Andersson, C Zeind, J Urman, Y Kent, G Alvarez, JG Freedman, SD AF Ollero, Mario Laposata, Michael Zaman, Munir M. Blanco, Paola G. Andersson, Charlotte Zeind, John Urman, Yana Kent, Geraldine Alvarez, Juan G. Freedman, Steven D. TI Evidence of increased flux to n-6 docosapentaenoic acid in phospholipids of pancreas from cftr(-/-) knockout mice SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CYSTIC-FIBROSIS; EPITHELIAL-CELLS; LIPID CLASSES; FATTY-ACIDS; DEFICIENCY; ABNORMALITIES; BIOSYNTHESIS; SEPARATION; MOUSE; LUNG AB An association has been reported between alterations in fatty acid metabolism and cystic fibrosis (CF). We hypothesized that these alterations are specific for a particular lipid component(s) and are the result of a specific metabolic defect. The different lipid classes were examined for fatty acid changes by using pancreatic homogenates and primary cultures of pancreatic acini from cftr(-/-) (CF) and wild-type mice. Lipid classes and phospholipids were separated by aminopropyl column chromatography and high-performance liquid chromatography, and fatty acid methyl esters were analyzed. The results indicate that in CF mice (1) linoleate was decreased in phospholipids but not in neutral lipids; (2) there was an increase in dihomo-gamma-linolenate and in docosapentaenoate, the terminal fatty acid of the n-6 pathway, in total lipids and total phospholipids, but not in the neutral lipid class; and (3) the docosapentaenoate (n-6)/ docosahexaenoate (n-3) ratio was significantly elevated in neutral phospholipids. This suggests an enhanced flux through the n-6 pathway beyond arachiclonate. This study provides a more in-depth understanding of the fatty acid alterations found in CF, as reflected by the cftr(-/-) mouse model. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, GCRC, Boston, MA 02115 USA. Hosp Sick Children, Dept Pathol & Pediat, Toronto, ON M5G 1X8, Canada. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. EM mlaposata@partners.org FU NIDDK NIH HHS [R01 DK52765-04] NR 23 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2006 VL 55 IS 9 BP 1192 EP 1200 DI 10.1016/j.metabol.2006.05.002 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 080WC UT WOS:000240278200009 PM 16919538 ER PT J AU Lewinsohn, DM Tydeman, IS Frieder, M Grotzke, JE Lines, RA Ahmed, S Prongay, KD Primack, SL Colgin, LMA Lewis, AD Lewinsohn, DA AF Lewinsohn, David M. Tydeman, Ian S. Frieder, Marisa Grotzke, Jeff E. Lines, Rebecca A. Ahmed, Sheela Prongay, Kamm D. Primack, Steven L. Colgin, Lois M. A. Lewis, Anne D. Lewinsohn, Deborah A. TI High resolution radiographic and fine immunologic definition of TB disease progression in the rhesus macaque SO MICROBES AND INFECTION LA English DT Article DE tuberculosis; CT scanning; macaque ID MYCOBACTERIUM-TUBERCULOSIS INFECTION; PULMONARY TUBERCULOSIS; CELLS; RESPONSES; LYMPHOCYTES; RESEMBLES; THERAPY; PROTEIN AB Mycobacterium tuberculosis infection in non-human primates parallels human tuberculosis, and provides a valuable vaccine evaluation model. However. this model is limited by the availability of real-time, non-invasive information regarding disease progression. Consequently, we have combined computed tomography scanning with enumeration of antigen-specific T cell responses. Four rhesus monkeys were infected with M. tuberculosis strain H37Rv (1000 cfu) in the right lower lobe via a bronchoscope. All uniformly developed progressive tuberculosis, and required euthanasia at 12 weeks. Computed tomography scanning provided detailed real-time imaging of disease progression. At necropsy, computed tomography and pathohistologic findings were tightly correlated, and characteristic of human disease. Immunologic monitoring demonstrated progressive evolution of high frequency M. tuberculosis-specific CD4(+) and CD8(+) T cell responses. Peripheral blood effector cell frequencies were similar to those observed in tissues. In summary, computed tomography scanning in conjunction with immunologic monitoring provides a non-invasive, accurate, and rapid assessment of tuberculosis in the non-human primate. Published by Elsevier Masson SAS. C1 Portland VA Med Ctr, Pulm & CCM, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Comparat Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Radiol, Portland, OR 97239 USA. Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. RP Lewinsohn, DM (reprint author), Portland VA Med Ctr, Pulm & CCM, R&D 11,3710 SW US Vet Rd, Portland, OR 97239 USA. EM lewinsod@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NCRR NIH HHS [RR15104]; NIAID NIH HHS [R01AI48090, 1K08AI01644, 1K08AI01645]; NICHD NIH HHS [HD33703] NR 25 TC 39 Z9 39 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD SEP PY 2006 VL 8 IS 11 BP 2587 EP 2598 DI 10.1016/j.micinf.2006.07.007 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 107YO UT WOS:000242207100003 PM 16952476 ER PT J AU Zarnitz, P Malone, E AF Zarnitz, Patricia Malone, Ellen TI Surgical nurse practitioners as registered nurse first assists: The role, historical perspectives, and educational training SO MILITARY MEDICINE LA English DT Article AB Advanced practice nurses (APN) who practice in the surgical subspecialty areas may have the opportunity to expand their scope of practice to include first assistant at surgery. Surgical APNs who practice as registered nurse first assistants (RNFA) should seek credentialing and apply for institutional privileges to assure the consumer of competent providers. Credentialing as an RNFA documents the educational learning process and skills acquired, and recognizes this area of expertise. The role of the APN as an RNFA at surgery is practiced within the specialty area of perioperative nursing which includes preoperative, intraoperative, and postoperative care. In this study, the nurse practitioners describe the role of the RNFA, its historical evolution over wartime, the required educational training, and the benefits of the role for patient care. The surgical nurse practitioner who undertakes training and education as a surgical RNFA is in an excellent position to provide patient care across the surgical continuum. C1 Philadelphia Vet Affairs Med Ctr, Dept Surg Sci, Philadelphia, PA 19104 USA. RP Zarnitz, P (reprint author), Philadelphia Vet Affairs Med Ctr, Dept Surg Sci, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 23 TC 0 Z9 0 U1 0 U2 2 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD SEP PY 2006 VL 171 IS 9 BP 875 EP 878 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 084LN UT WOS:000240534500015 PM 17036610 ER PT J AU Mori, DL Sogg, S Guarino, P Skinner, J Williams, D Barkhuizen, A Engel, C Clauw, D Donta, S Peduzzi, P AF Mori, DeAnna L. Sogg, Stephanie Guarino, Peter Skinner, James Williams, David Barkhuizen, Andre Engel, Charles Clauw, Daniel Donta, Sam Peduzzi, Peter TI Predictors of exercise compliance in individuals with Gulf War veterans illnesses: Department of Veterans affairs cooperative study 470 SO MILITARY MEDICINE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; CHRONIC-FATIGUE-SYNDROME; PHYSICAL-ACTIVITY; AEROBIC EXERCISE; DIABETES-MELLITUS; HEALTH; MAINTENANCE; FIBROMYALGIA; MANAGEMENT AB Although the health benefits of exercise for individuals with Persian Gulf War veterans illnesses (GWVI) are documented, many of these individuals do not exercise regularly enough to obtain benefits. The purpose of this study was to investigate factors predicting exercise compliance among individuals with GWVI in a multicenter, randomized, clinical trial. Participants were 1,092 veterans who reported at least two of the following cardinal symptoms of GWVI: (1) fatigue, (2) musculoskeletal pain, and (3) cognitive problems. Participants received exercise alone or exercise and cognitive-behavioral therapy. The overall level of compliance was relatively low during the exercise treatment phase (46.2%) and decreased by one-half during the follow-up period (23.0%). Predictors of compliance during treatment included less pain and greater age, motivation, and body mass index. Predictors of compliance during the follow-up period included less pain and greater age. The results highlight factors that affect adoption and maintenance of physical activity in a population with GWVI. C1 Vet Affairs Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. VA Connecticut Healthcare Syst, Cooperat Studies Program, Coordinating Ctr, West Haven, CT 06516 USA. Indiana Univ, Dept Kinesiol, Bloomington, IN 47405 USA. Univ Michigan, Chron Pain & Fatigue Res Program, Ann Arbor, MI 48106 USA. Oregon Hlth Sci Univ, Portland, OR 97239 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Mori, DL (reprint author), Vet Affairs Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. RI Williams, David/A-1180-2007 NR 37 TC 11 Z9 11 U1 3 U2 11 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD SEP PY 2006 VL 171 IS 9 BP 917 EP 923 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 084LN UT WOS:000240534500024 PM 17036619 ER PT J AU Lee-Lewandrowski, E Lewandrowski, K AF Lee-Lewandrowski, Elizabeth Lewandrowski, Kent TI Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon runners before and after the 2005 boston marathon SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 125 BP 30 EP 30 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400126 ER PT J AU Jackson, L Tabatabai, ZL AF Jackson, Lorren Tabatabai, Z. Laura TI Utility of fine needle aspiration cytology (FNAC) in the evaluation of superficial, palpable masses clinically presumed to be lymph nodes: A 5-year retrospective review with histopathological and clinical correlation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 142 BP 34 EP 34 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400143 ER PT J AU Wilbur, D Tambouret, R AF Wilbur, David Tambouret, Rosemary TI Automated detection of aberrant S-PHASE induction markers in cervical cytology specimens SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 161 BP 38 EP 38 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400162 ER PT J AU Posligua, L Michael, I Bhuvaneswari, K AF Posligua, Lorena Michael, Ittmann Bhuvaneswari, Krishnan TI Cellular angiofibroma of the corpus spongiosum: Case report SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Baylor Coll Med, Houston, TX 77030 USA. Baylor Sch Med, Michael E DE Bakey VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 202 BP 47 EP 47 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400203 ER PT J AU Koreishi, A Misdraji, J AF Koreishi, Aashiyana Misdraji, Joe TI Pneumatosis intestinalis: A challenging biopsy diagnosis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 272 BP 61 EP 61 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400273 ER PT J AU Post, M Young, RH AF Post, Miriam Young, Robert H. TI Problematic aspects of otherwise typical endometrial polyps: Diverse features of 68 cases from a consultation practice SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Labs, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 466 BP 102 EP 102 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400467 ER PT J AU Roehrl, M Rho, JH Wang, S Lauwers, G Wang, J AF Roehrl, Michael Rho, Jung-Hyun Wang, Sidney Lauwers, Gregory Wang, Julia TI Systems biology of cancer: Discovery of proteomic signature profiles of carcinomas of the colon and the lung SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 654 BP 142 EP 142 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400655 ER PT J AU Kurek, K Perez-Atayde, A Kozakewich, H Richkind, K Degar, B Vargas, S AF Kurek, Kyle Perez-Atayde, Antonio Kozakewich, Harry Richkind, Kathy Degar, Barbara Vargas, Sara TI Epstein-Barr virus-associated smooth muscle tumors: Observations expanding the clinical and cytogenetic spectrum of disease SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, US & Canadian Acad Pathol C1 Rhode Isl Hosp, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Genzyme Genet, Santa Fe, NM USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 714 BP 154 EP 155 PG 2 WC Pathology SC Pathology GA 077AF UT WOS:000239999400715 ER PT J AU Mandal, R Kradin, R AF Mandal, Rajni Kradin, Richard TI Pulmonary microvascular CD61+megakaryocytes predict mortality in diffuse alveolar damage SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 792 BP 172 EP 172 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400793 ER PT J AU Yonekura, S Ting, CY Neves, G Hung, K Hsu, SN Chiba, A Chess, A Lee, CH AF Yonekura, Shinichi Ting, Chun-Yuan Neves, Guilherme Hung, Kimberly Hsu, Shu-ning Chiba, Akira Chess, Andrew Lee, Chi-Hon TI The variable transmembrane domain of Drosophila N-cadherin regulates adhesive activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-ADHESION; IN-VIVO; LATERAL DIMERIZATION; CLASSIC CADHERIN; DN-CADHERIN; ORGANIZATION; DIVERSITY; RECEPTOR; GENES; CNS AB Drosophila N-cadherin (CadN) is an evolutionarily conserved classic cadherin which has a large, complex extracellular domain and a catenin-binding cytoplasmic domain. The CadN locus contains three modules of alternative exons (7a/b, 13a/b, and 18a/b) and undergoes alternative splicing to generate multiple isoforms. Using quantitative transcript analyses and green fluorescent protein-based cell sorting, we found that during development CadN alternative splicing is regulated in a temporal but not cell-type-specific fashion. In particular, exon 18b is predominantly expressed during early developmental stages, while exon 18a is prevalent at the late developmental and adult stages. All CadN isoforms share the same molecular architecture but have different sequences in their extracellular and transmembrane domains, suggesting functional diversity. In vitro quantitative cell aggregation assays revealed that all CadN isoforms mediate homophilic interactions, but the isoforms encoded by exon 18b have a higher adhesive activity than those by its alternative, 18a. Domain-swapping experiments further revealed that the different sequences in the transmembrane domains of isoforms are responsible for their differential adhesive activities. CadN alternative splicing might provide a novel mechanism to fine-tune its adhesive activity at different developmental stages or to restrict the use of high-affinity 18b-type isoforms at the adult stage. C1 NICHHD, Lab Gene Regulat & Dev, Unit Neuronal Connect, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Univ Illinois, Dept Cell & Struct Biol, Urbana, IL 61801 USA. RP Lee, CH (reprint author), NICHHD, Lab Gene Regulat & Dev, Unit Neuronal Connect, NIH, Bldg 18T,Room 106,MSC 5431, Bethesda, MD 20892 USA. EM leechih@mail.nih.gov RI Neves, Guilherme/G-8957-2011; Lee, Chi-Hon/G-9190-2012; Ting, chun-yuan/F-6448-2013 OI Neves, Guilherme/0000-0001-6463-6997; FU Intramural NIH HHS; NICHD NIH HHS [HD008748-03, Z01 HD008748] NR 48 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 17 BP 6598 EP 6608 DI 10.1128/MCB.00241-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 074YP UT WOS:000239848800024 PM 16914742 ER PT J AU Ho, GPH Margossian, S Taniguchi, T D'Andrea, AD AF Ho, Gary P. H. Margossian, Steven Taniguchi, Toshiyasu D'Andrea, Alan D. TI Phosphorylation of FANCD2 on two novel sites is required for mitomycin C resistance SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FANCONI-ANEMIA PROTEIN; DNA-DAMAGE RESPONSE; S-PHASE CHECKPOINT; ATAXIA-TELANGIECTASIA; HELICASE BRIP1; ATM KINASE; PATHWAY; BRCA1; ACTIVATION; BREAKAGE AB The Fanconi anemia (FA) pathway is a DNA damage-activated signaling pathway which regulates cellular resistance to DNA cross-linking agents. Cloned FA genes and proteins cooperate in this pathway, and monoubiquitination of FANCD2 is a critical downstream event. The cell cycle checkpoint kinase ATR is required for the efficient monoubiquitination of FANCD2, while another checkpoint kinase, ATM, directly phosphorylates FANCD2 and controls the ionizing radiation (IR)-inducible intra-S-phase checkpoint. In the present study, we identify two novel DNA damage-inducible phosphorylation sites on FANCD2, threonine 691 and serine 717. ATR phosphorylates FANCD2 on these two sites, thereby promoting FANCD2 monoubiquitination and enhancing cellular resistance to DNA cross-linking agents. Phosphorylation of the sites is required for establishment of the intra-S-phase checkpoint response. IR-inducible phosphorylation of threonine 691 and serine 717 is also dependent on ATM and is more strongly impaired when both ATM and ATR are knocked down. Threonine 691 is phosphorylated during normal S-phase progression in an ATM-dependent manner. These findings further support the functional connection of ATM/ATR kinases and FANCD2 in the DNA damage response and support a role for the FA pathway in the coordination of the S phase of the cell cycle. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu FU NCI NIH HHS [P50 CA105009, P50 CA 205009-01]; NHLBI NIH HHS [R01 HL 52725, R01 HL052725, P50 HL054785, P01 HL 54785]; NIDDK NIH HHS [R01 DK 43889, R01 DK043889]; PHS HHS [P01 50654] NR 44 TC 70 Z9 72 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 18 BP 7005 EP 7015 DI 10.1128/MCB.02018-05 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 084BB UT WOS:000240505400024 PM 16943440 ER PT J AU Valentine, CH Hellman, J Beasley-Topliffe, LK Bagchi, A Warren, HS AF Valentine, Catherine H. Hellman, Judith Beasley-Topliffe, Laura K. Bagchi, Aranya Warren, H. Shaw TI Passive immunization to outer membrane proteins MLP and PAL does not protect mice from sepsis SO MOLECULAR MEDICINE LA English DT Article ID PEPTIDOGLYCAN-ASSOCIATED LIPOPROTEIN; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI J5; HUMAN MONOCLONAL-ANTIBODY; PLACEBO-CONTROLLED TRIAL; SALMONELLA-MINNESOTA; MUREIN-LIPOPROTEIN; SEPTIC SHOCK; CROSS-REACTIVITY; CELL-ENVELOPE AB Multiple older studies report that immunoglobulin directed to rough mutant bacteria, such as E. coli J5, provides broad protection against challenge with heterologous strains of Gram-negative bacteria. This protection was initially believed to occur through binding of immunoglobulin to bacterial lipopolysaccharide (LIPS), However, hundreds of millions of dollars have been invested in attempting to develop clinically-effective anti-LPS monoclonal antibodies without success, and no study has shown that IgG from this antiserum binds LIPS. Identification of the protective mechanism would facilitate development of broadly protective human monoclonal antibodies for treating sepsis. IgG from this antiserum binds 2 bacterial outer membrane proteins: murein lipoprotein (MLP) and peptidoglycan-assocated lipoprotein (PAL), Both of these outer membrane proteins are highly conserved, have lipid domains that are anchored in the bacterial membrane, are shed from bacteria in blebs together with LPS, and activate cells through Toll-like receptor 2. Our goal in the current work was to determine if passive immunization directed to MLP and PAL protects mice from Gram-negative sepsis, Neither monoclonal nor polyclonal IgG directed to MLP or PAL conferred survival protection in 3 different models of sepsis: cecal ligation and puncture, an infected burn model, and an infected fibrin clot model mimicking peritonitis, Our results are not supportive of the hypothesis that either anti-MILP or anti-PAL IgG are the protective antibodies in the previously described anti-rough mutant bacterial antisera. These studies suggest that a different mechanism of protection is involved. C1 Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA USA. Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Dept Anesthesia & Crit Care & Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA USA. RP Warren, HS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 5th Floor,E 149,13th St, Charlestown, MA 02129 USA. EM swarren1@partners.org FU NIAID NIH HHS [R01 AI058106, 2T32AI007061-26, T32 AI007061, R01-AI058106]; NIGMS NIH HHS [R01 GM059694, R01-GM59694] NR 46 TC 5 Z9 5 U1 0 U2 0 PU FEINSTEIN INSTITUTE MED RES PI MANHASSET PA 350 COMMUNITY DRIVE, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD SEP-OCT PY 2006 VL 12 IS 9-10 BP 252 EP 258 DI 10.2119/2006-00065.Valentine PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 117FQ UT WOS:000242858700008 PM 17225874 ER PT J AU Schwab, SG Knapp, M Sklar, P Eckstein, GN Sewekow, C Borrmann-Hassenbach, M Albus, M Becker, T Hallmayer, JF Lerer, B Maier, W Wildenauer, DB AF Schwab, S. G. Knapp, M. Sklar, P. Eckstein, G. N. Sewekow, C. Borrmann-Hassenbach, M. Albus, M. Becker, T. Hallmayer, J. F. Lerer, B. Maier, W. Wildenauer, D. B. TI Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase II alpha gene (PIP5K2A) with schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE linkage disequilibrium; single nucleotide polymorphism; non-synonymous amino acid exchange; phosphoinositide cell signalling; candidate gene ID FAMILY-BASED ASSOCIATION; TIGHTLY LINKED MARKERS; SIB-PAIR FAMILIES; CHROMOSOME 6P; LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY LOCUS; VULNERABILITY LOCUS; PHOSPHATE KINASES; DYSBINDIN GENE; GENOME SCAN AB Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A), in a sample of 65 sib-pair families for which linkage had been reported. Evidence for association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic region of the gene between intron 4 and the 30 untranslated region, a region with high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP) rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange (asparagine/serine) produced a P-value of 0.001 (experiment-wide significance level 0.00275) for over-transmission of the major allele coding for serine, analysed by transmission disequilibrium test using FAMHAP. Association of this SNP with schizophrenia has been also described in a sample of 273 Dutch schizophrenic patients and 580 controls (P= 0.0004). PIP5K2A is involved in the biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5) P-2), one of the key metabolic crossroads in phosphoinositide signalling. PI(4,5)P-2 plays a role in membrane transduction of neurotransmitter signals as well as in intracellular signalling, pathways that may be impaired in schizophrenia. C1 Univ Western Australia, Western Australian Inst Med Res, Perth, WA 6009, Australia. Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia. Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet,Dept Psychiat,Psychiat & Neurodev, Charlestown, MA USA. GSF, Natl Res Ctr Environm & Hlth, Inst Human Genet, Munich, Germany. Mental State Hosp, Haar, Germany. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. Hadassah Hebrew Univ Med Ctr, Dept Psychiat, Jerusalem, Israel. Graylands Hosp, Ctr Clin Res Neuropsychiat, Mt Claremont, WA, Australia. RP Wildenauer, DB (reprint author), Graylands Hosp, CCRN, Private Bag 1, Claremont, WA 6910, Australia. EM dieter@ccrn.uwa.edu.au NR 77 TC 29 Z9 30 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2006 VL 11 IS 9 BP 837 EP 846 DI 10.1038/sj.mp.4001864 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 077PW UT WOS:000240043100007 PM 16801950 ER PT J AU Rosas, HD Tuch, DS Hevelone, ND Zaleta, AK Vangel, M Hersch, SM Salat, DH AF Rosas, H. Diana Tuch, David S. Hevelone, Nathanael D. Zaleta, Alexandra K. Vangel, Mark Hersch, Steven M. Salat, David H. TI Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures SO MOVEMENT DISORDERS LA English DT Article DE Huntington's disease ID DYSTROPHIC NEURITES; NERVOUS-SYSTEM; HUMAN BRAIN; MRI; LOCALIZATION; ATROPHY; NEOSTRIATUM; PROJECTIONS; INCLUSIONS; ACCURATE AB Atrophy of cortical and subcortical gray matter is apparent in Huntington's disease (HD) before symptoms manifest. We hypothesized that the white matter (WM) connecting cortical and subcortical regions must also be affected early and that select clinical symptoms were related to systems degeneration. We used diffusion tensor magnetic resonance imaging (DTI) to examine the regional nature of WM abnormalities in early HD, including the preclinical period, and to determine whether regional changes correlated with clinical features. We studied individuals in early stages (HD), presymptomatic individuals known to carry the genetic mutation that causes HD (Pre-HD), and matched healthy controls. DTI indices of tissue integrity were obtained from several regions of interest, including the corpus callosum (CC), internal capsule (IC), and basal ganglia, were compared across groups by t tests, and were correlated to cognitive and clinical measures. WM alterations were found throughout the CC, in the anterior and posterior limbs of the IC, and in frontal subcortical WM in HD subjects, supporting the selective involvement of the pyramidal tracts in HD; a similar distribution of changes was seen in Pre-HD subjects, supporting presymptomatic alterations. There was a significant relationship between select DTI measures and cognitive performance. Alterations in diffusion indices were also seen in the striatum that were independent of atrophy. Our findings support that WM alterations occur very early in HD. The distribution of the changes suggests that these changes contribute to the disruption of pyramidal and extrapyramidal circuits and also support a role of compromised cortical circuitry in early cognitive and subtle motor impairment during the preclinical stages of HD. (c) 2006 Movement Disorder Society. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Rosas, HD (reprint author), Ctr Neuroimaging Aging Neurodegenerat Dis, 149 13th St,Room 2273, Charlestown, MA 02129 USA. EM rosas@helix.mgh.harvard.edu OI Hevelone, Nathanael/0000-0003-4740-2085 FU NCCIH NIH HHS [AT00613]; NCRR NIH HHS [RR14075]; NINDS NIH HHS [NS042861, NS045242, NS46532]; PHS HHS [AB05886, NIAAG024898] NR 42 TC 167 Z9 168 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2006 VL 21 IS 9 BP 1317 EP 1325 DI 10.1002/mds.20979 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 091AO UT WOS:000240998100003 PM 16755582 ER PT J AU Brodsky, MA Hogarth, P Nutt, JG AF Brodsky, Matthew A. Hogarth, Penelope Nutt, John G. TI OFF-off rebound dyskinesia in subthalamic nucleus deep brain stimulation of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; dyskinesia; deep brain stimulation ID HIGH-FREQUENCY STIMULATION; GLOBUS-PALLIDUS; LEVODOPA AB A 61-year-old man with Parkinson's disease (PD), motor fluctuations, and dyskinesias underwent bilateral implantation of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). One month after surgery, DBS was optimized to bilateral monopolar settings at the most proximal electrode just superior to the STN, which improved motor fluctuations and dyskinesias. At several postoperative evaluations off medications overnight, both stimulators were turned off and within 60 seconds he developed severe dyskinesias. When the stimulators were turned back on, the dyskinesias soon resolved. This article is a first report of a unique pattern of rebound-type dyskinesia that occurred in the off medication state produced by stopping STN DBS. (c) 2006 Movement Disorder Society. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Care Ctr, Portland, OR USA. RP Brodsky, MA (reprint author), Oregon Hlth & Sci Univ, Parkinson Ctr Oregon, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM brodskym@ohsu.edu NR 15 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2006 VL 21 IS 9 BP 1487 EP 1490 DI 10.1002/mds.20964 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 091AO UT WOS:000240998100031 PM 16721730 ER PT J AU Samii, A Kelly, VE Slimp, JC Shumway-Cook, A Goodkin, R AF Samii, A. Kelly, V. E. Slimp, J. C. Shumway-Cook, A. Goodkin, R. TI Unilateral vs. bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 20th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 08, 2006 CL Chicago, IL C1 Univ Washington, Dept Neurol, PADRECC, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2006 VL 21 IS 9 BP 1552 EP 1553 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 091AO UT WOS:000240998100080 ER PT J AU Walker, M Kim, HM Samii, A AF Walker, M. Kim, H. M. Samii, A. TI Lower limb Holmes tremor with hypertrophic olivary degeneration SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 20th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 08, 2006 CL Chicago, IL C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. VA Puget Sound Hlth Care Syst, PADRECC, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2006 VL 21 IS 9 BP 1556 EP 1556 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 091AO UT WOS:000240998100092 ER PT J AU Gupta, ML Carvalho, P Roof, DM Pellman, D AF Gupta, Mohan L., Jr. Carvalho, Pedro Roof, David M. Pellman, David TI Plus end-specific depolymerase activity of Kip3, a kinesin-8 protein, explains its role in positioning the yeast mitotic spindle SO NATURE CELL BIOLOGY LA English DT Article ID REGULATE MICROTUBULE DYNAMICS; MOTOR PROTEINS; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; FISSION YEAST; NUCLEAR MIGRATION; CELL CORTEX; ANAPHASE; MICROSCOPY; MECHANISM AB The budding yeast protein Kip3p is a member of the conserved kinesin-8 family of microtubule motors, which are required for microtubule -cortical interactions, normal spindle assembly and kinetochore dynamics. Here, we demonstrate that Kip3p is both a plus end-directed motor and a plus end-specific depolymerase - a unique combination of activities not found in other kinesins. The ATPase activity of Kip3p was activated by both microtubules and unpolymerized tubulin. Furthermore, Kip3p in the ATP-bound state formed a complex with unpolymerized tubulin. Thus, motile kinesin-8s may depolymerize microtubules by a mechanism that is similar to that used by non-motile kinesin-13 proteins. Fluorescent speckle analysis established that, in vivo, Kip3p moved toward and accumulated on the plus ends of growing microtubules, suggesting that motor activity brings Kip3p to its site of action. Globally, and more dramatically on cortical contact, Kip3p promoted catastrophes and pausing, and inhibited microtubule growth. These findings explain the role of Kip3p in positioning the mitotic spindle in budding yeast and potentially other processes controlled by kinesin-8 family members. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Dept Biol Anim, Program Cell & Mol Biol, Philadelphia, PA 19104 USA. RP Pellman, D (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu OI Carvalho, Pedro/0000-0002-9691-5277 FU NIGMS NIH HHS [R01 GM61345] NR 54 TC 166 Z9 168 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2006 VL 8 IS 9 BP 913 EP U33 DI 10.1038/ncb1457 PG 22 WC Cell Biology SC Cell Biology GA 080IS UT WOS:000240241700007 PM 16906148 ER PT J AU Schoen, RE Hur, C AF Schoen, Robert E. Hur, Chin TI What is the clinical importance of small polyps with regard to colorectal cancer screening? SO NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material DE advanced histology; colorectal cancer; screening; small adenoma ID VIRTUAL COLONOSCOPY; CT COLONOGRAPHY C1 Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. 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. RP Schoen, RE (reprint author), Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Mezzanine Level C-Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM schoen@dom.pitt.edu OI Hur, Chin/0000-0002-2819-7576 NR 6 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4378 J9 NAT CLIN PRACT GASTR JI Nat. Clin. Pract. Gastroenterol. Hepatol. PD SEP PY 2006 VL 3 IS 9 BP 488 EP 489 DI 10.1038/ncpgasthep0599 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 079YW UT WOS:000240214800006 PM 16951664 ER PT J AU Humphreys, BD Vanguri, VK Henderson, J Antin, JH AF Humphreys, Benjamin D. Vanguri, Vijay K. Henderson, Joel Antin, Joseph H. TI Minimal-change nephrotic syndrome in a hematopoietic stem-cell transplant recipient SO NATURE CLINICAL PRACTICE NEPHROLOGY LA English DT Article DE acute renal failure; bone-marrow transplant; immunization; minimal-change disease; nephrotic syndrome ID RENAL-FAILURE; VACCINATION AB Background A 61-year-old woman received standard immunizations, including Haemophilus influenzae type B, diphtheria, tetanus toxoid, and unconjugated 23-valent pneumococcal vaccine (Pneumovax(R), Merck & Co., Inc., Whitehouse Station, NJ), 1 year after undergoing nonmyeloablative hematopoietic stem-cell transplantation for acute myelogenous leukemia. After 5 days, she developed fatigue with progressive weight gain and edema, and 14 days after immunization she presented with anasarca and was found to have acute renal failure and nephrotic proteinuria. Investigations Physical examination, serum chemistry, examination of urine sediment, renal ultrasound using Doppler scanning, 24 h urine collection, and renal biopsy. Diagnosis Minimal-change nephrotic syndrome with acute tubular injury. Management Aggressive diuresis and oral corticosteroid therapy. C1 Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Stem Cell Transplant Program, Boston, MA 02115 USA. RP Humphreys, BD (reprint author), Harvard Univ, Sch Med, Inst Med, Room 550,4 Blackfan Circle, Boston, MA 02115 USA. EM bhumphreys@partners.org FU NIDDK NIH HHS [F32 DK069037, DK073628-01, K08 DK073628] NR 15 TC 6 Z9 6 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8323 J9 NAT CLIN PRACT NEPHR JI Nat. Clin. Pract. Nephrol. PD SEP PY 2006 VL 2 IS 9 BP 535 EP 539 DI 10.1038/ncpneph0271 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 078ON UT WOS:000240113200007 PM 16941046 ER PT J AU Maller, J George, S Purcell, S Fagerness, J Altshuler, D Daly, MJ Seddon, JM AF Maller, Julian George, Sarah Purcell, Shaun Fagerness, Jes Altshuler, David Daly, Mark J. Seddon, Johanna M. TI Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration SO NATURE GENETICS LA English DT Article ID COMPLEMENT FACTOR-H; BODY-MASS INDEX; FAMILIAL AGGREGATION; EXTENDED FAMILIES; GENOMEWIDE-SCAN; MACULOPATHY; ASSOCIATION; SUSCEPTIBILITY; HAPLOTYPE; POLYMORPHISM AB Age-related macular degeneration (AMD) is a common, late-onset disease with seemingly typical complexity: recurrence ratios for siblings of an affected individual are three- to sixfold higher than in the general population, and family-based analysis has resulted in only modestly significant evidence for linkage. In a case-control study drawn from a US-based population of European descent, we have identified a previously unrecognized common, noncoding variant in CFH, the gene encoding complement factor H, that substantially increases the influence of this locus on AMD, and we have strongly replicated the associations of four other previously reported common alleles in three genes ( P values ranging from 10(-6) to 10(-70)). Despite excellent power to detect epistasis, we observed purely additive accumulation of risk from alleles at these genes. We found no differences in association of these loci with major phenotypic categories of advanced AMD. Genotypes at these five common SNPs define a broad spectrum of interindividual disease risk and explain about half of the classical sibling risk of AMD in our study population. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Epidemiol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Seddon, JM (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu; johanna_seddon@meei.harvard.edu RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Maller, Julian/0000-0002-1565-9559 FU NCRR NIH HHS [U54 RR020278]; NEI NIH HHS [EY11309] NR 28 TC 382 Z9 392 U1 6 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2006 VL 38 IS 9 BP 1055 EP 1059 DI 10.1038/ng1873 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 078OC UT WOS:000240112100024 PM 16936732 ER PT J AU van Loo, G De Lorenzi, R Schmidt, H Huth, M Mildner, A Schmidt-Supprian, M Lassmann, H Prinz, MR Pasparakis, M AF van Loo, Geert De Lorenzi, Rossana Schmidt, Hauke Huth, Marion Mildner, Alexander Schmidt-Supprian, Marc Lassmann, Hans Prinz, Marco R. Pasparakis, Manolis TI Inhibition of transcription factor NF-kappa B in the central nervous system ameliorates autoimmune encephalomyelitis in mice SO NATURE IMMUNOLOGY LA English DT Article ID CELL-ADHESION MOLECULE-1; MULTIPLE-SCLEROSIS LESIONS; DEFICIENT MICE; ANIMAL-MODEL; INFLAMMATION; ASTROCYTES; GENE; EXPRESSION; ACTIVATION; DISEASE AB Activation of transcription factor NF-kappa B in the central nervous system (CNS) has been linked to autoimmune demyelinating disease; however, it remains unclear whether its function is protective or pathogenic. Here we show that CNS-restricted ablation of 'upstream' NF-kappa B activators NEMO or IKK2 but not IKK1 ameliorated disease pathology in a mouse model of multiple sclerosis, suggesting that 'canonical' NF-kappa B activation in cells of the CNS has a mainly pathogenic function in autoimmune demyelinating disease. NF-kappa B inhibition prevented the expression of proinflammatory cytokines, chemokines and the adhesion molecule VCAM-1 from CNS-resident cells. Thus, NF-kappa B-dependent gene expression in non-microglial cells of the CNS provides a permissive proinflammatory milieu that is critical for CNS inflammation and tissue damage in autoimmune demyelinating disease. C1 European Mol Biol Lab, Mouse Biol Unit, I-00016 Monterotondo, Italy. Univ Gottingen, Dept Neuropathol, D-37075 Gottingen, Germany. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Vienna, Brain Res Inst, A-1090 Vienna, Austria. Univ Cologne, Inst Genet, D-50674 Cologne, Germany. RP Pasparakis, M (reprint author), European Mol Biol Lab, Mouse Biol Unit, I-00016 Monterotondo, Italy. EM pasparakis@uni-koeln.de RI van Loo, Geert/C-1505-2009; Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Pasparakis, Manolis/0000-0002-9870-0966 NR 45 TC 114 Z9 114 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2006 VL 7 IS 9 BP 954 EP 961 DI 10.1038/ni1372 PG 8 WC Immunology SC Immunology GA 076FL UT WOS:000239942300014 PM 16892069 ER PT J AU Root, DE Hacohen, N Hahn, WC Lander, ES Sabatini, DM AF Root, David E. Hacohen, Nir Hahn, William C. Lander, Eric S. Sabatini, David M. TI Genome-scale loss-of-function screening with a lentiviral RNAi library SO NATURE METHODS LA English DT Article ID HUMAN-CELLS; INTERFERENCE; CANCER; TUMORIGENICITY; EXPRESSION; TARGETS; VECTOR; MOUSE AB The discovery that RNA interference (RNAi) is functional in mammalian cells led us to form The RNAi Consortium (TRC) with the goal of enabling large-scale loss-of-function screens through the development of genome-scale RNAi libraries and methodologies for their use. These resources form the basis of a loss-of-function screening platform created at the Broad Institute. Our human and mouse libraries currently contain > 135,000 lentiviral clones targeting 27,000 genes. Initial screening efforts have demonstrated that these libraries and methods are practical and powerful tools for high-throughput lentivirus RNAi screens. C1 MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Dept Med Oncol, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Root, DE (reprint author), MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02142 USA. EM droot@broad.mit.edu NR 23 TC 229 Z9 233 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD SEP PY 2006 VL 3 IS 9 BP 715 EP 719 DI 10.1038/NMETH924 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 081AT UT WOS:000240290300015 PM 16929317 ER PT J AU Farazi, PA DePinho, RA AF Farazi, Paraskevi A. DePinho, Ronald A. TI Hepatocellular carcinoma pathogenesis: from genes to environment SO NATURE REVIEWS CANCER LA English DT Review ID HEPATITIS-C-VIRUS; COMPARATIVE GENOMIC HYBRIDIZATION; GROWTH-FACTOR-ALPHA; TELOMERASE REVERSE-TRANSCRIPTASE; BETA-CATENIN MUTATIONS; CHRONIC LIVER-DISEASE; COMPARATIVE FUNCTIONAL GENOMICS; MESSENGER-RNA EXPRESSION; ABERRANT DNA METHYLATION; LI-FRAUMENI-SYNDROME AB Hepatocellular carcinoma is among the most lethal and prevalent cancers in the human population. Despite its significance, there is only an elemental understanding of the molecular, cellular and environmental mechanisms that drive disease pathogenesis, and there are only limited therapeutic options, many with negligible clinical benefit. This Review summarizes the current state of knowledge of this, the most common and dreaded liver neoplasm, and highlights the principal challenges and scientific opportunities that are relevant to controlling this accelerating global health crisis. C1 Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Dept Genet, Div Med Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ron_depinho@dfci.harvard.edu NR 186 TC 1019 Z9 1059 U1 7 U2 105 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD SEP PY 2006 VL 6 IS 9 BP 674 EP 687 DI 10.1038/nrc1934 PG 14 WC Oncology SC Oncology GA 077JO UT WOS:000240025600014 PM 16929323 ER PT J AU Sharpless, NE DePinho, RA AF Sharpless, Norman E. DePinho, Ronald A. TI Model organisms - The mighty mouse: genetically engineered mouse models in cancer drug development SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID RECOMBINANT HUMAN ENDOSTATIN; TYROSINE KINASE INHIBITOR; HUMAN-MALIGNANT MELANOMA; CHRONIC MYELOID-LEUKEMIA; CELL-CYCLE INHIBITION; IN-VIVO MODEL; PHASE-I; TRANSGENIC MICE; CLINICAL-TRIALS; LUNG ADENOCARCINOMAS AB Deficiencies in the standard preclinical methods for evaluating potential anticancer drugs, such as xenograft mouse models, have been highlighted as a key obstacle in the translation of the major advances in basic cancer research into meaningful clinical benefits. In this article, we discuss the established uses and limitations of xenograft mouse models for cancer drug development, and then describe the opportunities and challenges in the application of novel genetically engineered mouse models that more faithfully mimic the genetic and biological evolution of human cancers. Greater use of such models in target validation, assessment of tumour response, investigation of pharmacodynamic markers of drug action, modelling resistance and understanding toxicity has the potential to markedly improve the success of cancer drug development. C1 Univ N Carolina, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, 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 Sharpless, NE (reprint author), Univ N Carolina, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM nes@med.unc.edu; ron_depinho@dfci.harvard.edu NR 107 TC 312 Z9 322 U1 10 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2006 VL 5 IS 9 BP 741 EP 754 DI 10.1038/nrd2110 PG 14 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 086EA UT WOS:000240655400021 PM 16915232 ER PT J AU Evgenov, OV Pacher, P Schmidt, PM Hasko, G Schmidt, HHHW Stasch, JP AF Evgenov, Oleg V. Pacher, Pal Schmidt, Peter M. Hasko, Gyoergy Schmidt, Harald H. H. W. Stasch, Johannes-Peter TI NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID NITRIC-OXIDE SYNTHASE; DEPENDENT PROTEIN-KINASE; PULMONARY ARTERIAL-HYPERTENSION; INHIBITS NEOINTIMA FORMATION; MUSCLE-CELL-PROLIFERATION; RABBIT CORPUS CAVERNOSUM; CONGESTIVE-HEART-FAILURE; SMOOTH-MUSCLE; IN-VIVO; PENILE ERECTION AB Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impaired bioavailability and/or responsiveness to endogenous NO has been implicated in the pathogenesis of cardiovascular and other diseases. Current therapies that involve the use of organic nitrates and other NO donors have limitations, including non-specific interactions of NO with various biomolecules, lack of response and the development of tolerance following prolonged administration. Compounds that activate sGC in an NO-independent manner might therefore provide considerable therapeutic advantages. Here we review the discovery, biochemistry, pharmacology and clinical potential of haem-dependent sGC stimulators ( including YC-1, BAY 41-2272, BAY 41-8543, CFM-1571 and A-350619) and haem-independent sGC activators ( including BAY 58-2667 and HMR-1766). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Dept Surg, Boston, MA 02111 USA. RP Evgenov, OV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St,CLN 309, Boston, MA 02114 USA. EM evgenov@etherdome.mgh.harvard.edu RI Schmidt, Harald H. H. W./B-1549-2008; Pacher, Pal/B-6378-2008 OI Schmidt, Harald H. H. W./0000-0003-0419-5549; Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02] NR 159 TC 336 Z9 356 U1 2 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2006 VL 5 IS 9 BP 755 EP 768 DI 10.1038/nrd2038 PG 14 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 086EA UT WOS:000240655400022 PM 16955067 ER PT J AU Pasinelli, P Brown, RH AF Pasinelli, Piera Brown, Robert H. TI Molecular biology of amyotrophic lateral sclerosis: insights from genetics SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID CU/ZN-SUPEROXIDE-DISMUTASE; MARIE-TOOTH-DISEASE; MOTOR-NEURON DISEASE; HEREDITARY SPASTIC PARAPLEGIA; TRANSGENIC MOUSE MODEL; SPINAL MUSCULAR-ATROPHY; GLUTAMATE TRANSPORTER EAAT2; NUCLEOTIDE EXCHANGE FACTOR; HEAVY NEUROFILAMENT SUBUNIT; GIANT AXONAL NEUROPATHY AB Amyotrophic lateral sclerosis (ALS) is a paralytic disorder caused by motor neuron degeneration. Mutations in more than 50 human genes cause diverse types of motor neuron pathology. Moreover, defects in five Mendelian genes lead to motor neuron disease, with two mutations reproducing the ALS phenotype. Analyses of these genetic effects have generated new insights into the diverse molecular pathways involved in ALS pathogenesis. Here, we present an overview of the mechanisms for motor neuron death and of the role of non-neuronal cells in ALS. C1 Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02429 USA. RP Pasinelli, P (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Room 3125,Bldg 114,16th St Navy Yard, Charlestown, MA 02429 USA. EM ppasinelli@partners.org; rhbrown@partners.org NR 213 TC 621 Z9 640 U1 9 U2 72 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 SEP PY 2006 VL 7 IS 9 BP 710 EP 723 DI 10.1038/nrn1971 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 084DP UT WOS:000240512500013 PM 16924260 ER PT J AU Steward, MM Lee, JS O'Donovan, A Wyatt, M Bernstein, BE Shilatifard, A AF Steward, Melissa M. Lee, Jung-Shin O'Donovan, Aisling Wyatt, Matt Bernstein, Bradley E. Shilatifard, Ali TI Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID HISTONE H3; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; COMPASS; METHYLATION; LYSINE-4; SET1 AB MLL complexes are homologs of yeast COMPASS capable of methylating histone H3 Lys4 (H3K4). ASH2L, RbBP5 and WDR5 are conserved subunits of MLL complexes with homology to the Cps40/Cps60, Cps50 and Cps30 subunits of COMPASS, respectively. We report that ASH2L differentially regulates MLL's catalysis of H3K4 trimethylation similarly to Cps40 and Cps60. Furthermore, WDR5 is required to maintain MLL complex integrity, including the stability of ASH2L within the complex. These findings offer insight into the molecular role of ASH2L, and by extension that of WDR5, in proper H3K4 trimethylation. C1 St Louis Univ, Sch Med, Dept Biochem, St Louis, MO 63104 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. St Louis Univ, Sch Med, Ctr Canc, St Louis, MO 63104 USA. RP Shilatifard, A (reprint author), St Louis Univ, Sch Med, Dept Biochem, 1402 S Grand Blvd, St Louis, MO 63104 USA. EM shilatia@slu.edu NR 12 TC 187 Z9 190 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD SEP PY 2006 VL 13 IS 9 BP 852 EP 854 DI 10.1038/nsmb1131 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 092MY UT WOS:000241102400022 PM 16892064 ER PT J AU Newton, JR Kelly, KA Mahmood, U Weissleder, R Deutscher, SL AF Newton, Jessica R. Kelly, Kimberly A. Mahmood, Umar Weissleder, Ralph Deutscher, Susan L. TI In vivo selection of phage for the optical Imaging of PC-3 human prostate carcinoma in mice SO NEOPLASIA LA English DT Article DE phage display; optical imaging; drug development; near-infrared (NIR); tumor-imaging agents ID QUANTUM DOTS; PEPTIDE LIBRARIES; DISPLAY SELECTION; BACTERIOPHAGE; BIND; CELLS; DATABASE; THERAPY; ANTIGEN AB There is an increasing medical need to detect and spatially localize early and aggressive forms of prostate cancer. Affinity ligands derived from bacteriophage (phage) library screens can be developed to molecularly target prostate cancer with fluorochromes for optical imaging. Toward this goal, we used in vivo phage display and a newly described micropanning assay to select for phage that extravasate and bind human PC-3 prostate carcinoma xenografts in severe combined immune deficiency mice. One resulting phage clone (G1) displaying the peptide sequence IAGLATPGWSHWLAL was fluorescently labeled with the near-infrared fluorophore AlexaFluor 680 and was evaluated both in vitro and in vivo for its ability to bind and target PC-3 prostate carcinomas. The fluorescently labeled phage clone (G1) had a tumor-to-muscle ratio of similar to 30 in experiments. In addition, prostate tumors (PC-3) were readily detectable by optical-imaging methods. These results show proof of principle that disease-specific library-derived fluorescent probes can be rapidly developed for use in the early detection of cancers by optical means. C1 Univ Missouri, Dept Biochem, Columbia, MO 65212 USA. Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harry S Truman Mem Vet Hosp, Columbia, MO 65212 USA. RP Deutscher, SL (reprint author), Univ Missouri, Dept Biochem, 1 Hosp Dr,M743 Med Sci Bldg, Columbia, MO 65212 USA. EM deutschers@missouri.edu FU NCI NIH HHS [P50 CA103130, P50 CA103130-01, P50 CA086355, P50 CA86355, R24 CA092782, R24 CA92782] NR 29 TC 72 Z9 78 U1 1 U2 10 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD SEP PY 2006 VL 8 IS 9 BP 772 EP 780 DI 10.1593/neo.06331 PG 9 WC Oncology SC Oncology GA 083MV UT WOS:000240460900009 PM 16984734 ER PT J AU Nishida, M Makris, N Kennedy, DN Vangel, M Fischl, B Krishnamoorthy, KS Caviness, VS Grant, PE AF Nishida, Mitsuhiro Makris, Nikolaos Kennedy, David N. Vangel, Mark Fischl, Bruce Krishnamoorthy, Kalpathy S. Caviness, Verne S. Grant, P. Ellen TI Detailed semiautomated MRI based morphometry of the neonatal brain: Preliminary results SO NEUROIMAGE LA English DT Article DE morphometry; brain; development; Neonate; MRI; gompertz ID LOW-BIRTH-WEIGHT; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEVELOPING RHESUS-MONKEY; TOPOGRAPHIC PARCELLATION; AXON OVERPRODUCTION; WHITE-MATTER; GROWTH; PREMATURE; INFANTS; AGE AB In the neonate, regional growth trajectories provide information about the coordinated development of cerebral substructures and help identify regional vulnerability by identifying times of faster growth. Segmentation of magnetic resonance images (MRI) has provided detailed information for the myelinated brain but few reports of regional neonatal brain growth exist. We report the method and preliminary results of detailed semiautomated segmentation of 12 normative neonatal brains (gestational age 31.1-42.6 weeks at time of MRI) using volumetric T1-weighted images. Accuracy was confirmed by expert review of every segmented image. In 5 brains, repeat segmentation resulted in intraclass correlation coefficients > 0.9 (except for the right amygdala) and an average percent voxel overlap of 90.0%. Artifacts or image quality limited the number of regions segmented in 9/12 data sets and 1/12 was excluded from volumetric analysis due to ventriculomegaly. Brains were segmented into cerebral exterior (N = 8), cerebral lobes (N = 5), lateral ventricles (N = 8), cerebral cortex (N = 6), white matter (N = 6), corpus callosum (N = 7), deep central gray (N = 8), hippocampi (N = 8), amygdalae (N = 8), cerebellar hemispheres (N = 8), vermis (N = 8), midbrain (N = 8), pons (N = 8) and medulla (N = 8). Linear growth (P < 0.05) was identified in all regions except the cerebral white matter, medulla and ventricles. Striking differences in regional growth rates were noted. These preliminary results are consistent with the heterochronous nature of cerebral development and provide initial estimates of regional brain growth and therefore regional vulnerability in the perinatal time period. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Div Pediat Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Morphomet Anal, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pediat, Tokyo, Japan. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Pediat Neurol, Dept Neurol, Boston, MA 02114 USA. RP Grant, PE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, 34 Fruit St,Ellison 237, Boston, MA 02114 USA. EM ellen@nmr.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NCRR NIH HHS [P41 RR 14075]; NINDS NIH HHS [K23 NS 42758, NS 34189] NR 42 TC 42 Z9 43 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2006 VL 32 IS 3 BP 1041 EP 1049 DI 10.1016/j.neuroimage.2006.05.020 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 083PI UT WOS:000240470300008 PM 16857388 ER PT J AU Napadow, V Dhond, R Kennedy, D Hui, KKS Makris, N AF Napadow, Vitaly Dhond, Rupali Kennedy, David Hui, Kathleen K. S. Makris, Nikos TI Automated brainstem co-registration (ABC) for MRI SO NEUROIMAGE LA English DT Article DE functional MRI; tractography; talairach and tournoux; alignment ID PERIAQUEDUCTAL GRAY; COORDINATE SYSTEM; CORTICAL SURFACE; HUMANS; PAIN; ACTIVATION; NUCLEI; FMRI AB Group data analysis in brainstem neuroimaging is predicated on accurate co-registration of anatomy. As the brainstem is comprised of many functionally heterogeneous nuclei densely situated adjacent to one another, relatively small errors in co-registration can manifest in increased variance or decreased sensitivity (or significance) in detecting activations. We have devised a 2-stage automated, reference mask guided registration technique (Automated Brainstem Coregistration, or ABC) for improved brainstem co-registration. Our approach utilized a brainstem mask dataset to weight an automated coregistration cost function. Our method was validated through measurement of RMS error at 12 manually defined landmarks. These landmarks were also used as guides for a secondary manual coregistration option, intended for outlier individuals that may not adequately co-register with our automated method. Our methodology was tested on 10 healthy human subjects and compared to traditional co-registration techniques (Talairach transform and automated affine transform to the MNI-152 template). We found that ABC had a significantly lower mean RMS error (1.22 +/- 0.39 mm) than Talairach transform(2.88 +/- 1.22 mm, mu +/- sigma) and the global affine (3.26 +/- 0.81 mm) method. Improved accuracy was also found for our manual-landmark-guided option (1.51 +/- 0.43 mm). Visualizing individual brainstem borders demonstrated more consistent and uniform overlap for ABC compared to traditional global co-registration techniques. Improved robustness (lower susceptibility to outliers) was demonstrated with ABC through lower inter-subject RMS error variance compared with traditional co-registration methods. The use of easily available and validated tools (AFNI and FSL) for this method should ease adoption by other investigators interested in brainstem data group analysis. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Charlestown, MA USA. RP Napadow, V (reprint author), 149,13th Rm 2301, Charlestown, MA 02119 USA. EM vitaly@nmr.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NCCIH NIH HHS [K01 AT 002166-01, P01 AT 002048-02]; NCRR NIH HHS [P41 RR 14075] NR 30 TC 43 Z9 43 U1 0 U2 9 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 SEP PY 2006 VL 32 IS 3 BP 1113 EP 1119 DI 10.1016/j.neuroimage.2006.05.050 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 083PI UT WOS:000240470300016 PM 16839781 ER PT J AU Thoma, RJ Yeo, RA Gangestad, S Halgren, E Davis, J Paulson, KM Lewine, JD AF Thoma, Robert J. Yeo, Ronald A. Gangestad, Steven Halgren, Eric Davis, John Paulson, Kim M. Lewine, Jeffrey David TI Developmental instability and the neural dynamics of the speed-intelligence relationship SO NEUROIMAGE LA English DT Article ID PROTON MR SPECTROSCOPY; NORMAL HUMAN BRAIN; FLUCTUATING ASYMMETRY; REACTION-TIME; PSYCHOMETRIC INTELLIGENCE; INTELLECTUAL ABILITY; BIOCHEMICAL MARKERS; SENSORY CONDUCTION; PERCEPTUAL SPEED; RT PARADIGM AB Two of the most securely established findings in the biology of intelligence are the relationship between reaction time (RT) and intelligence, and the heritability of intelligence. To investigate why RT may related to intelligence, researchers have used a variety of techniques to subdivide RT into cognitive and motor components. In the current study, magnetoencephalographic (MEG) dipole latencies were used to examine the speed and timing of specific brain processing stages engaged during visually cued simple and choice reaction time tasks. Simple and choice reaction time and timing of MEG sources were considered in relation to fluid intelligence (as measured by the Raven's Advanced Progressive Matrices, RAPM). To address heritability of intelligence, developmental instability (DI) was assessed, measured here as fluctuating asymmetry. DI represents the degree to which an organism is susceptible to developmental stress arising from both environmental and genomic sources. Analyses showed that choice, but not simple reaction time was negatively correlated with RAPM score. MEG revealed a set of complex relationships between the timing of regional brain activations and psychometric intelligence. The neural component associated with integration of sensory and motor information was most associated with RAPM compared to other components. Higher values of fluctuating asymmetry predicted reduced psychometric intelligence, a result suggesting that some part of the variance of the heritability of intelligence reflects DI. Fluctuating asymmetry was significantly and negatively correlated with timing during all components of task completion. These observations suggest that fluid intelligence is primarily related to speed during processing associated with decision time, while fluctuating asymmetry predicted slower processing across all stages of information processing. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. MIND Inst, Albuquerque, NM USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. RP Thoma, RJ (reprint author), Univ New Mexico, Ctr Neurophysiol Serv, 915 Vassar NE,MSC11 6094, Albuquerque, NM 87131 USA. EM rjthoma@salud.unm.edu OI Gangestad, Steven/0000-0002-8879-4348 NR 60 TC 12 Z9 12 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2006 VL 32 IS 3 BP 1456 EP 1464 DI 10.1016/j.neuroimage.2006.05.016 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 083PI UT WOS:000240470300057 PM 16829138 ER PT J AU Desai, M Kennedy, DN Mangoubi, R Shah, J Karl, C Worth, A Makris, N Pien, H AF Desai, Mukund Kennedy, David N. Mangoubi, Rami Shah, Jayant Karl, Clem Worth, Andrew Makris, Nikos Pien, Homer TI Model-based variational smoothing and segmentation for diffusion tensor imaging in the brain SO NEUROINFORMATICS LA English DT Article DE cerebral white matter; diffusion tensor imaging (DTI); magnetic resonance imaging (MRI); variational segmentation functional AB This article applies a unified approach to variational smoothing and segmentation to brain diffusion tensor image data along user-selected attributes derived from the tensor, with the aim of extracting detailed brain structure information. The application of this framework simultaneously segments and denoises to produce edges and smoothed regions within the white matter of the brain that are relatively homogeneous with respect to the diffusion tensor attributes of choice. This approach enables the visualization of a smoothed, scale invariant representation of the tensor data field in a variety of diverse forms. In addition to known attributes such as fractional anisotropy, these representations include selected directional tensor components and additionally associated continuous valued edge fields that might be used for further segmentation. A comparison is presented of the results of three different data model selections with respect to their ability to resolve white matter structure. The resulting images are integrated to provide better perspective of the model properties (edges, smoothed image, and so forth) and their relationship to the underlying brain anatomy. The improvement in brain image quality is illustrated both qualitatively and quantitatively, and the robust performance of the algorithm in the presence of added noise is shown. Smoothing occurs without loss of edge features because of the simultaneous segmentation aspect of the variational approach, and the output enables better delineation of tensors representative of local and long-range association, projection, and commissural fiber systems. C1 [Desai, Mukund; Mangoubi, Rami] Charles Stark Draper Lab Inc, Control & Informat Syst Div, Cambridge, MA 02139 USA. [Kennedy, David N.; Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02129 USA. [Kennedy, David N.; Makris, Nikos] Massachusetts Gen Hosp, MIT Athinoula A Martinos Ctr Biomed Imaging, Dept Neurol, Boston, MA 02129 USA. [Shah, Jayant] Northeastern Univ, Dept Math, Boston, MA 02115 USA. [Karl, Clem] Boston Univ, Dept Elect Comp & Syst Engn, Boston, MA 02215 USA. [Karl, Clem] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Worth, Andrew] Neuromorphometr, Somerville, MA 02144 USA. [Pien, Homer] Massachusetts Gen Hosp, Dept Radiol, Ctr Biomarkers Imaging, MGH HST, Boston, MA 02129 USA. RP Desai, M (reprint author), Charles Stark Draper Lab Inc, Control & Informat Syst Div, Cambridge, MA 02139 USA. EM mdesai@draper.com RI Kennedy, David/H-3627-2012 FU NINDS NIH HHS [2R01NS34189] NR 55 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD SEP PY 2006 VL 4 IS 3 BP 217 EP 233 DI 10.1385/NI:4:3:217 PG 17 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA V44NZ UT WOS:000203010700002 PM 16943628 ER PT J AU Kennedy, DN Haselgrove, C AF Kennedy, David N. Haselgrove, Christian TI The internet analysis tools registry - A public resource for image analysis SO NEUROINFORMATICS LA English DT Editorial Material C1 [Kennedy, David N.; Haselgrove, Christian] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. [Kennedy, David N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kennedy, DN (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. EM dave@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NINDS NIH HHS [NS34189] NR 2 TC 9 Z9 9 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD SEP PY 2006 VL 4 IS 3 BP 263 EP 270 DI 10.1385/NI:4:3:263 PG 8 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA V44NZ UT WOS:000203010700005 PM 16943631 ER PT J AU Bergmann, C Sano, M AF Bergmann, Christine Sano, Mary TI Cardiac risk factors and potential treatments in Alzheimer's disease SO NEUROLOGICAL RESEARCH LA English DT Review DE Alzheimer's disease; risk factor; hypertension; diabetes mellitus; hyperlipidemia; cognition ID ANTIHYPERTENSIVE-MEDICATION-USE; ISOLATED SYSTOLIC HYPERTENSION; LIPID-LOWERING AGENTS; IMPROVED GLYCEMIC CONTROL; IMPAIRED FASTING GLUCOSE; CALCIUM-CHANNEL BLOCKERS; TOTAL CHOLESTEROL LEVEL; POPULATION-BASED COHORT; ELDERLY PROGRAM SHEP; AGED 75 YEARS AB Dementia is one of the commonest neurological disorders in the elderly population. In regards to the increasing longevity of populations worldwide, prevention of dementia has become a major public health challenge. There has been an intense research in the identification of modifiable risk factors for dementia. These risk factors could then be used as targets for intervention, pharmacologic or non-pharmacologic. Numerous reports of the relation between cardiovascular risk factors and cognitive decline and dementia have been published over the past years. This review focuses on the cardiovascular risk factors hypertension, hyperlipidemia and diabetes mellitus as targets for prevention of cognitive decline, overall dementia and Alzheimer's disease. Observational studies and clinical trials regarding the association between antihypertensive, lipid lowering and antidiabetic medications and the risk of impaired cognition, dementia or Alzheimer's disease are reviewed. Based on these data, we propose that early interventions at reducing these cardiovascular risk factors may have an impact on future incidence and prevalence of cognitive deficits of many etiologies including Alzheimer's disease. C1 Mt Sinai Sch Med, Alzheimer Dis Res Ctr, New York, NY USA. James J Peters VAMC, Bronx, NY USA. RP Sano, M (reprint author), Mt Sinai Sch Med, 130 Kingsbridge Rd,Rm1F01, Bronx, NY 10468 USA. EM mary.sano@mssm.edu NR 135 TC 24 Z9 25 U1 2 U2 7 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD SEP PY 2006 VL 28 IS 6 BP 595 EP 604 DI 10.1179/016164106X130498 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 078YI UT WOS:000240142300004 PM 16945210 ER PT J AU Rush, AJ Kraemer, HC Sackeim, HA Fava, M Trivedi, MH Frank, E Ninan, PT Thase, ME Gelenberg, AJ Kupfer, DJ Regier, DA Rosenbaum, JF Ray, O Schatzberg, AF AF Rush, A. John Kraemer, Helena C. Sackeim, Harold A. Fava, Maurizio Trivedi, Madhukar H. Frank, Ellen Ninan, Philip T. Thase, Michael E. Gelenberg, Alan J. Kupfer, David J. Regier, Darrel A. Rosenbaum, Jerrold F. Ray, Oakley Schatzberg, Alan F. TI Report by the ACNP Task Force on response and remission in major depressive disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE response; remission; recovery; relapse; recurrence; depression ID SEQUENCED TREATMENT ALTERNATIVES; MEDICATION ALGORITHM PROJECT; STAR-ASTERISK-D; TREATMENT-RESISTANT DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; MONTGOMERY-ASBERG DEPRESSION; COGNITIVE-BEHAVIOR-THERAPY; QUALITY-OF-LIFE; REPORT QIDS-SR; ELECTROCONVULSIVE-THERAPY AB This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA USA. Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ USA. Amer Psychiat Assoc, Amer Psychiat Inst Res & Educ, Arlington, VA USA. Amer Psychiat Assoc, Div Res, Arlington, VA USA. Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. Vanderbilt Univ, Dept Psychiat, Nashville, TN 37240 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37240 USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM john.rush@utsouthwestern.edu OI Rush, Augustus/0000-0003-2004-2382; Ninan, Philip/0000-0001-6633-1142 NR 118 TC 277 Z9 286 U1 5 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2006 VL 31 IS 9 BP 1841 EP 1853 DI 10.1038/sj.npp.1301131 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 075XJ UT WOS:000239920400001 PM 16794566 ER PT J AU Buchsbaum, MS Buchsbaum, BR Chokron, S Tang, C Wei, TC Byne, W AF Buchsbaum, Monte S. Buchsbaum, Bradley R. Chokron, Sylvie Tang, Cheuk Wei, Tse-Chung Byne, William TI Thalamocortical circuits: fMRI assessment of the pulvinar and medial dorsal nucleus in normal volunteers SO NEUROSCIENCE LETTERS LA English DT Article DE attention; blood oxygen level; cerebral blood flow; flanker task ID POSITRON-EMISSION-TOMOGRAPHY; ATTENTIONAL CONTROL; EFFECTIVE CONNECTIVITY; MEDIODORSAL NUCLEUS; GLUCOSE-METABOLISM; PREFRONTAL CORTEX; RHESUS-MONKEY; FRONTAL-LOBE; HUMAN BRAIN; SCHIZOPHRENIA AB This fMRI study investigates the activation of the thalamic nuclei in a spatial focusing-of-attention task previously shown to activate the pulvinar with FDG-PET and assesses the connectivity of the thalamic nuclei with cortical areas. Normal right-handed subjects (eight men, eight women, average age=32 years) viewed four types of stimuli positioned to the right or left of the central fixation point (left hemifield-large letter, left hemitield-small letter display with flanking letters; fight hemifield-large letter, fight hemifield-small letter display with flankers). BOLD responses to small letters surrounded by flankers were compared with responses to large isolated letters. To examine maximum functional regional connectivity, we modeled "subject" as a random effect and attained fixed effect parameter estimates and t-statistics for functional connectivity between each of the thalamic nuclei (pulvinar, medial dorsal, and anterior) as the seed region and each non-seed voxel. Greater BOLD activation for letters surrounded by flankers than for large letters was observed in the pulvinar as anticipated and was also marked in the medial dorsal nucleus (MDN), anterior and superior cingulate (BA24 and BA24' dorsolateral prefrontal cortex, and frontal operculum and insula. For the MDN, maximal functional connectivity was with the dorsolateral prefrontal cortex; correlations with left superior temporal, parietal, posterior frontal, and occipital regions were also observed. For the pulvinar, maximal functional connectivity was with parietal BA39; for anterior thalamus, with anterior cingulate. (c) 2006 Published by Elsevier Ireland Ltd. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. CNRS, Expt Psychol Lab, UMR 5105, Grenoble, France. Fdn Ophthalmol Rothschild, Neurol Serv, Paris, France. Mt Sinai Sch Med, Dept Radiol, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Buchsbaum, MS (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505, New York, NY 10029 USA. EM monte.buchsbaum@mssm.edu FU NIMH NIH HHS [MH-60023] NR 38 TC 29 Z9 29 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 1 PY 2006 VL 404 IS 3 BP 282 EP 287 DI 10.1016/j.neulet.2006.05.063 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 079GM UT WOS:000240163800008 PM 16860474 ER PT J AU Herbert, MR Russo, JP Yang, S Roohi, J Blaxill, A Kahler, SG Cremer, L Hatchwell, E AF Herbert, M. R. Russo, J. P. Yang, S. Roohi, J. Blaxill, A. Kahler, S. G. Cremer, L. Hatchwell, E. TI Autism and environmental genomics SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE autism; genetics; environmental genomics; toxicogenomics; systems biology; bioinformatics; genomics; immune ID TOXICOGENOMICS DATABASE CTD; SPECTRUM DISORDERS; GENE-EXPRESSION; EPIGENETIC REGULATION; SOCIAL COMMUNICATION; CHANGING PREVALENCE; CONGENITAL-RUBELLA; LIPID-PEROXIDATION; OXIDATIVE STRESS; CANDIDATE GENES AB Autism spectrum disorders (ASD) are defined by behavior and diagnosed by clinical history and observation but have no biomarkers and are presumably, etiologically and biologically heterogeneous. Given brain abnormalities and high monozygotic concordance, ASDs have been framed as neurobiologically based and highly genetic, which has shaped the research agenda and in particular criteria for choosing candidate ASD genes. Genetic studies to date have not uncovered genes of strong effect, but a move toward "genetic complexity" at the neurobiological level may not suffice, as evidence of systemic abnormalities (e.g. gastrointestinal and immune), increasing rates and less than 100% monozygotic concordance support a more inclusive refraining of autism as a multisystern disorder with genetic influence and environmental contributors. We review this evidence and also use a bioinformatic approach to explore the possibility that "environmentally responsive genes" not specifically associated with the nervous system, but potentially associated with systemic changes in autism, have not hitherto received sufficient attention in autism genetics investigations. We overlapped genes from NIEHS Environmental Genome Project, the Comparative Toxicogenomics Database, and the SeattleSNPs database of genes relevant to the human immune and inflammatory response with linkage regions identified in published autism genome scans. We identified 135 genes in overlap regions, of which 56 had never previously been studied in relation to autism and 47 had functional SNPs (in coding regions). Both our review and the bioinformatics exercise support the expansion of criteria for evaluating the relevance of genes to autism risk to include genes related to systemic impact and environmental responsiveness. This review also suggests the utility of environmental genomic resources in highlighting the potential relevance of particular genes within linkage regions. Environmental responsiveness and systems impacts consistent with system-wide findings in autism are thus supported as important considerations in identifying the numerous and complex modes of gene-environment interaction in autism. (C) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA 02129 USA. Boston Univ, Boston, MA 02215 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. RP Herbert, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal, 149 13th St,Room 6012, Charlestown, MA 02129 USA. EM mherbertl@partners.org FU NIGMS NIH HHS [T32 GM008444] NR 103 TC 87 Z9 93 U1 2 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 671 EP 684 DI 10.1016/j.neuro.2006.03.017 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800004 PM 16644012 ER PT J AU Herbert, MR Russo, J Yang, S Roohi, J Blaxill, M Kahler, S Mccoy, L Ziegler, DA Hatchwell, E AF Herbert, Martha R. Russo, J. P. Yang, S. Roohi, J. Blaxill, M. Kahler, S. G. McCoy, L. Ziegler, D. A. Hatchwell, E. TI Autism, genes and the environment. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, CMA & Pediat Neurol, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 877 EP 877 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800029 ER PT J AU Weisskopf, MG O'Reilly, E McCullough, ML Calle, EE Thun, MJ Cudkowicz, M Ascherio, A AF Weisskopf, M. G. O'Reilly, E. McCullough, M. L. Calle, E. E. Thun, M. J. Cudkowicz, M. Ascherio, A. TI Prospective study of military service and risk of amyotrophic lateral sclerosis and Parkinson's disease. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Amer Canc Soc, Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trial Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 885 EP 885 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800054 ER PT J AU Herbert, MR Russo, JP Yang, S Roohi, J Blaxill, M Kahler, SG McCoy, L Ziegler, DA Hatchwell, E AF Herbert, M. R. Russo, J. P. Yang, S. Roohi, J. Blaxill, M. Kahler, S. G. McCoy, L. Ziegler, D. A. Hatchwell, E. TI Autism and environmental genomics. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, CMA & Pediat Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 906 EP 907 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800099 ER PT J AU Khan, M Jatana, M Elango, C Paintlia, AS Singh, AK Singh, I AF Khan, Mushfiquddin Jatana, Manu Elango, Chinnasamy Paintlia, Ajaib Singh Singh, Avtar K. Singh, Inderjit TI Cerebrovascular protection by various nitric oxide donors in rats after experimental stroke SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE cerebral ischemia; nitric oxide; nitrosoglutathione; vasculature; NO donors; endothelial dysfunction ID FOCAL CEREBRAL-ISCHEMIA; BRAIN DOPAMINE NEURONS; S-NITROSOGLUTATHIONE; SODIUM-NITROPRUSSIDE; LIPID-PEROXIDATION; OXIDATIVE STRESS; ENDOTHELIAL DYSFUNCTION; REDUCES INFLAMMATION; REPERFUSION INJURY; L-ARGININE AB The efficacy of nitric oxide (NO) treatment in ischemic stroke, though well recognized, is yet to be tested in clinic. NO donors used to treat ischemic injury are structurally diverse compounds. We have shown that treatment of S-nitrosoglutathione (GSNO) protects the brain against injury and inflammation in rats after experimental stroke [M. Khan, B. Sekhon, S. Giri, M. Jatana, A. G. Gilg, K. Ayasolla, C. Elango, A. K. Singh, I. Singh, S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke, J. Cereb. Blood Flow Metab. 25 (2005) 177-192.]. In this study, we tested structurally different NO donors including GSNO, S-nitroso-N-acetyl-penicillamine (SNAP), sodium nitroprusside (SNP), methylamine hexamethylene methylamine NONOate (MAHMA), propylamine propylamine NONOate (PAPA), 3-morpholinosydnonimine (SIN-1) and compared their neuroprotective efficacy and antioxidant property in rats after ischemia/reperfusion (I/R). GSNO, in addition to neuroprotection, decreased nitrotyrosine formation and lipid peroxidation in blood and increased the ratio of reduced versus oxidized glutathione (GSH/GSSG) in brain as compared to untreated animals. GSNO also prevented the I/R-induced increase in mRNA expression of ICAM-1 and E-Selectin. SNAP and SNP extended limited neuroprotection, reduced nitrotyrosine formation in blood and blocked increase in mRNA expression of ICAM-1 and E-Selectin in brain tissue. PAPA, MAHMA, and SIN-I neither protected the brain nor reduced oxidative stress. We conclude that neuroprotective action of NO donors in experimental stroke depends on their ability to reduce oxidative stress both in brain and blood. (c) 2006 Elsevier Inc. All rights reserved. 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, 171 Ashley Ave, Charleston, SC 29425 USA. EM khanm@musc.edu FU NCRR NIH HHS [C06 RR015455]; NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40144, NS-40810] NR 60 TC 53 Z9 56 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD SEP PY 2006 VL 15 IS 2 BP 114 EP 124 DI 10.1016/j.niox.2006.01.008 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 077DG UT WOS:000240007300003 PM 16524750 ER PT J AU Sisterson, JM Vincent, J AF Sisterson, J. M. Vincent, J. TI Cross section measurements for proton-induced reactions in Fe and Ni producing relatively short-lived radionuclides at E-p=140-500 MeV SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article DE spallation reactions; proton beams; cross section measurements ID NEUTRON-INDUCED REACTIONS; COSMOGENIC RADIONUCLIDES; ENERGY-RANGE; NOBLE-GASES; CHONDRITE; NUCLIDES; TI AB Cross sections for proton-induced reactions in Fe and Ni targets that produce relatively short-lived radionuclides were measured at several proton energies between 140 and 500 MeV. There are few reported measured cross sections for these reactions in this energy range and these new measurements 'help fill in the gap' between the many measurements at lower proton energies and the few measurements at higher energies. Thin target techniques were used in these measurements made at two accelerator facilities. Most of these radionuclides are produced in cosmic ray interactions with extraterrestrial materials and have been measured in meteorites and lunar rocks. Cross sections for proton-induced reactions are essential input to the theoretical models used to interpret these cosmogenic nuclide archives to learn more about the object itself or the history of the cosmic rays that fell upon it. These new cross section measurements will improve the database used as input in these analyses. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Fracis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ British Columbia, TRIUMF, Vancouver, BC V6T 2A3, Canada. RP Sisterson, JM (reprint author), Massachusetts Gen Hosp, Fracis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM jsisterson@partners.org NR 20 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD SEP PY 2006 VL 251 IS 1 BP 1 EP 8 DI 10.1016/j.nimb.2006.05.015 PG 8 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 094GD UT WOS:000241226900001 ER PT J AU Rich, DQ Kim, MH Turner, JR Mittleman, MA Schwartz, J Catalano, PJ Dockery, DW AF Rich, D. Q. Kim, M. H. Turner, J. R. Mittleman, M. A. Schwartz, J. Catalano, P. J. Dockery, D. W. TI Association of ventricular arrhythmias detected by implantable cardioverter defibrillator and ambient air pollutants in the St Louis, Missouri metropolitan area SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID HEART-RATE-VARIABILITY; TRIGGERING MYOCARDIAL-INFARCTION; CASE-CROSSOVER ANALYSIS; HOSPITAL ADMISSIONS; DAILY MORTALITY; POLLUTION CONCENTRATIONS; CARDIOVASCULAR-DISEASE; CARDIAC-ARRHYTHMIA; PARTICULATE; EXPOSURE AB Background: It has previously been reported that the risk of ventricular arrhythmias is positively associated with ambient air pollution among patients with implantable cardioverter defibrillators (ICD) in Boston. Aims: To assess the association of community exposures to air pollution with ventricular arrhythmias in a cohort of ICD patients in metropolitan St Louis, Missouri. Methods: ICD detected episodes reported during clinical follow up were abstracted and reviewed by an electrophysiologist to identify ventricular arrhythmias. A total of 139 ventricular arrhythmias were identified among 56 patients. A case-crossover design was used with control periods matched on weekday and hour of the day within the same calendar month. Conditional logistic regression models were adjusted for temperature, barometric pressure, and relative humidity in the 24 hours preceding the event. Results: There was a significant (24%, 95% CI 7% to 44%) increase in risk of ventricular arrhythmias associated with each 5 ppb increase in mean sulphur dioxide and non-significantly increased risk (22%, 95% CI 26% to 60%; and 18%, 95% CI 27% to 50%) associated with increases in nitrogen dioxide ( 6 ppb) and elemental carbon (0.5 mg/m(3)), respectively in the 24 hours before the arrhythmia. Conclusions: These results provide evidence of an association between ventricular arrhythmias and ambient air pollutants in St Louis. This is consistent with previous results from Boston, although the pollutants responsible for the increased risk are different. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Reg Hosp & Univ Minnesota, St Paul, MN USA. Washington Univ, Dept Chem Engn, St Louis, MO 63130 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Dockery, DW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Suite 415,401 Pk Dr W, Boston, MA 02115 USA. EM ddockery@hsph.harvard.edu FU NIEHS NIH HHS [P30 ES000002, ES-09825, ES00002]; PHS HHS [T32 E207069] NR 47 TC 48 Z9 50 U1 0 U2 2 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 SEP PY 2006 VL 63 IS 9 BP 591 EP 596 DI 10.1136/oem.2005.023457 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 076EG UT WOS:000239939200004 PM 16698809 ER PT J AU Slattery, JM Sahani, DV AF Slattery, James M. Sahani, Dushyant V. TI What is the current state-of-the-art imaging for detection and staging of cholangiocarcinoma? SO ONCOLOGIST LA English DT Article DE cholangiocarcinorna; hepatectomy; imaging; resectability ID BILE-DUCT CANCER; POSITRON-EMISSION-TOMOGRAPHY; MULTIPHASIC HELICAL CT; HILAR CHOLANGIOCARCINOMA; INTRAHEPATIC CHOLANGIOCARCINOMA; SPIRAL CT; PERIPHERAL CHOLANGIOCARCINOMA; PREOPERATIVE EVALUATION; DIAGNOSTIC-ACCURACY; BILIARY OBSTRUCTION AB Cholangiocarcinoma is an adenocarcinoma that arises from the bile duct epithelium and is the second most common primary hepatobiliary cancer, after hepatocellular cancer, with approximately 2,500 cases annually in the U.S. However, cholangiocarcinoma remains a relatively rare disease, accounting for < 2% of all human malignancies. Although the entire biliary tree is potentially at risk, tumors involving the biliary confluence or the right or left hepatic ducts (hilar cholangiocarcinoma) are most common and account for 40%-60% of all cases. Most patients present with advanced disease that is not amenable to surgical treatment. The median survival time for patients with intrahepatic cholangiocarcinoma without involvement of the hilum varies among centers from 18-30 months. The median survival time for patients with perihilar cholangiocarcinoma is slightly less, varying from 12-24 months. Despite the overall poor prognosis, survival after surgical treatment of hilar cholangiocarcinoma has improved during the past 10-15 years. This review highlights the imaging features of cholangiocarcinoma, with particular emphasis on the imaging techniques that can best assess tumor resectability and guide the surgeon regarding the potential extent of resection required in operable candidates. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 270 White Bldg,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 56 TC 40 Z9 46 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD SEP PY 2006 VL 11 IS 8 BP 913 EP 922 DI 10.1634/theoncologist.11-8-913 PG 10 WC Oncology SC Oncology GA 085TS UT WOS:000240627900007 PM 16951395 ER PT J AU Lin, AL Johnson, DA Sims, CA Stephan, KT Yeh, CK AF Lin, Alan L. Johnson, Dorthea A. Sims, Carol Ann Stephan, Kevin T. Yeh, Chih-Ko TI Salivary gland function in HIV-infected patients treated with highly active antiretroviral therapy (HAART) SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ANTICANDIDAL ACTIVITIES; PROTEASE INHIBITORS; PAROTID-SALIVA; AIDS; TRIMETHOPRIM; HYPOURICEMIA; CANDIDIASIS; IMPACT AB Objective. This study was undertaken to determine if HAART alters salivary oral host defense in HIV(+) men. Study design. Whole, parotid, and submandibular/sublingual saliva was collected from 39 healthy men and 147 HIV(+) patients with mild to moderate immune dysfunction (69 treated with HAART [HAART(+)]; 78 not treated [HAART(-)]). Salivary flow rates, anticandidal activities, electrolytes, and antimicrobial/antifungal proteins were determined. Results. While CD4(+) cell counts were not different between the HIV(+) groups, the median viral load for HAART(-) was 15 times greater than HAART(+). For both HAART groups, salivary yeast carriage rates and concentration were comparable and both showed similar reductions in salivary flow rates. Salivary anticandidal activities were not altered. Saliva composition of both HIV(+) groups was different from control, but only uric acid in parotid saliva of HAART(+) differed from HAART(-). Conclusions. HAART does not adversely affect inherent salivary oral host defense in HIV(+) patients with mild to moderate immune dysfunction. C1 S Texas Vet Hlth Care Syst, Audie Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Dept Community Dent, San Antonio, TX 78285 USA. Wilford Hall USAF Med Ctr, Dept Infect Dis, San Antonio, TX 78236 USA. RP Yeh, CK (reprint author), S Texas Vet Hlth Care Syst, Audie Murphy Div, Ctr Geriatr Res Educ & Clin, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Yeh@uthscsa.edu FU NCRR NIH HHS [M01-RR-01346]; NIDCR NIH HHS [DE12188] NR 33 TC 13 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD SEP PY 2006 VL 102 IS 3 BP 318 EP 324 DI 10.1016/j.tripleo.2005.07.021 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 084AA UT WOS:000240502600009 PM 16920540 ER PT J AU Levy, AG Hershey, JC AF Levy, Andrea Gurmankin Hershey, John C. TI Distorting the probability of treatment success to justify treatment decisions SO ORGANIZATIONAL BEHAVIOR AND HUMAN DECISION PROCESSES LA English DT Article DE value-induced bias; cognitive dissonance; subjective probability; risk perception ID INFORMATION; INTERNET AB This research examines the value-induced bias: do people justify medical decisions by distorting their perception of relevant probabilities? Subjects were given a "close-call" decision which involved weighing one week of treatment side effects with a low probability of treatment success against seven more weeks of having the disease symptoms. They were told a numeric probability estimate of treatment success for the population as a whole. Those subjects with the ability to justify getting (not getting) treatment inflated (reduced) their numeric probability judgment of treatment success relative to those without this ability. As in cognitive dissonance reduction, risk perceptions can be distorted to align beliefs with preferences. Distorted risk perceptions may lead to suboptimal medical decisions. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Populat Sci, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Levy, AG (reprint author), Dana Farber Canc Inst, Dept Populat Sci, Ctr Community Based Res, Boston, MA 02115 USA. EM andrea_gurmankin@dfci.harvard.edu NR 29 TC 11 Z9 11 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0749-5978 J9 ORGAN BEHAV HUM DEC JI Organ. Behav. Hum. Decis. Process. PD SEP PY 2006 VL 101 IS 1 BP 52 EP 58 DI 10.1016/j.obhdp.2006.04.003 PG 7 WC Psychology, Applied; Management; Psychology, Social SC Psychology; Business & Economics GA 097QL UT WOS:000241463000004 ER PT J AU Kwon, YM Morshed, S Malchau, H AF Kwon, Young-Min Morshed, Saam Malchau, Henrik TI Cemented or cementless stem fixation in THA: What is the current evidence? SO ORTHOPEDICS LA English DT Article ID TOTAL HIP-ARTHROPLASTY; REGISTER C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthoped Dept,Adult Reconstruct Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Sch Med, Dept Orthoped Surg, San Francisco, CA USA. RP Malchau, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthoped Dept,Adult Reconstruct Unit, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 2006 VL 29 IS 9 BP 793 EP 794 PG 2 WC Orthopedics SC Orthopedics GA 092HN UT WOS:000241087700015 PM 17004593 ER PT J AU McCarthy, JC Lee, JA AF McCarthy, Joseph C. Lee, Jo-ann TI Proximal fixation with a modular stem in complex revision THA SO ORTHOPEDICS LA English DT Article ID HIP-ARTHROPLASTY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Newton Wellesley Hosp, Newton, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP McCarthy, JC (reprint author), 125 Parker Hill Ave, Boston, MA 02120 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 2006 VL 29 IS 9 BP 816 EP 817 PG 2 WC Orthopedics SC Orthopedics GA 092HN UT WOS:000241087700026 PM 17004604 ER PT J AU Grandis, JR Battey, JF Califf, RM Chole, RA Gantz, BJ Gates, GA Gorelic, L Hannley, MT Hardwick, KS Harris, JP Kapoor, WN Lai, SY Lalwani, AK Minor, LB Nadol, JP Post, JC Roland, PS Schechter, AM Schuller, DE Sklare, DA Wackym, PA Weber, RS Weymuller, EA Wolf, GT Woodson, GE AF Grandis, Jennifer R. Battey, James F. Califf, Robert M. Chole, Richard A. Gantz, Bruce J. Gates, George A. Gorelic, Lester Hannley, Maureen T. Hardwick, Kevin S. Harris, Jeffrey P. Kapoor, Wishwa N. Lai, Stephen Y. Lalwani, Anil K. Minor, Lloyd B. Nadol, Joseph P. Post, J. Christopher Roland, Peter S. Schechter, Alan M. Schuller, David E. Sklare, Daniel A. Wackym, P. Ashley Weber, Randal S. Weymuller, Ernest A., Jr. Wolf, Gregory T. Woodson, Gayle E. TI Research education and training in otolaryngology: Meeting summary and research opportunities SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID RESIDENCY C1 Univ Pittsburgh, Inst Canc, Dept Otolaryngol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Inst Canc, Dept Pharmacol, Pittsburgh, PA 15260 USA. NIDCD, Bethesda, MD USA. Duke Univ, Duke Clin Res Inst, Dept Otolaryngol, Durham, NC USA. Washington Univ, St Louis, MO USA. Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. Univ Washington, Dept Otolaryngol, Seattle, WA 98195 USA. NCI, Canc Training Branch, Bethesda, MD 20892 USA. Amer Acad Otolaryngol Head & Neck Surg Fdn, Alexandria, VA USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Calif San Diego, Dept Otolaryngol, San Diego, CA 92103 USA. Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA 15260 USA. NYU, Dept Otolaryngol, New York, NY 10016 USA. NYU, Dept Physiol, New York, NY USA. NYU, Dept Neurosci, New York, NY USA. Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21218 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Drexel Univ, Coll Med, Dept Otolaryngol, Philadelphia, PA 19104 USA. Drexel Univ, Coll Med, Ctr Genom Sci, Philadelphia, PA 19104 USA. Univ Texas SW, Dept Otolaryngol, Dallas, TX USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Otolaryngol, Columbus, OH 43210 USA. Med Coll Wisconsin, Dept Otolaryngol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Commun Sci & Physiol, Milwaukee, WI 53226 USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. Univ Michigan, Dept Otorhinolaryngol, Ann Arbor, MI 48109 USA. So Illinois Univ, Div Otolaryngol, Dept Surg, Springfield, IL 62794 USA. Univ Pittsburgh, Ctr Canc, Dept Otolaryngol, Pittsburgh, PA 15213 USA. RP Grandis, JR (reprint author), Univ Pittsburgh, Ctr Canc, Dept Otolaryngol, Suite 500,Eye & Ear Inst Bldg,200 Lothrop St, Pittsburgh, PA 15213 USA. EM jgrandis@pitt.edu OI Woodson, Gayle/0000-0002-0315-5329; Roland, Peter/0000-0003-4152-7346 NR 5 TC 9 Z9 9 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2006 VL 135 IS 3 BP 361 EP 367 DI 10.1016/j.otohns.2006.05.014 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 082FF UT WOS:000240371400004 PM 16949965 ER PT J AU Wang, PC Li, HY Shih, TS Gliklich, RE Chen, NH Liao, YF AF Wang, Pa-Chun Li, Hsueh-Yu Shih, Tung-Sheng Gliklich, Richard E. Chen, Ning-Hung Liao, Yu-Fang TI Generic and specific quality-of-life measures in Taiwanese adults with sleep-disordered breathing SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID HEALTH-STATUS; CHINESE VERSION; APNEA; POPULATION; VALIDATION AB OBJECTIVE: To investigate the quality-of-life status of Taiwanese adult patients with sleep-disordered breathing (SDB). STUDY DESIGN AND SETTING: A prospective, quality-of-life survey in a tertiary referral sleep center on 94 consecutive adult SDB patients. Patients were evaluated with polysomnogram, Medical Outcome Study SF-36 Health Survey, Snore Outcome Survey (SOS), and Epworth Sleepiness Scale (ESS). RESULTS: SDB patients have significantly lower scores in all 8 SF-36 subscales (P < 0.05) than do normative Taiwan adult population. Apnea patients have lower SOS (34.5 +/- 7.5 vs 40.1 +/- 10.3, P = 0.005) and higher ESS scores than do simple snorers (8.8 +/- 5.1 vs 11.7 +/- 5.2, P = 0.03). Patients with a higher degree of sleepiness show worse performance in all dimensions of their general health status (P values 0.0005 to 0.01). Deep sleep (stage 3 + 4) is predictive of SF-36 role: physical (beta = 1.63, P = 0.04), bodily pain (beta = 1.22, P = 0.01), vitality (beta = 1.05, P = 0.01), subscales scores (adjusted R-2 0.005 to 0.1). CONCLUSION: SDB has considerable impact on a patient's global health status. SIGNIFICANCE: Daytime sleepiness, rather than apnea, is a major quality-of-life determinant. EBM rating: B-2b (C) 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 Cathay Gen Hosp, Dept Otolaryngol, Taipei, Taiwan. Fu Jen Catholic Univ, Sch Med, Taipei, Taiwan. China Med Univ, Dept Publ Hlth, Taichung, Taiwan. Chang Gung Mem Hosp, Dept Otolaryngol, Taoyuan, Taiwan. Chang Gung Inst Technol, Taoyuan, Taiwan. Inst Occupat Safety & Hlth, Taipei, Taiwan. China Med Univ, Coll Publ Hlth, Grad Inst Environm Hlth, Taichung, Taiwan. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Chang Gung Mem Hosp, Sleep Ctr, Taoyuan, Taiwan. Chang Gung Inst Technol, Taoyuan, Taiwan. Chang Gung Univ, Taoyuan, Taiwan. Chang Gung Mem Hosp, Dept Craniofacial Orthodont, Sleep Ctr, Taoyuan, Taiwan. Chang Gung Mem Hosp, Fac Dent, Taoyuan, Taiwan. RP Chen, NH (reprint author), Cathay Gen Hosp, Dept Otolaryngol, Taipei, Taiwan. EM ninghung@yahoo.com.tw RI Hsieh, Tsun-Yu/B-7791-2011 NR 20 TC 3 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2006 VL 135 IS 3 BP 421 EP 426 DI 10.1016/j.otohns.2006.05.005 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 082FF UT WOS:000240371400015 PM 16949976 ER PT J AU Watters, KF Rosowski, JJ Sauter, T Lee, DJ AF Watters, Karen F. Rosowski, John J. Sauter, Todd Lee, Daniel J. TI Superior semicircular canal dehiscence presenting as postpartum vertigo SO OTOLOGY & NEUROTOLOGY LA English DT Review DE childbirth; dizziness; postpartum; superior semicircular canal dehiscence; vertigo ID CONDUCTIVE HEARING-LOSS; EVOKED MYOGENIC POTENTIALS; PRESSURE-INDUCED VERTIGO; TYMPANIC MEMBRANE; BONE DEHISCENCE; SOUND; MANAGEMENT; MECHANISMS; CHINCHILLA AB Objective: To describe the clinical and diagnostic features of superior semicircular canal dehiscence (SSCD) in patients with postpartum vertigo. Study Design: Retrospective review, meta-analysis. Setting: Tertiary neurotologic and audiologic center. Patients: Two women who presented with a history of acute postpartum vertigo and SSCD confirmed on high-resolution computed tomography (CT) were included. Our meta-analysis of the surgical SSCD literature comprised a total of 43 patients. Intervention: Patients with postpartum vertigo and SSCD underwent a complete medical evaluation, audiometric testing, CT imaging, magnetic resonance imaging studies, vestibular evoked myogenic potential testing, and laser Doppler vibrometer testing. Case 2 was managed with a middle fossa craniotomy and SSCD repair. Results: The first patient presented with normal hearing and aural fullness, autophony, and sound sensitivity of the left ear. A 1-mm left-sided SSCD was seen on CT imaging. She is being managed conservatively. The second patient had left-sided conductive hearing loss with sound and pressure sensitivity. The contralateral ear was congenitally deaf. CT imaging revealed a 4-mm left-sided SSCD. Because of her disabling symptoms, the patient underwent a middle fossa cramotomy and superior canal plugging. Her vestibular symptoms resolved with improvement in hearing. Vestibular evoked myogenic potential and laser Doppler vibrometer testing in both cases were consistent with SSCD. Conclusion: This is the first description of patients with SSCD presenting after childbirth and should be included in the differential diagnosis of acute postpartum vertigo or disequilibrium. SSCD plugging can provide a stable repair with resolution of symptoms, reversal of diagnostic indicators, and hearing improvement. C1 Univ Massachusetts, Mem Med Ctr, Dept Otolaryngol, Worcester, MA 01655 USA. Univ Massachusetts, Mem Med Ctr, Dept Audiol, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, Boston, MA 02114 USA. RP Lee, DJ (reprint author), Univ Massachusetts, Mem Med Ctr, Dept Otolaryngol, 55 Lake Ave N, Worcester, MA 01655 USA. EM djlee@massmed.org NR 33 TC 18 Z9 18 U1 1 U2 3 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 SEP PY 2006 VL 27 IS 6 BP 756 EP 768 DI 10.1097/01.mao.0000227894.27291.9f PG 13 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 082BA UT WOS:000240360200002 PM 16936563 ER PT J AU Raphael, KG Janal, MN Nayak, S Schwartz, JE Gallagher, RM AF Raphael, Karen G. Janal, Malvin N. Nayak, Sangeetha Schwartz, Joseph E. Gallagher, Rollin M. TI Psychiatric comorbidities in a community sample of women with fibromyalgia SO PAIN LA English DT Article DE fibromyalgia; epidermology; comorbidity; depression; psychiatric disorder; anxiety disorders; community study; minority women ID POSTTRAUMATIC-STRESS-DISORDER; CHRONIC WIDESPREAD PAIN; STRUCTURED CLINICAL INTERVIEW; CARE-SEEKING BEHAVIOR; DIAGNOSTIC-INTERVIEW; GENERAL-POPULATION; MAJOR DEPRESSION; PSYCHOLOGICAL DISTRESS; RHEUMATOID-ARTHRITIS; FAMILIAL AGGREGATION AB Prior studies of careseeking fibromyalgia (FM) patients often report that they have an elevated risk of psychiatric disorders, but biased sampling may distort true risk. The current investigation utilizes state-of-the-art diagnostic procedures for both FM and psychiatric disorders to estimate prevalence rates of FM and the comorbidity of FM and specific psychiatric disorders in a diverse community sample of women. Participants were screened by telephone for FM and MDD, by randomly selecting telephone numbers from a list of households with women in the NY/NJ metropolitan area. Eligible women were invited to complete physical examinations for FM and clinician-administered psychiatric interviews. Data were weighted to adjust for sampling procedures and population demographics. The estimated overall prevalence of FM among women in the NY/NJ metropolitan area was 3.7% (95% CI = 3.2, 4.4), with higher rates among racial minorities. Although risk of current MDD was nearly 3-fold higher in community women with than without FM, the groups had similar risk of lifetime MDD. Risk of lifetime anxiety disorders, particularly obsessive compulsive disorder and post-traumatic stress disorder, was approximately 5-fold higher among women with FM. Overall, this study found a community prevalence for FM among women that replicates prior North American studies, and revealed that FM may be even more prevalent among racial minority women. These community-based data also indicate that the relationship between MDD and FM may be more complicated than previously thought, and call for an increased focus on anxiety disorders in FM. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Psychiat, Newark, NJ 07103 USA. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. Vet Affairs Med Ctr, Pain Management Serv, Philadelphia, PA 19104 USA. RP Raphael, KG (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Psychiat, Newark, NJ 07103 USA. EM raphaekg@umdnj.edu OI Raphael, Karen/0000-0002-2804-8124 FU NIDCR NIH HHS [R01 DE13486] NR 61 TC 62 Z9 65 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2006 VL 124 IS 1-2 BP 117 EP 125 DI 10.1016/j.pain.2006.04.004 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 085CV UT WOS:000240581700019 PM 16698181 ER PT J AU Arguelles, LM Afari, N Buchwald, DS Clauw, DJ Furrier, S Goldberg, J AF Arguelles, Lester M. Afari, Niloofar Buchwald, Dedra S. Clauw, Daniel J. Furrier, Sylvia Goldberg, Jack TI A twin study of posttraumatic stress disorder symptoms and chronic widespread pain SO PAIN LA English DT Article DE chronic widespread pain; fibromyalgia; genetic; posttraurnatic stress disorder; twins ID CARE-SEEKING BEHAVIOR; FIBROMYALGIA SYNDROME; GENERAL-POPULATION; RISK-FACTORS; FOLLOW-UP; FUNCTIONAL IMPAIRMENT; MUSCULOSKELETAL PAIN; MUTUAL MAINTENANCE; PERSISTENT PAIN; MENTAL-DISORDER AB Previous studies of the association between posttraumatic stress disorder (PTSD) and chronic widespread pain (CWP) or fibromyalgia have not examined the role of familial or genetic factors. The goals of this study were to determine if symptoms of PTSD are related to CWP in a genetically informative community-based sample of twin pairs, and if so, to ascertain if the association is due to familial or genetic factors. Data were obtained from the University of Washington Twin Registry, which contains 1042 monozygotic and 828 dizygotic twin pairs. To assess the symptoms of PTSD, we used questions from the Impact of Events Scale (IES). IES scores were partitioned into terciles. CWP was defined as pain located in 3 body regions lasting at least I week during the past 3 months. Random-effects regression models, adjusted for demographic features and depression, examined the relationship between IES and CWP. IES scores were strongly associated with CWP (P < 0.0001). Compared to those in the lowest IES tercile, twins in the highest tercile were 3.5 times more likely to report CWP. Although IES scores were associated with CWP more strongly among dizygotic than among monozygotic twins, this difference was not significant. Our findings suggest that PTSD symptoms, as measured by IES, are strongly linked to CWP, but this association is not explained by a common familial or genetic vulnerability to both conditions. Future research is needed to understand the temporal association of PTSD and CWP, as well as the physiological underpinnings of this relationship. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Michigan, Dept Internal Med, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Vietnam Era Twin Registry, Seattle, WA USA. RP Afari, N (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM afari@u.washington.edu FU NIAID NIH HHS [5 U19 AI38429-08, U19 AI038429-07, U19 AI038429]; NIAMS NIH HHS [R01 AR051524-01A2, R01 AR051524, R55AR051524, R55 AR051524, R55 AR051524-01] NR 67 TC 31 Z9 31 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2006 VL 124 IS 1-2 BP 150 EP 157 DI 10.1016/j.pain.2006.04.008 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 085CV UT WOS:000240581700023 PM 16701954 ER PT J AU Gallagher, RM AF Gallagher, Rollin M. TI Pulsed radiofrequency treatment: What is the evidence of its effectiveness and should it be used in clinical practice? SO PAIN MEDICINE LA English DT Article C1 Univ Penn, Pain Med Serv, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Pain Med Serv, Philadelphia VA Med Ctr, Univ & Woodland, Philadelphia, PA 19104 USA. EM rgallagh@mail.med.upenn.edu NR 8 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD SEP-OCT PY 2006 VL 7 IS 5 BP 408 EP 410 DI 10.1111/j.1526-4637.2006.00211.x PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 087KJ UT WOS:000240741000008 PM 17014599 ER PT J AU Haidet, P Kroll, TL Sharf, BF AF Haidet, Paul Kroll, Tony L. Sharf, Barbara F. TI The complexity of patient participation: Lessons learned from patients' illness narratives SO PATIENT EDUCATION AND COUNSELING LA English DT Article; Proceedings Paper CT AAPP 2005 Forum/ International Conference on Communication in Healthcare CY OCT, 2005 CL Northwestern Univ Feinberg Sch Med, Chicago, IL SP AAPP HO Northwestern Univ Feinberg Sch Med DE (MeSH): physician-patient relations; primary health care; patient-centered care; communication; persuasive communication; qualitative research; patient participation; narration ID MEDICAL DECISION-MAKING; SELF-MANAGEMENT; COMMUNICATION; CARE; INTERVENTION; INVOLVEMENT; PHYSICIANS; ENCOUNTER; SURGERY; BELIEFS AB Objective: To describe the meaning of active participation from the patient's perspective. Methods: We used a narrative framework to analyze transcripts generated from 16 qualitative open-ended, semi-structured interviews with primary care patients in Houston, Texas. Results: Patients' illness narratives reflected several themes related to patient participation. These included patients' perspectives of illness (i.e., how central the illness is in the patient's overall life story and how changeable the patient believes their illness to be) and aspects of actions pursued in the context of patients' illness narratives (i.e., the degree of illness-related activity that a patient engages in and the role of partnership with the patient's physician in health decision making and illness management). The relationships among these themes explained a limited number of distinct illness-management strategies pursued by patients. Conclusion: Our findings revealed a level of complexity to patients' healthcare participation that has not been previously described. Patients' illness-management strategies were explained by four thematic story elements in dynamic interplay with unique variations for each individual. Further research is needed to explore how these story elements influence communication between patients and physicians. Practice implications: By understanding the nature of and relationships between the thematic elements in patients' illness narratives, practitioners will be able to better inform their negotiations with patients regarding participation in healthcare. Published by Elsevier Ireland Ltd. C1 DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. So Methodist Univ, Meadows Sch Arts, Dallas, TX 75275 USA. Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Haidet, P (reprint author), DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM phaidet@bcm.tmc.edu FU AHRQ HHS [P01HS10876] NR 37 TC 39 Z9 39 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD SEP PY 2006 VL 62 IS 3 SI SI BP 323 EP 329 DI 10.1016/j.pec.2006.06.005 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 082KP UT WOS:000240386000007 PM 16887319 ER PT J AU Roberts, CWM AF Roberts, Charles W. M. TI Genetic causes of familial risk in rhabdoid tumores SO PEDIATRIC BLOOD & CANCER LA English DT Article ID MUTATIONS; CANCER; INI1 C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, M657,44 Binney St, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2006 VL 47 IS 3 BP 235 EP 237 DI 10.1002/pbc.20672 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 068FY UT WOS:000239359300004 PM 16304667 ER PT J AU St Clair, NE Kim, CC Semrin, G Woodward, AL Liang, MG Glickman, JN Leichtner, AM Binstadt, BA AF Clair, Nicole E. St. Kim, Caroline Choi Semrin, Gaith Woodward, Amy L. Liang, Marilyn G. Glickman, Jonathan N. Leichtner, Alan M. Binstadt, Bryce A. TI Celiac disease presenting with chilblains in an adolescent girl SO PEDIATRIC DERMATOLOGY LA English DT Article ID IMMUNOGLOBULIN-A DEFICIENCY; ANOREXIA-NERVOSA; PERNIOSIS; DIAGNOSIS; FEATURES; CHILDREN AB Chilblains, or pernio, are cutaneous lesions that may accompany systemic illnesses including states of malnutrition and autoimmune diseases. We report an adolescent girl in whom chilblains were the chief presenting sign of celiac disease. A gluten-free diet led to weight gain and resolution of the chilblains. We speculate that in this patient, weight loss due to celiac disease contributed to the development of chilblains. C1 Childrens Hosp, Div Immunol, Rheumatol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Div Pediat Gastroenterol & Nutr, Dallas, TX USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Binstadt, BA (reprint author), Childrens Hosp, Div Immunol, Rheumatol Program, 300 Longwood Ave, Boston, MA 02115 USA. EM bryce.binstadt@childrens.harvard.edu RI Binstadt, Bryce/N-1305-2013 OI Binstadt, Bryce/0000-0003-3127-3856 NR 18 TC 3 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD SEP-OCT PY 2006 VL 23 IS 5 BP 451 EP 454 PG 4 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 086HF UT WOS:000240663700007 PM 17014640 ER PT J AU Guinan, EC Kalish, LA Berry, WS McDaniel, S Lehmann, LE Diller, LR AF Guinan, Eva C. Kalish, Leslie A. Berry, Winter S. McDaniel, Samuel Lehmann, Leslie E. Diller, Lisa R. TI A novel pattern of transaminase elevation associated with autologous transplant for neuroblastoma SO PEDIATRIC TRANSPLANTATION LA English DT Article DE regimen-related toxicity; neuroblastoma; transplantation; hepatotoxicity; pediatric ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; HEPATIC VENOOCCLUSIVE DISEASE; HIGH-RISK NEUROBLASTOMA; VENO-OCCLUSIVE DISEASE; TOTAL-BODY IRRADIATION; MULTIPLE-MYELOMA; SOLID TUMORS; CONDITIONING REGIMENS AB To determine the pattern and degree of hepatic transaminitis experienced by children undergoing autologous transplantation for neuroblastoma. Sixty-four children with high-risk neuroblastoma received an autologous transplant with cyclophosphamide, etoposide, and carboplatin conditioning. Forty-eight went on to receive a second transplant with M and TBI conditioning. Charts were reviewed for evidence of hepatic regimen-related toxicity. A high rate of transaminitis was observed after both regimens. In each transplant, there was an early period of transaminitis during conditioning, from which patients recovered, followed by a second period of transaminase elevation. The degree of elevation was not associated with age, whether the administered dose was calculated based on a per kg or per M-2 basis or the presence of regimen-related severe mucositis. Elevated transaminases at admission were not associated with maximal hepatotoxicity during the first transplant although there was an association in the second transplant. However, the magnitude of transaminase elevation was less in the second transplant. VOD occurred in one and three patients in transplants 1 and 2, respectively. Both conditioning regimens were associated with an early and late elevation of transaminases without significant cholestasis. This biphasic pattern of transaminitis has not been reported previously. The high prevalence of transaminase elevation at time of both transplants was not associated with an increased incidence of VOD. We conclude that elevated transaminases should not preclude proceeding to a first or second autologous transplant with these regimens. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA USA. Childrens Hosp Boston, Clin Res Program, Boston, MA 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 NR 42 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD SEP PY 2006 VL 10 IS 6 BP 669 EP 676 DI 10.1111/j.1399-3046.2006.00546.x PG 8 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 070GR UT WOS:000239509300006 PM 16911489 ER PT J AU Wilens, TE Prince, JB Spencer, TJ Biederman, J AF Wilens, Timothy E. Prince, Jefferson B. Spencer, Thomas J. Biederman, Joseph TI Stimulants and sudden death: What is a physician to do? SO PEDIATRICS LA English DT Article DE ADHD; attention deficit/hyperactivity disorder; stimulant; methylphenidate; amphetamine; sudden death; cardiovascular; blood pressure; pulse; electrophysiology ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SALTS EXTENDED-RELEASE; RANDOMIZED CLINICAL-TRIAL; AMBULATORY BLOOD-PRESSURE; DOUBLE-BLIND; SHORT-TERM; FOLLOW-UP; OROS METHYLPHENIDATE; MEDICATION TREATMENT AB OBJECTIVE. Recently, a US Food and Drug Administration advisory committee raised concerns about cardiovascular risks and sudden death in children and adolescents with attention-deficit/hyperactivity disorder who are receiving stimulants. METHODS. We comment on the risk of sudden death in children/adolescents taking stimulants compared with population rates, biological plausibility, and known cardiovascular effects of stimulants to determine specific risk. RESULTS. There does not seem to be higher risk of sudden death in stimulant-treated individuals compared with the general population. Although there is evidence of biological plausibility, the known effects of the stimulants on cardiovascular electrophysiology and vital signs seem to be benign. CONCLUSIONS. There does not seem to be compelling findings of a medication-specific risk necessitating changes in our stimulant treatment of children and adolescents with attention-deficit/hyperactivity disorder. The use of existing guidelines on the use of stimulants (and psychotropic agents) may identify children, adolescents, and adults who are vulnerable to sudden death. C1 Massachusetts Gen Hosp, Harvard Med Sch, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. N Shore Med Ctr, Dept Child Psychiat, Salem, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Clin Res Program Pediat Psychopharmacol, YAW 6A,55 Parkman St, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [K24 DA016264] NR 45 TC 57 Z9 57 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP 1215 EP 1219 DI 10.1542/peds.2006-0942 PG 5 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100045 PM 16951018 ER PT J AU O'Sullivan, BP Zwerdling, RG Dorkin, HL Comeau, AM Parad, R AF O'Sullivan, Brian P. Zwerdling, Robert G. Dorkin, Henry L. Comeau, Anne Marie Parad, Richard TI Early pulmonary manifestation of cystic fibrosis in children with the Delta F508/R117H-7T genotype SO PEDIATRICS LA English DT Article DE cystic fibrosis; pulmonary; newborn screening; gene mutation; R117H ID CONGENITAL BILATERAL ABSENCE; VAS-DEFERENS; IMMUNOREACTIVE TRYPSINOGEN; DISEASE; CFTR; MUTATIONS; INFECTION; INFANTS; GENE; INFLAMMATION AB We report 3 cystic fibrosis newborn screen-positive infants with the Delta F508/R117H-7T genotype who had Pseudomonas aeruginosa detected in oropharyngeal cultures early in life and a fourth who had pulmonary symptoms and Gram-negative growth on multiple oropharyngeal cultures. All 4 patients were followed prospectively from the time of genetic diagnosis. As many regions implement newborn screening for cystic fibrosis, there is concern regarding which mutations should be included in genetic panels used to make the cystic fibrosis diagnosis. Some have recommended that mutations not specifically associated with classic cystic fibrosis be excluded. Our cases highlight the importance of considering keeping so-called mild mutations on cystic fibrosis newborn screening panels and the need to follow children with these mutations closely. C1 Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, New England Newborn Screening Program, Jamaica Plain, MA USA. Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP O'Sullivan, BP (reprint author), Univ Massachusetts, Sch Med, Dept Pediat, 55 Lake Ave, Worcester, MA 01655 USA. EM osullivb@ummhc.org RI Parad, Richard/E-8559-2010 NR 28 TC 29 Z9 29 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP 1260 EP 1265 DI 10.1542/peds.2006-0399 PG 6 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100051 PM 16951024 ER PT J AU Prokhorov, AV Winickoff, JP Ahluwalia, JS Ossip-Klein, D Tanski, S Lando, HA Moolchan, ET Muramoto, M Klein, JD Weitzman, M Ford, KH AF Prokhorov, Alexander V. Winickoff, Jonathan P. Ahluwalia, Jasjit S. Ossip-Klein, Deborah Tanski, Susanne Lando, Harry A. Moolchan, Eric T. Muramoto, Myra Klein, Jonathan D. Weitzman, Michael Ford, Kentya H. CA Tobacco Consortium, Amer Acad Pedi TI Youth tobacco use: A global perspective for child health care clinicians SO PEDIATRICS LA English DT Review DE youth; smoking; tobacco ID FAGERSTROM TOLERANCE QUESTIONNAIRE; ADDRESSING PARENTAL SMOKING; WATER-PIPE SMOKING; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; ADOLESCENT SMOKERS; ADVISING PARENTS; MATERNAL SMOKING; BIDI CIGARETTES; STOP SMOKING AB Tobacco dependence, responsible for similar to 4 million annual deaths worldwide, is considered to be a "pediatric disease." The smoking epidemic is spreading rapidly in developing countries. Factors contributing to youth smoking in developing countries include cultural traditions, tobacco's easy accessibility and moderate pricing, peer and family influences, and tobacco companies' advertisements and promotional activities. Secondhand tobacco smoke exposure is a substantial problem that causes increased rates of pneumonia, otitis media, asthma, and other short- and long-term pediatric conditions. Parental tobacco use results in children's deprivation of essential needs such as nutrition and education. In this article we review contemporary evidence with respect to the etiology of nicotine dependence among youth, the forms of youth tobacco products worldwide, global youth tobacco-control efforts to date, medical education efforts, and child health care clinicians' special role in youth tobacco-control strategies. In addition, we provide a review of currently available funding opportunities for development and implementation of youth tobacco-control programs. C1 Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. Massachusetts Gen Hosp, Gen Pediat Div, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Univ Kansas, Sch Med, Dept Prevent Med, Kansas City, KS 66103 USA. Univ Rochester, Sch Med, Dept Community & Prevent Med, Rochester, NY 14627 USA. Univ Rochester, Med Ctr, Dept Pediat, Ctr Child Hlth Res, Rochester, NY 14627 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Natl Inst Drug Abuse, Teen Tobacco Addict Treatment Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Arizona, Hlth Sci Ctr, Dept Family & Community Med, Tucson, AZ 85721 USA. Univ Rochester, Dept Pediat, Rochester, NY 14627 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. Univ Rochester, Ctr Child Hlth Res, Dept Pediat, Rochester, NY 14627 USA. RP Prokhorov, AV (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, 1515 Holcombe Blvd,POB 301439, Houston, TX 77030 USA. EM aprokhor@mdanderson.org NR 130 TC 41 Z9 45 U1 3 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP E890 EP E903 DI 10.1542/peds.2005-0810 PG 14 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100118 PM 16950972 ER PT J AU Redmond, RW Kochevar, IE AF Redmond, Robert W. Kochevar, Irene E. TI Spatially resolved cellular responses to singlet oxygen SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID ACID-PHOTODYNAMIC THERAPY; ASSISTED LIGHT INACTIVATION; L1210 LEUKEMIA-CELLS; DNA STRAND BREAKS; 5-AMINOLEVULINIC ACID; RHEUMATOID-ARTHRITIS; LIPID-PEROXIDATION; ENDOTHELIAL-CELLS; STRESS RESPONSES; ACNE-VULGARIS AB Singlet oxygen (O-1(2)) is unique amongst reactive oxygen species formed in cells in that it is an excited state molecule with an inherent upper lifetime of 4 mu s in water. Whether the lifetime Of O-1(2) in cells is shortened by reactions with cellular molecules or reaches the inherent maximum value is still unclear. However, even with the maximum lifetime, the diffusion radius is only similar to 220 nm during three lifetimes (similar to 5% O-1(2) remaining), much shorter than cellular dimensions indicating that the primary reactions Of O-1(2) will be subcellularly localized near the site Of O-1(2) formation. This fact has raised the question of whether spatially resolved cellular responses to O-1(2) occur, i.e. whether responses can be initiated by generation and reaction Of O-1(2) at a particular subcellular location that would not have been produced by O-1(2) generation at other subcellular sites. In this paper, we discuss examples of spatially resolved responses initiated by O-1(2) as a function of distance from the site of generation Of O-1(2). Three levels are recognized, namely, a molecular level where the primary oxidation product directly modifies the behavior of a cell, an organelle level where the initial photo-oxidation products initiate mechanisms that are unique to the organelle and the cellular level where mediators diffuse from their site of formation to the target molecules that initiate the response. These examples indicate that, indeed, spatially resolved responses to O-1(2) occur in cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Kochevar, IE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA. EM Redmond@helix.mgh.harvard.edu; Kochevar@helix.mgh.harvard.edu FU NCI NIH HHS [P01 CA095227]; NIGMS NIH HHS [R01 GM030755] NR 75 TC 189 Z9 192 U1 2 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2006 VL 82 IS 5 BP 1178 EP 1186 DI 10.1562/2006-04-14-IR-874 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 097DK UT WOS:000241426600004 PM 16740059 ER PT J AU Gibbs, SL Chen, B O'Hara, JA Hoopes, PJ Hasan, T Pogue, BW AF Gibbs, Summer L. Chen, Bin O'Hara, Julia A. Hoopes, P. Jack Hasan, Tayyaba Pogue, Brian W. TI Protoporphyrin IX level correlates with number of mitochondria, but increase in production correlates with tumor cell size SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID DELTA-AMINOLEVULINIC-ACID; INDUCED PHOTODYNAMIC THERAPY; 5-AMINOLEVULINIC ACID; IN-VITRO; PORPHOBILINOGEN DEAMINASE; CANCER-CELLS; ADENOCARCINOMA CELLS; BETA TRANSPORTERS; PROSTATE-CANCER; ACCUMULATION AB Protoporphyrin IX (PpIX) is produced in cells via the heme synthesis pathway, from the substrate aminolevulinic acid (ALA), and can be used for tumor detection, monitoring or photodynamic therapy. PpIX production varies considerably between tumor cell types, and determining the cell types and methods to optimize production is a central issue in properly utilizing this drug. A panel of eight cancer cell types was examined for PpIX production capacity, including breast, prostate, and brain cancer tumors, and the production varied up to 10-fold among cell types. A positive correlation was seen between mitochondrial content and naturally occurring PpIX prior to ALA administration, but mitochondrial content did not correlate to the yield of PpIX resulting from the addition of ALA. Interestingly, total cell size was positively correlated to the yield of PpIX from ALA administration. Addition of an iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) in combination with ALA allows the final step in the heme synthesis pathway, conversion of PpIX to heme, to be delayed, thereby further increasing the yield of PpIX. Those cell types that had the lowest ALA to PpIX production without L1 showed the largest percentage increase in production with L1. The study indicates that use of L1 in tumors with a lower innate production of PpIX with ALA alone may be the most productive approach to this combined delivery. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Dartmouth Coll, Dept Surg, Hanover, NH 03755 USA. Dartmouth Coll, Dept Diagnost Radiol, Hanover, NH 03755 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Gibbs, SL (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM Summer.L.Gibbs@Dartmouth.edu FU NCI NIH HHS [P01CA84203, R01CA109558] NR 34 TC 29 Z9 29 U1 0 U2 4 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2006 VL 82 IS 5 BP 1334 EP 1341 DI 10.1562/2006-03-11-RA-843 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 097DK UT WOS:000241426600025 PM 16771607 ER PT J AU Zhou, XD Chen, B Hoopes, PJ Hasan, T Pogue, BW AF Zhou, Xiaodong Chen, Bin Hoopes, P. Jack Hasan, Tayyaba Pogue, Brian W. TI Tumor vascular area correlates with photosensitizer uptake: Analysis of verteporfin microvascular delivery in the dunning rat prostate tumor SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INTERMITTENT BLOOD-FLOW; PHOTODYNAMIC THERAPY; SOLID TUMORS; HOST MICROENVIRONMENT; COLORECTAL-CARCINOMA; NEOPLASTIC TISSUES; IMPLANTATION SITE; MURINE TUMORS; FLUENCE RATE; IN-VITRO AB The parameters that limit supply of photosensitizer to the cancer cells in a solid tumor were systematically analyzed with the use of microvascular transport modeling and histology data from frozen sections. In particular, the vascular permeability transport coefficient and the effective interstitial diffusion coefficient were quantified for Verteporfin-for-Injection delivery of benzoporphyrin derivative (BPD). Orthotopic tumors had higher permeability and diffusion coefficients (P-d = 0.036 mu m/s and D = 1.6 mu m(2)/s, respectively) as compared to subcutaneously grown tumors (P-d = 0.025 mu m/s and D = 0.9 mu m(2)/s, respectively), likely due to the fact that the vessel patterns are more homogeneous orthotopically. In general, large intersubject and intratumor variability exist in the verteporfin concentration, in the range of 25% in plasma concentration and in the range of 20% for tissue concentrations, predominantly due to these microregional variations in transport. However, the average individual uptake of photosensitizer in tumor tissue was only correlated to the total vascular area within the tumor (R-2 = 64.1%, P < 0.001). The data are consistent with a view that microregional variation in the vascular permeability and interstitial diffusion rate contribute the spatial heterogeneity observed in verteporfin uptake, but that average supply to the tissue is limited by the total area of perfused blood vessels. This study presents a method to systematically analyze microheterogeneity as well as possible methods to increase delivery and homogeneity of photosensitizer within tumor tissue. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Dartmouth Coll, Dept Surg, Hanover, NH 03755 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM pogue@dartmouth.edu FU NCI NIH HHS [P01CA84203] NR 62 TC 10 Z9 10 U1 0 U2 5 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2006 VL 82 IS 5 BP 1348 EP 1357 DI 10.1562/2006-03-25-RA-858 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 097DK UT WOS:000241426600027 PM 17421078 ER PT J AU Chen, LY McKenna, T Reisner, A Reifman, J AF Chen, Liangyou McKenna, Thomas Reisner, Andrew Reifman, Jaques TI Algorithms to qualify respiratory data collected during the transport of trauma patients SO PHYSIOLOGICAL MEASUREMENT LA English DT Article DE respiratory rate qualification; breath identification; waveform qualification; ambiguous breath; moving average; noisy waveform ID SLEEP-APNEA; IMPEDANCE PNEUMOGRAPHY; SINUS ARRHYTHMIA; VENTILATION; SCORE; PLETHYSMOGRAPHY; INJURY; SIGNAL; RHYTHM AB We developed a quality indexing system to numerically qualify respiratory data collected by vital-sign monitors in order to support reliable post-hoc mining of respiratory data. Each monitor-provided (reference) respiratory rate (RRR) is evaluated, second-by-second, to quantify the reliability of the rate with a quality index (QIR). The quality index is calculated from: (1) a breath identification algorithm that identifies breaths of 'typical' sizes and recalculates the respiratory rate (RRC); (2) an evaluation of the respiratory waveform quality (QIW) by assessing waveform ambiguities as they impact the calculation of respiratory rates and (3) decision rules that assign a QIR based on RRR, RRC and QIW. RRC, QIW and QIR were compared to rates and quality indices independently determined by human experts, with the human measures used as the 'gold standard', for 163 randomly chosen 15 s respiratory waveform samples from our database. The RRC more closely matches the rates determined by human evaluation of the waveforms than does the RRR (difference of 3.2 +/- 4.6 breaths min(-1) versus 14.3 +/- 19.3 breaths min(-1), mean +/- STD, p < 0.05). Higher QI(W) is found to be associated with smaller differences between calculated and human-evaluated rates (average differences of 1.7 and 8.1 breaths min(-1) for the best and worst QI(W), respectively). Establishment of QIW and QIR, which ranges from 0 for the worst-quality data to 3 for the best, provides a succinct quantitative measure that allows for automatic and systematic selection of respiratory waveforms and rates based on their data quality. C1 USA, Med Res & Mat Command, ATTN MCMR ZB T, Ft Detrick, MD 21702 USA. Massachusetts Gen Hosp, Dept Emergency Med, MGH, Boston, MA 02114 USA. RP Chen, LY (reprint author), USA, Med Res & Mat Command, ATTN MCMR ZB T, Bldg 363,Miller Dr, Ft Detrick, MD 21702 USA. EM lchen@bioanalysis.org; tmckenna@bioanalysis.org; andrewtreisner@yahoo.com; jaques.reifman@us.army.mil NR 38 TC 28 Z9 28 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0967-3334 J9 PHYSIOL MEAS JI Physiol. Meas. PD SEP PY 2006 VL 27 IS 9 BP 797 EP 816 DI 10.1088/0967-3334/27/9/004 PG 20 WC Biophysics; Engineering, Biomedical; Physiology SC Biophysics; Engineering; Physiology GA 078DI UT WOS:000240081300004 PM 16868347 ER PT J AU Bindschedler, LV Dewdney, J Blee, KA Stone, JM Asai, T Plotnikov, J Denoux, C Hayes, T Gerrish, C Davies, DR Ausubel, FM Bolwell, GP AF Bindschedler, Laurence V. Dewdney, Julia Blee, Kris A. Stone, Julie M. Asai, Tsuneaki Plotnikov, Julia Denoux, Carine Hayes, Tezni Gerrish, Chris Davies, Dewi R. Ausubel, Frederick M. Bolwell, G. Paul TI Peroxidase-dependent apoplastic oxidative burst in Arabidopsis required for pathogen resistance SO PLANT JOURNAL LA English DT Article DE apoplastic peroxidase; Arabidopsis; oxidative burst; reactive oxygen species ID ENHANCED DISEASE SUSCEPTIBILITY; PROGRAMMED CELL-DEATH; PSEUDOMONAS-SYRINGAE; PLANT-DISEASE; GENE FAMILY; HYPERSENSITIVE REACTION; OXIDASE GP91(PHOX); EFFECTOR AVRRPT2; SALICYLIC-ACID; SIGNAL NETWORK AB The oxidative burst is an early response to pathogen attack leading to the production of reactive oxygen species (ROS) including hydrogen peroxide. Two major mechanisms involving either NADPH oxidases or peroxidases that may exist singly or in combination in different plant species have been proposed for the generation of ROS. We identified an Arabidopsis thaliana azide-sensitive but diphenylene iodonium-insensitive apoplastic oxidative burst that generates H2O2 in response to a Fusarium oxysporum cell-wall preparation. Transgenic Arabidopsis plants expressing an anti-sense cDNA encoding a type III peroxidase, French bean peroxidase type 1 (FBP1) exhibited an impaired oxidative burst and were more susceptible than wild-type plants to both fungal and bacterial pathogens. Transcriptional profiling and RT-PCR analysis showed that the anti-sense (FBP1) transgenic plants had reduced levels of specific peroxidase-encoding mRNAs, including mRNAs corresponding to Arabidopsis genes At3g49120 (AtPCb) and At3g49110 (AtPCa) that encode two class III peroxidases with a high degree of homology to FBP1. These data indicate that peroxidases play a significant role in generating H2O2 during the Arabidopsis defense response and in conferring resistance to a wide range of pathogens. C1 Univ London Royal Holloway & Bedford New Coll, Sch Biol Sci, Egham TW20 0EX, Surrey, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Bolwell, GP (reprint author), Univ London Royal Holloway & Bedford New Coll, Sch Biol Sci, Egham TW20 0EX, Surrey, England. EM p.bolwell@rhul.ac.uk RI poinssot, benoit/B-2569-2009; OI Bindschedler, Laurence/0000-0002-0421-9857 FU NIDDK NIH HHS [P30 DK040561-11, P30 DK040561]; NIGMS NIH HHS [R37 GM048707, R37 GM48707] NR 62 TC 242 Z9 259 U1 3 U2 53 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0960-7412 J9 PLANT J JI Plant J. PD SEP PY 2006 VL 47 IS 6 BP 851 EP 863 DI 10.1111/j.1365-313X.2006.02837.x PG 13 WC Plant Sciences SC Plant Sciences GA 079AE UT WOS:000240147100003 PM 16889645 ER PT J AU Kuraguchi, M Wang, XP Bronson, RT Rothenberg, R Ohene-Baah, NY Lund, JJ Kucherlapati, M Maas, RL Kucherlapati, R AF Kuraguchi, Mari Wang, Xiu-Ping Bronson, Roderick T. Rothenberg, Rebecca Ohene-Baah, Nana Yaw Lund, Jennifer J. Kucherlapati, Melanie Maas, Richard L. Kucherlapati, Raju TI Adenomatous polyposis coli (APC) is required for normal development of skin and thymus SO PLOS GENETICS LA English DT Article ID HAIR FOLLICLE DEVELOPMENT; MOUSE MODEL; BETA-CATENIN; CELL DIFFERENTIATION; INTESTINAL TUMORS; GENE-EXPRESSION; STEM-CELLS; MICE; MORPHOGENESIS; EPITHELIUM AB The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis. Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality. To understand the role of Apc in development we generated a floxed allele. These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning. Histological and immunochemical examinations revealed that K14-cre-mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia. In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus. The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; Apc(CKO/CKO) mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial mesenchymal interactions for their development. C1 Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Gen, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Kucherlapati, R (reprint author), Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Gen, Boston, MA 02115 USA. EM rkucherlapati@partners.org FU NCI NIH HHS [CA-084301, U01 CA084301]; NIDCR NIH HHS [DE-11697, DE-16140, R01 DE011697, R01 DE016140, R37 DE011697]; NIEHS NIH HHS [ES-11040, U01 ES011040] NR 40 TC 92 Z9 99 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2006 VL 2 IS 9 BP 1362 EP 1374 AR e146 DI 10.1371/journal.pgen.0020146 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 089GF UT WOS:000240867700010 PM 17002498 ER PT J AU Isselbacher, KJ AF Isselbacher, Kurt J. TI Barrett's esophagus: Diagnosis by endomicroscopy SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Isselbacher, KJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD SEP-OCT PY 2006 VL 119 IS 2 BP 58 EP 58 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA V44DS UT WOS:000202984000013 ER PT J AU Covell, NH Jackson, CT Weissman, EM AF Covell, Nancy H. Jackson, Carlos T. Weissman, Ellen M. TI Health monitoring for patients who have schizophrenia Summary of the Mount Sinai Conference recommendations SO POSTGRADUATE MEDICINE LA English DT Article AB Schizophrenia is associated with several chronic medical illnesses and a reduced life expectancy. This paper summarizes findings and recommendations from "The Mount Sinai Conference," held at the Mount Sinai School of Medicine in New York on October 17-18, 2002, and discusses the implications for improving medical monitoring of patients with schizophrenia who are managed in outpatient settings from the initiation of treatment. The Mount Sinai Conference involved a diverse panel of experts, including specialists on schizophrenia, obesity, diabetes, cardiology, endocrinology, and ophthalmology. Consensus recommendations included baseline measurement and regular monitoring of body mass index, blood glucose, lipid profiles, signs of prolactin elevation or sexual dysfunction, and movement disorders. Information from such measurements should be considered when selecting or switching antipsychotic agents and should trigger an evaluation of medication when abnormalities are detected. C1 [Covell, Nancy H.] Mt Sinai Sch Med, Div Hlth Serv Res, Dept Psychiat, Connecticut DMHAS Res Div, Hartford, CT 06134 USA. [Jackson, Carlos T.] Mt Sinai Sch Med, Div Hlth Serv Res, Dept Psychiat, New York, NY 10029 USA. [Weissman, Ellen M.] James J Peters Vet Affairs Med Ctr, Educ & Clin Ctr Vet Integrated Serv Network 3, Bronx, NY 10468 USA. RP Covell, NH (reprint author), Mt Sinai Sch Med, Div Hlth Serv Res, Dept Psychiat, Connecticut DMHAS Res Div, 410 Capitol Ave,MS 14RSD,POB 341431, Hartford, CT 06134 USA. EM Nancy.covell@po.state.ct.us NR 38 TC 7 Z9 8 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0032-5481 EI 1941-9260 J9 POSTGRAD MED JI Postgrad. Med. PD SEP PY 2006 SI SI BP 20 EP 26 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA V06EE UT WOS:000207176100003 ER PT J AU Ding, ZP Bradley, KA Arnaout, MA Xiong, JP AF Ding, Zhiping Bradley, Kenneth A. Arnaout, M. Amin Xiong, Jian-Ping TI Expression and purification of functional human anthrax toxin receptor (ATR/TEM8) binding domain from Escherichia coli SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE anthrax; anthrax toxin receptor; VWA domain; expression; purification ID CAPILLARY MORPHOGENESIS PROTEIN-2; INFANTILE SYSTEMIC HYALINOSIS; A-DOMAIN; PROTECTIVE ANTIGEN; CRYSTAL-STRUCTURE; TUMOR ENDOTHELIUM; LETHAL FACTOR; I-DOMAIN; PATHOGENESIS; AFFINITY AB Anthrax is caused by the gram-positive, spore-forming bacterium, Bacillus anthracis. Anthrax receptors play a crucial role in the pathogenesis of the anthrax disease. Anthrax toxin receptor ATR/TEM8 VWA domain is responsible for the binding of protective antigen (PA) of B. anthracis, and thus an attractive target for structure-based drug therapies. However, the production of soluble and functional ATR/TEM8 VWA domain currently requires the use of mammalian expression systems. In this work, we expressed the ATR/TEM8 VWA domain as a fusion protein in Escherichia coli. Recombinant ATR/TEM8 VWA domain has been purified to homogeneity, and its identity has been verified by both N-terminal protein microsequencing and mass spectrometry. The purified ATR/TEM8 VWA domain exhibits very high affinity to PA based on BIAcore assay. Moreover, like the domain expressed in mammalian system, the bacterially expressed ATR/TEM8 VWA domain can block cytotoxicity induced by anthrax toxins, suggesting that the bacterially expressed ATR/TEM8 VWA domain is properly folded and fully functional. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Leukocyte Biol & Inflammat Program,Renal Unit,Nep, Charlestown, MA 02129 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Xiong, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Leukocyte Biol & Inflammat Program,Renal Unit,Nep, 149 13th St, Charlestown, MA 02129 USA. EM xiong@helix.mgh.harvard.edu FU NIAID NIH HHS [AI-057870]; NIDDK NIH HHS [DK048549] NR 44 TC 9 Z9 9 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD SEP PY 2006 VL 49 IS 1 BP 121 EP 128 DI 10.1016/j.pep.2006.04.011 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 085CJ UT WOS:000240580500018 PM 16798009 ER PT J AU Das, J Zhou, XJ Miller, KW AF Das, Joydip Zhou, Xiaojuan Miller, Keith W. TI Identification of an alcohol binding site in the first cysteine-rich domain of protein kinase C delta SO PROTEIN SCIENCE LA English DT Article DE protein kinase C; diazirine; mass spectrometry; anesthesia; photolabeling; fluorescence; binding site ID NICOTINIC ACETYLCHOLINE-RECEPTOR; PHORBOL ESTERS; ALPHA; ACTIVATION; DIACYLGLYCEROLS; ANESTHETICS; INHIBITION; PROTEOMICS; MECHANISM; SYSTEM AB Protein kinase C (PKC) is an important signal transduction protein whose cysteine-rich regulatory domain C1 has been proposed to interact with general anesthetics in both of its diacylglycerol/ phorbol ester -binding subdomains, the tandem repeats C1A and C1B. Previously, we identified an allosteric binding site on one of the two cysteine-rich domains, PKC delta C1B. To test the hypothesis that there is an additional anesthetic site on the other cysteine-rich subdomain, C1A, we subcloned, expressed in Escherichia coli, purified, and characterized mouse PKCd C1A. Octanol and butanol both quenched the intrinsic fluorescence of PKCd C1A in a saturable manner, suggesting the presence of a binding site. To locate this site, PKC delta C1A was photolabeled with three diazirine-containing alkanols, 3-azioctanol, 7-azioctanol, and 3-azibutanol. Mass spectrometry revealed that at low concentrations all three photoincorporated into PKC delta C1A with a stoichiometry of 1: 1 in the labeled fraction, but higher stoichiometries occurred at higher concentrations, particularly with azibutanol. Photocomplexes of PKCd C1A with azioctanols were separated from the unlabeled protein by HPLC, reduced, alkylated, digested with trypsin, and sequenced by mass spectrometry. All the azioctanols photolabeled PKCd C1A at residue Tyr-29, corresponding to Tyr-187 of the full-length PKC delta, and at a neighboring residue, Lys-40, suggesting there is an alcohol site in this vicinity. In addition, Glu-2 was photolabeled more efficiently by 3-azibutanol than by the azioctanols, suggesting the existence of a second, smaller site. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Das, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM joydip_das@hms.harvard.edu FU NIGMS NIH HHS [R01 GM069726, GM 069726] NR 40 TC 19 Z9 19 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD SEP PY 2006 VL 15 IS 9 BP 2107 EP 2119 DI 10.1110/ps.062237606 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 079DT UT WOS:000240156400008 PM 16943444 ER PT J AU Donahue, SA Lanzara, CB Felton, CJ Essock, SM Carpinello, S AF Donahue, Sheila. A. Lanzara, Carol B. Felton, Chip J. Essock, Susan M. Carpinello, Sharon TI Project Liberty: New York's crisis counseling program created in the aftermath of September 11, 2001 SO PSYCHIATRIC SERVICES LA English DT Article C1 CUNY Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Essock, SM (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 15 TC 17 Z9 18 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1253 EP 1258 DI 10.1176/appi.ps.57.9.1253 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800002 PM 16968752 ER PT J AU Donahue, SA Covell, NH Foster, MJ Felton, CJ Essock, SM AF Donahue, Sheila A. Covell, Nancy H. Foster, M. Jameson Felton, Chip J. Essock, Susan M. TI Demographic characteristics of individuals who received Project Liberty crisis counseling services SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH-SERVICE; NEW-YORK-CITY; TERRORIST ATTACKS; SEPTEMBER-11; COMORBIDITY; NEEDS AB Objectives: This article describes demographic characteristics of service recipients and their patterns of use of crisis counseling services provided under Project Liberty during the 27 months after the September 11, 2001, attacks on the World Trade Center. It also examines the extent to which service recipients reflected the demographic characteristics of their home communities. Methods: A total of 753,015 service encounter logs submitted by 177 providers were analyzed to determine rates of use by different demographic groups and to evaluate patterns of use over time with goodness-of-fit and logistic regression models. Results: A total of 687,848 individual crisis counseling sessions were provided to an estimated 465,428 individuals, including large numbers of persons from racial or ethnic minority groups and non-English-speaking individuals. Most of these services were provided to residents of the five New York City boroughs, with a small percentage of services to residents from the ten surrounding counties. Most services were provided in community settings rather than provider offices. African-American and Hispanic individuals showed the greatest increase in rates of accessing services over time. Follow-up visits were significantly more likely to be by Caucasians than by non-Caucasians, and children were more likely than adults to receive follow-up visits. Demographic characteristics of individuals using Project Liberty crisis counseling services generally were representative of the five boroughs and ten other counties constituting the greater metropolitan region and representative of estimated need. Conclusions: Project Liberty provided services that were accessible to individuals of diverse racial and ethnic backgrounds. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Essock, SM (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 18 TC 10 Z9 10 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1261 EP 1267 DI 10.1176/appi.ps.57.9.1261 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800003 PM 16968753 ER PT J AU Covell, NH Donahue, SA Allen, G Foster, MJ Felton, CJ Essock, SM AF Covell, Nancy H. Donahue, Sheila. A. Allen, George Foster, M. Jameson Felton, Chip J. Essock, Susan M. TI Use of Project Liberty counseling services over time by individuals in various risk categories SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TERRORIST ATTACKS; RESCUE WORKERS; DISASTER; TRAUMA AB Objective: The authors examined temporal changes in the rates at which people sought access to Project Liberty services after the attacks of September 11, 2001, according to risk category (family of missing or deceased, persons directly affected, uniformed personnel, other rescue or recovery workers, schoolchildren, displaced employed and unemployed workers, persons with disabilities, and the general population). Methods: First visits to individual counseling services, as determined from logs of 465,428 service encounters, were proportioned among risk categories and plotted across 27 months. Results: Individuals who lost family members accounted for 40 percent of visits in the first month but dropped to 5 percent or fewer visits by five months. Uniformed personnel used disproportionately larger percentages of services after the first year. Occupationally displaced and unemployed workers sought counseling at relatively steady rates. Conclusions: Postdisaster counseling should be made available for extended periods, with shifting emphases to meet the changing needs of high-risk groups. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. Univ Connecticut, Dept Psychol, Storrs, CT USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Essock, SM (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM susan.essok@mssm.edu NR 10 TC 11 Z9 11 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1268 EP 1270 DI 10.1176/appi.ps.57.9.1268 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800004 PM 16968754 ER PT J AU Jackson, CT Allen, G Essock, SM Foster, MJ Lanzara, CB Felton, CJ Donahue, SA AF Jackson, Carlos T. Allen, George Essock, Susan M. Foster, M. Jameson Lanzara, Carol B. Felton, Chip J. Donahue, Sheila. A. TI Clusters of event reactions among recipients of Project Liberty mental health counseling SO PSYCHIATRIC SERVICES LA English DT Article ID SEPTEMBER-11 TERRORIST ATTACKS; NEW-YORK-CITY; NEEDS AB Objective: This study aimed to determine a pattern in the frequency with which individuals who manifested distress reactions resembling diagnostic syndromes of posttraumatic stress disorder (PTSD) and major depressive disorder accessed services provided by Project Liberty. Methods: Hierarchical cluster analysis was applied to 31 reactions to stress (event reactions) shown by 465,428 recipients of Project Liberty counseling, to determine how well event reactions mapped onto traditional diagnostic criteria. Service recipients were tracked when they first sought Project Liberty counseling during the 27 months after the attacks. Those who reported three or more reactions associated with these clusters were characterized as having possible diagnosable conditions. Results: Strong consistent clusters corresponding to traumatic stress and depressive symptoms emerged, with 26 percent, 16 percent, and 8 percent of service recipients rated as having possible PTSD, major depressive disorder, or both, respectively. Taken together, this group constituted over 40 percent of service recipients served by Project Liberty almost every month throughout the 27 months of its existence. Conclusions: Event reactions, as reported by Project Liberty crisis counselors, many of whom were nonclinicians, mapped coherently onto diagnostic syndromes, suggesting that a checklist of such reactions may be useful to disaster counselors as a cost-effective screening and planning instrument. The steady entry over time into Project Liberty counseling by a substantial number of individuals experiencing high levels of distress underscores the need for providing long-term access to mental health services postdisaster. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Univ Connecticut, Dept Psychol, Storrs, CT USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 14 TC 8 Z9 8 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1271 EP 1276 DI 10.1176/appi.ps.57.9.1271 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800005 PM 16968755 ER PT J AU Covell, NH Allen, G Essock, SM Pease, EA Felton, CJ Lanzara, CB Donahue, SA AF Covell, Nancy H. Allen, George Essock, Susan M. Pease, Elizabeth A. Felton, Chip J. Lanzara, Carol B. Donahue, Sheila A. TI Service utilization and event reaction patterns among children who received Project Liberty counseling services SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; WORLD-TRADE-CENTER; NEW-YORK-CITY; DEPRESSIVE REACTIONS; SCHOOL-CHILDREN; ADOLESCENTS; ATTACKS; SEPTEMBER-11; TERRORISM; DISASTER AB Objectives: This study examined service utilization and event reaction patterns among children who used crisis counseling services provided under Project Liberty for 27 months after the September 11, 2001, terrorist attacks on the World Trade Center. Methods: The authors analyzed logs of 681,318 service encounters submitted by Project Liberty counselors, paying particular attention to demographic characteristics and reported event reactions. Results: Nine percent of service recipients reached by community-based Project Liberty providers were children, whereas census data for the 15 counties and boroughs served by Project Liberty indicated that children constituted 25 percent of the population. Service use as a function of race or ethnicity and of gender was consistent with census data. Similar to findings for adults, the most common emotional event reactions reported for children were experiencing sadness and tearfulness, being anxious and fearful, having difficulty concentrating, experiencing irritability and anger, having intrusive thoughts or images, and having difficulty sleeping. Behavioral event reactions listed on service logs suggested that older children (12 to 17 years) were more likely to use drugs whereas elementary school-age children were more likely to display signs of anxiety, isolation and withdrawal, and difficulties with concentration and memory. Conclusions: Sensitivity to differences in the event reaction patterns shown by younger and older children may be useful in refining treatments to help reduce the psychological impact of children's trauma after terrorist incidents. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Univ Connecticut, Dept Psychol, Storrs, CT USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 25 TC 8 Z9 8 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1277 EP 1282 DI 10.1176/appi.ps.57.9.1277 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800006 PM 16968756 ER PT J AU Jackson, CT Covell, NH Shear, KM Zhu, C Donahue, SA Essock, SM Felton, CJ AF Jackson, Carlos T. Covell, Nancy H. Shear, Katherine M. Zhu, Carolyn Donahue, Sheila. A. Essock, Susan M. Felton, Chip J. TI The road back: Predictors of regaining preattack functioning among Project Liberty clients SO PSYCHIATRIC SERVICES LA English DT Article ID NEW-YORK-CITY; SEPTEMBER-11 TERRORIST ATTACKS; MENTAL-HEALTH-SERVICE; NEEDS AB Objectives: This study determined the likelihood and predictors of Project Liberty counseling recipients' reporting their return to satisfactory life functioning 16 to 26 months after the September 11, 2001, attacks. Methods: Using anonymous brief paper-and-pencil questionnaires or structured telephone interviews, 452 respondents provided retrospective ratings of their functioning in five life domains during the month before the World Trade Center attacks and the month immediately before the assessment. Information on demographic characteristics and exposure to risk during the World Trade Center attacks also was obtained and used in logistic regression models. The 153 respondents who were interviewed by telephone also rated helpfulness of various coping strategies. Results: In the five domains, 77 to 87 percent of the sample reported good to excellent functioning in the month before the attacks; 55 to 68 percent reported returning to at least the same level of daily functioning after the attacks. African Americans were two to four times more likely than respondents of all other races to report a return to good or excellent functioning after the attack in four domains. Compared with respondents who did not lose their job as a result of the attacks, those who did lose their job were less likely to return to good preattack functioning in two domains. Project Liberty counseling reportedly helped 90 percent of respondents return to predisaster levels of functioning. Conclusions: Responses to future terrorist attacks should consider demographic characteristics and the impact of the attack because they can affect return to preattack functioning. Counselors should support activities that facilitate positive responses and ameliorate negative psychological responses. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. Mental Illness Res Educ & Clin Care Ctr, Bronx, NY USA. James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. Columbia Univ, Coll Phys & Surg, Sch Social Work, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 21 TC 8 Z9 8 U1 3 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1283 EP 1290 DI 10.1176/appi.ps.57.9.1283 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800007 PM 16968757 ER PT J AU Shear, KM Jackson, CT Essock, SM Donahue, SA Felton, CJ AF Shear, Katherine M. Jackson, Carlos T. Essock, Susan M. Donahue, Sheila A. Felton, Chip J. TI Screening for complicated grief among Project liberty service recipients 18 month after September 11, 2001 SO PSYCHIATRIC SERVICES LA English DT Article ID TERRORIST ATTACKS; TRAUMATIC GRIEF; BEREAVEMENT; DISORDER; ADAPTATION; ATTACHMENT; CRITERIA; DISTINCT; HEALTH AB Objective: The authors surveyed a sample of Project Liberty crisis counseling recipients approximately 1.5 years after the terrorist attacks on September 11, 2001, to determine the proportion of respondents who screened positive for complicated grief, a recently identified condition marked by symptoms of continuing separation distress and accompanying bereavement-related traumatic distress. Methods: A total of 149 service recipients drawn from eight high-volume providers responded to a telephone survey that included questions to screen for complicated grief. Results: Approximately half of the recipients knew someone who had been killed in the attacks. Of those recipients, 44 percent screened positive for complicated grief. Individuals who lost a family member were more likely than those who lost an acquaintance to screen positive for complicated grief. Positive screens were associated with functional impairment independent of the presence of symptoms consistent with full or subthreshold major depression or posttraumatic stress disorder (PTSD). Thirty-two percent of those who screened positive for complicated grief did not meet even subthreshold criteria for major depression or PTSD. Conclusions: Results affirmed the importance of complicated grief as a unique condition and indicated the need to attend to the psychological consequences of bereavement in disaster-related mental health services. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. Columbia Univ Coll Phys & Surg, Sch Social Work, Dept Psychiat, New York, NY 10032 USA. James J Peters Vet Affairs Med Syst, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 25 TC 60 Z9 60 U1 4 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1291 EP 1297 DI 10.1176/appi.ps.57.9.1291 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800008 PM 16968758 ER PT J AU Donahue, SA Jackson, CT Shear, KM Felton, CJ Essock, SM AF Donahue, Sheila A. Jackson, Carlos T. Shear, Katherine M. Felton, Chip J. Essock, Susan M. TI Outcomes of enhanced counseling services provided to adults through Project liberty SO PSYCHIATRIC SERVICES LA English DT Article ID SEPTEMBER-11 TERRORIST ATTACKS; NEW-YORK-CITY; DISORDER AB Objective: Project Liberty provided brief crisis counseling to 753,015 residents of New York City and surrounding counties after the attacks on the World Trade Center. Most regained predisaster functioning after counseling. For those who did not, Project Liberty provided enhanced services by specially trained, licensed mental health professionals. Individuals receiving crisis counseling and enhanced services responded to confidential telephone interviews about 18 and 24 months, respectively, after the attacks. Impairment was compared between groups to determine whether enhanced services recipients reported improved functioning and fewer symptoms of depression, posttraumatic stress, and complicated grief. Methods: Crisis counseling recipients (N=153) were interviewed once and enhanced services recipients (N=76) were interviewed twice about symptomatology and daily functioning. Results: The samples did not differ in age or gender. Significantly greater proportions of enhanced services recipients reported knowing someone who died as a result of the attacks, having been involved in rescue efforts, or having lost their job because of the attacks. Compared with crisis counseling respondents, enhanced services recipients at their first interview reported significantly more symptoms of depression, grief, and traumatic stress and significantly poorer daily functioning in five life areas. At follow-up, enhanced services respondents reported significant improvement in three of five functioning domains, significantly fewer symptoms of depression and grief, and marginally less traumatic stress. Conclusions: Recipients of enhanced services were more impaired than people who received only crisis counseling. On the basis of reports from service recipients, meaningful improvements in functioning and symptoms may be associated with the receipt of enhanced services. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Columbia Univ Coll Phys & Surg, Sch Social Work, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM susan.essock@mssm.edu FU NIMH NIH HHS [MH-52247, MH-60783, MH-30915] NR 18 TC 19 Z9 19 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1298 EP 1303 DI 10.1176/appi.ps.57.9.1298 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800009 PM 16968759 ER PT J AU Frank, RG Pindyck, T Donahue, SA Pease, EA Foster, MJ Felton, CJ Essock, SM AF Frank, Richard G. Pindyck, Talia Donahue, Sheila A. Pease, Elizabeth A. Foster, M. Jameson Felton, Chip J. Essock, Susan M. TI Impact of a media campaign for disaster mental health counseling in post-September 11 New York SO PSYCHIATRIC SERVICES LA English DT Article AB Objective: After the September 11, 2001, terrorist attacks on the World Trade Center, the New York State Office of Mental Health (NYOMH) initiated a three-phase multifaceted, multilingual media campaign that advertised the availability of counseling services. This study evaluated the association between patterns of spending within this campaign and the volume of calls received and referred to a counseling program. Methods: Spending on television, radio, print, and other advertising was examined, as was the corresponding volume of calls to the NetLife hotline seeking referrals to counseling services. Results: From September 2001 to December 2002, $9.38 million was spent on Project Liberty media campaigns. Call volumes increased during months when total monthly expenditures peaked. Initially, flyers, billboards, and other material items accounted for most monthly expenses. Over time, spending for television and radio advertisements increased, whereas other advertising declined. Temporal patterns show that in periods after an increase in media spending, call volumes increased independently of other sentinel events such as the one-year anniversary of the attacks. Conclusions: Sustained advertising through multiple media outlets appeared to be effective in encouraging individuals to seek mental health services. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. Harvard Univ, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 8 TC 14 Z9 15 U1 0 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1304 EP 1308 DI 10.1176/appi.ps.57.9.1304 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800010 PM 16968760 ER PT J AU Gomes, C McGuire, TG Foster, MJ Donahue, SA Felton, CJ Essock, SM AF Gomes, Carla McGuire, Thomas G. Foster, M. Jameson Donahue, Sheila A. Felton, Chip J. Essock, Susan M. TI Did Project Liberty displace community-based Medicaid services in New York? SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH RESPONSE; TERRORIST ATTACKS; LESSONS; NEEDS; CITY AB Objective: This study analyzed how the introducion of Project Liberty services after the September 11, 2001, terrorist attacks affected agencies' provision of community-based Medicaid mental health services in the New York metropolitan area. Methods: Provision of Medicaid mental health services was tracked between January 2000 and June 2003 for provider agencies participating in Project Liberty (N=164) and for a comparison group of mental health provider agencies that did not participate in this program (N=94). Results: Overall, participation in Project Liberty did not significantly affect the volume of Medicaid services provided. However, for agencies with one site, a statistically significant difference was seen; compared with agencies in the comparison group, agencies that participated in Project Liberty claimed a mean SE decrease of $4.66 +/- 3.57 less in Medicaid services per month per Project Liberty visit. Conclusions: Project Liberty permitted rapid expansion of the total volume of services provided by community-based organizations without interfering with the provision of traditional services, although a modest effect was seen for smaller agencies. Although the results do not imply that "supply side" planning for disaster needs would not improve system response, they do imply that implementation of flexible "demand side" financing can call forth a large volume of new services rapidly and without interfering with other community services. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 5 TC 6 Z9 6 U1 3 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1309 EP 1312 DI 10.1176/appi.ps.57.9.1309 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800011 PM 16968761 ER PT J AU Covell, NH Essock, SM Felton, CJ Donahue, SA AF Covell, Nancy H. Essock, Susan M. Felton, Chip J. Donahue, Sheila. A. TI Characteristics of Project Liberty clients that predicted referrals to intensive mental health services SO PSYCHIATRIC SERVICES LA English DT Article ID TERRORIST ATTACKS AB Objective: The authors describe characteristics of Project Liberty crisis counseling recipients that predicted referral to more intensive professional mental health treatments over the two-year period after the terrorist attacks on the World Trade Center. Methods: Random-effects ordinal regression models were applied to data from 684,500 logs of Project Liberty service encounters for individual counseling sessions. Results: Overall, about 9 percent of individual counseling visits ended with a referral to professional mental health services. Individuals needing intensive mental health treatment continued to enter Project Liberty for two years after the World Trade Center attacks. The strongest predictor of referral was having reactions to the attack that fell into a greater number of the four domains assessed-behavioral, emotional, physical, or cognitive domains. Individuals with reactions in four domains were most likely to be referred. Those who had greater attack-related exposure were also more likely to be referred. Conclusions: It is important to provide long-term access to brief counseling and triage services and to target these interventions specifically to individuals displaying greater distress or impairment and having more traumatic exposure. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Care Ctr, Bronx, NY USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 10 TC 10 Z9 10 U1 3 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1313 EP 1315 DI 10.1176/appi.ps.57.9.1313 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800012 PM 16968762 ER PT J AU Jackson, CT Allen, G Essock, SM Felton, CJ Donahue, SA AF Jackson, Carlos T. Allen, George Essock, Susan M. Felton, Chip J. Donahue, Sheila A. TI Clients' satisfaction with Project Liberty counseling services SO PSYCHIATRIC SERVICES LA English DT Article ID SEPTEMBER-11 TERRORIST ATTACKS; NEW-YORK-CITY; CONSUMER-REPORTS; PSYCHOTHERAPY AB Objective: Satisfaction with 11 aspects of service quality and four domains of effectiveness was assessed for counseling services offered through Project Liberty after the September 11, 2001, attacks on the World Trade Center. Methods: A total of 607 Project Liberty service recipients completed anonymous questionnaires, telephone interviews, or both. The 11 aspects of quality were counselor respect for client, willingness to listen, cultural sensitivity, speaking the same language as the client, amount of counseling time, convenience of meeting time and location, information received, whether the service would be used again, whether the service would be recommended to friends or family, and overall quality of service. The four effectiveness domains were daily responsibilities, relationships, physical health, and community involvement. Results: At least 89 percent of service recipients rated Project Liberty as either good or excellent across 11 service quality dimensions and four effectiveness domains. The counselor's respect for clients and his or her cultural sensitivity were rated particularly favorably. Conclusions: These ratings suggest that, from the viewpoint of these recipients of counseling services, Project Liberty counselors were largely successful in providing accessible, acceptable, and useful services after the World Trade Center disaster. Such evaluations can be conducted in a cost-effective manner and integrated with evidence-based practice to ultimately ensure that recipients of counseling receive the most efficient and effective interventions. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Univ Connecticut, Dept Psychol, Storrs, CT USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 11 TC 9 Z9 9 U1 3 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1316 EP 1319 DI 10.1176/appi.ps.57.9.1316 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800013 PM 16968763 ER PT J AU Essock, SM Covell, NH Shear, KM Donahue, SA Felton, CJ AF Essock, Susan M. Covell, Nancy H. Shear, Katherine M. Donahue, Sheila A. Felton, Chip J. TI Use of clients' self-reports to monitor Project Liberty clinicians' fidelity to a cognitive-behavioral intervention SO PSYCHIATRIC SERVICES LA English DT Article AB Objective: This study examined outcomes associated with clinicians' fidelity to key elements of a cognitive-behavioral treatment intervention developed for Project Liberty's enhanced services counseling program. Methods: In telephone interviews 60 individuals reported how often their clinicians provided six components considered central to the intervention by the intervention developers. Respondents received services at sites where some (25 to 50 percent) or all clinicians had received training in the intervention. Results: Compared with respondents who received services where only some clinicians had received training (N=19), those who received services where all clinicians had received training (N=41) were significantly more likely to report that their clinicians applied techniques central to the intervention (p <.01). Additionally, those who received services from sites where all clinicians were trained were significantly more likely to report that they had been given homework (p <.05). Conclusions: Brief questions to service recipients are a useful and cost-effective way to monitor intervention fidelity. C1 Mt Sinai Sch Med, Div Hlth Serv Res, Dept Psychiat, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Columbia Univ Coll Phys & Surg, Sch Social Work, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Div Hlth Serv Res, Dept Psychiat, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM susan.essock@mssm.edu FU NIMH NIH HHS [MH-30915, MH-52247, MH-60783] NR 11 TC 10 Z9 11 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1320 EP 1323 DI 10.1176/appi.ps.57.9.1320 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800014 PM 16968764 ER PT J AU Covell, NH Donahue, SA Ulaszek, WR Dunakin, L Essock, SM Felton, CJ AF Covell, Nancy H. Donahue, Sheila A. Ulaszek, Wendy R. Dunakin, Linda Essock, Susan M. Felton, Chip J. TI Effectiveness of two methods of obtaining feedback on mental health services provided to anonymous recipients SO PSYCHIATRIC SERVICES LA English DT Article ID SEPTEMBER-11 TERRORIST ATTACKS; NEW-YORK-CITY AB Objective: The authors examined alternative methods for obtaining feedback from people receiving anonymous mental health services via Project Liberty, an initiative that provided free counseling to residents of the New York City area after the 2001 attacks on the World Trade Center. Methods: Counselors offered all English-speaking and Spanish-speaking adults who used Project Liberty crisis counseling services the opportunity to evaluate Project Liberty via a telephone interview (eight sites) or a brief questionnaire (four sites). Results: A total of 107 service recipients provided feedback via a brief 32-item questionnaire, and 153 gave feedback via a 45-minute telephone interview. Although the overall participation rates were modest (less than 20 percent), nearly threequarters of those who volunteered to participate in the telephone interview (for which they received $20) did so. Neither gender nor racial or ethnic group was associated with a greater likelihood of participating in one method over another. Conclusions: Responses to items on the brief questionnaire and in the telephone interview were similar, and offering multiple response methods increased participation rates. Although telephone interviews were more costly than the questionnaire to administer, they provided important additional information about ongoing symptoms and problems that individuals experienced after the attacks. The modest response rates obtained in the evaluation indicate that future evaluations of postdisaster services need to use methods to maximize response rates and provider adherence to administrative tasks that are critical to the evaluation. C1 Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. Univ Connecticut, Dept Psychol, Storrs, CT USA. State Connecticut Dept Mental Hlth & Addict Serv, Hartford, CT USA. RP Essock, SM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM susan.essock@mssm.edu NR 6 TC 5 Z9 5 U1 3 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1324 EP 1327 DI 10.1176/appi.ps.57.9.1324 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800015 PM 16968765 ER PT J AU Stoddard, FJ AF Stoddard, Frederick J., Jr. TI On the ground after September 11: Mental health responses and practical knowledge gained SO PSYCHIATRIC SERVICES LA English DT Book Review C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stoddard, FJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2006 VL 57 IS 9 BP 1343 EP 1344 DI 10.1176/appi.ps.57.9.1343 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 081PF UT WOS:000240328800020 ER PT J AU Kornblith, AB Regan, MM Kim, YM Greer, G Parker, B Bennett, S Winer, E AF Kornblith, Alice B. Regan, Meredith M. Kim, Youngmee Greer, Greta Parker, Beverly Bennett, Samantha Winer, Eric TI Cancer-related communication between female patients and male partners scale: A pilot study SO PSYCHO-ONCOLOGY LA English DT Article DE communication; cancer; scale; couples; quality of life; oncology ID QUALITY-OF-LIFE; PROSTATE-CANCER; PSYCHOLOGICAL DISTRESS; BREAST-CANCER; COLON-CANCER; ADJUSTMENT; COUPLES; PATTERNS; DISCLOSURE; SURVIVORS AB Background: The study's objective was to evaluate the reliability and validity of the Cancer-Related Communication Problems within Couples Scale (CRCP), a measure to assess whether patients and their partners have difficulty talking about cancer with each other. Methods: The CRCP Scale included 18 items concerning open communication/emotional support, treatment-specific issues, self-protection, and protective buffering. Patients and partners responded through the American Cancer Society's website and mailed questionnaires through Y-ME. The CRCP's validity was tested using the Hospital Anxiety and Depression Scale (HADS) and the Dyadic Adjustment Scale (DAS, marital relationship). Results: 189 female patients and 135 male partners participated in the survey. Three items were deleted based on lack of clarity or an item not being applicable to many respondents, resulting in a 15 item scale. The number of CRCP problems' internal consistency in the 15 item scale was good for both patients and partners (alpha coefficient = 0.87, 0.8 1, respectively). The number of patients' CRCP problems correlated with the DAS (p < 0.0001), and the number of partners' CRCP problems correlated with the HADS (p < 0.0001) and the DAS (p < 0.0001). Conclusion: Analyses supported the CRCP Scale's reliability and validity for female cancer patients and male partners. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Dana Farber Canc Inst, Womens Canc Program D 1210, Boston, MA 02115 USA. Amer Canc Soc, Atlanta, GA 30329 USA. YME Natl Breast Canc Org, Chicago, IL USA. RP Kornblith, AB (reprint author), Dana Farber Canc Inst, Womens Canc Program D 1210, 44 Binney St, Boston, MA 02115 USA. EM alice_kornblith@dfci.harvard.edu OI Kim, Youngmee/0000-0002-3109-6362 NR 29 TC 34 Z9 35 U1 1 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 SEP PY 2006 VL 15 IS 9 BP 780 EP 794 DI 10.1002/pon.1004 PG 15 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 086JT UT WOS:000240670300004 PM 16308887 ER PT J AU Zhang, JP Niaura, R Dyer, JR Shen, BJ Todaro, JF McCaffery, JM Spiro, A Ward, KD AF Zhang, Jianping Niaura, Raymond Dyer, Joshua R. Shen, Biing-Jiun Todaro, John F. McCaffery, Jeanne M. Spiro, Avron, III Ward, Kenneth D. TI Hostility and urine norepinephrine interact to predict insulin resistance: The VA normative aging study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE hostility; norepinephrine; insulin resistance; HOMA; metabolic syndrome ID HOMEOSTASIS MODEL ASSESSMENT; SYMPATHETIC NERVOUS-SYSTEM; CORONARY HEART-DISEASE; METABOLIC SYNDROME-X; CARDIOVASCULAR-DISEASE; ADIPOSE-TISSUE; GLUCOSE-TOLERANCE; CHRONIC STRESS; RISK-FACTORS; SENSITIVITY AB Objective: Previous research has produced mixed results pertaining to the association between hostility and insulin resistance. These inconsistent findings may be the result of a lack of studies examining potential moderators of this relationship and inconsistent measures of insulin resistance and/or hostility. We hypothesized that hostility may interact with circulating norepinephrine (KEPI) levels, indexed by 24-hour urine concentrations, to affect insulin resistance. Methods: Six hundred forty-three men (mean age = 63.1 years) free of diabetic medications completed the Minnesota Multiphasic Personality Inventory and participated in a laboratory assessment. The Cook-Medley Hostility (Ho) and 24-hour urine NEPI were used to predict insulin resistance defined by the homeostatic model assessment (HOMA) index, 2-hour postchallenge glucose (PCGL), and insulin levels (PCIL) after controlling for nine common covariates. Results: Multiple regression showed that the two-way interaction between Ho and NEPI significantly predicted HOMA and PCIL, but not PCGL, after controlling for covariates. Simple regression slopes of Ho on HOMA and PCIL were explored and indicated that, at higher levels of NEPI, higher Ho was associated with higher HOMA (beta = 0.14, p < .05). Ho was not a significant predictor of HOMA at mean and lower levels of NEPI. Similar results were obtained for PCIL, but not PCGL. Cynicism, but not other subscales of Ho, was similarly related to insulin resistance and NEPI. Conclusion: Individuals with high stress and high hostility were more likely to have insulin resistance. It is important to study moderators in the relationship between hostility and insulin resistance. C1 Indiana Univ Purdue Univ, Dept Psychol, Indianapolis, IN 46205 USA. Butler Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Univ Miami, Dept Psychol, Miami, FL 33152 USA. Miriam Hosp, Ctr Behav Med, Providence, RI 02906 USA. Miriam Hosp, Ctr Prevent Med, Providence, RI 02906 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. VA Boston Healthcare Syst, Massachussetts Vet Epidemiol Res Informat Ctr, MAVERIC, Boston, MA USA. Univ Memphis, Dept Hlth & Sport Sci, Memphis, TN 38152 USA. Univ Memphis, Ctr Community Hlth, Memphis, TN 38152 USA. RP Zhang, JP (reprint author), Cleveland Clin Fdn, Dept Psychiat & Psychol, 9500 Euclid Ave,P57, Cleveland, OH 44195 USA. EM jpzhang2005@gmail.com RI Zhang, Jianping/L-9805-2016; OI Zhang, Jianping/0000-0001-6363-6362; Spiro III, Avron/0000-0003-4080-8621 FU NHLBI NIH HHS [HL37871]; NIA NIH HHS [AG02287] NR 62 TC 27 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 2006 VL 68 IS 5 BP 718 EP 726 DI 10.1097/01.psy.0000228343.89466.11 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 093YH UT WOS:000241205700011 PM 17012525 ER PT J AU Guerry, M Gimenes, M Caplan, D Rigalleau, F AF Guerry, Michele Gimenes, Manuel Caplan, David Rigalleau, Francois TI How long does it take to find a cause? An online investigation of implicit causality in sentence production SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY LA English DT Article ID PRONOMINAL COINDEXATION; PRONOUN RESOLUTION; DISCOURSE MODELS; TIME-COURSE; GENDER; COMPREHENSION; INFORMATION; INTEGRATION; VERBS AB Some interpersonal verbs show an implicit causality bias in favour of their subject or their object. Such a bias is generally seen in offline continuation tasks where participants are required to finish a fragment containing the verb (e. g., Peter annoyed Jane because...). The implicit causality bias has been ascribed to the subject's focusing on the initiator of the event denoted by the verb. According to this "focusing theory" the implicit cause has a higher level of activation, at least after the connective "because" has been read. Recently, the focusing theory has been criticized by researchers who used a probe recognition or reading-time methodology. However no clear alternative has been proposed to explain the offline continuation data. In this paper, we report three experiments using an online continuation task, which showed that subjects took more time to imagine an ending when the fragment to be completed contained an anaphor that was incongruent with the verbal bias (e. g., Peter annoyed Jane because she...). This result suggests that the offline continuation data could reflect the cognitive effort associated with finding a predicate with an agent incongruent with the implicit causality bias of a verb. In the discussion, we suggest that this effort could be related to the number of constraints that an incongruent clause must satisfy to be consistent with the causal structure of the discourse. C1 Univ Poitiers, Poitiers, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Guerry, M (reprint author), CNRS, FRE 2725, Lab Langage & Cognit, 99 Ave Recteur Pineau, F-86022 Poitiers, France. EM michele.guerry@mshs.univ-poitiers.fr FU NIDCD NIH HHS [DC04608] NR 27 TC 10 Z9 10 U1 1 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0218 J9 Q J EXP PSYCHOL JI Q. J. Exp. Psychol. PD SEP PY 2006 VL 59 IS 9 BP 1535 EP 1555 DI 10.1080/17470210500269105 PG 21 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA 073QD UT WOS:000239756800004 PM 16873107 ER PT J AU Blake, MA Singh, A Setty, BN Slattery, J Kalra, M Maher, MM Sahani, DV Fischman, AJ Mueller, PR AF Blake, Michael A. Singh, Ajay Setty, Bindu N. Slattery, James Kalra, Mannudeep Maher, Michael M. Sahani, Dushyant V. Fischman, Alan J. Mueller, Peter R. TI Pearls and pitfalls in interpretation of abdominal and pelvic PET-CT SO RADIOGRAPHICS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; DELAYED ENHANCED CT; FDG-PET; ADRENAL MASSES; HEPATOCELLULAR-CARCINOMA; ORAL CONTRAST; TECHNICAL CONSIDERATIONS; ATTENUATION CORRECTION; INTRAVENOUS CONTRAST; INITIAL-EXPERIENCE AB The interpretation of images obtained in the abdomen and pelvis can be challenging, and the coregistration of positron emission tomographic (PET) and computed tomographic (CT) scans may be especially valuable in the evaluation of these anatomic areas. PET-CT represents a major technologic advance, consisting of generally complementary modalities whose combined strength tends to overcome their respective weaknesses. However, this combined functional-structural imaging approach raises a number of controversial questions and presents some unique interpretative challenges. Accurate PET-CT scan interpretation requires awareness of the various pitfalls associated with the imaging components, both individually and in combination. The results of recent PET-CT studies have been very encouraging, but larger prospective studies will be needed to establish optimal hybrid scanning protocols. Applying sound imaging principles, paying attention to detail, and staying abreast of advances in this exciting new modality are necessary for harnessing the full diagnostic power of abdominopelvic PET-CT. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. RP Setty, BN (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM bsetty@partners.org OI Setty, Bindu/0000-0002-2749-6822 NR 58 TC 41 Z9 45 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2006 VL 26 IS 5 BP 1335 EP 1353 DI 10.1148/rg.265055208 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 083NR UT WOS:000240464900006 PM 16973768 ER PT J AU Ross, R Harisinghani, M AF Ross, Robert Harisinghani, Mukesh TI Prostate cancer imaging - What the urologic oncologist needs to know SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SUPERPARAMAGNETIC IRON-OXIDE; ASSESSING BIOCHEMICAL FAILURE; LYMPH-NODE METASTASES; CONTRAST-ENHANCED MRI; COLOR DOPPLER US; RADICAL PROSTATECTOMY; ENDORECTAL MR; LOCAL RECURRENCE; (18)FLUORINE-LABELED DEOXYGLUCOSE AB Appropriate imaging for prostate cancer patients depends on the clinical disease state of the patient and the question being asked. For patients who do not have a cancer diagnosis, ultrasound is the standard approach, in combination with a sextant biopsy. In the future, contrast-enhanced ultrasound and MR imaging-directed biopsy may improve biopsy yield and decrease biopsy number. For clinically localized disease, endorectal coil MR imaging and bone scanning may play a role in patients who have risk factors for extracapsular extension, but more data are needed to define the role of MR spectroscopy and lymphtrophic nanoparticle MR imaging. In the rising prostate-specific antigen (PSA) setting after definitive local therapy, endorectal coil MR imaging may help define local recurrence, whereas bone scanning can be useful in the setting of higher PSA or rapid PSA velocity. C1 Dana Farber Canc Inst, Boston, MA 02111 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Ross, R (reprint author), Dana Farber Canc Inst, Dana 1230,44 Binney St, Boston, MA 02111 USA. EM rwross@partners.org NR 91 TC 4 Z9 5 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 2006 VL 44 IS 5 BP 711 EP + DI 10.1016/j.rcl.2006.07.002 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 100LX UT WOS:000241671700006 PM 17030222 ER PT J AU Mahmood, U AF Mahmood, Umar TI Science to practice: Can a clinically used chemoembolization vehicle improve transgene delivery? SO RADIOLOGY LA English DT Editorial Material ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; GENE-THERAPY AB Kim et al have demonstrated in an animal model that focal transgene delivery to hepatic tumors is improved when performed with a clinically used chemoembolization vehicle. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 185 Cambridge St,Rm 8226, Boston, MA 02114 USA. EM mahmood@helix.mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2006 VL 240 IS 3 BP 619 EP 620 DI 10.1148/radiol.2403060761 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 078JF UT WOS:000240098200001 PM 16926318 ER PT J AU Visser, JJ van Sambeek, MRHM Hunink, MGM Redekop, WK van Dijk, LC Hendriks, JM Bosch, JL AF Visser, Jacob J. van Sambeek, Marc R. H. M. Hunink, M. G. Myriam Redekop, W. Ken van Dijk, Lukas C. Hendriks, Johanna M. Bosch, Johanna L. TI Acute abdominal aortic aneurysms: Cost analysis of endovascular repair and open surgery in hemodynamically stable patients with 1-year follow-up SO RADIOLOGY LA English DT Article ID EMERGENCY TREATMENT; FEASIBILITY; EUROSTAR; AAA AB Purpose: To retrospectively assess the in-hospital and 1-year follow-up costs of endovascular aneurysm repair and conventional open surgery in patients with acute infrarenal abdominal aortic aneurysm ( AAA) by using a resource-use approach. Materials and Methods: Institutional Review Board approval was obtained, and informed consent was waived. In-hospital costs for all consecutive patients ( 61 men, six women; mean age, 72.0 years) who underwent endovascular repair ( n = 32) or open surgery ( n = 35) for acute infrarenal AAA from January 1, 2001, to December 31, 2004, were assessed by using a resource-use approach. Patients who did not undergo computed tomography before the procedure were excluded from analysis. One-year follow-up costs were complete for 30 patients who underwent endovascular repair and for 34 patients who underwent open surgery. Costs were assessed from a health care perspective. Mean costs were calculated for each treatment group and were compared by using the Mann-Whitney U test ( alpha = .05). The influence of clinical variables on the total in-hospital cost was investigated by using univariate and multivariate analyses. Costs were expressed in euros for the year 2003. Results: Sex, age, and comorbidity did not differ between treatment groups ( P > .05). The mean total in-hospital costs were lower for patients who underwent endovascular repair than for those who underwent open surgery ( euro20 767 vs euro35 470, respectively; P = .004). The total costs, including those for 1-year follow-up, were euro23 588 for patients who underwent endovascular repair and euro36 448 for those who underwent open surgery ( P = .05). The results of multivariate analysis indicated that complications had a significant influence on total in-hospital cost; patients who had complications incurred total in-hospital costs that were 2.27 times higher than those for patients who had no complications. Conclusion: Total in-hospital costs and total overall costs, which included 1-year follow-up costs, were lower in patients with acute AAA who underwent endovascular repair than in those who underwent open surgery. C1 Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, NL-3015 GD Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Radiol, NL-3015 GD Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Surg, NL-3015 GD Rotterdam, Netherlands. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Erasmus Univ, Inst Med Technol Assessment, NL-3000 DR Rotterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. RP Bosch, JL (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Room Ee21-40B,Dr Molewaterplein 40, NL-3015 GD Rotterdam, Netherlands. EM j.l.bosch@erasmusmc.nl NR 29 TC 13 Z9 13 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2006 VL 240 IS 3 BP 681 EP 689 DI 10.1148/radiol.2403051005 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 078JF UT WOS:000240098200009 PM 16837669 ER PT J AU Ferencik, M Chan, RC Achenbach, S Lisauskas, JB Houser, SL Hoffmann, U Abbara, S Cury, RC Bouma, BE Tearney, GJ Brady, TJ AF Ferencik, Maros Chan, Raymond C. Achenbach, Stephan Lisauskas, Jennifer B. Houser, Stuart L. Hoffmann, Udo Abbara, Suhny Cury, Ricardo C. Bouma, Brett E. Tearney, Guillermo J. Brady, Thomas J. TI Arterial wall imaging: Evaluation with 16-section multidetector CT in blood vessel phantoms and ex vivo coronary arteries SO RADIOLOGY LA English DT Article ID SPIRAL COMPUTED-TOMOGRAPHY; OPTICAL COHERENCE TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC LESIONS; HISTOLOGICAL CLASSIFICATION; PLAQUE MORPHOLOGY; IN-VIVO; 16-SLICE; ACCURACY; STENOSES AB Purpose: To evaluate the diagnostic performance of 16-section multidetector computed tomography ( CT) for assessment of plaques in phantoms and ex vivo coronary arteries, with intravascular ultrasonography ( US) and optical coherence tomography ( OCT) as reference standards. Materials and Methods: Research protocol was HIPAA compliant and approved by institutional review board, without informed consent required. Blood vessel and lesion composition phantoms and ex vivo coronary arteries were imaged with 16-section CT. Wall areas of phantoms and ex vivo coronary arteries were measured with multidetector CT and intravascular US. Sensitivity and specificity for lipid detection were determined in lesion composition phantoms. CT numbers of blood vessel wall were determined in ex vivo coronary arteries and compared with lesion classification results from OCT. Agreement in dimensional measurements was compared ( paired t tests). CT numbers within blood vessel wall of CT cross sections classified as lipid rich, fibrous, and calcified at OCT were compared ( Kruskal-Wallis tests). Results: Mean blood vessel wall areas measured with CT and US in phantoms were 9.2 mm(2) +/- 1.8 ( standard deviation) and 10.4 mm(2) +/- 3.4 ( bias, -1.3 mm(2) +/- 3.1; P < .05), respectively. Mean blood vessel wall areas measured in ex vivo coronary arteries with CT and US were 10.9 mm(2) +/- 4.1 and 9.1 mm(2) +/- 3.1 ( bias, 1.8 mm(2) +/- 3.0; P < .001), respectively. Sensitivity and specificity of 93% and 92%, respectively, for identification of lipid-rich lesions were observed in lesion composition phantoms. Mean CT numbers in blood vessel wall of ex vivo coronary arteries identified at OCT as predominantly lipid rich, fibrous, and calcified were 29 HU +/- 43, 101 HU +/- 21, and 135 HU +/- 199, respectively ( P < .001). Conclusion: Determination of composition of individual plaques from attenuation values can be more challenging because of overlapping values for different tissue types. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Med 2, D-8520 Erlangen, Germany. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM maros_ferencik@hms.harvard.edu; rchan@alum.mit.edu FU NCI NIH HHS [5-T32 CA 09362 E20] NR 32 TC 33 Z9 35 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 SEP PY 2006 VL 240 IS 3 BP 708 EP 716 DI 10.1148/radiol.2403051204 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 078JF UT WOS:000240098200012 PM 16857982 ER PT J AU Mori, S Endo, M Kohno, R Asakura, H Kohno, K Yashiro, T Komatsu, S Kandatsu, S Baba, M AF Mori, Shinichiro Endo, Masahiro Kohno, Ryosuke Asakura, Hiroshi Kohno, Kazutoshi Yashiro, Tomoyasu Komatsu, Shuhei Kandatsu, Susumu Baba, Masayuki TI Respiratory correlated segment reconstruction algorithm towards four-dimensional radiation therapy using carbon ion beams SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE respiration; target volume; image quality; temporal resolution; carbon-beam ID BREATHING CONTROL ABC; CELL LUNG-CANCER; DEEP INSPIRATION; HOLD TECHNIQUE; CT-SCANNER; PERFORMANCE EVALUATION; TEMPORAL RESOLUTION; COMPUTED-TOMOGRAPHY; CLINICAL POTENTIALS; MOTION AB Purpose: To enhance the precision of treatment planning for tumors which move under respiration, we developed a respiratory-correlated segment reconstruction method (RS) based on the Feldkamp-Davis-Kress algorithm (FDK) which provides high temporal resolution and a high signal-to-noise ratio. We compared full-scan (FS-FDK) and RS-FDK with regard to dose distribution in heavy ion treatment planning. Materials and methods: Data acquisition for RS-FDK is done using a respiratory sensing system in cine scan mode with a 256-multi-detector row CT (256-MDCT). To evaluate the accuracy of irradiation of moving tumors, dose distributions with each algorithm were compared in heavy ion treatment planning using beam parameters obtained with FS-FDK. Results: Images obtained using RS-FDK did not show motion artifacts and visualized the edges of the liver and pulmonary vessels more clearly than those with FS-FDK. The iso-dose distributions for FS-FDK covered the target volume; in contrast, RS-FDK with the beam parameter of FS-FDK image provided an insufficient dose to the target and a considerable dose to normal tissues around it. Conclusions: The information provided by RS-FDK improves accuracy in the prescription of dose-to-target volume. Further, RS-FDK allows greater precision in the delivery of radiotherapy, including 4D radiation therapy. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Radiol Sci, Radiol Protect Sect, Chiba 260, Japan. Natl Inst Radiol Sci, Dept Planning & Management, Chiba 260, Japan. Natl Canc Ctr E, Dept Radiat Oncol, Kashiwa, Chiba, Japan. Accelerator Engn Corp, Inage Ku, Chiba, Japan. Hosp Chiba, Natl Inst Radiol Sci, Chiba, Japan. RP Mori, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM smori1@partners.org OI Mori, Shinichiro/0000-0002-0412-4399 NR 45 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2006 VL 80 IS 3 BP 341 EP 348 DI 10.1016/j.radonc.2006.07.035 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094TF UT WOS:000241261200012 PM 16949695 ER PT J AU Siddiqa, A Cavazos, DA Marciniak, RA AF Siddiqa, Aisha Cavazos, David A. Marciniak, Robert A. TI Targeting telomerase SO REJUVENATION RESEARCH LA English DT Article ID IMMORTAL HUMAN-CELLS; HUMAN CANCER-CELLS; IN-VITRO; SACCHAROMYCES-CEREVISIAE; ALTERNATIVE MECHANISM; MAMMALIAN TELOMERES; CELLULAR SENESCENCE; LENGTH MAINTENANCE; GENE-EXPRESSION; ALT CELLS AB Given the constitutive expression of telomerase in the majority of human tumors, telomerase inhibition is an attractive, broad-spectrum therapeutic target for cancer treatment. Therapeutic strategies for inhibiting telomerase activity have included both targeting components of telomerase (the protein component, TERT, or the RNA component, TERC) or by directly targeting telomere DNA structures. Recently a combination telomerase inhibition therapy has been studied also. The TERT promoter has been used to selectively express cytotoxic gene(s) in cancer cells and a TERT vaccine for immunization against telomerase has been tested. The 10% to 15% of immortalized cancer cells that do not express telomerase use a recombination-based mechanism for maintaining telomere structures that has been called the alternative lengthening of telomeres (ALT). In view of the increasing study of telomerase inhibitors as anticancer treatments, it will be crucial to determine whether inhibition of telomerase will select for cancer cells that activate ALT mechanisms of telomere maintenance. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Marciniak, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM marciniak@uthscsa.edu FU NIA NIH HHS [1T32AG021890]; NIDCR NIH HHS [DE14318] NR 78 TC 10 Z9 11 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD FAL PY 2006 VL 9 IS 3 BP 378 EP 390 DI 10.1089/rej.2006.9.378 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 074TN UT WOS:000239834800003 PM 16859479 ER PT J AU Adams, SG Anzueto, A Briggs, DD Menjoge, SS Kesten, S AF Adams, Sandra G. Anzueto, Antonio Briggs, Dick D., Jr. Menjoge, Shailendra S. Kesten, Steven TI Tiotropium in COPD patients not previously receiving maintenance respiratory medications SO RESPIRATORY MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; dyspnea; forced expiratory volume in 1 s; lung function; quality of life; tiotropium ID OBSTRUCTIVE-PULMONARY-DISEASE; TRANSITION DYSPNEA INDEX; QUALITY-OF-LIFE; OFFICE SPIROMETRY; DIAGNOSIS; PROGRAM AB Introduction: Use of maintenance bronchodilator therapy is currently recommended in symptomatic patients with Chronic obstructive pulmonary disease (COPD) and in those with Stage 11 or greater COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Because no prospective data describe when rescue therapy alone is insufficient or the optimal time to start maintenance therapy, it is unclear whether maintenance therapy has benefits in milder disease. To explore potential benefits we asked: Does once-daily tiotropium improve lung function, health status, and/or symptoms in "undertreated" COPD patients (i.e., those who are not receiving maintenance bronchodilator therapy) or patients considered by their health care providers as having milder disease? Methods: A post-hoc analysis of data from COPD patients participating in two, 1-year, placebo-controtted trials with tiotropium was performed. Patients were defined as "undertreated" if they received no respiratory medication or only as needed short-acting beta-agonists prior to enrollment. Measures included serial spirometry, Transition Dyspnea Index (TDI), and St. George's Respiratory Questionnaire (SGRQ). Results: Of 921 patients enrolled, 218 (23.7%) were "undertreated": 130 received tiotropium; 88 received placebo. Demographics for the two treatment groups were comparable. Tiotropium-treated patients had significantly improved forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) compared with patients using placebo on all study days. Additionally, TDI and SGRQ scores significantly improved with tiotropium compared with placebo. Conclusions: Once-daily tiotropium provides significant improvement in lung function, health status, and dyspnea when used as maintenance therapy in undertreated COPD patients who were not previously receiving maintenance bronchodilator therapy. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Alabama, Birmingham, AL 35294 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Adams, SG (reprint author), Univ Texas, Hlth Sci Ctr, 7400 Merton Minter 111E, San Antonio, TX 78229 USA. EM adamssg@uthscsa.edu NR 29 TC 16 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD SEP PY 2006 VL 100 IS 9 BP 1495 EP 1503 DI 10.1016/j.rmed.2006.03.034 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 074TE UT WOS:000239833900002 PM 16698259 ER PT J AU Warden, SM Mukai, S AF Warden, Scott M. Mukai, Shizuo TI Pars plana vitrectomy in eyes treated for retinoblastoma SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT Conference of the Pediatric-Retinal-Study-Group CY JAN 27-30, 2005 CL Hawks Cay, FL SP Pediat Retinal Study Grp ID INTRAOCULAR SURGERY; RETINAL-DETACHMENT; REPAIR AB Background: As conservative treatments for retinoblastoma become more prevalent, there will be a greater number of ocular complications developing in eyes that previously would have been enucleated. Pars plana vitrectomy (PPV) is needed to manage some of these complications. Methods: The authors evaluated three consecutive cases of PPV in eyes that were successfully treated for retinoblastoma from the Retina Service of the Massachusetts Eye and Ear Infirmary (MEEI) performed between 1989 and 2004. A review of the literature to date regarding PPV after treatment for retinoblastoma was also performed. Results: There was no tumor reactivation in the three cases at MEEI. Vision was maintained at light perception in one case, and there was improvement in vision from hand motions to 20/80 and 20/400 to 20/160 in two cases. Twelve of the 24 cases reviewed in the literature were found to have significant complications of recurrent tumor, need for enucleation, and/or systemic metastasis. Conclusion: PPV is associated with significant risks in eyes previously treated for retinoblastoma and should be reserved for monocular patients with no other alternative for retaining visual function. Areas that may influence outcome include different treatment modalities and length of time of documented tumor inactivity before PPV. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Warden, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM shizuo_mukai@meei.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2006 VL 26 IS 7 SU S BP S53 EP S56 DI 10.1097/01.iae.0000244289.01875.78 PG 4 WC Ophthalmology SC Ophthalmology GA 176LK UT WOS:000247086400012 PM 16946680 ER PT J AU Wang, X Hsu, HC Wang, Y Edwards, CK Yang, P Wu, Q Mountz, JD AF Wang, X. Hsu, H. -C. Wang, Y. Edwards, C. K., III Yang, P. Wu, Q. Mountz, J. D. TI Phenotype of genetically regulated thymic involution in young BXD RI strains of mice SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; OXIDATIVE STRESS; INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; APOPTOSIS; AGE; IL-7; EXPRESSION; THYMOPOIESIS; MOUSE AB Age-related thymic involution is a multifactorial process related to age-related changes in intrathymic T-cell development and cytokines. In contrast, early thymic involution, because of genetic differences that cause rapid or slow thymic involution at younger age, is less well characterized. Here, we analysed three representative rapid-involuting strains of mice, BXD 8, 18 and 32, compared with three representative slow-involuting strains, BXD 9, 19 and 29, all at 2 months of age. In rapid-involuting strains compared with slow involution strains, thymocyte production, as indicated by CD4(+) and CD8(+) T-cell receptor recombination excision circle (TREC), were decreased. Rapid-involution strains of mice exhibited a developmental block at the DN1 to DN2 and CD4(-)CD8(-) (DN) to CD4(+)CD8(+) (double positive, DP) transition stages. There was also increased susceptibility to H2O2-induced apoptosis, decreased thymic expression of IL-7, decreased expression of an IL-7 downstream anti-apoptosis gene, Bcl-2, and increased expression of a pro-apoptotic gene, Bad. In contrast, IL-7R expression was higher on DN thymocytes of rapid-involution strains. The increased expression of IL-7R was associated with an increased thymocyte proliferation in response to anti-CD3 + IL-7 or anti-CD3 + IL-12 + IL-7. These findings indicate that, even at young age, genetic differences of IL-7/IL-7R regulation pathway in BXD strains of mice can lead to characteristic phenotypic changes that have been previously associated with age-related thymic involution. C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Colorado, Dept Dermatol, Aurora, CO USA. Hlth Sci Ctr Fitzsimmons, Aurora, CO USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, 701 S 19th St,LHRB 473, Birmingham, AL 35294 USA. EM john.mountz@ccc.uab.edu FU NIAID NIH HHS [R01 AI046990, R01 AI 046990-05]; NIAMS NIH HHS [P30 AR050948, P30 AR 50948] NR 44 TC 9 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD SEP PY 2006 VL 64 IS 3 BP 287 EP 294 DI 10.1111/j.1365-3083.2006.01813.x PG 8 WC Immunology SC Immunology GA 072GI UT WOS:000239661500017 PM 16918698 ER PT J AU Fan, XD Liu, E Pristach, C Goff, DC Henderson, DC AF Fan, Xiaoduo Liu, Emily Pristach, Cynthia Goff, Donald C. Henderson, David C. TI Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE insulin; psychopathology; schizophrenia ID INDUCED WEIGHT-GAIN; CLINICAL ANTIPSYCHOTIC TRIALS; CENTRAL NERVOUS-SYSTEM; METABOLIC SYNDROME; BODY-WEIGHT; RAT-BRAIN; PREVALENCE; CLOZAPINE; RECEPTORS; MEMORY AB Objective: Recent studies have suggested a beneficial role of insulin on brain function and psychological well-being. This study was undertaken to examine whether fasting serum insulin levels are associated with the psychopathology profile in a cross-sectional sample of acutely ill non-diabetic inpatients with schizophrenia. Methods: Subjects were recruited from a county hospital. Each subject underwent a psychopathology assessment with the Positive and Negative Syndrome Scale (PANSS). A fasting blood sample was taken to measure serum insulin, plasma glucose and lipids. Results: Twenty-six subjects (7 females, 19 males) were included in the study. Pearson correlation analysis showed significant inverse relationships between serum insulin level and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores (r=-0.41, p=0.037; r=-0.49, p=0.010; r=-0.45, p=0.023, respectively). However, there was no significant relationship between serum insulin level and PANSS-Negative Symptom subscale score (r= -0.13, p = 0.53). Partial correlation analysis showed that the inverse relationships between serum insulin levels and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores became even stronger after controlling for potential confounding variables including age, gender, race, family history of mental illness, age of illness onset and body-mass index (BMI). Conclusions: Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia. It is speculated that insulin might improve clinical symptoms of schizophrenia by interacting with dopamine and other neurotransmitter systems. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Womens & Childrens Hosp, Div Endocrinol, Buffalo, NY USA. SUNY Buffalo, Sch Biol & Med Sci, Buffalo, NY 14260 USA. Erie Cty Med Ctr & Labs, Dept Psychiat, Buffalo, NY USA. RP Fan, XD (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM xfan@partners.org NR 36 TC 8 Z9 9 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2006 VL 86 IS 1-3 BP 30 EP 35 DI 10.1016/j.schres.2006.04.010 PG 6 WC Psychiatry SC Psychiatry GA 130BV UT WOS:000243775100004 PM 16750348 ER PT J AU Talamo, A Centorrino, F Tondo, L Dimitri, A Hennen, J Baldessarini, RJ AF Talamo, A. Centorrino, F. Tondo, L. Dimitri, A. Hennen, J. Baldessarini, R. J. TI Comorbid substance-use in schizophrenia: Relation to positive and negative symptoms SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; comorbidity; substance use disorder; negative symptoms; positive symptoms; PANSS ID USE DISORDERS; RISK FACTOR; DRUG-ABUSE; CANNABIS; PSYCHOSIS; ONSET; PSYCHOPATHOLOGY; IMPULSIVITY; PREVALENCE; SEVERITY AB As substance use disorders (SUD) are common in schizophrenia patients, we tested the hypothesis that comorbid patients (SUD [+]) have more positive vs. negative symptoms than non-comorbid (SUD[-]) patients. From reports identified by literature-searching we compared Positive and Negative Syndrome Scale (PANSS) ratings in schizophrenia patients with and without SUD using meta-analytic methods. Among 9 comparisons (N=725 subjects), SUD[+] patients were more often men, and abused alcohol > cannabis > cocaine. SUD[+] patients had very significantly higher PANSS-positive, and lower PANSS-negative scores. Comorbid SUD in schizophrenia patients was associated with male sex and higher PANSS positive to lower negative scores. Cause-effect relationships remain to be clarified. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Mclean Div, Int Consortium Psychot & Bipolar Disorders Res, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Roma La Sapienza, S Andrea Hosp, I-00185 Rome, Italy. Univ Cagliari, Dept Psychol, Sardinia, Italy. RP Centorrino, F (reprint author), McLean Hosp, N Belknap 3, 115 Mill St, Belmont, MA 02478 USA. EM fcentorrino@mclean.harvard.edu OI Talamo, Alessandra/0000-0001-7321-9247 NR 38 TC 47 Z9 48 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2006 VL 86 IS 1-3 BP 251 EP 255 DI 10.1016/j.schres.2006.04.004 PG 5 WC Psychiatry SC Psychiatry GA 130BV UT WOS:000243775100032 PM 16750347 ER PT J AU Kassarjian, A AF Kassarjian, Ara TI Hip MR arthrography and femoroacetabular impingement SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE hip; impingement; labrum; MR; arthrography; MR arthrography; sport injuries ID ACETABULAR LABRUM; CARTILAGE LESIONS; FEMORAL-NECK; RETROVERSION; OSTEOTOMY; FEATURES; ANATOMY AB Hip pain is a common complaint among athletes of all ages. Advances in imaging and treatment are changing the paradigm of evaluation and management of hip pain. The role of abnormal femoral and acetabular morphology and lesions of the acetabular labrum and cartilage is increasingly recognized as being crucial in the development of degenerative change. In addition, femoroacetabular impingement is increasingly recognized as an eiiologic factor in hip pain. This article discusses techniques of hip magnetic resonance (MR) arthrography, normal anatomy seen at hip MR arthrography, common intraarticular pathologies in patients with hip pain, and imaging findings of femoroacetabular impingement. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Musculoskeletal Radiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Kassarjian, A (reprint author), Paseo Castellano 141 Planta 18,Edificio Cuzco 4, Madrid 28046, Spain. NR 27 TC 19 Z9 20 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD SEP PY 2006 VL 10 IS 3 BP 208 EP 219 DI 10.1055/s-2006-957174 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 177KH UT WOS:000247151500005 PM 17195129 ER PT J AU Greer, DM AF Greer, David M. TI Mechanisms of injury in hypoxic-ischemic encephalopathy: Implications to therapy SO SEMINARS IN NEUROLOGY LA English DT Article DE hypoxia; ischemia; cardiac arrest; encephalopathy ID HOSPITAL CARDIAC-ARREST; HIPPOCAMPAL CA1 NEURONS; CIRCULATORY ARREST; COMATOSE SURVIVORS; CEREBRAL-ISCHEMIA; CARDIOPULMONARY-RESUSCITATION; HYPERBARIC-OXYGEN; MILD HYPOTHERMIA; CLINICAL-TRIAL; BRAIN AB Cardiac arrest survivors commonly suffer ischemic brain injury, and understanding the mechanisms of injury is essential to providing insight for effective therapies for brain protection. Injury can occur at the time of the cardiac arrest and is dependent not only on the duration but also the degree of impaired circulation. Injury can be ongoing even after the return of spontaneous circulation, giving the clinician an additional window of opportunity to treat and protect the injured brain. This section will review the molecular basis of injury with cardiac arrest and will elucidate the different mechanisms of injury between cardiac arrest, pure respiratory arrest, and arrest secondary to toxins (e.g., carbon monoxide). The rationale for multiple postarrest therapies, such as hypothermia and induced hypertension, will also be reviewed. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, 32 Fruit St, Boston, MA 02114 USA. NR 46 TC 33 Z9 41 U1 0 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD SEP PY 2006 VL 26 IS 4 BP 373 EP 379 DI 10.1055/s-2006-948317 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 075OX UT WOS:000239896200003 PM 16969737 ER PT J AU Rosenthal, DI AF Rosenthal, Daniel I. TI What makes a case report publishable? SO SKELETAL RADIOLOGY LA English DT Editorial Material DE journalism; medical; editorial policies; publication formats C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Radiol, Suite 250,175 Cambridge St, Boston, MA 02114 USA. EM dirosenthal@partners.org NR 2 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD SEP PY 2006 VL 35 IS 9 BP 627 EP 628 DI 10.1007/s00256-006-0188-z PG 2 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 072DJ UT WOS:000239652500001 PM 16874520 ER PT J AU Ouellette, H Thomas, BJ Nelson, E Torriani, M AF Ouellette, Hugue Thomas, Bijoy J. Nelson, Erik Torriani, Martin TI MR imaging of rectus femoris origin injuries SO SKELETAL RADIOLOGY LA English DT Article DE MR imaging; rectus femoris origin; injury ID AVULSION FRACTURE; MUSCLE AB Objective: To describe the MR imaging findings of acute and chronic rectus femoris origin (RFO) injuries. Materials and methods: A retrospective review of pelvic and hip MR imaging procedures was performed over a 4-year period for detection of cases with injuries to the RFO. Subjects were classified as having either acute or chronic symptoms. MR imaging studies, radiographs, CT scans, radiology reports, medical records, and operative notes were reviewed. Imaging analysis was directed to assess injuries affecting the direct and indirect heads of the RFO. Concurrent osseous, cartilaginous and musculotendinous injuries were tabulated. Results: The incidence of RFO injuries on MR imaging was 0.5% (17/3160). With the exception of one case of anterior inferior iliac spine apophysis avulsion and partial tear of the direct head of RFO, all subjects had indirect head of RFO injuries (acute injury 8/9, chronic injury 8/8). Partial tear of the direct head of RFO was less frequently seen (acute injury 3/9, chronic injury 2/8). Partial tears of the conjoint tendon were least frequent (acute 1/9, chronic 2/8). No full-thickness tears of the RFO were noted. Associated labral tears were seen in only one case, with no other concomitant abnormality of the articular cartilage or surrounding soft tissues. All RFO injuries were treated non-operatively. Conclusion: Injuries of the RFO are uncommon on MR examinations of pelvis/hips and may occur in a sequence progressing from indirect head injury to involvement of direct head and conjoint tendon in more severe cases. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Ouellette, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Yaw 6046, Cambridge, MA 02138 USA. EM haouellette@partners.org NR 12 TC 23 Z9 23 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD SEP PY 2006 VL 35 IS 9 BP 665 EP 672 DI 10.1007/s00256-006-0162-9 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 072DJ UT WOS:000239652500007 PM 16738911 ER PT J AU Chang, VW AF Chang, Virginia W. TI Racial residential segregation and weight status among US adults SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE racial segregation; obesity; body mass index; socioeconomic factors; contextual analysis; health inequalities; USA ID BODY-MASS-INDEX; BLACK-AND-WHITE; UNITED-STATES; AFRICAN-AMERICANS; INFANT-MORTALITY; OBESITY; HEALTH; RACE; POVERTY; DISPARITIES AB While the segmentation of residential areas by race is well known to affect the social and economic well-being of the segregated minority group in the United States, the relationship between segregation and health has received less attention. This study examines the association between racial residential segregation, as measured by the isolation index, and individual weight status in US metropolitan areas. Multi-level, nationally representative data are used to consider the central hypothesis that segregation is positively associated with weight status among African Americans, a group that is hyper-segregated and disproportionately affected by unhealthy weight outcomes. Results show that among non-Hispanic blacks, higher racial isolation is positively associated with both a higher body mass index (BMI) and greater odds of being overweight, adjusting for multiple covariates, including measures of individual socioeconomic status. An increase of one standard deviation in the isolation index is associated with a 0.423 unit increase in BMI (p < 0.01), and a 14% increase in the odds of being overweight (p < 0.01). Among whites, there is no significant association between the isolation index and weight status. These findings suggest that in addition to differences among people, differences among places and, in particular, differences in the spatial organization of persons may be relevant to health policy and promotion efforts. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. Univ Penn, Populat Studies Ctr, Philadelphia, PA 19104 USA. VAMC, Ctr Hlth Eqi Res & Promot, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Chang, VW (reprint author), Univ Penn, Sch Med, Dept Med, 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vwchang@mail.med.upenn.edu FU NICHD NIH HHS [K12-HD-043459] NR 47 TC 102 Z9 102 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD SEP PY 2006 VL 63 IS 5 BP 1289 EP 1303 DI 10.1016/j.socscimed.2006.03.049 PG 15 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 075HS UT WOS:000239876000016 PM 16707199 ER PT J AU DeAngelis, MM AF DeAngelis, Margaret M. TI Retinitis pigmentosa and common variable immunodeficiency disease: Associated or separate? SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID USHER-SYNDROME; MUTATIONS; SPECTRUM; GENES; RPGR; RP2 C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP DeAngelis, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM margaret_deangelis@hms.harvard.edu RI DeAngelis, e/J-7863-2015 NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD SEP PY 2006 VL 99 IS 9 BP 914 EP 914 DI 10.1097/01.smj.0000232974.47599.16 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 134GY UT WOS:000244072700004 PM 17004520 ER PT J AU Gazda, HT Kho, AT Sanoudou, D Zaucha, JM Kohane, IS Sieff, CA Beggs, AH AF Gazda, Hanna T. Kho, Alvin T. Sanoudou, Despina Zaucha, Jan M. Kohane, Isaac S. Sieff, Colin A. Beggs, Alan H. TI Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia SO STEM CELLS LA English DT Article DE Diamond-Blackfan anemia; bone marrow failure; global gene expression; ribosomal protein genes; apoptosis cancer ID IN-VITRO; PROGENITOR CELLS; LEPTIN RECEPTOR; DNA-DAMAGE; C-MYB; DIFFERENTIATION; HEMATOPOIESIS; S19; IDENTIFICATION; DEFICIENCY AB Diamond-Blackfan anemia (DBA) is a broad developmental disease characterized by anemia, bone marrow (BM) erythroblastopenia, and an increased incidence of malignancy. Mutations in ribosomal protein gene S19 (RPS19) are found in similar to 25% of DBA patients; however, the role of RPS19 in the pathogenesis of DBA remains unknown. Using global gene expression analysis, we compared highly purified multipotential, erythroid, and myeloid BM progenitors from RPS19 mutated and control individuals. We found several ribosomal protein genes downregulated in all DBA progenitors. Apoptosis genes, such as TNFRSF10B and FAS, transcriptional control genes, including the erythropoietic transcription factor MYB (encoding c-myb), and translational genes were greatly dysregulated, mostly in diseased erythroid cells. Cancer-related genes, including RAS family oncogenes and tumor suppressor genes, were significantly dysregulated in all diseased progenitors. In addition, our results provide evidence that RPS19 mutations lead to codownregulation of multiple ribosomal protein genes, as well as downregulation of genes involved in translation in DBA cells. In conclusion, the altered expression of cancer-related genes suggests a molecular basis for malignancy in DBA. Downregulation of c-myb expression, which causes complete failure of fetal liver erythropoiesis in knockout mice, suggests a link between RPS19 mutations and reduced erythropoiesis in DBA. C1 Childrens Hosp, Genom Program, Informat Program, Boston, MA 02115 USA. Childrens Hosp, Div Geriatr, Informat Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. Acad Athens, Fdn Biomed Res, GR-10673 Athens, Greece. Univ Gdansk, Sch Med, Dept Hematol Oncol, PL-80952 Gdansk, Poland. RP Gazda, HT (reprint author), Childrens Hosp, Genom Program, Informat Program, 300 Longwood Ave, Boston, MA 02115 USA. EM hanna.gazda@childrens.harvard.edu RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Sanoudou, Despina/0000-0003-3704-1941; Beggs, Alan/0000-0001-8818-0568 FU NHLBI NIH HHS [P01-HL99021, R01 HL064775, R01-HL64775]; NIAMS NIH HHS [R01 AR044345, R01-AR044345]; NINDS NIH HHS [NS40828, P01 NS040828, P01-NS40828, P50 NS040828, R01 NS047527, R01-NS047527] NR 46 TC 48 Z9 50 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 2006 VL 24 IS 9 BP 2034 EP 2044 DI 10.1634/stemcells.2005-0554 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085YG UT WOS:000240639700005 PM 16741228 ER PT J AU Warshaw, AL Sarr, MG AF Warshaw, Andrew L. Sarr, Michael G. TI Special section: International medical graduates and surgical training in the United States SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT506, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 SEP PY 2006 VL 140 IS 3 BP 335 EP 335 DI 10.1016/j.surg.2006.06.003 PG 1 WC Surgery SC Surgery GA 084ED UT WOS:000240513900002 ER PT J AU Sandberg, WS Canty, T Sokal, SM Daily, B Berger, DL AF Sandberg, Warren S. Canty, Timothy Sokal, Suzanne M. Daily, Bethany Berger, David L. TI Financial and operational impact of a direct-from-PACU discharge pathway for laparoscopic cholecystectomy patients SO SURGERY LA English DT Article ID OUTPATIENT PROCEDURE; ANALGESIA; RECOVERY; SAFE; CARE AB Background. We assessed the operational and financial impact of discharging laparoscopic cholecystectomy (LC) patients directly from the postanesthetic care unit (PACU) in comparison with post-transfer discharge from a hospital bed in a busy academic hospital. Methods. We retrospectively compared 6 months of performance (bed utilization; recovery room and hospital length of stay; complications; readmissions; hospital costs, revenue, and margin) after implementation of PACU discharges (case patients) to the corresponding 6 months in the prior year (control patients). Results. After implementation, 66% of LC case patients were discharged on the day of surgery, compared with 29% in the control group (P < .05). Eighty percent of the day-of-surgery discharges were directly from the PACU Shifting to PACU discharge saved 1 in-hospital bed transfer and 1 bed-day for each PACU discharge. Recovery room length of stay for PACU discharge patients was 26% longer than for hospital discharge patients (P = NS). Average hospital length of stay for all patients discharged on the day of surgery was 3.2 hours shorter (P < .05) for case patients (80% PACU discharge) than for control patients. There were no readmissions in the PACU discharge group and no difference in complications. While costs, revenue, and net margin for PACU discharge patients were reduced by 40% to 50% (P < .02) relative to floor discharge patients, the hospital's net margin for the combined case patient group was preserved relative to the control group. Conclusions. PACU discharge of LC patients significantly reduces bed utilization, decreases in-hospital transfers, and allows congested hospitals to better accommodate patient care needs and generate additional revenue. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Decis Support & Qual Management Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Operating Room Adm, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM wsandberg@partners.org OI Sandberg, Warren/0000-0002-9246-777X NR 20 TC 9 Z9 9 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 SEP PY 2006 VL 140 IS 3 BP 372 EP 378 DI 10.1016/j.surg.2006.02.007 PG 7 WC Surgery SC Surgery GA 084ED UT WOS:000240513900011 PM 16934598 ER PT J AU Avansino, JR Chen, DC Hoagland, VD Woolman, JD Stelzner, M AF Avansino, Jeffrey R. Chen, David C. Hoagland, Vicki D. Woolman, Jacob D. Stelzner, Matthias TI Orthotopic transplantation of intestinal mucosal organoids in rodents SO SURGERY LA English DT Article ID BILE-ACID MALABSORPTION; STEM-CELL TRANSPLANTATION; NUTRIENT TRANSPORT; ILEAL RESECTION; SMALL-BOWEL; RAT; DIFFERENTIATION; IDENTIFICATION; ENTEROCYTES; ONTOGENY AB Background. Orthotopic transplantation of intestinal mucosal organoids that contain putative mucosal stem cells serves as an important step toward implementing intestinal gene therapy and treatment for malabsorption syndromes in animals and humans. We hypothesized that intestinal mucosal organoids can be transplanted along the axis of the small bowel giving rise to a neomucosa expressing proteins of its donor origin. Methods. Epithelial organoids were harvested from neonatal mice or rat small intestine with the use of a combination of enzymatic digestion with dispose and collagenase, and gravity sedimentation. In adult syngeneic recipients, a 7-cm segment of midjejunum was isolated, leaving its vascular pedicle intact. The remaining proximal and distal segments were anastomosed to restore intestinal continuity. The isolated segments were randomly subjected to surgical or chemical mucosectomy with a chelator solution for 30, 45, or 60 minutes and then compared. Histologic examination was used to confirm the presence of enterocytes, goblet cells, enteroendocrine cells, and Paneth cells in the neomucosal segments. To confirm the presence of ileal bile acid transporter (IBAT) gene message and function, we measured sodium-dependent We acid uptake and IBAT-messenger RNA. Immunohistochemical examination using anti-IBAT antibodies was performed to demonstrate the expression of IBAT in the neomucosal segments. Experiments were repeated in a murine model transgenic for the green fluorescent protein to verify donor origin of the engrafted mucosa expressing IBAT. Results. The area of peak IBAT function was found to be located in the terminal ileum. Organoid units harvested from this region were capable of generating a small-bowel neoileal mucosa after being seeded into the jejunum. This mucosa was histologically confirmed to differentiate into all 4 intestinal lineages and to express MAT signal, confirming its donor-derived origin. Optimal engraftment of mucosa expressing the IBAT protein was found in isolated jejunal segments debrided for 45 minutes. Sodium-dependent bile acid uptake was 5 fold higher in the neoileum, compared with the jejunum. IBAT-mRNA levels in the neoileum were 18-100-fold higher than those in the jejunum. Areas of green fluorescent protein-positive mucosa stained positively with anti-IBAT antibody in adjacent sections,. suggesting that the regenerated mucosa is from transplanted ileal stem cells. Conclusions. Orthotopic transplantation of epithelial organoids containing ileal stem cells was used to generate a neoileal mucosa that expressed all 4 intestinal lineages along with a new zone of active bile acid uptake and IBA T expression in a recipient jejunal segment. C1 Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90024 USA. Univ Washington, Dept Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Chen, DC (reprint author), Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Hlth Care Syst, 10833 Le Conte Ave, Los Angeles, CA 90024 USA. EM dcchen@mednet.ucla.edu NR 38 TC 21 Z9 21 U1 0 U2 1 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 SEP PY 2006 VL 140 IS 3 BP 423 EP 434 DI 10.1016/j.surg.2006.03.012 PG 12 WC Surgery SC Surgery GA 084ED UT WOS:000240513900018 PM 16934605 ER PT J AU Warshaw, AL AF Warshaw, Andrew L. TI Ether Day, 1846, revisited SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), 55 Fruit St,WHT506, Boston, MA 02114 USA. EM awarshaw@partners.org NR 2 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 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2006 VL 140 IS 3 BP 472 EP 473 DI 10.1016/j.surg.2006.06.011 PG 2 WC Surgery SC Surgery GA 084ED UT WOS:000240513900025 PM 16934612 ER PT J AU Greenberg, JH Reivich, M Gordon, JT Schoenhoff, MB Patlak, CS Dratman, MB AF Greenberg, Joel H. Reivich, Martin Gordon, Janice T. Schoenhoff, Monika B. Patlak, Clifford S. Dratman, Mary B. TI Imaging triiodothyronine binding kinetics in rat brain: A model for studies in human subjects SO SYNAPSE LA English DT Article DE thyroid; autoradiography; receptors; triiodothyronine ID POSITRON-EMISSION-TOMOGRAPHY; THYROID-HORMONE RECEPTORS; TIME UPTAKE DATA; C-ERB; REGIONAL DISTRIBUTION; GRAPHICAL EVALUATION; TRANSFER CONSTANTS; AXONAL-TRANSPORT; MOOD DISORDERS; LOCALIZATION AB Many lines of evidence indicate a role for thyroid hormones in the expression of cognitive and affective disorders. These conditions constitute a large proportion of the illness burden in the general population. Unfortunately, presently available diagnostic procedures cannot adequately identify these problems. To determine whether imaging studies of thyroid hormone kinetics in brain might be feasible in patients with these disorders, an autoradiographic method for measuring thyroid hormone kinetics was developed. Twenty-five awake adult rats received high specific activity [I-125]-triiodothyronine (T-3*). Brains were obtained at intervals from 5 through 300 min after i.v, hormone administration. Every 5th frozen section was thaw mounted and exposed to film. To determine whether T-3 was responsible for the autoradiographic images, the intervening sections were assembled while frozen in regional tissue pools and were extracted and then analyzed by high-performance liquid chromatography. The results demonstrated that radioactivity was almost entirely due to T-3*(similar to 90%) while small amounts of hormone metabolites, including [I-125]iodine accounted for the remainder. Regional concentrations of label in autoradiograms were measured by densitometry in hippocampus (CA1, CA2, CA3, and dentate gyrus), cerebellum (molecular and granular cell layers), caudate nucleus, and amygdala. Unexpectedly and interestingly, the results demonstrated that binding through 5 h was mainly irreversible. Regional values of the net uptake rate constant of T-3* or influx constant, K-i, were determined from the time course of the T-3* data, showing significant differences among regions. These results suggest that imaging of labeled thyroid hormone ligands by positron emission tomography or single photon emission computed tomography may be feasible and would potentially provide useful information relevant to T-3 processing in the brain during a variety of drug and disease-induced conditions. C1 Univ Penn, Cerebrovasc Res Ctr, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Greenberg, JH (reprint author), Univ Penn, Cerebrovasc Res Ctr, Dept Neurol, 415 Stemmler Hall,3450 Hamilton Walk, Philadelphia, PA 19104 USA. EM joel@mail.med.upenn.edu FU NIMH NIH HHS [MH45252, MH44210]; NINDS NIH HHS [NS33875, NS10939] NR 54 TC 5 Z9 5 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP 1 PY 2006 VL 60 IS 3 BP 212 EP 222 DI 10.1002/syn.20293 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 061SY UT WOS:000238894100004 PM 16739120 ER PT J AU Xiang, Z Liao, RL Kelly, MS Spector, M AF Xiang, Zhou Liao, Ronglih Kelly, Matthew S. Spector, Myron TI Collagen-GAG scaffolds grafted onto myocardial infarcts in a rat model: A delivery vehicle for mesenchymal stem cells SO TISSUE ENGINEERING LA English DT Article ID BONE-MARROW-CELLS; BIOENGINEERED CARDIAC GRAFTS; SMOOTH-MUSCLE ACTIN; MYOBLAST TRANSPLANTATION; CARDIOMYOCYTE GRAFTS; HEART-FAILURE; IN-VITRO; REPAIR; REGENERATION; SURVIVAL AB Various cell delivery methods have been investigated for cell transplantation treatment of cardiac infarcts. In this study, we investigated a type I collagen-glycosaminoglycan (GAG) scaffold for the implantation of adult bone marrow-derived mesenchymal stem cells (MSCs) into the infarcted region in the rat heart. The objective was to evaluate the tissue response to collagen-GAG scaffolds prepared using 2 cross- linking methods. The left coronary artery of female Wistar rats was occluded for 60 min, followed by reperfusion. One week later, the infarcted region was implanted with (1) collagen-GAG scaffolds cross- linked by dehydrothermal treatment alone (DHT; n = 10); (2) collagen-GAG scaffolds cross-linked by DHT followed by carbodiimide treatment (EDAC; n = 8); or (3) DHT cross- linked collagen-GAG scaffolds seeded with bromodeoxyuridine (BrdU)- labeled allogeneic MSCs (cell-scaffold; n = 9). Sham-operated rats served as controls (n = 4). Specimens were harvested 3 weeks after the implantation surgery. The tissue response was evaluated histomorphometrically and by immunohistochemistry to track the BrdU-labeled MSCs. Most of the DHT cross- linked collagen-GAG scaffolds degraded, whereas the scaffolds in the EDAC group appeared to be largely intact. There were no signs of acute inflammation in any of the groups. A substantial amount of neovascularization was seen in the infarcted region in the implant groups and in the scaffolds themselves. BrdU-positive cells appeared both in the degraded scaffold and the infarct region. DHT cross- linked collagen-GAG scaffolds warrant continued investigation as delivery vehicles for implantation of cells into infarcted cardiac tissue. C1 VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. Sichuan Univ, Huaxi Hosp, Dept Orthopaed Surg, Chengdu 610064, Peoples R China. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, Boston Campus,Room D1-152,Mail Stop 151 Res,150 S, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu NR 45 TC 59 Z9 59 U1 1 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SEP PY 2006 VL 12 IS 9 BP 2467 EP 2478 DI 10.1089/ten.2006.12.2467 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA 087ZI UT WOS:000240780900007 PM 16995780 ER PT J AU Chung, C Mesa, J Miller, GJ Randolph, MA Gill, TJ Burdick, JA AF Chung, Cindy Mesa, John Miller, Gregory J. Randolph, Mark A. Gill, Thomas J. Burdick, Jason A. TI Effects of auricular chondrocyte expansion on neocartilage formation in photocrosslinked hyaluronic acid networks SO TISSUE ENGINEERING LA English DT Article ID BOVINE ARTICULAR-CARTILAGE; AGAROSE GELS; COLLAGEN; REPAIR; NASAL; PHENOTYPE; SCAFFOLDS; ALGINATE; CULTURE; ASSAY AB The overall objective of this study was to examine the effects of in vitro expansion on neocartilage formation by auricular chondrocytes photoencapsulated in a hyaluronic acid (HA) hydrogel as a next step toward the clinical application of tissue engineering therapies for treatment of damaged cartilage. Swine auricular chondrocytes were encapsulated either directly after isolation (p = 0), or after further in vitro expansion (p = 1 and p = 2) in a 2 wt%, 50-kDa HA hydrogel and implanted subcutaneously in the dorsum of nude mice. After 12 weeks, constructs were explanted for mechanical testing and biochemical and immunohistochemical analysis and compared to controls of HA gels alone and native cartilage. The compressive equilibrium moduli of the p = 0 and p = 1 constructs (51.2 +/- 8.0 and 72.5 +/- 35.2 kPa, respectively) were greater than the p = 2 constructs (26.8 +/- 14.9 kPa) and the control HA gel alone (12.3 +/- 1.3 kPa) and comparable to auricular cartilage (35.1 +/- 12.2 kPa). Biochemical analysis showed a general decrease in glycosaminoglycan (GAG), collagen, and elastin content with chondrocyte passage, though no significant differences were found between the p = 0 and p = 1 constructs for any of the analyses. Histological staining showed intense and uniform staining for aggrecan, as well as greater type II collagen versus type I collagen staining in all constructs. Overall, this study illustrates that constructs with the p = 0 and p = 1 auricular chondrocytes produced neocartilage tissue that resembled native auricular cartilage after 12 weeks in vivo. However, these results indicate that further expansion of the chondrocytes (p = 2) can lead to compromised tissue properties. C1 Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA USA. RP Burdick, JA (reprint author), Univ Penn, Dept Bioengn, 120 Hayden Hall,3320 Smith Walk, Philadelphia, PA 19104 USA. EM burdick2@seas.upenn.edu FU NIDCR NIH HHS [K22 DE-015761, K22 DE015761-02, K22 DE015761] NR 31 TC 73 Z9 77 U1 2 U2 19 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SEP PY 2006 VL 12 IS 9 BP 2665 EP 2673 DI 10.1089/ten.2006.12.2665 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 087ZI UT WOS:000240780900027 PM 16995800 ER PT J AU Robinson, EM Phipps, M Purtilo, RB Tsoumas, A Hamel-Nardozzi, M AF Robinson, Ellen M. Phipps, Marion Purtilo, Ruth B. Tsoumas, Angelica Hamel-Nardozzi, Marguerite TI Complexities in decision making for persons with disabilities nearing end of life SO TOPICS IN STROKE REHABILITATION LA English DT Article DE complexities in decision making; dignity; disability; ethics; life-sustaining treatment decisions ID ADVANCE DIRECTIVES; PREFERENCES; STABILITY; ETHICS; CARE AB Good end-of-life care requires that clinicians, families, and ethicists be aware of biases that influence patient cases, particularly in the acute care setting where the aim is primarily cure and return to optimal functional level. Persons with disabilities may pose unique challenges; their potential for quality of life is viewed through the lens of highly functional clinicians who might have a biased view of the disabled person's quality of life. The authors aim to present three categories of disability that do not claim to be absolute but rather offer clinicians and ethicists a lens through which to reflect on bias that unconsciously may influence their approach to the patient who is seriously ill and may be nearing the end of life. The categories include (a) a person who has lived with a disability from birth or early life, due to trauma or disease, and is now faced with a serious illness that requires that life-sustaining treatment, (b) the otherwise healthy person who acquires a disability through an acute event of disease or trauma and whose condition requires that life-sustaining treatment decisions be made; and (c) the person who has lived with a progressive chronic illness, such as lung or heart disease or amyotrophic lateral sclerosis, and may have gradually adjusted to disabilities imposed by the condition and now is faced with life-sustaining treatment decisions. The concept of inherent dignity (Pellegrino 2005) is suggested as a filtering lens in case consideration. C1 Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. MGH Inst Hlth Profess, Eth Initiat, Boston, MA USA. RP Robinson, EM (reprint author), Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. NR 28 TC 7 Z9 7 U1 0 U2 7 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1074-9357 J9 TOP STROKE REHABIL JI Top. Stroke Rehabil. PD FAL PY 2006 VL 13 IS 4 BP 54 EP 67 DI 10.1310/tsr1304-54 PG 14 WC Rehabilitation SC Rehabilitation GA 130YU UT WOS:000243835700009 PM 17082170 ER PT J AU Cserti, CM Stevenson, KE Kim, HT Kao, GS AF Cserti, C. M. Stevenson, K. E. Kim, H. T. Kao, G. S. TI Protocol-based peripheral CD34 trigger to initiate stem cell collection for auto transplants: Preserved cell yield and reduced collections SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 Harvard Univ, Joint Program Transfus Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 49A EP 50A PG 2 WC Hematology SC Hematology GA 084SG UT WOS:000240554100147 ER PT J AU Berg, A Kao, GS AF Berg, A. Kao, G. S. TI Impact of filtering thawed hematopoietic progenitor cells (HPC) with routine blood filter on CD34+cell number SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02115 USA. EM gkao@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 61A EP 61A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100183 ER PT J AU Gusella, JF MacDonald, ME AF Gusella, James F. MacDonald, Marcy E. TI Huntington's disease: seeing the pathogenic process through a genetic lens SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID LENGTH MUTANT HUNTINGTIN; YAC128 MOUSE MODEL; AGE-OF-ONSET; IN-VITRO; RNA INTERFERENCE; NEURONAL DEATH; AGGREGATION; POLYGLUTAMINE; EXPRESSION; PROTEIN AB Thirteen years ago, the culmination of genetic rather than biochemical strategies resulted in the identification of the root cause of Huntington's disease: an expanded CAG trinucleotide repeat that leads to an elongated polyglutamine tract in the huntingtin protein. Since then, biochemical and cell biological attempts to elucidate pathogenesis have largely focused on N-terminal polyglutamine-containing huntingtin fragments. However, continued application of genetic strategies has suggested that the disease process is, in fact, triggered by the presence of expanded polyglutamine in intact huntingtin. An increased emphasis on the earliest presymptornatic stages of the disease, facilitated by incorporating genetic lessons from human patients into the search for biochemical targets, could provide a route to a rational treatment to prevent or slow the onset of this devastating neurodegenerative disorder. C1 Massachusetts Gen Hosp, Mol Neurogenet Lab, Ctr Human Genet Res, Richard B Simches Res Ctr, Boston, MA 02114 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Lab, Ctr Human Genet Res, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu; macdonam@helix.mgh.harvard.edu FU NINDS NIH HHS [NS 16367, NS 32765]; NLM NIH HHS [LM 008748] NR 74 TC 78 Z9 79 U1 2 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD SEP PY 2006 VL 31 IS 9 BP 533 EP 540 DI 10.1016/j.tibs.2006.06.009 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 088CR UT WOS:000240789600009 PM 16829072 ER PT J AU Levy, C Khaled, M Fisher, DE AF Levy, Carmit Khaled, Mehdi Fisher, David E. TI MITF: master regulator of melanocyte development and melanoma oncogene SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID MICROPHTHALMIA TRANSCRIPTION FACTOR; WAARDENBURG SYNDROME TYPE-2; STEM-CELL MAINTENANCE; MALIGNANT-MELANOMA; TYROSINASE GENE; CUTANEOUS MELANOMA; PROGNOSTIC MARKER; LINEAGE SURVIVAL; TUMOR-SUPPRESSOR; BRAF MUTATIONS AB Microphthalmia-associated transcription factor (MITF) acts as a master regulator of melanocyte development, function and survival by modulating various differentiation and cell-cycle progression genes. It has been demonstrated that MITF is an amplified oncogene in a fraction of human melanomas and that it also has an oncogenic role in human clear cell sarcoma. However, MITF also modulates the state of melanocyte differentiation. Several closely related transcription factors also function as translocated oncogenes in various human malignancies. These data place MITF between instructing melanocytes towards terminal differentiation and/or pigmentation and, alternatively, promoting malignant behavior. In this review, we survey the roles of MITF as a master lineage regulator in melanocyte development and its emerging activities in malignancy. Understanding the molecular function of MITF and its associated pathways will hopefully shed light on strategies for improving therapeutic approaches for these diseases. C1 Childrens Hosp, Dana Farber Canc Inst, Melanoma Program, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Childrens Hosp, Dana Farber Canc Inst, Melanoma Program, 44 Binney St, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu RI khaled, mehdi/C-4854-2012 NR 98 TC 441 Z9 449 U1 2 U2 46 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD SEP PY 2006 VL 12 IS 9 BP 406 EP 414 DI 10.1016/j.molmed.2006.07.008 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 089ND UT WOS:000240886400004 PM 16899407 ER PT J AU Shah, KK Ko, DSC Mercer, J Dahl, DM AF Shah, Ketul K. Ko, Dicken S. C. Mercer, Jonathan Dahl, Douglas M. TI Laparoscopic radical prostatectomy in a renal allograft recipient SO UROLOGY LA English DT Article ID KIDNEY-TRANSPLANT RECIPIENTS; CANCER AB In the current immunosuppression era, most renal transplant recipients with a functioning allograft are living healthier and longer lives. In men, because of prostate-specific antigen screening, more patients are diagnosed with early prostate cancer and offered curative treatment with radical prostatectomy. Laparoscopic radical prostatectomy is an accepted minimally invasive treatment for a middle-aged man with organ-confined prostate cancer. To our knowledge, laparoscopic prostatectomy has not yet been reported in renal transplant recipients. This is a case report of laparoscopic prostatectomy for biopsy-proven localized prostate cancer in a renal transplant recipient. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Shah, KK (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM shahkk74@gmail.com NR 11 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 0090-4295 J9 UROLOGY JI Urology PD SEP PY 2006 VL 68 IS 3 AR 672.e5 DI 10.1016/j.urology.2006.03.029 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 101EL UT WOS:000241721600051 ER PT J AU El Sayed, HF Kougias, P Zhou, W Lin, PH AF El Sayed, Hosarn F. Kougias, Panos Zhou, Wei Lin, Peter H. TI Utility of retrievable vena cava filters and mechanical thrombectomy in the endovascular management of acute deep venous thrombosis SO VASCULAR LA English DT Article DE deep venous thrombosis; inferior vena cava filter; retrievable inferior vena cava filter; thrombectomy; thrombolysis AB Endovascular interventions of symptomatic deep venous thrombosis (DVT) using various therapeutic modalities, such as thrombolysis, mechanical thrombectomy, and inferior vena cava (lVC) filter placement, have received increased focus owing in part to advances in catheter-based interventional technologies. Although systemic anticoagulation remains the primary treatment modality in DVT, catheter-based interventions can provide rapid removal of large thrombus burden and possibly preserve venous valvular function in patients with symptomatic DVT. This article reviews current endovascular treatment strategies for acute DVT. Specifically, the utility of mechanical thrombectomy along with various temporary lVC filters in the setting of DVT is examined. Lastly, an illustrative case of acute DVT that was treated with endovascular intervention with lVC filter placement is presented. C1 Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, N Florida S Georgia VA Med Ctr, Houston, TX 77030 USA. RP Lin, PH (reprint author), Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston VAMC, 2002 Holcomb Blvd 112, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 26 TC 7 Z9 7 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1708-5381 J9 VASCULAR JI Vascular PD SEP-OCT PY 2006 VL 14 IS 5 BP 305 EP 312 DI 10.2310/6670.2006.00046 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V44FY UT WOS:000202989800009 PM 17038301 ER PT J AU Yano, EM Goldzweig, C Canelo, I Washington, DL AF Yano, Elizabeth M. Goldzweig, Caroline Canelo, Ismelda Washington, Donna L. TI Diffusion of innovation in women's health care delivery: The department of veterans affairs' adoption of women's health clinics SO WOMENS HEALTH ISSUES LA English DT Article ID MEDICAL-CENTER; NATIONAL-CENTERS; FEMALE VETERANS; QUALITY; EXCELLENCE; PHYSICIANS; PROJECT AB Background. In response to concerns about the availability and quality of women's health services in Department of Veterans Affairs (VA) medical centers in the early 1990s, Congress approved landmark legislation earmarking funds to enhance women's health services. A portion of the appropriation was used to launch Comprehensive Women's Health Centers as exemplars for the development of VA women's health care throughout the system. We report on the diffusion and characteristics of VA women's health clinics (WHCs) 10 years later. Methods. In 2001, we surveyed the senior women's health clinician at each VA medical center serving 400 women veterans (83% response rate) regarding their internal organizational characteristics in relation to factors associated with organizational innovation (centralization, complexity, formalization, interconnectedness, organizational slack, size). We evaluated the comparability of WHCs (n = 66) with characteristics of the original comprehensive women's health centers (CWHCs; n = 8). Results. Gender-specific service availability in WHCs was comparable to that of CWHCs with important exceptions in mental health, mammography and osteoporosis management. WHCs were less likely to have same-gender providers (p < .05), women's health training programs (p < .01), separate women's mental health clinics (p < .001), separate space (p < .05), or adequate privacy (p < .05); however, they were less likely to have experienced educational program closures (p < .001) and staffing losses (p < .05 ) compared to CWHCs. Conclusions. Diffusion of comprehensive women's health care is as yet incomplete. More research is needed to examine the quality of care associated with these models and to establish the business case for managers faced with small female patient caseloads. C1 VA Greater Los Angeles, HSR&D, Ctr Excellence, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Med, Los Angeles, CA 90024 USA. RP Yano, EM (reprint author), VA Greater Los Angeles, HSR&D, Ctr Excellence, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov NR 49 TC 42 Z9 42 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD SEP-OCT PY 2006 VL 16 IS 5 BP 226 EP 235 DI 10.1016/j.whi.2006.07.002 PG 10 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 099MH UT WOS:000241598500001 PM 17055375 ER PT J AU Bertagnolli, MM Eagle, CJ Zauber, AG Redston, M Solomon, SD Kim, KM Tang, J Rosenstein, RB Wittes, J Corle, D Hess, TM Woloj, GM Boisserie, F Anderson, WF Viner, JL Bagheri, D Burn, J Chung, DC Dewar, T Foley, TR Hoffman, N Macrae, F Pruitt, RE Saltzman, JR Salzberg, B Sylwestrowicz, T Gordon, GB Hawk, ET AF Bertagnolli, Monica M. Eagle, Craig J. Zauber, Ann G. Redston, Mark Solomon, Scott D. Kim, KyungMann Tang, Jie Rosenstein, Rebecca B. Wittes, Janet Corle, Donald Hess, Timothy M. Woloj, G. Mabel Boisserie, Frederic Anderson, William F. Viner, Jaye L. Bagheri, Donya Burn, John Chung, Daniel C. Dewar, Thomas Foley, T. Raymond Hoffman, Neville Macrae, Finlay Pruitt, Ronald E. Saltzman, John R. Salzberg, Bruce Sylwestrowicz, Thomas Gordon, Gary B. Hawk, Ernest T. CA APC Study Investigators TI Celecoxib for the prevention of sporadic colorectal adenomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HIGH-FIBER DIET; RANDOMIZED-TRIAL; VITAMIN-D; LOW-FAT; CANCER; RECURRENCE; ASPIRIN; SUPPLEMENTATION; POLYPS; RISK AB Background: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia. Methods: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test. Results: Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P < 0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P < 0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9). Conclusions: These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. C1 Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. Pfizer, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Wisconsin, Madison, WI USA. Stat Collaborat, Washington, DC USA. NCI, Bethesda, MD 20892 USA. CCS Associates, Mountain View, CA USA. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harris Methodist Hosp Ft Worth, Ft Worth, TX USA. Reg Gastroenterol Associates Lancaster, Lancaster, PA USA. Sir Charles Gairdner Hosp, Perth, WA, Australia. Royal Melbourne Hosp, Melbourne, Vic, Australia. Nashville Med Res Inst, Nashville, TN USA. Atlanta Gastroenterol Associates, Atlanta, GA USA. Univ Saskatchewan, St Pauls Hosp, Saskatoon, SK, Canada. GD Searle & Co, Skokie, IL 60077 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org RI Solomon, Scott/I-5789-2013; Zavoral, Miroslav/D-9174-2017 OI Zavoral, Miroslav/0000-0001-7883-7431 FU NCI NIH HHS [N01-CN-95015] NR 25 TC 626 Z9 645 U1 2 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 31 PY 2006 VL 355 IS 9 BP 873 EP 884 DI 10.1056/NEJMoa061355 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 078OM UT WOS:000240113100005 PM 16943400 ER PT J AU Pelton, SI Kim, JY Kradin, RL Lee, MS Harris, NL Pasternack, MS Goldstein, MA AF Pelton, Stephen I. Kim, John Y. Kradin, Richard L. Lee, Melissa Sue Harris, Nancy Lee Pasternack, Mark S. Goldstein, Mark A. TI A 17-year-old boy with fever and lesions in the liver and spleen - Hepatitis caused by Bartonella henselae. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CAT-SCRATCH DISEASE; YERSINIA-ENTEROCOLITICA; BACILLARY ANGIOMATOSIS; MULTIPLE ABSCESSES; MICROABSCESSES; INFECTION C1 Boston Med Ctr, Dept Pediat Infect Dis, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pelton, SI (reprint author), Boston Med Ctr, Dept Pediat Infect Dis, Boston, MA 02118 USA. NR 23 TC 8 Z9 8 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 31 PY 2006 VL 355 IS 9 BP 941 EP 948 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 078OM UT WOS:000240113100013 PM 16943407 ER PT J AU Swick, D Senkfor, AJ Van Petten, C AF Swick, Diane Senkfor, Ava J. Van Petten, Cyma TI Source memory retrieval is affected by aging and prefrontal lesions: Behavioral and ERP evidence SO BRAIN RESEARCH LA English DT Article DE prefrontal cortex; episodic memory; source memory; aging; frontal; event-related potentials ID EVENT-RELATED POTENTIALS; FRONTAL-LOBE DAMAGE; PERFORMING OLDER-ADULTS; AGE-RELATED DIFFERENCES; VERBAL-LEARNING TEST; RECOGNITION MEMORY; EPISODIC MEMORY; TEMPORAL-ORDER; BRAIN ACTIVITY; FALSE RECOGNITION AB Age-related deficits in source memory have been attributed to alterations in prefrontal cortex (PFC) function, but little is known about the neural basis of such changes. The present study examined the time course of item and source memory retrieval by recording event-related potentials (ERPs) in patients with focal lesions in lateral PFC and in healthy older and young controls. Both normal aging and PFC lesions were associated with decrements in item and source memory. However, older controls showed a decrease in item hit rate with no change in false alarms, whereas patients showed the opposite pattern. Furthermore, ERPs revealed notable differences between the groups. The early positive-going old/new effect was prominent in the young but reduced in patients and older adults, who did not differ from each other. In contrast, older adults displayed a prominent left frontal negativity (6001200 ms) not observed in the young. This left frontal effect was substantially smaller and delayed in the patients. The current results provide novel insights into the effects of aging on source memory and the role of the lateral PFC in these processes. Older controls appeared to adopt alternate memory strategies and to recruit compensatory mechanisms in left PFC to support task performance. In contrast, the lateral frontal patients were unable to use these mechanisms, thus exhibiting difficulties with strategic memory and monitoring processes. (c) 2006 Elsevier B.V. All rights reserved. C1 VANCHCS, Dept Neurol, Martinez, CA 94553 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. RP Swick, D (reprint author), VANCHCS, Dept Neurol, 150 Muir Rd, Martinez, CA 94553 USA. EM diane@ebire.org FU NIA NIH HHS [AG14792, R01 AG014792, R01 AG014792-06A2]; NIDCD NIH HHS [DC03424, R29 DC003424] NR 83 TC 51 Z9 53 U1 6 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 30 PY 2006 VL 1107 BP 161 EP 176 DI 10.1016/j.brainres.2006.06.013 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 083TN UT WOS:000240481200016 PM 16828722 ER PT J AU Cummings, DE AF Cummings, David E. TI Ghrelin and the short- and long-term regulation of appetite and body weight SO PHYSIOLOGY & BEHAVIOR LA English DT Article; Proceedings Paper CT 3rd Food Summit Meeting on Making Sense of Food CY DEC, 2005 CL Wageningen, NETHERLANDS SP Wageningen Ctr Food Sci DE ghrelin; obesity; body-weight regulation; energy homeostasis; weight loss; cachexia; reward; meals; meal initiation ID PRADER-WILLI-SYNDROME; GROWTH-HORMONE SECRETAGOGUE; GASTRIC BYPASS-SURGERY; HYPOTHALAMIC ARCUATE NUCLEUS; AGOUTI-RELATED PROTEIN; INCREASES FOOD-INTAKE; FASTING PLASMA GHRELIN; DEPENDENT INSULINOTROPIC POLYPEPTIDE; LEFT-VENTRICULAR FUNCTION; PLACEBO-CONTROLLED TRIAL AB Ghrelin, an acylated upper gastrointestinal peptide, is the only known orexigenic hormone. Considerable evidence implicates ghrelin in mealtime hunger and meal initiation. Circulating levels decrease with feeding and increase before meals, achieving concentrations sufficient to stimulate hunger and food intake. Preprandial ghrelin surges occur before every meal on various fixed feeding schedules and also among individuals initiating meals voluntarily without time- or food-related cues. Ghrelin injections stimulate food intake rapidly and transiently, primarily by increasing appetitive feeding behaviors and the number of meals. Preprandial ghrelin surges are probably triggered by sympathetic nervous output. Postprandial suppression is not mediated by nutrients in the stomach or duodenum, where most ghrelin is produced. Rather, it results from post-ingestive increases in lower intestinal osmolarity (information probably relayed to the foregut via enteric nervous signaling), as well as from insulin surges. Consequently, ingested lipids suppress ghrelin poorly compared with other macronutrients. Beyond a probable role in meal initiation, ghrelin also fulfills established criteria for an adiposity-related hormone involved in long-term body-weight regulation. Ghrelin levels circulate in relation to energy stores and manifest compensatory changes in response to body-weight alterations. Ghrelin crosses the bloodbrain barrier and stimulates food intake by acting on several classical body-weight regulatory centers, including the hypothalamus, hindbrain, and mesolimbic reward system. Chronic ghrelin administration increases body weight via diverse, concerted actions on food intake, energy expenditure, and fuel utilization. Congenital ablation of the ghrelin or ghrelin-receptor gene causes resistance to diet-induced obesity, and pharmacologic ghrelin blockade reduces food intake and body weight. Ghrelin levels are high in Prader-Willi syndrome and low after gastric bypass surgery, possibly contributing to body-weight alterations in these settings. Extant evidence favors roles for ghrelin in both short-term meal initiation and long-term energy homeostasis, making it an attractive target for drugs to treat obesity and/or wasting disorders. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu FU NIDDK NIH HHS [P01 DK68384, R01 DK61516, U01 DK66568] NR 263 TC 352 Z9 364 U1 3 U2 48 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD AUG 30 PY 2006 VL 89 IS 1 BP 71 EP 84 DI 10.1016/j.physbeh.2006.05.022 PG 14 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 078FK UT WOS:000240087400014 PM 16859720 ER PT J AU Gukovskaya, AS AF Gukovskaya, Anna S. TI Supramaximal cholecystokinin stimulates apoptosis and necrosis in pancreatic acinar cells: Role in pancreatitis SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 16th International Symposium on Regulatory Peptides CY AUG 31-SEP 02, 2006 CL Hakone, JAPAN C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD AUG 30 PY 2006 VL 135 IS 3 BP 105 EP 106 DI 10.1016/j.regpep.2006.06.009 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 083ZB UT WOS:000240499800010 ER PT J AU Tache, Y Yuan, PQ Wu, V Million, M AF Tache, Yvette Yuan, Pu-Qing Wu, Vincent Million, Mulugeta TI Corticotropin releasing factor (CRF) receptors 1 and 2 (CRF1 and CRF2): Differential distribution and action in upper and lower gut function SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 16th International Symposium on Regulatory Peptides CY AUG 31-SEP 02, 2006 CL Hakone, JAPAN C1 Univ Calif Los Angeles, David Geffen Sch Med, Digest Dis Res Ctr,Div Digest Dis, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD AUG 30 PY 2006 VL 135 IS 3 BP 109 EP 109 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 083ZB UT WOS:000240499800020 ER PT J AU Wu, SV Yuan, P Jiang, M Lin, P Wang, L Tache, Y AF Wu, S. V. Yuan, P. Jiang, M. Lin, P. Wang, L. Tache, Y. TI Characterization of corticotropin-releasing factor (CRF) receptor isoforms identified from human and rodent GI endocrine cells SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 16th International Symposium on Regulatory Peptides CY AUG 31-SEP 02, 2006 CL Hakone, JAPAN C1 Univ Calif Los Angeles, David Geffen Sch Med, CURE, Dept Med,Dept Pharmacol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, CNS WH, Dept Med,Dept Pharmacol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD AUG 30 PY 2006 VL 135 IS 3 BP 168 EP 168 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 083ZB UT WOS:000240499800181 ER PT J AU Zhou, XH Li, SM AF Zhou, Xiao-Hua Li, Sierra M. TI ITT analysis of randomized encouragement design studies with missing data SO STATISTICS IN MEDICINE LA English DT Article DE causal inference; flu shots; non-compliance; intention-to-treat analysis; missing data ID BAYESIAN-INFERENCE; NONCOMPLIANCE AB In this paper, we considered a missing outcome problem in causal inferences for a randomized encouragement design study. We proposed both moment and maximum likelihood estimators for the marginal distributions of potential outcomes and the local complier average causal effect (CACE) parameter. We illustrated our methods in a randomized encouragement design study on the effectiveness of flu shots. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Washington, Dept Biostat, HOB, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, HOB, F600,Box 357232, Seattle, WA 98195 USA. EM azhou@u.washington.edu FU NHLBI NIH HHS [R01HL62567] NR 13 TC 26 Z9 27 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 30 PY 2006 VL 25 IS 16 BP 2737 EP 2761 DI 10.1002/sim.2388 PG 25 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 073NS UT WOS:000239750500003 PM 16287216 ER PT J AU Chen, J Yang, W Kim, M Carman, CV Springer, TA AF Chen, JianFeng Yang, Wei Kim, Minsoo Carman, Christopher V. Springer, Timothy A. TI Regulation of outside-in signaling and affinity by the beta(2) I domain of integrin alpha(L)beta(2) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lymphocyte function-associated antigen-1; CD11a/CD18; adhesion ID FUNCTION-ASSOCIATED ANTIGEN-1; ADHESION MOLECULE-1 ICAM-1; C-TERMINAL REGION; BETA-A DOMAIN; INTEGRIN ALPHA(L)BETA(2); CRYSTAL-STRUCTURE; FIRM ADHESION; CONFORMATIONAL REGULATION; EXTRACELLULAR SEGMENT; LIGAND RECOGNITION AB The adhesiveness of integrin alpha(1)beta(2) is modulated by divalent cations. We mutated three metal ion-binding sites in the beta(2) I domain. The metal ion-dependent adhesion site (MIDAS) and the ligand-induced metal-binding site are required for ligand binding and sufficient for synergism between Ca2+ and Mg2+. Adjacent to MIDAS (ADMIDAS) mutants are constitutively active but remain bent, with poor exposure of a beta(2) stalk region epitope. Fluorescence resonance energy transfer between fluorescent protein-fused alpha(L) and beta(2) cytoplasmic domains showed that ADMIDAS mutation abrogated ligand binding-induced spatial separation of cytoplasmic domains. Furthermore, ADMIDAS mutation abolished spreading on ligand-bearing substrates. Thus, beta(2) I domain metal ion-binding sites regulate alpha(L) I domain affinity, and the ADMIDAS is required for outside-in signaling. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, 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 Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NCI NIH HHS [R01 CA031798, R37 CA031798, CA31798]; NHLBI NIH HHS [HL48675, P01 HL048675] NR 41 TC 23 Z9 25 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 AUG 29 PY 2006 VL 103 IS 35 BP 13062 EP 13067 DI 10.1073/pnas.0605666103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 082IU UT WOS:000240380800023 PM 16920795 ER PT J AU Yosefy, C Jafari, J Klainman, E Brodkin, B Handschumacher, MD Vaturi, M AF Yosefy, Chaim Jafari, Jamal Klainman, Eliezer Brodkin, Boris Handschumacher, Mark D. Vaturi, Mordehay TI The prognostic value of post-exercise blood pressure reduction in patients with hypertensive response during exercise stress test SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE exercise stress test; blood pressure; cardiovascular risk factors ID CORONARY-ARTERY DISEASE; SYSTEMIC HYPERTENSION; RISK; MEN; MORTALITY; PROGRAM; ADULTS AB Background: Hypertensive response at peak-exercise and during the recovery phase of exercise stress test (ET) is associated with poor cardiovascular prognosis. We investigated whether decrease in blood pressure (BP) from peak to post-exercise would identify a subgroup at higher cardiovascular risk. Methods: Eighty-six non-hypertensive patients (0-4 cardiovascular risk factors) with hypertensive reaction at peak-ET (systolic > 180 mm Hg and/or diastolic > 100 mm Hg) were divided based on BP 5 min after exercise termination into two groups: Normal response (NrmR) (< 160/90 mm Hg), Hypertensive response (HypR) (>= 160/90 mm Hg). Five years later the prevalence of cardiovascular risk factors and cardiovascular morbidity and mortality was assessed for each group. Results: Both groups had similar pre- and peak-exercise BP. However the HypR group had higher post-exercise BP (systolic: 163 +/- 13 vs. 125 +/- 14 mm Hg, respectively, p < 0.01, and diastolic: 74 +/- 6 vs. 75 +/- 4 mm Hg, respectively, p < 0.01), smaller decrease in BP after exercise (A systolic: 46.9 +/- 3.1 vs. 73.9 +/- 3.6 min Hg, respectively, p < 0.01, A diastolic: 12.4 +/- 1.5 vs. 26.5 +/- 2.2 mm, Hg, respectively, p < 0.01), and higher post- than pre-exercise BP (A systolic: 24.5 +/- 3.5 vs. -6 +/- 4.1 mm Hg, respectively, p < 0.01, A diastolic: 19 +/- 2.1 vs. - 13 +/- 2.3 turn Hg, respectively, p < 0.01). Five years later, HypR group had higher prevalence of abnormal cholesterol serum level (p < 0.01), hypertension (p < 0.01) and combined ischemic heart disease and cerebrovascular disease (RR 1.32, 95% CI = 1.13-1.54, p < 0.01). Conclusion: During ET evaluation, it is important to evaluate the BP at 5 min after exercise because reduced BP drop, at this routinely measured point, identifies a subgroup with higher cardiovascular risk. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Ben Gurion Univ Negev, Dept Cardiol, Barzilai Med Ctr, Ashqelon, Israel. Harvard Univ, Sch Med, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Boston, MA USA. Tel Aviv Univ, Gefen Cardiac Hlth Ctr, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Dept Cardiol, Echocardiog Unit, Rabin Med Ctr, Petah Tiqwa, Israel. RP Yosefy, C (reprint author), Ben Gurion Univ Negev, Cardiol Outpatient Clin, Barzilai Med Ctr Campus, Ashqelon, Israel. EM yosefy@barzi.health.gov.il NR 27 TC 5 Z9 8 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD AUG 28 PY 2006 VL 111 IS 3 BP 352 EP 357 DI 10.1016/j.ijcard.2005.07.039 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 084JE UT WOS:000240528400003 PM 16239041 ER PT J AU Oh, J Feldman, MD Kim, J Condit, C Emelianov, S Milner, TE AF Oh, Junghwan Feldman, Marc D. Kim, Jeehyun Condit, Chris Emelianov, Stanislav Milner, Thomas E. TI Detection of magnetic nanoparticles in tissue using magneto-motive ultrasound SO NANOTECHNOLOGY LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; MICROBUBBLE CONTRAST AGENT; LYMPH-NODE METASTASES; ATHEROSCLEROTIC PLAQUES; ENHANCED MRI; IN-VIVO; PARTICLES; CANCER; VISUALIZATION; EXPERIENCE AB The purpose of this study was to demonstrate the magneto-motive ultrasonic detection of superparamagnetic iron oxide (SPIO) nanoparticles as a marker of macrophage recruitment in tissue. The capability of ultrasound to detect SPIO nanoparticles ( core diameter similar to 20 nm) taken up by murine liver macrophages was investigated. Eight mice were sacrificed two days after the intravenous administration of four SPIO doses (1.5, 1.0, 0.5, and 0.1 mmol Fe/kg body weight). In the iron-laden livers, ultrasound Doppler measurements showed a frequency shift in response to an applied time-varying magnetic field. M-mode scan and colour power Doppler images of the iron-laden livers also demonstrated nanoparticle movement under focused magnetic field excitation. In the livers of two saline injected control mice, no movement was observed using any ultrasound imaging modes. The results of our experiments indicate that ultrasound imaging of magneto-motive excitation is a candidate imaging modality to identify tissue-based macrophages containing SPIO nanoparticles. C1 Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. S Texas Audie Murphy Hosp, Dept Vet Affairs, San Antonio, TX USA. Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92715 USA. RP Oh, J (reprint author), Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. EM jhoh@mail.utexas.edu NR 33 TC 83 Z9 88 U1 1 U2 15 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0957-4484 J9 NANOTECHNOLOGY JI Nanotechnology PD AUG 28 PY 2006 VL 17 IS 16 BP 4183 EP 4190 DI 10.1088/0957-4484/17/16/031 PG 8 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA 077FE UT WOS:000240012600031 PM 21727557 ER PT J AU Elwyn, G O'Connor, A Stacey, D Volk, R Edwards, A Coulter, A Thomson, R Barrat, A Butow, P Barry, M Mulley, AG Sepucha, K Bernstein, S Clarke, A Entwistle, V Feldman-Stewart, D Holmes-Rovner, M Llewellyn-Thomas, H Moumjid, N Ruland, C Sykes, A Whelan, T AF Elwyn, Glyn O'Connor, Annette Stacey, Dawn Volk, Robert Edwards, Adrian Coulter, Angela Thomson, Richard Barrat, Alexandra Butow, Phyllis Barry, Michael Mulley, Albert G. Sepucha, Karen Bernstein, Steven Clarke, Aileen Entwistle, Vikki Feldman-Stewart, Deb Holmes-Rovner, Margaret Llewellyn-Thomas, Hilary Moumjid, Nora Ruland, Cornelia Sykes, Alan Whelan, Tim CA IPDAS Collaboration TI Developing a quality criteria framework for patient decision aids: online international Delphi consensus process SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; GENERAL-PRACTICE; HEALTH INFORMATION; TREATMENT CHOICES; INDICATORS; INSTRUMENT; STATEMENT; KNOWLEDGE AB Objective To develop a set of quality criteria for patient decision support technologies (decision aids). Design and setting Two stage web, based Delphi process using online rating process to enable international collaboration. Participants Individuals from four stakeholder groups (researchers, practitioners, patients, policy makers) representing 14 countries reviewed evidence summaries and rated the importance of 80 criteria in 12 quality domains on a I to 9 scale. Second round participants received feedback from the first round and repeated their assessment of the 80 criteria plus three new ones. Main outcome measure Aggregate ratings for each criterion calculated using medians weighted to compensate for different numbers in stakeholder groups; criteria rated between 7 and 9 were retained. Results 212 nominated people were invited to participate. Of those invited, 122 participated in the first round (77 researchers, 21 patients, 10 practitioners, 14 policy makers); 104/122 (85%) participated in the second round. 74 of 83 criteria were retained in the following domains: systematic development process (9/9 criteria); providing information about options (13/13); presenting probabilities (11/13); clarifying and expressing values (3/3); using patient stories (2/5); guiding/coaching (3/5); disclosing conflicts of interest (5/5); providing internet access (6/6); balanced presentation of options (3/3); using plain language (4/6); basing information on tip to date evidence (7/7); and establishing effectiveness (8/8). Conclusions Criteria were given the highest ratings where evidence existed, and these were retained. Gaps in research were highlighted. Developers, users, and purchasers of patient decision aids now have a checklist for appraising quality. An instrument for measuring quality of decision aids is being developed. C1 [Elwyn, Glyn; Edwards, Adrian] Cardiff Univ, Ctr Hlth Sci Res, Dept Gen Practice, Cardiff CF14 4YS, Wales. [O'Connor, Annette; Stacey, Dawn] Univ Ottawa, Ottawa, ON K1Y 4E9, Canada. [O'Connor, Annette] Ottawa Hlth Res Inst, Clin Epidemiol Program, Ottawa, ON K1Y 4E9, Canada. Univ Ottawa, Sch Nursing, Ottawa, ON K1H 8M5, Canada. [Volk, Robert] Baylor Coll Med, Dept Family & Community Med, Houston, TX 77098 USA. [Coulter, Angela] Picker Inst Europe, Oxford OX1 1RX, England. Med Sch Newcastle Upon Tyne, Sch Populat & Hlth Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Thomson, Richard; Barrat, Alexandra] Univ Sydney, Sch Publ Hlth, Screening & Testing Program, Sydney, NSW 2006, Australia. [Butow, Phyllis] Univ Sydney, Sch Psychol, Med Psychol Res Unit, Sydney, NSW 2006, Australia. [Barry, Michael; Mulley, Albert G.; Sepucha, Karen] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bernstein, Steven] VA Ann Arbor Healthcare Syst, HS R&D Ctr Excellence, Ann Arbor, MI USA. [Clarke, Aileen] Publ Hlth Resource Unit, Oxford OX4 2GX, England. [Entwistle, Vikki] Univ Dundee, Social Dimens Hlth Inst, Dundee DD1 4HJ, Scotland. [Feldman-Stewart, Deb] Queens Univ, Div Canc Care & Epidemiol, Canc Res Inst, Kingstown, ON, Canada. [Holmes-Rovner, Margaret] Michigan State Univ, Ctr Eth, E Lansing, MI 48824 USA. [Llewellyn-Thomas, Hilary] Dartmouth Med Sch, Dept Community & Family Med, Ctr Evaluat Clin Sci, Hanover, NH USA. [Moumjid, Nora] GRESAC, Ctr Leon Berard, F-69008 Lyon, France. [Ruland, Cornelia] Rikshosp Radiumhosp, Oslo, Norway. [Sykes, Alan] Acadvent Ltd, Swansea, Wales. [Whelan, Tim] McMaster Univ, Dept Med, Hamilton, ON, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. RP Elwyn, G (reprint author), Cardiff Univ, Ctr Hlth Sci Res, Dept Gen Practice, Cardiff CF14 4YS, Wales. EM elwyng@cardiff.ac.uk RI Elwyn, Glyn/B-4798-2009; Elwyn, G./L-4292-2015; Whelan, Timothy/D-3185-2017; OI Coulter, Angela/0000-0002-6308-8375; Elwyn, Glyn/0000-0002-0917-6286; Volk, Robert/0000-0001-8811-5854 NR 33 TC 536 Z9 544 U1 9 U2 42 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD AUG 26 PY 2006 VL 333 IS 7565 BP 417 EP 419 DI 10.1136/bmj.38926.629329.AE PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 081AO UT WOS:000240289800019 PM 16908462 ER PT J AU Bianchi, MT Alexander, BM AF Bianchi, Matt T. Alexander, Brian M. TI Diagnostic skills - Evidence based diagnosis: does language reflect the theory? SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID CLINICAL DECISION-MAKING; EVIDENCE-BASED MEDICINE; LIKELIHOOD RATIOS; PROBABILITY; DISEASE; UTILITY C1 Massachusetts Gen Hosp, Partners Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners Radiat Oncol, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Partners Neurol, Boston, MA 02114 USA. EM mtbianchi@partners.org NR 20 TC 30 Z9 30 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD AUG 26 PY 2006 VL 333 IS 7565 BP 442 EP 445 DI 10.1136/bmj.38915.558738.55 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 081AO UT WOS:000240289800025 PM 16931846 ER PT J AU Chen, XH Kokkotou, EG Mustafa, N Bhaskar, KR Sougioultzis, S O'Brien, M Pothoulakis, C Kelly, CP AF Chen, Xinhua Kokkotou, Efi G. Mustafa, Nasima Bhaskar, K. Ramakrishnan Sougioultzis, Stavros O'Brien, Michael Pothoulakis, Charalabos Kelly, Ciaran P. TI Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against Clostridium difficile toxin A-induced enteritis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL-CELLS; T84 CELLS; PREVENTS CYTOKINE; CHOLERA-TOXIN; RABBIT ILEUM; RAT ILEUM; KAPPA-B; RECEPTOR; INDUCTION; INTESTINE AB Saccharomyces boulardii (Sb), a probiotic yeast, protects against intestinal injury and inflammation caused by a wide variety of enteric pathogens, including Clostridium difficile. Given the broad range of protective effects of Sb in multiple gastrointestinal disorders, we hypothesize that Sb modulates host signaling pathways involved in intestinal inflammatory responses. In this study, we found that Sb culture supernatant (SbS) inhibits interleukin-8 production induced by C. difficile toxin A or IL-1 beta in human colonocyte NCM460 cells in a dose-dependent fashion. Furthermore, SbS inhibited IL-1 beta and toxin A induced Erk1/2 and JNK/SAPK but not p38 activation in NCM460 cells. To test whether this inhibition also occurs in vivo, we used a previously established mouse ileal loop model. On its own, SbS had no significant effect on basal fluid secretion or intestinal histology. However, Erk1/2 activation was significantly inhibited by SbS in toxin A exposed mouse ileal mucosa. In control loops, toxin A increased fluid secretion (2.2-fold), histological score (3.3-fold), and levels of the chemokine KC (4.5-fold). SbS pretreatment completely normalized toxin A mediated fluid secretion (p < 0.01), and histopathologic changes (p < 0.01) and substantially inhibited toxin A-associated KC increases (p < 0.001). In summary, the probiotic yeast S. boulardii inhibits C. difficile toxin A-associated enteritis by blocking the activation of Erk1/2 MAP kinases. This study indicates a new mechanism whereby Sb protects against intestinal inflammation and supports the hypothesis that Sb modulates host inflammatory signaling pathways to exert its beneficial effects. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Boston Univ, Dept Pathol, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Boston, MA 02215 USA. RP Kelly, CP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Dana 601A,330 Brookline Ave, Boston, MA 02215 USA. EM ckelly2@bidmc.harvard.edu OI O'Brien, Michael J/0000-0003-1124-3537 FU NIAID NIH HHS [AI53069]; NIDDK NIH HHS [P01 DK033506] NR 37 TC 69 Z9 70 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 2006 VL 281 IS 34 BP 24449 EP 24454 DI 10.1074/jbc.M605200200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074YF UT WOS:000239847800039 PM 16816386 ER PT J AU Nikolaev, VO Hoffmann, C Bunemann, M Lohse, MJ Vilardaga, JP AF Nikolaev, Viacheslav O. Hoffmann, Carsten Buenemann, Moritz Lohse, Martin J. Vilardaga, Jean-Pierre TI Molecular basis of partial agonism at the neurotransmitter alpha(2A)-adrenergic receptor and G(i)-protein heterotrimer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; LIVING CELLS; CONFORMATIONS; ACTIVATION; MODEL AB To characterize the mechanism by which heterotrimeric G-proteins interpret the signals coming from various neurotransmitters of diverse efficacies (agonists and partial agonists) acting on alpha(2A)-adrenergic receptors, we used a fluorescent resonance energy transfer-based approach to study the effects of these partial agonists on the activation process of both the alpha(2A)-adrenergic receptor and its cognate G(i)-protein. We show that ligands of different efficacies switch the receptor into distinct conformational states, which in turn set the speed and extent of the G(i)-protein signaling. Thus, in cells the efficacy by which a receptor responds to diverse ligands is caused by the ability of the G-protein to differentiate between distinct receptor conformations. The data provide a new key characteristic underlying the mechanism of partial agonism at G-protein-coupled receceptors. C1 Univ Wurzburg, Inst Pharmacol & Toxicol, D-97078 Wurzburg, Germany. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Vilardaga, JP (reprint author), Simches Res Ctr, Program Membrane Biol, 185 Cambridge St,CPZN-8218, Boston, MA 02114 USA. EM jvilardaga@partners.org RI Lohse, Martin/A-7160-2012 OI Lohse, Martin/0000-0002-0599-3510 NR 16 TC 69 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 AUG 25 PY 2006 VL 281 IS 34 BP 24506 EP 24511 DI 10.1074/jbc.M603266200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074YF UT WOS:000239847800046 PM 16787921 ER PT J AU Foley, JW Song, XZ Demidova, TN Jilal, F Hamblin, MR AF Foley, James W. Song, Xiangzhi Demidova, Tatiana N. Jilal, Fatima Hamblin, Michael R. TI Synthesis and properties of benzo[a]phenoxazinium chalcogen analogues as novel broad-spectrum antimicrobial photosensitizers SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GRAM-NEGATIVE BACTERIA; PHOTODYNAMIC THERAPY; MALIGNANT-TUMORS; SINGLET OXYGEN; INFECTIONS; AGENTS; CELLS; BLUE; BENZOPHENOTHIAZINE; INACTIVATION AB The goal of this investigation was to develop improved photosensitizers for use as antimicrobial drugs in photodynamic therapy of localized infections. Replacement of the oxygen atom in 5-(ethylamino)-9-diethylaminobenzo[a]phenoxazinium chloride ( 1) with sulfur and selenium afforded thiazinium and selenazinium analogues 2 and 3, respectively. All three dyes are water soluble, lipophilic, and red light absorbers. The relative photodynamic activities of the chalcogen series were evaluated against a panel of prototypical pathogenic microorganisms: the Gram-positive Enterococcus faecalis, the Gram-negative Escherichia coli, and the fungus Candida albicans. Selenium dye 3 was highly effective as a broad-spectrum antimicrobial photosensitizer with fluences of 4-32 J/cm(2) killing 2-5 more logs of all cell types than sulfur dye 2, which was slightly more effective than oxygen analogue 1. These data, taken with the findings of uptake and retention studies, suggest that the superior activity of selenium derivative 3 can be attributed to its much higher triplet quantum yield. C1 Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Tufts Univ, Sch Med, Grad Program Cell Mol & Dev Biol, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Aga Khan Med Sch, Karachi, Pakistan. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Foley, JW (reprint author), Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02142 USA. EM foley@rowland.harvard.edu; hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-05A1, R01AI050875] NR 47 TC 36 Z9 37 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 24 PY 2006 VL 49 IS 17 BP 5291 EP 5299 DI 10.1021/JM060153i PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 074ND UT WOS:000239818200026 PM 16913718 ER PT J AU Greene, AK Winograd, JM AF Greene, Ann K. Winograd, Jonathan M. TI Skin redundancy after massive weight loss SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, AK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 AUG 24 PY 2006 VL 355 IS 8 BP 830 EP 830 DI 10.1056/NEJMicm062339 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 076KA UT WOS:000239955200011 PM 16928998 ER PT J AU Venna, N Sims, KB Grant, PE Alcalay, RN AF Venna, Nagagopal Sims, Katherine B. Grant, P. Ellen Alcalay, Roy N. TI A 19-year-old woman with difficulty walking - Dopamine-responsive dystonia caused by a mutation (E6 del GT635-636) in the GCH1 gene. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GTP-CYCLOHYDROLASE-I; DEFICIENCY; DISORDERS; DIAGNOSIS C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Venna, N (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NR 35 TC 4 Z9 4 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 AUG 24 PY 2006 VL 355 IS 8 BP 831 EP 839 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 076KA UT WOS:000239955200013 PM 16928999 ER PT J AU Raina, D Ahmad, R Kumar, S Ren, J Yoshida, K Kharbanda, S Kufe, D AF Raina, Deepak Ahmad, Rehan Kumar, Shailendra Ren, Jian Yoshida, Kiyotsugu Kharbanda, Surender Kufe, Donald TI MUC1 oncoprotein blocks nuclear targeting of c-Abl in the apoptotic response to DNA damage SO EMBO JOURNAL LA English DT Article DE apoptosis; c-Abl; DNA damage; MUC1; 14-3-3 ID CARCINOMA-ASSOCIATED ANTIGEN; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; BETA-CATENIN; SUBCELLULAR-LOCALIZATION; PROTEOLYTIC ACTIVATION; GENE-TRANSCRIPTION; CELLULAR-RESPONSE; INDUCE APOPTOSIS; STRESS-RESPONSE AB The nonreceptor c-Abl tyrosine kinase binds to cytosolic 14-3-3 proteins and is targeted to the nucleus in the apoptotic response to DNA damage. The MUC1 oncoprotein is overexpressed by most human carcinomas and blocks the induction of apoptosis by genotoxic agents. Using human carcinoma cells with gain and loss of MUC1 function, we show that nuclear targeting of c-Abl by DNA damage is abrogated by a MUC1-dependent mechanism. The results demonstrate that c-Abl phosphorylates MUC1 on Tyr-60 and forms a complex with MUC1 by binding of the c-Abl SH2 domain to the pTyr-60 site. Binding of MUC1 to c-Abl attenuates phosphorylation of c-Abl on Thr-735 and the interaction between c-Abl and cytosolic 14-3-3. We also show that expression of MUC1 with a mutation at Tyr-60 (i) disrupts the interaction between MUC1 and c-Abl, (ii) relieves the MUC1-induced block of c-Abl phosphorylation on Thr-735 and binding to 14-3-3, and (iii) attenuates the MUC1 antiapoptotic function. These findings indicate that MUC1 sequesters c-Abl in the cytoplasm and thereby inhibits apoptosis in the response to genotoxic anticancer agents. 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, Binny St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA097098, CA29431, R01 CA029431, R01 CA097098] NR 48 TC 61 Z9 64 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 23 PY 2006 VL 25 IS 16 BP 3774 EP 3783 DI 10.1038/sj.emboj.7601263 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087SW UT WOS:000240763700005 PM 16888623 ER PT J AU Higgs, MH Slee, SJ Spain, WJ AF Higgs, Matthew H. Slee, Sean J. Spain, William J. TI Diversity of gain modulation by noise in neocortical neurons: Regulation by the slow afterhyperpolarization conductance SO JOURNAL OF NEUROSCIENCE LA English DT Article DE noise; gain; pyramidal neuron; interneuron; sAHP; coincidence detection ID ACTION-POTENTIAL INITIATION; RAT VISUAL-CORTEX; PYRAMIDAL NEURONS; IN-VIVO; SENSORIMOTOR CORTEX; LAYER 5; PHYSIOLOGICAL-PROPERTIES; COINCIDENCE DETECTION; SOMATOSENSORY CORTEX; SHUNTING INHIBITION AB Neuronal firing is known to depend on the variance of synaptic input as well as the mean input current. Several studies suggest that input variance, or "noise," has a divisive effect, reducing the slope or gain of the firing frequency-current (f-I) relationship. We measured the effects of current noise on f-I relationships in pyramidal neurons and fast-spiking (FS) interneurons in slices of rat sensorimotor cortex. In most pyramidal neurons, noise had a multiplicative effect on the steady-state f-I relationship, increasing gain. In contrast, noise reduced gain in FS interneurons. Gain enhancement in pyramidal neurons increased with stimulus duration and was correlated with the amplitude of the slow afterhyperpolarization (sAHP), a major mechanism of spike-frequency adaptation. The 5-HT2 receptor agonist alpha-methyl-5-HT reduced the sAHP and eliminated gain increases, whereas augmenting the sAHP conductance by spike-triggered dynamic-current clamp enhanced the gain increase. These results indicate that the effects of noise differ fundamentally between classes of neocortical neurons, depending on specific biophysical properties including the sAHP conductance. Thus, noise from background synaptic input may enhance network excitability by increasing gain in pyramidal neurons with large sAHPs and reducing gain in inhibitory FS interneurons. C1 Univ Washington, Dept Physiol & Biophys, Seattle, WA 98105 USA. Univ Washington, Dept Neurol, Seattle, WA 98105 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Spain, WJ (reprint author), Dept Neurol 128, 1660 S Columbian Way, Seattle, WA 98108 USA. EM spain@u.washington.edu FU BLRD VA [I01 BX000386] NR 67 TC 83 Z9 84 U1 3 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 23 PY 2006 VL 26 IS 34 BP 8787 EP 8799 DI 10.1523/JNEUROSCI.1792-06.2006 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 077CV UT WOS:000240006200016 PM 16928867 ER PT J AU Zhang, Y Qu, DB Morris, EJ O'Hare, MJ Callaghan, SM Slack, RS Geller, HM Park, DS AF Zhang, Yi Qu, Dianbo Morris, Erick J. O'Hare, Michael J. Callaghan, Steven M. Slack, Ruth S. Geller, Herbert M. Park, David S. TI The Chk1/Cdc25A pathway as activators of the cell cycle in neuronal death induced by camptothecin SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Chk1; Cdc25A; DNA damage; cell cycle; apoptosis; neurons ID DEPENDENT KINASE INHIBITORS; SINGLE-STRAND BREAKS; OXIDATIVE DNA-DAMAGE; TYROSINE PHOSPHATASE; ALZHEIMERS-DISEASE; SYMPATHETIC NEURONS; POSTMITOTIC NEURONS; PARKINSONS-DISEASE; CEREBRAL-ISCHEMIA; CORTICAL-NEURONS AB Cell cycle regulators appear to play a paradoxical role in neuronal death. We have shown previously that cyclin-dependent kinases (CDKs), along with their downstream effectors, Rb (retinoblastoma) and E2F/DP1 (E2 promoter binding factor/deleted in polyposis 1), regulate neuronal death evoked by the DNA damaging agent camptothecin. However, the mechanism by which CDKs are activated in this model is unclear. The cell division cycle 25A (Cdc25A) phosphatase is a critical regulator of cell cycle CDKs in proliferating cells. In cortical neurons, we presently show that expression of Cdc25A promotes death even in the absence of DNA damage. Importantly, Cdc25A activity is rapidly increased during DNA damage treatment. Inhibition of Cdc25A blocks death and reduces cyclin D1-associated kinase activity and Rb phosphorylation. This indicates that endogenous Cdc25A activity is important for regulation of cell cycle-mediated neuronal death. We also examined how Cdc25A activity is regulated after DNA damage. Cultured embryonic cortical neurons have a significant basal activity of checkpoint kinase 1 (Chk1), a kinase that regulates cell cycle arrest. During camptothecin treatment of neurons, this activity is rapidly downregulated with a concomitant increase in Cdc25A activity. Importantly, expression of wild-type Chk1, but not kinase-dead Chk1, inhibits the camptothecin-induced increase in Cdc25A activity. In addition, Chk1 expression also promotes survival in the presence of the DNA-damaging agent. Together, our data suggest that a Chk1/Cdc25A activity participates in activation of a cell cycle pathway-mediated death signal in neurons. These data also define how a proliferative signal may be abnormally activated in a postmitotic environment. C1 Univ Ottawa, Ottawa Hlth Res Inst, Neurosci Grp, Ottawa, ON K1H 8M5, Canada. NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA. RP Park, DS (reprint author), Univ Ottawa, Ottawa Hlth Res Inst, Neurosci Grp, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. EM dpark@uottawa.ca RI Qu, Dianbo/C-5121-2011; OI Geller, Herbert/0000-0002-7048-6144 NR 81 TC 40 Z9 41 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 23 PY 2006 VL 26 IS 34 BP 8819 EP 8828 DI 10.1523/JNEUROSCI.2593-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 077CV UT WOS:000240006200020 PM 16928871 ER PT J AU Khuri, SF AF Khuri, Shukri F. TI To skeletonize the internal thoracic artery or not?: Is that the question? SO CIRCULATION LA English DT Editorial Material ID INFECTION; GRAFTS C1 Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Khuri, SF (reprint author), VA Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM shukri.khuri@med.va.gov NR 15 TC 4 Z9 5 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 AUG 22 PY 2006 VL 114 IS 8 BP 754 EP 756 DI 10.1161/CIRCULATIONHA.106.646737 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 075XF UT WOS:000239920000004 PM 16923766 ER PT J AU Beckman, JA Jaff, MR Creager, MA AF Beckman, Joshua A. Jaff, Michael R. Creager, Mark A. TI The United States Preventive Services Task Force Recommendation Statement on Screening for Peripheral Arterial Disease - More harm than benefit? SO CIRCULATION LA English DT Article DE peripheral vascular disease; diagnosis; tests; mortality; atherosclerosis ID ANGIOGRAPHY-AND-INTERVENTIONS; GUIDELINES WRITING COMMITTEE; ANKLE-BRACHIAL INDEX; LOWER-EXTREMITY; CARDIOVASCULAR HEALTH; COLLABORATIVE REPORT; DEVELOP GUIDELINES; VASCULAR-SURGERY; MORTALITY; RISK AB Under the auspices of the Agency for Healthcare Research and Quality, the United States Preventive Services Task Force (USPSTF) recently released an update to its 1996 Peripheral Arterial Disease ( PAD) Screening Recommendation Statement. The USPSTF recommended against PAD screening, giving the practice a "D" level recommendation. This level suggests that little or no benefit could accrue from PAD screening and that screening-associated harm could occur. The present commentary disputes the Task Force's recommendation. The USPSTF statement omitted important peer- reviewed data on the prevalence, screening efficacy, and short-term adverse prognosis of patients with PAD and failed to consider the beneficial outcomes that probably would result from timely diagnosis and treatment of this important manifestation of atherosclerosis. The Task Force implied that screening may lead to unnecessary tests, including increased risk associated with use of contrast angiographic studies. However, most patients with PAD have neither classic symptoms of leg claudication nor threatened limbs but have an extraordinarily high rate of adverse cardiovascular events, such as myocardial infarction, stroke, and death-events that should serve as a key rationale for screening. Medical therapy, including risk factor modification and antiplatelet medications, is known to reduce cardiovascular morbidity and mortality rates in these patients. The Task Force's recommendation against PAD detection may itself adversely result in inadequate recognition and treatment of PAD, with adverse public health consequences. We encourage the USPSTF to reevaluate the extant data, add vascular specialty expertise to its review group, and reconsider its recommendation. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. RP Beckman, JA (reprint author), Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM jbeckman@partners.org OI Beckman, Joshua/0000-0001-8332-8439 NR 32 TC 49 Z9 49 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 AUG 22 PY 2006 VL 114 IS 8 BP 861 EP 866 DI 10.1161/CIRCULATIONAHA.105.607846 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 075XF UT WOS:000239920000019 PM 16923770 ER PT J AU Zabetian, CP Morino, H Ujike, H Yamamoto, M Oda, M Maruyama, H Izumi, Y Kaji, R Griffith, A Leis, BC Roberts, JW Yearout, D Samii, A Kawakami, H AF Zabetian, C. P. Morino, H. Ujike, H. Yamamoto, M. Oda, M. Maruyama, H. Izumi, Y. Kaji, R. Griffith, A. Leis, B. C. Roberts, J. W. Yearout, D. Samii, A. Kawakami, H. TI Identification and haplotype analysis of LRRK2 G2019S in Japanese patients with Parkinson disease SO NEUROLOGY LA English DT Article ID COMMON FOUNDER; MUTATION AB LRRK2 G2019S is the most common known cause of Parkinson disease (PD) in patients of European origin, but little is known about its distribution in other populations. The authors identified two of 586 Japanese patients with PD heterozygous for the mutation who shared a haplotype distinct from that observed in Europeans. This suggests that G2019S originated from separate founders in Europe and Japan and is more widely dispersed than previously recognized. C1 Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. Hiroshima Univ, Grad Sch Biomed Sci, Res Inst Radiat Biol & Med, Dept Epidemiol, Hiroshima 730, Japan. Hiroshima Univ, Grad Sch Biomed Sci, Dept Clin Neurosci & Therapeut, Hiroshima 730, Japan. Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neuropsychiat, Okayama 7008530, Japan. Kagawa Prefectural Cent Hosp, Dept Neurol, Takamatsu, Kagawa, Japan. Sumimoto Hosp, Dept Neurol, Osaka, Japan. Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Clin Neurosci, Tokushima 770, Japan. Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. RP Zabetian, CP (reprint author), Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, S-182 ,1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Maruyama, Hirofumi/B-9333-2011; Kawakami, Hideshi/A-2086-2009; Morino, Hiroyuki/H-9583-2013; OI Kawakami, Hideshi/0000-0002-1405-0901; Morino, Hiroyuki/0000-0002-5190-3547; Zabetian, Cyrus/0000-0002-7739-4306 FU NINDS NIH HHS [K08-NS044138] NR 10 TC 42 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 22 PY 2006 VL 67 IS 4 BP 697 EP 699 DI 10.1212/01.wnl.0000227732.37801.d4 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 075XG UT WOS:000239920100034 PM 16728648 ER PT J AU Martini, SR Hill, MD Alexandrov, AV Molina, CA Kent, TA AF Martini, S. R. Hill, M. D. Alexandrov, A. V. Molina, C. A. Kent, T. A. TI Outcome in hyperglycemic stroke with ultrasound-augmented thrombolytic therapy SO NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; OXIDE SYNTHASE ACTIVITY AB Hyperglycemia independently predicts poor outcome after acute ischemic stroke. CLOTBUST ( Combined Lysis Of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic tPA) demonstrated that ultrasound-augmented thrombolysis improves recanalization and 24-hour outcome in patients with acute ischemic stroke. We hypothesized that ultrasound would preferentially benefit hyperglycemic patients, and reviewed CLOTBUST with respect to admission glucose and good outcome. We found that ultrasound's benefit on 90-day outcome was primarily apparent at higher glucose levels, suggesting that ultrasound therapy may improve outcome following hyperglycemic stroke. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Stroke Program, Houston, TX USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Community Hlth Sci, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Med, Calgary, AB T2N 1N4, Canada. Univ Texas, Sch Med, Stroke Treatment Team, Houston, TX USA. Hosp Gen Valle Hebron, Neurovasc Unit, Barcelona, Spain. RP Kent, TA (reprint author), Baylor Coll Med, Dept Neurol, 2002 Holocombe Blvd,Room 2B223, Houston, TX 77030 USA. EM tkent@bcm.tmc.edu OI Alexandrov, Andrei V/0000-0001-8871-1023; Hill, Michael/0000-0002-6269-1543; Kent, Thomas/0000-0002-9877-7584 FU NINDS NIH HHS [1K23NS02229-01, 1P50NS044227] NR 10 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 22 PY 2006 VL 67 IS 4 BP 700 EP 702 DI 10.1212/01.wnl.0000229926.85117.75 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 075XG UT WOS:000239920100035 PM 16924029 ER PT J AU Lo, TS Williams, O AF Lo, Timothy S. Williams, Olajide TI Unilateral acroparesthesias - An unusual presentation of an acute stroke SO NEUROLOGY LA English DT Editorial Material ID PURE SENSORY STROKE C1 Columbia Univ, Med Ctr, New York, NY USA. RP Lo, TS (reprint author), Massachusetts Gen Hosp, Pain Ctr, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM timothy_s_lo@yahoo.com NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 22 PY 2006 VL 67 IS 4 BP E9 EP E9 DI 10.1212/01.wnl.0000230143.34760.64 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 075XG UT WOS:000239920100055 PM 16924000 ER PT J AU Caviness, VS Grant, PE AF Caviness, V. S. Grant, P. E. TI Our unborn children at risk? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID ULTRASOUND EXAMINATIONS; CELL-DEATH C1 Massachusetts Gen Hosp, Dept Neurol, Div Pediat Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Caviness, VS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Pediat Radiol, Boston, MA 02114 USA. EM caviness@helix.mgh.harvard.edu NR 15 TC 3 Z9 3 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 AUG 22 PY 2006 VL 103 IS 34 BP 12661 EP 12662 DI 10.1073/pnas.0605505103 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 077NI UT WOS:000240035900003 PM 16912111 ER PT J AU Hase, H Ando, T Eldeiry, L Brebene, A Peng, YZ Liu, LY Amano, H Davies, TF Sun, L Zaidi, M Abe, E AF Hase, Hidenori Ando, Takao Eldeiry, Leslie Brebene, Alina Peng, Yuanzhen Liu, Lanying Amano, Hitoshi Davies, Terry F. Sun, Li Zaidi, Mone Abe, Etsuko TI TNF alpha mediates the skeletal effects of thyroid-stimulating hormone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bone remodeling; osteoclast; macrophage; cytokine ID NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; THYROTROPIN RECEPTOR; BONE METABOLISM; GRAVES-DISEASE; UP-REGULATION; TSH RECEPTOR; T-CELL; HYPERTHYROIDISM; EXPRESSION AB We have shown recently that by acting on the thyroid-stimulating hormone (TSH) receptor (TSHR), TSH negatively regulates osteoclast differentiation. Both heterozygotic and homozygotic TSHR null mice are osteopenic with evidence of enhanced osteoclast differentiation. Here, we report that the accompanying elevation of TNF alpha, an osteoclastogenic cytokine, causes the increased osteoclast differentiation. This enhancement in TSHR-/- and TSHR+/- mice is abrogated in compound TSHR-/-/TNF alpha(-/-) and TSHR+/-/ TNF alpha(+/-) mice, respectively. In parallel studies, we find that TSH directly inhibits TNFa production, reduces the number of TNF alpha- producing osteoclast precursors, and attenuates the induction of TNF alpha expression by IL-1, TNF alpha, and receptor activator of NF-kappa B ligand. TSH also suppresses osteoclast formation in murine macrophages and RAW-C3 cells. The suppression is more profound in cells that overexpress the TSHR than those transfected with empty vector. The overexpression of ligand-independent, constitutively active TSHR abrogates osteoclast formation even under basal conditions and in the absence of TSH. Finally, IL-1/TNF alpha and receptor activator of NF-kappa B ligand fail to stimulate AM and NF-kappa B binding to DNA in cells transfected with TSHR or constitutively active TSHR. The results suggest that TNFa is the critical cytokine mediating the downstream antiresorptive effects of TSH on the skeleton. C1 Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. Showa Univ, Sch Dent, Dept Pharmacol, Tokyo 142, Japan. RP Abe, E (reprint author), Mt Sinai Sch Med, Dept Med, 1 Gustave L Levy Pl,Box 1055, New York, NY 10029 USA. EM etsuko.abe@mssm.edu FU NIA NIH HHS [AG14917, AG23176, R01 AG023176]; NIAMS NIH HHS [AR 052258]; NIDDK NIH HHS [DK52464, DK70526, R01 DK052464, R01 DK070526] NR 35 TC 53 Z9 57 U1 0 U2 3 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 AUG 22 PY 2006 VL 103 IS 34 BP 12849 EP 12854 DI 10.1073/pnas.0600427103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 077NI UT WOS:000240035900038 PM 16908863 ER PT J AU Fulci, G Breymann, L Gianni, D Kurozomi, K Rhee, SS Yu, JH Kaur, B Louis, DN Weissleder, R Caligiuri, MA Chiocca, EA AF Fulci, Giulia Breymann, Laura Gianni, Davide Kurozomi, Kazuhiko Rhee, Sarah S. Yu, Jianhua Kaur, Balveen Louis, David N. Weissleder, Ralph Caligiuri, Michael A. Chiocca, E. Antonio TI Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene therapy; innate immunity; oncolytic virus; brain tumor; herpes simplex virus ID HERPES-SIMPLEX-VIRUS; NATURAL-KILLER-CELLS; PHASE-I TRIAL; ONCOLYTIC VIRUS; TUMOR-CELLS; MALIGNANT GLIOMAS; BRAIN-TUMORS; MUTANT; ADENOVIRUS; THERAPY AB Clinical trials are testing oncolytic viruses (OVs) as therapies for cancer. We have shown that animals that have brain tumors and are treated with a herpes simplex virus (HSV)-derived OV live significantly longer when cyclophosphamide (CPA) is preadministered. Here, we explore the mechanisms behind this finding. In a syngeneic rat glioma model, intratumoral HSV administration is associated with rapid increase of natural killer cells, microglia/ macrophages (CD68(+) and CD163(+)), and IFN-gamma. Pretreatment with CPA enhances HSV replication and oncolysis and reduces an HSV-mediated increase in CD68(+) and CD163+ cells and intratumoral IFN-gamma. Molecular imaging shows CPA pretreatment to inhibit HSV-induced infiltration of tumor-associated phagocytic cells. Our results reveal molecular and cellular mechanisms that inhibit intratumoral spread of HSV and suggest a therapeutic path for improving the efficacy of virotherapy as a treatment for cancer. C1 Ohio State Univ, Med Ctr, James Canc Hosp, Dardinger Ctr Neurooncol & Neurosci,Dept Neurol S, Columbus, OH 43210 USA. Ohio State Univ, Med Ctr, Solove Res Inst, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurosurg Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Pathol Serv, Charlestown, MA 02129 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Chiocca, EA (reprint author), Ohio State Univ, Med Ctr, James Canc Hosp, Dardinger Ctr Neurooncol & Neurosci,Dept Neurol S, N-1017 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM ea.chiocca@osumc.edu RI kaur, Balveen/E-3355-2011 FU NCI NIH HHS [CA68458, CA95426, CA16058, P01 CA069246, P01 CA095426, P01 CA69246, P30 CA016058, R01 CA068458, R01 CA085139, R01 CA85139, R37 CA068458]; NINDS NIH HHS [NS41571, R01 NS041571] NR 39 TC 190 Z9 193 U1 2 U2 9 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 AUG 22 PY 2006 VL 103 IS 34 BP 12873 EP 12878 DI 10.1073/pnas.0605496103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 077NI UT WOS:000240035900042 PM 16908838 ER PT J AU Sinha, AK Anand, S Ortel, BJ Chang, Y Mai, Z Hasan, T Maytin, EV AF Sinha, A. K. Anand, S. Ortel, B. J. Chang, Y. Mai, Z. Hasan, T. Maytin, E. V. TI Methotrexate used in combination with aminolaevulinic acid for photodynamic killing of prostate cancer cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE chemotherapy; phototherapy; cellular differentiation; porphyrin ID 5-AMINOLEVULINIC ACID; COPROPORPHYRINOGEN OXIDASE; CLINICAL-EXPERIENCE; HUMAN KERATINOCYTES; INDUCED PORPHYRIN; DIFFERENTIATION; THERAPY; INDUCTION; PROTOPORPHYRIN; FLUORESCENCE AB Photodynamic therapy ( PDT) using 5-aminolaevulinic acid ( ALA) to drive production of an intracellular photosensitiser, protoporphyrin IX ( PpIX), is a promising cancer treatment. However, ALA-PDT is still suboptimal for thick or refractory tumours. Searching for new approaches, we tested a known inducer of cellular differentiation, methotrexate ( MTX), in combination with ALA-PDT in LNCaP cells. Methotrexate alone promoted growth arrest, differentiation, and apoptosis. Methotrexate pretreatment ( 1 mg l(-1), 72 h) followed by ALA ( 0.3mM, 4 h) resulted in a three-fold increase in intracellular PpIX, by biochemical and confocal analyses. After exposure to 512 nm light, killing was significantly enhanced in MTX-preconditioned cells. The reverse order of treatments, ALA-PDT followed by MTX, yielded no enhancement. Methotrexate caused a similar relative increase in PpIX, whether cells were incubated with ALA, methyl-ALA, or hexyl-ALA, arguing against a major effect upon ALA transport. Searching for an effect among porphyrin synthetic enzymes, we found that coproporphyrinogen oxidase ( CPO) was increased three-fold by MTX at the mRNA and protein levels. Transfection of LNCaP cells with a CPO-expressing vector stimulated the accumulation of PpIX. Our data suggest that MTX, when used to modulate intracellular production of endogenous PpIX, may provide a new combination PDT approach for certain cancers. C1 Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Wellman Ctr Photomed, Dept Dermatol, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Dermatol, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Maytin, EV (reprint author), Cleveland Clin Fdn, Dept Biomed Engn, 9500 Euclid Ave,ND-20, Cleveland, OH 44195 USA. EM maytine@ccf.org FU NCI NIH HHS [P01 CA 84203, P01 CA084203] NR 34 TC 67 Z9 71 U1 0 U2 6 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 AUG 21 PY 2006 VL 95 IS 4 BP 485 EP 495 DI 10.1038/sj.bjc.6603273 PG 11 WC Oncology SC Oncology GA 075IG UT WOS:000239877500010 PM 16868543 ER PT J AU Blood, AJ Tuch, DS Makris, N Makhlouf, ML Sudarsky, LR Sharma, N AF Blood, Anne J. Tuch, David S. Makris, Nikos Makhlouf, Miriam L. Sudarsky, Lewis R. Sharma, Nutan TI White matter abnormalities in dystonia normalize after botulinum toxin treatment SO NEUROREPORT LA English DT Article DE basal ganglia; botulinum toxin; diffusion imaging; dystonia; plasticity; white matter ID MASSIVE CORTICAL REORGANIZATION; SOMATOSENSORY CORTEX; CERVICAL DYSTONIA; NERVOUS-SYSTEM; FOCAL DYSTONIA; DIFFUSION; REPRESENTATION; MOTOR; HAND AB The pathophysiology of dystonia is still poorly understood. We used diffusion tensor imaging to screen for white matter abnormalities in regions between the basal ganglia and the thalamus in cervical and hand dystonia patients. All patients exhibited an abnormal hemispheric asymmetry in a focal region between the pallidum and the thalamus. This asymmetry was absent 4 weeks after the same patients were treated with intramuscular botulinum toxin injections. These findings represent a new systems-level abnormality in dystonia, which may lead to new insights about the pathophysiology of movement disorders. More generally, these findings demonstrate central nervous system changes following peripheral reductions in muscle activity. This raises the possibility that we have observed activity-dependent white matter plasticity in the adult human brain. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dept Neurol, Charlestown, MA USA. Dept Radiol, Charlestown, MA USA. Ctr Morphometr Anal, Charlestown, MA USA. RP Blood, AJ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, CNY 149-2301,13th St, Charlestown, MA 02129 USA. EM ablood@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR014075, P41 RR14075]; NIBIB NIH HHS [U54 EB005149]; NINDS NIH HHS [P01 NS037409, P01 NS037409-07, R21 NS046348, R21 NS046348-01] NR 25 TC 30 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 21 PY 2006 VL 17 IS 12 BP 1251 EP 1255 DI 10.1097/01.wnr.0000230500.03330.01 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 080VW UT WOS:000240277600005 PM 16951564 ER PT J AU Lee, H Alt, C Pitsillides, CM Puoris'haag, M Lin, CP AF Lee, Ho Alt, Clemens Pitsillides, Costas M. Puoris'haag, Mehron Lin, Charles P. TI In vivo imaging flow cytometer SO OPTICS EXPRESS LA English DT Article ID CELLS AB We introduce an in vivo imaging flow cytometer, which provides fluorescence images simultaneously with quantitative information on the cell population of interest in a live animal. As fluorescent cells pass through the slit of light focused across a blood vessel, the excited fluorescence is confocally detected. This cell signal triggers a strobe beam and a high sensitivity CCD camera that captures a snapshot image of the cell as it moves down-stream from the slit. We demonstrate that the majority of signal peaks detected in the in vivo flow cytometer arise form individual cells. The instrument's capability to image circulating T cells and measure their speed in the blood vessel in real time in vivo is demonstrated. The cell signal irradiance variation, clustering percentage, and potential applications in biology and medicine are discussed. (c) 2006 Optical Society of America. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Kyungpook Natl Univ, Taegu 702701, South Korea. Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Lee, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM holee@knu.ac.kr; lin@helix.mgh.harvard.edu FU NEI NIH HHS [R01 EY014106, R01 EY014106-03] NR 7 TC 16 Z9 16 U1 1 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD AUG 21 PY 2006 VL 14 IS 17 BP 7789 EP 7800 DI 10.1364/OE.14.007789 PG 12 WC Optics SC Optics GA 079GO UT WOS:000240164100036 PM 19529148 ER PT J AU Mori, S Endo, M Komatsu, S Kandatsu, S Yashiro, T Baba, M AF Mori, Shinichiro Endo, Masahiro Komatsu, Shuhei Kandatsu, Susumu Yashiro, Tomoyasu Baba, Masayuki TI A combination-weighted Feldkamp-based reconstruction algorithm for cone-beam CT SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PERFORMANCE EVALUATION; TOMOGRAPHY; SCANNER AB The combination-weighted Feldkamp algorithm (CW-FDK) was developed and tested in a phantom in order to reduce cone-beam artefacts and enhance cranio-caudal reconstruction coverage in an attempt to improve image quality when utilizing cone-beam computed tomography (CBCT). Using a 256-slice cone-beam CT (256CBCT), image quality (CT-number uniformity and geometrical accuracy) was quantitatively evaluated in phantom and clinical studies, and the results were compared to those obtained with the original Feldkamp algorithm. A clinical study was done in lung cancer patients under breath holding and free breathing. Image quality for the original Feldkamp algorithm is degraded at the edge of the scan region due to the missing volume, commensurate with the cranio-caudal distance between the reconstruction and central planes. The CW-FDK extended the reconstruction coverage to equal the scan coverage and improved reconstruction accuracy, unaffected by the cranio-caudal distance. The extended reconstruction coverage with good image quality provided by the CW-FDK will be clinically investigated for improving diagnostic and radiotherapy applications. In addition, this algorithm can also be adapted for use in relatively wide cone-angle CBCT such as with a flat-panel detector CBCT. RP Mori, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX 3, Boston, MA 02114 USA. EM smori1@partners.org OI Mori, Shinichiro/0000-0002-0412-4399 NR 20 TC 35 Z9 38 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 21 PY 2006 VL 51 IS 16 BP 3953 EP 3965 DI 10.1088/0031-9155/51/16/005 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 078CP UT WOS:000240079100006 PM 16885617 ER PT J AU Soubret, A Ntziachristos, V AF Soubret, Antoine Ntziachristos, Vasilis TI Fluorescence molecular tomography in the presence of background fluorescence SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID OPTICAL DIFFUSION TOMOGRAPHY; NEWTONS OPTIMIZATION SCHEME; DOMAIN PHOTON MIGRATION; TURBID MEDIA; IMAGE-RECONSTRUCTION; BOUNDARY-CONDITIONS; RADIATIVE-TRANSFER; SCATTERING MEDIA; TISSUE PHANTOMS; CONTRAST AGENTS AB Fluorescence molecular tomography is an emerging imaging technique that resolves the bio-distribution of engineered fluorescent probes developed for in vivo reporting of specific cellular and sub-cellular targets. The method can detect fluorochromes in picomole amounts or less, imaged through entire animals, but the detection sensitivity and imaging performance drop in the presence of background, non-specific fluorescence. In this study, we carried out a theoretical and an experimental investigation on the effect of background fluorescence on the measured signal and on the tomographic reconstruction. We further examined the performance of three subtraction methods based on physical models of photon propagation, using experimental data on phantoms and small animals. We show that the data pre-processing with subtraction schemes can improve image quality and quantification when non-specific background florescence is present. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. RP Soubret, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. FU NCI NIH HHS [R33 CA 91807]; NIBIB NIH HHS [R01 EB 000750-2] NR 52 TC 58 Z9 58 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 21 PY 2006 VL 51 IS 16 BP 3983 EP 4001 DI 10.1088/0031-9155/51/16/007 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 078CP UT WOS:000240079100008 PM 16885619 ER PT J AU Yock, TI Krailo, M Fryer, CJ Donaldson, SS Miser, JS Chen, ZJ Bernstein, M Laurie, F Gebhardt, MC Grier, HE Tarbell, NJ AF Yock, Torunn I. Krailo, Mark Fryer, Christopher J. Donaldson, Sarah S. Miser, James S. Chen, Zhengjia Bernstein, Mark Laurie, Fran Gebhardt, Mark C. Grier, Holcombe E. Tarbell, Nancy J. TI Local control in pelvic Ewing sarcoma: Analysis from INT-0091 - A report from the Children's Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol ID SURGICAL RESECTION; RADIATION-THERAPY; TUMORS; FAMILY; RADIOTHERAPY; IRRADIATION; EXPERIENCE; SURVIVAL; SURGERY; CESS-86 AB The impact of the modality used for local control of Ewing sarcoma is uncertain. We investigated the relationship between the type of local control modality, surgery, radiation (RT) or both (S+RT), and subsequent risk for local failure (LF) in patients with nonmetastatic pelvic Ewing sarcoma treated on INT-0091. Patients and Methods Patients <= 30 years with Ewing sarcoma, primitive neuroectodermal tumor or primitive sarcoma of bone were randomly assigned to receive chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin, (VACA) or with these four drugs alternating with ifosfamide and etoposide (VACA-IE). The local control modality, surgery, RT or both was chosen by the treating physicians. The effect of local control modality was assessed after adjusting for the size of tumor (<8 cm, >= 8 cm) and chemotherapy type. Results Seventy-five patients with pelvic tumors and a median follow-up of 4.4 years (0.6 to 11.4 years) comprised the study population. Twelve underwent surgery, 44 received RT, and 19 received both. The 5-year event-free survival (EFS) and cumulative incidence of LF was 49% and 21% (16%, LF only; 5%, LF and distant failure). There was no significant difference in EFS or LF by tumor size (<8 cm, >= 8 cm), local control (LC) modality, or chemotherapy. However, VACA-IE seems to confer an LC benefit (11% v 30%; P=.06). Conclusion There was no significant effect of local control modality (surgery, RT or S+RT) selected by the treating physicians on rates of local failure or EFS. However, VACA-IE improves LC (11%) compared with previously published results for pelvic Ewing sarcoma. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. COG Stat & Data Ctr, Arcadia, CA USA. British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. Hop St Justine, Quebec City, PQ, Canada. Qual Assurance Review Ctr, Providence, RI USA. RP Yock, TI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 341, Boston, MA 02114 USA. EM TYOCK@PARTNERS.ORG FU NCI NIH HHS [CA 13539, CA 30969, CA 98543] NR 29 TC 63 Z9 67 U1 0 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 AUG 20 PY 2006 VL 24 IS 24 BP 3838 EP 3843 DI 10.1200/JCO.2006.05.9188 PG 6 WC Oncology SC Oncology GA 077TD UT WOS:000240052300007 PM 16921035 ER PT J AU Recklitis, CJ Lockwood, RA Rothwell, MA Diller, LR AF Recklitis, Christopher J. Lockwood, Rebecca A. Rothwell, Monica A. Diller, Lisa R. TI Suicidal ideation and attempts in adult survivors of childhood cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the American-Psychosocial-Oncology-Society CY JAN 27-29, 2005 CL Phoenix, AZ SP Amer Psychosocial Oncol Soc ID ACUTE LYMPHOBLASTIC-LEUKEMIA; UNITED-STATES; RISK; DEPRESSION; TRENDS; DEATH; SCALE; PLANS; LIFE AB Purpose This study examined the prevalence of suicidal ideation and past suicide attempt in adult survivors of childhood cancer and investigated the relationship of suicidal symptoms to cancer treatment and current health. The hypothesis that poor physical health would be significantly associated with suicidality after adjusting for mental health variables was specifically tested. Methods Two hundred twenty-six adult survivors of childhood cancer (mean age, 28 years) seen in a survivor clinic completed the Short Form-36 and the Beck Depression Inventory (BDI), as well as suicide items from the Symptom Checklist-90 Revised, and Beck Scale for Suicide Ideation. Participants reporting current suicide ideation or any past suicide attempt were classified as suicidal. Results Twenty-nine participants (12.83%) reported suicidality, although only 11 of these were significantly depressed by BDI criteria. Univariate analyses found suicidality unrelated to age or sex but positively associated with younger age at diagnosis, longer time since diagnosis, cranial radiation treatment, leukemia diagnosis, depression, hopelessness, pain, and physical appearance concern. A hierarchical logistic regression showed that current physical functioning, including pain, was significantly associated with suicidality even after adjusting for treatment and depression variables. Conclusion Suicidal symptoms, which are reported by a significant minority of adult survivors of childhood cancer, are related to cancer treatments and post-treatment mental and physical health. Association of suicidal symptoms with physical health problems is important because these represent treatable conditions for which survivors may seek follow-up care. The relationship of physical well-being to suicidality underscores the need for a multidisciplinary approach to survivor care. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. Suffolk Univ, Boston, MA 02114 USA. RP Recklitis, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, 44 Binney St,SW320B, Boston, MA 02115 USA. EM christopher_recklitis@dfci.harvard.edu NR 44 TC 68 Z9 70 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2006 VL 24 IS 24 BP 3852 EP 3857 DI 10.1200/JCO.2006.06.5409 PG 6 WC Oncology SC Oncology GA 077TD UT WOS:000240052300009 PM 16921037 ER PT J AU Taghian, AG Jeong, JH Mamounas, EP Parda, DS Deutsch, M Costantino, JP Wolmark, N AF Taghian, Alphonse G. Jeong, Jong-Hyeon Mamounas, Eleftherios P. Parda, David S. Deutsch, Melvin Costantino, Joseph P. Wolmark, Norman TI Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy 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 ID RECEPTOR-POSITIVE TUMORS; POSTMASTECTOMY RADIOTHERAPY; RADIATION-THERAPY; POSTOPERATIVE RADIOTHERAPY; SEQUENTIAL METHOTREXATE; PREMENOPAUSAL WOMEN; RISK-FACTORS; CHEMOTHERAPY; TAMOXIFEN; IRRADIATION AB Purpose Lymph node (LN)-negative breast cancer tumors >= 5 cm occur infrequently, and their optimal management is not well defined. In this study, we assess patterns of locoregional failure (LRF) in LN-negative patients who underwent mastectomy, either with or without adjuvant chemotherapy or hormonal therapy and without postmastectomy radiation therapy (PMRT). Patients and Methods Of 8,878 breast cancer patients enrolled onto National Surgical Adjuvant Breast and Bowel Project B-13, B-14, B-19, B-20, and B-23 node-negative trials, 313 had tumors that were 5 cm or larger (median, 5.5 cm; range, 5.0 to 15.5 cm) at pathology and were treated by mastectomy. Median follow-up time was 15.1 years. Therapy included adjuvant chemotherapy in 34.2% of patients; tamoxifen in 21.1%; chemotherapy plus tamoxifen in 19.2%; and no systemic therapy in 25.5%. Results Twenty-eight patients experienced LRF. The overall 10-year cumulative incidences of isolated LRF, LRF with and without distant failure (DF) and DF alone as first event were 7.1%, 10.0%, and 23.6%, respectively. cumulative incidences for isolated LRF as first event for patients with tumors of 5 cm or more than 5 cm were 7.0% and 7.2%, respectively (P=.9). For patients who underwent no systemic treatment, chemotherapy alone, tamoxifen alone, of chemotherapy plus tamoxifen, the incidences were 12.6%, 5.6%, 4.6%, and 5.3%, respectively (P=.2). The majority of failures occurred on the chest wall (24 of 28 patients). Multivariate analysis did not identify significant prognostic factors for LRF. Conclusion In patients with LN-negative tumors >= 5 cm who are treated by mastectomy with or without adjuvant systemic therapy and no PMRT, LRF as first event remains low. PMRT should not be routinely used for these patients. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project Operat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Pittsburgh, PA USA. Allegheny Gen Hosp, Dept Radiat Oncol, Pittsburgh, PA 15212 USA. Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA 15212 USA. Boston Med Ctr, Boston, MA USA. Aultman Canc Ctr, Canton, OH USA. Northeastern Ohio Univ Coll Med & Pharm, Kootstown, OH USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ataghian@partners.org FU NCI NIH HHS [U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651] NR 36 TC 45 Z9 46 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2006 VL 24 IS 24 BP 3927 EP 3932 DI 10.1200/JCO.2006.06.9054 PG 6 WC Oncology SC Oncology GA 077TD UT WOS:000240052300019 PM 16921044 ER PT J AU Li, AG Piluso, LG Cai, X Wei, G Sellers, WR Liu, X AF Li, Andrew G. Piluso, Landon G. Cai, Xin Wei, Gang Sellers, William R. Liu, Xuan TI Mechanistic insights into maintenance of high p53 acetylation by PTEN SO MOLECULAR CELL LA English DT Article ID TETRAMERIZATION DOMAIN; TUMOR-SUPPRESSOR; DNA-BINDING; TRANSCRIPTIONAL REGULATION; SELECTIVE ACTIVATION; LI-FRAUMENI; IN-VITRO; P300; OLIGOMERIZATION; UBIQUITINATION AB Earlier studies have shown that PTEN regulated p53 protein stability both in a phosphatase-dependent manner through antagonizing Akt-Mdm2 pathway and in a phosphatase-in dependent manner through interacting with p53. In this study, we report that PTEN forms a complex with p300 in the nucleus and plays a role in maintenance of high p53 acetylation in response to DNA damage. Furthermore, p300 is required for nuclear PTEN-regulated cell cycle arrest. Interestingly, however, p53 acetylation was found to promote PTEN-p53 interaction. To investigate the molecular mechanisms, we show that acetylation promotes p53 tetramerization, which, in turn, is required for the PTEN-p53 interaction and subsequent maintenance of high p53 acetylation. Taken together, our results suggest a physiological role for the PTEN tumor suppressor in the nucleus and provide a molecular explanation for our previous observation that PTEN controls p53 protein levels independent of its phosphatase activity. C1 Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Liu, X (reprint author), Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. EM xuan.liu@ucr.edu RI cai, xin/J-2051-2014 FU NCI NIH HHS [CA75180] NR 46 TC 92 Z9 97 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG 18 PY 2006 VL 23 IS 4 BP 575 EP 587 DI 10.1016/j.molcel.2006.06.028 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 079DF UT WOS:000240155000012 PM 16916644 ER PT J AU Machida, YJ Machida, Y Chen, YF Gurtan, AM Kupfer, GM D'Andrea, AD Dutta, A AF Machida, Yuichi J. Machida, Yuka Chen, Yuefeng Gurtan, Allan M. Kupfer, Gary M. D'Andrea, Alan D. Dutta, Anindya TI UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation SO MOLECULAR CELL LA English DT Article ID ISG15 MODIFICATION; DNA-REPAIR; IN-VIVO; UBIQUITIN; PROTEIN; CELLS; ASSOCIATION; SUBUNIT; FANCD2 AB The Fanconi anemia pathway is required for the efficient repair of damaged DNA. A key step in this pathway is the monoubiquitination of the FANCD2 protein by the ubiquitin ligase (0) composed of Fanconi anemia core complex proteins. Here, we show that UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway. UBE2T binds to FANCIL, the ubiquitin ligase subunit of the Fanconi anemia core complex, and is required for the monoubiquitination of FANCD2 in vivo. DNA damage in UBE2T-depleted cells leads to the formation of abnormal chromosomes that are a hallmark of Fanconi anemia. In addition, we show that UBE2T undergoes automonoubiquitination in vivo. This monoubiquitination is stimulated by the presence of the FANCIL protein and inactivates UBE2T. Therefore, UBE2T is the E2 in the Fanconi anemia pathway and has a self-inactivation mechanism that could be important for negative regulation of the Fanconi anemia pathway. C1 Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Dept Radiat Oncol, Boston, MA 02115 USA. Univ Virginia, Sch Med, Dept Pediat, Dept Microbiol, Charlottesville, VA 22908 USA. RP Dutta, A (reprint author), Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. EM ad8q@virginia.edu RI Dutta, Anindya/P-3203-2016; OI Dutta, Anindya/0000-0002-4319-0073 FU NCI NIH HHS [R01 CA060499, R01 CA060499-13, R01 CA60499]; NHLBI NIH HHS [R01 HL063776] NR 26 TC 125 Z9 131 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG 18 PY 2006 VL 23 IS 4 BP 589 EP 596 DI 10.1016/j.molcel.2006.06.024 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 079DF UT WOS:000240155000013 PM 16916645 ER PT J AU Li, JL Hayden, MR Warby, SC Durr, A Morrison, PJ Nance, M Ross, CA Margolis, RL Rosenblatt, A Squitieri, F Frati, L Gomez-Tortosa, E Garcia, CA Suchowersky, O Klimek, ML Trent, RJA McCusker, E Novelletto, A Frontali, M Paulsen, JS Jones, R Ashizawa, T Lazzarini, A Wheeler, VC Prakash, R Xu, G Djousse, L Mysore, JS Gillis, T Hakky, M Cupples, LA Saint-Hilaire, MH Cha, JHJ Hersch, SM Penney, JB Harrison, MB Perlman, SL Zanko, A Abramson, RK Lechich, AJ Duckett, A Marder, K Conneally, PM Gusella, JF MacDonald, ME Myers, RH AF Li, Jian-Liang Hayden, Michael R. Warby, Simon C. Durr, Alexandra Morrison, Patrick J. Nance, Martha Ross, Christopher A. Margolis, Russell L. Rosenblatt, Adam Squitieri, Ferdinando Frati, Luigi Gomez-Tortosa, Estrella Garcia, Carmen Ayuso Suchowersky, Oksana Klimek, Mary Lou Trent, Ronald J. A. McCusker, Elizabeth Novelletto, Andrea Frontali, Marina Paulsen, Jane S. Jones, Randi Ashizawa, Tetsuo Lazzarini, Alice Wheeler, Vanessa C. Prakash, Ranjana Xu, Gang Djousse, Luc Mysore, Jayalakshmi Srinidhi Gillis, Tammy Hakky, Michael Cupples, Adrienne Saint-Hilaire, Marie H. Cha, Jang-Ho J. Hersch, Steven M. Penney, John B. Harrison, Madaline B. Perlman, Susan L. Zanko, Andrea Abramson, Ruth K. Lechich, Anthony J. Duckett, Ayana Marder, Karen Conneally, P. Michael Gusella, James F. MacDonald, Marcy E. Myers, Richard H. TI Genome-wide significance for a modifier of age at neurological onset in Huntington's Disease at 6q23-24: the HD MAPS study SO BMC MEDICAL GENETICS LA English DT Article ID OF-ONSET; TRINUCLEOTIDE REPEAT; GENETIC MAPS; SERUM AB Background: Age at onset of Huntington's disease (HD) is correlated with the size of the abnormal CAG repeat expansion in the HD gene; however, several studies have indicated that other genetic factors also contribute to the variability in HD age at onset. To identify modifier genes, we recently reported a whole-genome scan in a sample of 629 affected sibling pairs from 295 pedigrees, in which six genomic regions provided suggestive evidence for quantitative trait loci (QTL), modifying age at onset in HD. Methods: In order to test the replication of this finding, eighteen microsatellite markers, three from each of the six genomic regions, were genotyped in 102 newly recruited sibling pairs from 69 pedigrees, and data were analyzed, using a multipoint linkage variance component method, in the follow-up sample and the combined sample of 352 pedigrees with 753 sibling pairs. Results: Suggestive evidence for linkage at 6q23-24 in the follow-up sample (LOD = 1.87, p = 0.002) increased to genome-wide significance for linkage in the combined sample (LOD = 4.05, p = 0.00001), while suggestive evidence for linkage was observed at 18q22, in both the follow-up sample (LOD = 0.79, p = 0.03) and the combined sample (LOD = 1.78, p = 0.002). Epistatic analysis indicated that there is no interaction between 6q23-24 and other loci. Conclusion: In this replication study, linkage for modifier of age at onset in HD was confirmed at 6q23-24. Evidence for linkage was also found at 18q22. The demonstration of statistically significant linkage to a potential modifier locus opens the path to location cloning of a gene capable of altering HD pathogenesis, which could provide a validated target for therapeutic development in the human patient. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. Wyeth Ayerst Res, Dept Biol Technol, Cambridge, MA USA. Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada. Hop La Pitie Salpetriere, INSERM, U679, Paris, France. Belfast City Hosp, Dept Med Genet, Belfast BT9 7AD, Antrim, North Ireland. Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland. Hennepin Cty Med Ctr, Dept Neurol, Minneapolis, MN 55415 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Program Cellular & Mol Med, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. IRCCS Neuromed, Neurogenet Unit, Pozzilli, Italy. Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00185 Rome, Italy. Fdn Jimenez Diaz, Serv Neurol & Genet, E-28040 Madrid, Spain. Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Med Genet, Calgary, AB T2N 1N4, Canada. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Westmead Hosp, Dept Neurol, Sydney, NSW 2145, Australia. Univ Roma Tor Vergata, Dept Biol, I-00133 Rome, Italy. CNR, Inst Neurobiol & Mol Med, Rome, Italy. Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Univ Texas, Med Branch, Dept Neurol, Galveston, TX 77550 USA. Robert Wood Johnson Sch Med & Dent, Dept Neurol, New Brunswick, NJ 08903 USA. Novartis Pharmaceut, New Brunswick, NJ USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Genet Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22903 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Div Med Genet, San Francisco, CA 94143 USA. WMS Hall Psychiat Inst, Columbia, SC USA. Columbia Coll Phys, Dept Neurol, New York, NY USA. Indiana Univ, Sch Med, Dept Genet, Indianapolis, IN 46204 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Myers, RH (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM jlli@alum.bu.edu; mrh@cmmt.ubc.ca; simon@cmmt.ubc.ca; durr@moka.ccr.jussieu.fr; Patrick.Morrison@bch.n-i.nhs.uk; nancem@parknicollet.com; car@welchlink.welch.jhu.edu; rmargoli@welchlink.welch.jhu.edu; arosenba@jhmi.edu; neurogen@neuromed.it; luigi.frati@uniroma1.it; EGomezT@fjd.es; CAyuso@fjd.es; osuchowe@ucalgary.ca; klimek@ucalgary.ca; rtrent@med.usyd.edu.au; elizabeth_mccusker@mail.wmi.usyd.edu.au; novelletto@bio.uniRoma2.it; marina.frontali@ims.rm.cnr.it; jane-paulsen@uiowa.edu; randi852@mindspring.com; tetsuoa@bcm.tmc.edu; lazzaral@optonline.net; wheeler@helix.mgh.harvard.edu; ranjana@bu.edu; xugang05@gmail.com; ldjousse@bu.edu; srinidhi@helix.mgh.harvard.edu; magencor@helix.mgh.harvard.edu; magencor@helix.mgh.harvard.edu; adrienne@bu.edu; neuromsh@bu.edu; cha@helix.mgh.harvard.edu; hersch@helix.mgh.harvard.edu; mghneurology@partners.org; MBH3Y@hscmail.mcc.virginia.edu; sperlman@ucla.edu; azanko@itsa.ucsf.edu; rka07@dmh.state.sc.us; alechich@chcsnet.org; ad498@columbia.edu; marderk@sergievsky.cpmc.columbia.edu; pconneal@iupui.edu; gusella@helix.mgh.harvard.edu; macdonam@helix.mgh.harvard.edu; rmyers@bu.edu RI Hayden, Michael/D-8581-2011; Ross, Christopher/H-8395-2013; Djousse, Luc/F-5033-2017; OI Li, Jian-Liang/0000-0002-6487-081X; Myers, Richard/0000-0002-8365-2674; Novelletto, Andrea/0000-0002-1146-7680; Squitieri, Ferdinando /0000-0002-7397-1727; Hayden, Michael/0000-0001-5159-1419; Djousse, Luc/0000-0002-9902-3047; Saint-Hilaire, Marie-Helene/0000-0002-2355-5979; Cupples, L. Adrienne/0000-0003-0273-7965 FU NCRR NIH HHS [1S10RR163736-01A1]; NINDS NIH HHS [NS16375, NS32765, P01 NS016375, P50 NS016367, P50NS016367, R01 NS032765] NR 25 TC 49 Z9 50 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD AUG 17 PY 2006 VL 7 AR 71 DI 10.1186/1471-2350-7-71 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 090YV UT WOS:000240993100001 PM 16914060 ER PT J AU Sharon, E Galun, M Sharon, D Basri, R Brandt, A AF Sharon, Eitan Galun, Meirav Sharon, Dahlia Basri, Ronen Brandt, Achi TI Hierarchy and adaptivity in segmenting visual scenes SO NATURE LA English DT Article ID IMAGE SEGMENTATION; CORTEX AB Finding salient, coherent regions in images is the basis for many visual tasks, and is especially important for object recognition. Human observers perform this task with ease, relying on a system in which hierarchical processing seems to have a critical role(1). Despite many attempts, computerized algorithms(2-5) have so far not demonstrated robust segmentation capabilities under general viewing conditions. Here we describe a new, highly efficient approach that determines all salient regions of an image and builds them into a hierarchical structure. Our algorithm, segmentation by weighted aggregation, is derived from algebraic multigrid solvers for physical systems(6), and consists of fine-to-coarse pixel aggregation. Aggregates of various sizes, which may or may not overlap, are revealed as salient, without predetermining their number or scale. Results using this algorithm are markedly more accurate and significantly faster ( linear in data size) than previous approaches. C1 Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Weizmann Inst Sci, Moross Lab Vis & Motor Control, IL-76100 Rehovot, Israel. RP Sharon, E (reprint author), Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel. EM eitan.sharon@weizmann.ac.il RI anzhi, yue/A-8609-2012 NR 17 TC 107 Z9 121 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 17 PY 2006 VL 442 IS 7104 BP 810 EP 813 DI 10.1038/nature04977 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 074DK UT WOS:000239792700045 PM 16810176 ER PT J AU Krivtsov, AV Twomey, D Feng, ZH Stubbs, MC Wang, YZ Faber, J Levine, JE Wang, J Hahn, WC Gilliland, DG Golub, TR Armstrong, SA AF Krivtsov, Andrei V. Twomey, David Feng, Zhaohui Stubbs, Matthew C. Wang, Yingzi Faber, Joerg Levine, Jason E. Wang, Jing Hahn, William C. Gilliland, D. Gary Golub, Todd R. Armstrong, Scott A. TI Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9 SO NATURE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC PROGENITORS; FUSION GENE; HOXA9; MICE; IMMORTALIZATION; TRANSLOCATIONS; IDENTIFICATION; MLL-GAS7; TARGETS AB Leukaemias and other cancers possess a rare population of cells capable of the limitless self-renewal necessary for cancer initiation and maintenance(1-7). Eradication of these cancer stem cells is probably a critical part of any successful anti-cancer therapy, and may explain why conventional cancer therapies are often effective in reducing tumour burden, but are only rarely curative. Given that both normal and cancer stem cells are capable of self-renewal, the extent to which cancer stem cells resemble normal tissue stem cells is a critical issue if targeted therapies are to be developed. However, it remains unclear whether cancer stem cells must be phenotypically similar to normal tissue stem cells or whether they can retain the identity of committed progenitors. Here we show that leukaemia stem cells (LSC) can maintain the global identity of the progenitor from which they arose while activating a limited stem-cell- or self-renewal-associated programme. We isolated LSC from leukaemias initiated in committed granulocyte macrophage progenitors through introduction of the MLL - AF9 fusion protein encoded by the t(9; 11)(p22; q23). The LSC were capable of transferring leukaemia to secondary recipient mice when only four cells were transferred, and possessed an immunophenotype and global gene expression profile very similar to that of normal granulocyte macrophage progenitors. However, a subset of genes highly expressed in normal haematopoietic stem cells was re-activated in LSC. LSC can thus be generated from committed progenitors without widespread reprogramming of gene expression, and a leukaemia self-renewal-associated signature is activated in the process. Our findings define progression from normal progenitor to cancer stem cell, and suggest that targeting a self-renewal programme expressed in an abnormal context may be possible. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Broad Inst, Cambridge, MA 02142 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Armstrong, SA (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM Scott.Armstrong@childrens.harvard.edu RI Faber, Joerg/G-4549-2010; OI Krivtsov, Andrei/0000-0002-5511-1686 NR 30 TC 741 Z9 780 U1 6 U2 36 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 17 PY 2006 VL 442 IS 7104 BP 818 EP 822 DI 10.1038/nature04980 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 074DK UT WOS:000239792700047 PM 16862118 ER PT J AU Krispel, CM Chen, D Melling, N Chen, YJ Martemyanov, KA Quillinan, N Arshavsky, VY Wensel, TG Chen, CK Burns, ME AF Krispel, Claudia M. Chen, Desheng Melling, Nathan Chen, Yu-Jiun Martemyanov, Kirill A. Quillinan, Nidia Arshavsky, Vadim Y. Wensel, Theodore G. Chen, Ching-Kang Burns, Marie E. TI RGS expression rate-limits recovery of rod photoresponses SO NEURON LA English DT Article ID GTPASE ACCELERATING PROTEIN; SINGLE-PHOTON RESPONSES; RETINAL RODS; RHODOPSIN KINASE; BETA-SUBUNIT; PHOTOTRANSDUCTION CASCADE; MICE LACKING; LIGHT; KINETICS; MOUSE AB Signaling through G protein-coupled receptors (GPCRs) underlies many cellular processes, yet it is not known which molecules determine the duration of signaling in intact cells. Two candidates are G protein-coupled receptor kinases (GRKs) and Regulators of G protein signaling (RGSs), deactivation enzymes for GPCRs and G proteins, respectively. Here we investigate whether GRK or RGS governs the overall rate of recovery of the light response in mammalian rod photoreceptors, a model system for studying GPCR signaling. We show that overexpression of rhodopsin kinase (GRK1) increases phosphorylation of the GPCR rhodopsin but has no effect on photoresponse recovery. In contrast, overexpression of the photoreceptor FIGS complex (RGS9-1(.)G beta 5L(.)R9AP) dramatically accelerates response recovery. Our results show that G protein deactivation is normally at feast 2.5 times slower than rhodopsin deactivation, resolving a long-standing controversy concerning the mechanism underlying the recovery of rod visual transduction. C1 Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA. Harvard Univ, Howe Lab Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. RP Chen, CK (reprint author), Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. EM cjchen@vcu.edu; meburns@ucdavis.edu OI Wensel, Theodore/0000-0003-3518-9352 FU NEI NIH HHS [EY012859, R01 EY014047-05, EY014047, R01 EY014047, EY011900, EY013811, EY12576] NR 43 TC 154 Z9 161 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD AUG 17 PY 2006 VL 51 IS 4 BP 409 EP 416 DI 10.1016/j.neuron.2006.07.010 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 084AU UT WOS:000240504700005 PM 16908407 ER PT J AU Campen, RB Duncan, LM Sang, CN Harris, NL Cusack, JC AF Campen, Rebecca B. Duncan, Lyn M. Sang, Christine N. Harris, Nancy Lee Cusack, James C. TI Case 25-2006: A 41-year-old woman with painful subcutaneous nodules - Adiposis dolorosa (Dercum's disease) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID AUTOSOMAL DOMINANT INHERITANCE; INTRAVENOUS LIDOCAINE; SYMMETRICAL LIPOMATOSIS; INTRACTABLE PAIN; HYPERALGESIA; MANAGEMENT; ALLODYNIA; RELIEF; NERVE C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Anesthesiol Perioperat &Pain Med, Boston, MA 02115 USA. RP Campen, RB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 25 TC 10 Z9 11 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 17 PY 2006 VL 355 IS 7 BP 714 EP 722 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 074AN UT WOS:000239784500012 PM 16914708 ER PT J AU Hammer, SM Saag, MS Schechter, M Montaner, JSG Schooley, RT Jacobsen, DM Thompson, MA Carpenter, CCJ Fischl, MA Gazzard, BG Gatell, JM Hirsch, MS Katzenstein, DA Richman, DD Vella, S Yeni, PG Volberding, PA AF Hammer, Scott M. Saag, Michael S. Schechter, Mauro Montaner, Julio S. G. Schooley, Robert T. Jacobsen, Donna M. Thompson, Melanie A. Carpenter, Charles C. J. Fischl, Margaret A. Gazzard, Brian G. Gatell, Jose M. Hirsch, Martin S. Katzenstein, David A. Richman, Douglas D. Vella, Stefano Yeni, Patrick G. Volberding, Paul A. TI Treatment for adult HIV infection - 2006 recommendations of the International AIDS Society-USA panel SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HEPATITIS-B-VIRUS; TENOFOVIR DISOPROXIL FUMARATE; EARLY VIROLOGICAL FAILURE; DRUG-RESISTANCE; HIV-1-INFECTED PATIENTS; COMBINATION THERAPY; DISEASE PROGRESSION; INITIAL TREATMENT AB Context Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society - USA panel has updated its recommendations as warranted by new developments in the field. Objective To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. Data Sources and Study Selection A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. Data Extraction and Synthesis Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. Conclusions Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/mu L and before it declines to 200/mu L. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside ( or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced. C1 Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Fed Rio de Janeiro, Dept Prevent Med, BR-21941 Rio De Janeiro, Brazil. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Int AIDS Soc USA, San Francisco, CA USA. AIDS Res Consortium, Atlanta, GA USA. Brown Univ, Sch Med, Dept Biomed, Providence, RI 02912 USA. Univ Miami, Sch Med, Dept Med, Coral Gables, FL 33124 USA. Chelsea & Westminster Hosp, Dept HIV Med, London, England. Univ Barcelona, Hosp Clin, IDIBAPS, Dept Med, Barcelona, Spain. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Stanford Univ, Med Ctr, Dept Med, Stanford, CA 94305 USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. San Diego Vet Affairs Healthcare Syst, San Diego, CA USA. Ist Super Sanita, Dept Drug Discovery & Evaluat, I-00161 Rome, Italy. Hop Bichat Claude Bernard, X Bichat Med Sch, Dept Infect Dis, F-75877 Paris 18, France. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Hammer, SM (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168th St,Box 82, New York, NY 10032 USA. EM smh48@columbia.edu RI Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 NR 133 TC 567 Z9 592 U1 2 U2 25 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 16 PY 2006 VL 296 IS 7 BP 827 EP 843 DI 10.1001/jama.296.7.827 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 073SR UT WOS:000239763400023 PM 16905788 ER PT J AU Hassett, MJ O'Malley, AJ Pakes, JR Newhouse, JR Earle, CC AF Hassett, Michael J. O'Malley, A. James Pakes, Juliana R. Newhouse, Joseph R. Earle, Craig C. TI Frequency and cost of chemotherapy-related serious adverse effects in a population sample of women with breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID QUALITY-OF-LIFE; CLINICAL-TRIALS; DRUG-REACTIONS; RANDOMIZED TRIALS; COMORBIDITY INDEX; ELDERLY-PATIENTS; OLDER WOMEN; CLAIMS DATA; PARTICIPATION; ENROLLMENT AB Background. The number, nature, and costs of serious adverse effects experienced by younger women receiving chemotherapy for breast cancer outside of clinical trials are unknown. Methods: From a database of medical claims made by individuals with employer-provided health insurance between January 1998 and December 2002, we identified 12239 women 63 years of age or younger with newly diagnosed breast cancer, of whom 4075 received chemotherapy during the 12 months after the initial breast cancer diagnosis and 8164 did not. Diagnostic codes for eight chemotherapy-related adverse effects were identified. Total hospitalizations for all causes, hospitalizations or emergency room visits for adverse effects that are typically related to chemotherapy, and health care expenditures were compared between the two groups of women. All statistical tests were two-sided. Results: Women who received chemotherapy were more likely than those who did not to be hospitalized or to visit the emergency room for all causes (61% versus 42%; mean difference=19%, 95% confidence interval [CI]=16.7% to 21.3%, P <.001) and for chemotherapy-related serious adverse effects (16% versus 5%, mean difference=11%, 95% CI=9.6% to 12.4%, P<.001). The percentages of chemotherapy recipients who were hospitalized or visited the emergency room during the year after their breast cancer diagnosis were 8.4% for fever or infection; 5.5% for neutropenia or thrombocytopenia; 2.5% for dehydration or electrolyte disorders; 2.4% for nausea, emesis, or diarrhea; 2.2% for anemia; 2% for constitutional symptoms; 1.2% for deep venous thrombosis or pulmonary embolus; and 0.9% for malnutrition. Chemotherapy recipients incurred large incremental expenditures for chemotherapy-related serious adverse effects ($1271 per person per year) and ambulatory encounters ($17617 per person per year). Conclusions: Chemotherapy-related serious adverse effects among younger, commercially insured women with breast cancer may be more common than reported by large clinical trials and lead to more patient suffering and health care expenditures than previously estimated. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St,454-STE 21, Boston, MA 02115 USA. EM mhassett@partners.org FU AHRQ HHS [P01-HS10803] NR 41 TC 151 Z9 151 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 16 PY 2006 VL 98 IS 16 BP 1108 EP 1117 DI 10.1093/jnci/djj305 PG 10 WC Oncology SC Oncology GA 101ED UT WOS:000241720800008 PM 16912263 ER PT J AU Butt, AA Justice, AC Skanderson, M Good, C Kwoh, CK AF Butt, A. A. Justice, A. C. Skanderson, M. Good, C. Kwoh, C. K. TI Rates and predictors of hepatitis C virus treatment in HCV-HIV-coinfected subjects SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ALPHA-2A PLUS RIBAVIRIN; HEPATOCELLULAR-CARCINOMA; PEGINTERFERON ALPHA-2A; INTERFERON THERAPY; INFECTED VETERANS; POST-HAART; CIRRHOSIS; RISK; COHORT; CANCER AB Background True treatment rates and the impact of comorbidities on treatment rates for hepatitis C virus in the HCV-HIV-coinfected subjects are unknown. Aim To quantify the rates of treatment prescription and the effect of comorbidities on hepatitis C virus treatment rates in HCV-HIV-coinfected veterans. Methods The Veterans Affairs National Patient Care Database was used to identify all hepatitis C virus-infected subjects between 1999 and 2003 using ICD-9 codes. Demographics, comorbidities and pharmacy data were retrieved. We used logistic regression to compare the predictors of hepatitis C virus treatment in hepatitis C virus-monoinfected and HCV-HIV-coinfected subjects. Findings We identified 120 507 hepatitis C virus-infected subjects, of which 6502 were HIV coinfected. 12% of the hepatitis C virus-monoinfected and 7% of the -coinfected subjects were prescribed hepatitis C virus treatment (P < 0.0001). Those not prescribed treatment were older (48.6 years vs. 47.7 years, P = 0.007) and more likely to be black (52% vs. 32%, P < 0.0001). HIV coinfected was less likely to be prescribed hepatitis C virus treatment (OR 0.74, 95% CI: 0.67-0.82). Among the coinfected subjects, the following were associated with non-treatment (OR, 95% CI): black race (0.45, 0.35-0.57); Hispanic race (0.56, 0.38-0.82); drug use (0.68, 0.53-0.88); anaemia (0.17, 0.11-0.26); bipolar disorder (0.63, 0.40-0.99); major depression (0.72, 0.53-0.99); mild depression (0.47, 0.35-0.62). Conclusions A small number of HCV-HIV-coinfected veterans are prescribed treatment for hepatitis C virus. Non-treatment is associated with increasing age, minority race, drug use and psychiatric illness. Further studies are needed to determine the eligibility for treatment and reasons for non-treatment for hepatitis C virus. C1 Univ Pittsburgh, Med Ctr, Sch Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Yale Univ, Sch Med, Ctr Hlth Equ Res & Promot, New Haven, CT 06520 USA. RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, 3601 5th Ave,Suite 3A,Falk Med Bldg, Pittsburgh, PA 15213 USA. EM butta@dom.pitt.edu FU NIDA NIH HHS [DA016175-01A1] NR 24 TC 30 Z9 30 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD AUG 15 PY 2006 VL 24 IS 4 BP 585 EP 591 DI 10.1111/j.1365-2036.2006.03020.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 067MJ UT WOS:000239306800003 PM 16907891 ER PT J AU Quiroz, R Gerhard-Herman, M Kosowsky, JM DeSantis, SM Kucher, N McKean, SC Goldhaber, SZ AF Quiroz, Rene Gerhard-Herman, Marie Kosowsky, Joshua M. DeSantis, Stacia M. Kucher, Nils McKean, Sylvia C. Goldhaber, Samuel Z. TI Comparison of a single end point to determine optimal initial warfarin dosing (5 mg versus 10 mg) for venous thromboembolism SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID 10-MG; 5-MG; TRIAL AB There remains considerable controversy regarding optimal initial warfarin dosing in patients with acute venous thromboembolism. Therefore, an open-label, randomized trial comparing 2 warfarin initiation nomograms (5 vs 10 mg) was conducted in patients with acute venous thromboembolism. All participants received fondaparinux for >= 5 days as a "bridge" to warfarin. The primary end point was defined as the number of days necessary to achieve 2 consecutive international normalized ratio laboratory test values > 1.9. A total of 50 patients were enrolled and randomly assigned to each of the treatment arms. The median time to 2 consecutive international normalized ratios was 5 days in the 2 groups. There was no statistical difference in achieving the primary end point using either the 5- or the 10-mg nomogram (p = 0.69). These results should provide clinicians with increased warfarin dosing options in patients presenting with acute venous thromboembolism. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Zurich Hosp, Div Cardiovasc, CH-8091 Zurich, Switzerland. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Goldhaber, SZ (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. EM sgoldhaber@partners.org NR 5 TC 10 Z9 11 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 2006 VL 98 IS 4 BP 535 EP 537 DI 10.1016/j.amjcard.2006.02.063 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 077OO UT WOS:000240039500021 PM 16893712 ER PT J AU Shlipak, MG Katz, R Sarnak, MJ Fried, LF Newman, AB Stehman-Breen, C Seliger, SL Kestenbaum, B Psaty, B Tracy, RP Siscovick, DS AF Shlipak, Michael G. Katz, Ronit Sarnak, Mark J. Fried, Linda F. Newman, Anne B. Stehman-Breen, Catherine Seliger, Stephen L. Kestenbaum, Brian Psaty, Bruce Tracy, Russell P. Siscovick, David S. TI Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; RENAL-FUNCTION; HEART-FAILURE; CREATININE CLEARANCE; THYROID-DYSFUNCTION; RISK-FACTOR; HEALTH; MORTALITY; EVENTS; DEFINITION AB Background: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] >= 60 mL/min per 1.73 m(2)). Objective: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease. Design: Cohort study. Setting: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States. Participants: 4663 elderly persons Measurements: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years). Results: At baseline, 78% of participants did not have chronic kidney disease (estimated GFR 60 mL/min per 1.73 m(2)) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 mu mol/L (0.9 mg/dL, and 83 mL/min per 1.73 m(2), respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.401), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.381), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (>= 1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L. Limitations: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease. Conclusions: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR. C1 Vet Adm Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Washington, Seattle, WA 98195 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Vermont, Coll Med, Burlington, VT USA. RP Shlipak, MG (reprint author), Vet Adm Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [R01 HL073208-01, N01-HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086]; NIA NIH HHS [R01 AG027002]; NIDDK NIH HHS [R01 DK066488] NR 41 TC 306 Z9 332 U1 1 U2 10 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 AUG 15 PY 2006 VL 145 IS 4 BP 237 EP 246 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 075CC UT WOS:000239858800001 PM 16908914 ER PT J AU Rauch, SL Shin, LM Phelps, EA AF Rauch, Scott L. Shin, Lisa M. Phelps, Elizabeth A. TI Neurocircuitry models of posttraumatic stress disorder and extinction: Human neuroimaging research - Past, present, and future SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 1st International Conference on Extinction - The Neural Mechanisms of Behavior Change CY FEB, 2005 CL Ponce, PR SP Natl Inst Metal Hlth, Ponce Sch Med DE ventromedial prefrontal cortex; anterior cingulate cortex; orbitofrontal cortex; amygdala; hippocampus; magnetic resonance imaging; anxiety disorders; fear conditioning ID CHILDHOOD SEXUAL-ABUSE; MEDIAL PREFRONTAL CORTEX; SCRIPT-DRIVEN IMAGERY; CEREBRAL-BLOOD-FLOW; EMOTIONAL FACIAL EXPRESSIONS; POSITRON-EMISSION-TOMOGRAPHY; SMALLER HIPPOCAMPAL VOLUME; ANTERIOR CINGULATE; FEAR EXTINCTION; FUNCTIONAL MRI AB The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD. C1 NYU, Dept Psychol, Ctr Neural Sci, New York, NY 10003 USA. Massachusetts Gen Hosp, Psychiat Neurosci Div, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Phelps, EA (reprint author), NYU, Dept Psychol, Ctr Neural Sci, 6 Washington Pl,Room 863, New York, NY 10003 USA. EM liz.phelps@nyu.edu FU NIMH NIH HHS [R01MH62104, R21MH072279, R21MH72156] NR 83 TC 573 Z9 593 U1 13 U2 85 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 AUG 15 PY 2006 VL 60 IS 4 BP 376 EP 382 DI 10.1016/j.biopsych.2006.06.004 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 074UK UT WOS:000239837100010 PM 16919525 ER PT J AU Geller, AC Emmons, KM Brooks, DR Powers, C Zhang, Z Koh, HK Heeren, T Sober, AJ Li, F Gilchrest, BA AF Geller, Alan C. Emmons, Karen M. Brooks, Daniel R. Powers, Catherine Zhang, Zi Koh, Howard K. Heeren, Timothy Sober, Arthur J. Li, Frederick Gilchrest, Barbara A. TI A Randomized trial to improve early detection and prevention practices among siblings of melanoma patients SO CANCER LA English DT Article DE melanoma; skin cancer; screening; prevention; family history; selfexamination; early detection; education ID SKIN SELF-EXAMINATION; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; SCREENING-PROGRAM; SUN-PROTECTION; RISK; SURVEILLANCE; BEHAVIORS; HISTORY; DISEASE AB BACKGROUND. Identifying high-risk individuals for melanoma education and risk reduction may be a viable strategy to curb the incidence of melanoma, which has risen precipitously in the past 50 years. The first-degree relatives of melanoma patients represent a risk group who may experience a 'teachable moment' for enhanced education and risk reduction. METHODS. We report a randomized trial testing an intervention that provided personalized telephone counseling and individually tailored materials to siblings of recently-diagnosed melanoma patients. The purpose of this study was to test whether an intervention could lead to improvements in siblings' skin cancer risk reduction practices. Intervention condition participants received the following: 1) an initial motivational and goal-setting telephone intervention session delivered by the health educator; 2) three sets of computer-generated materials specifically tailored to individual responses from the baseline survey; 3) three telephone counseling sessions with the health educator, timed to follow receipt of the mailed materials; and 4) linkages to free screening programs. Families in the usual care arm received the suggestion from the physician that patients diagnosed with melanoma notify the family members about their diagnosis and encourage the family members to be screened. RESULTS. 494 siblings were recruited to the study and 403 siblings remained in the study through at least 6 months. At 12 months, intervention siblings were more likely to examine all moles, including those on the back (OR, 1.76; 95% CI, 1.062.91). Compared with baseline, the number of participants in both groups that had received a skin cancer examination more than doubled, with no differences between groups. At 12 months, two-thirds of siblings in both groups reported routine use of sunscreen, but there were no differences in change over baseline between the two groups. CONCLUSIONS. This study is the one of the first, to our knowledge, to address skin cancer risk-reduction strategies in a sample of individuals who have a recent family diagnosis of melanoma. Diagnosis of melanoma in a family member provides an important opportunity to intervene with others in that family. The components of the intervention may provide a useful foundation for future efforts to target the more than half million siblings at risk for melanoma, a lethal but preventable disease. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Massachusetts Dept Publ Hlth, Hlth Survey Program, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Clin Clin Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Dept Dermatol, 720 Harrison Ave,DOB801A, Boston, MA 02118 USA. EM ageller@bu.edu OI Heeren, Timothy/0000-0001-5643-3559; Brooks, Daniel/0000-0001-6220-6889 FU NCI NIH HHS [R01CA76333] NR 32 TC 32 Z9 32 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2006 VL 107 IS 4 BP 806 EP 814 DI 10.1002/cncr.22050 PG 9 WC Oncology SC Oncology GA 076II UT WOS:000239950000018 PM 16832795 ER PT J AU Joazeiro, CAP Anderson, KC Hunter, T AF Joazeiro, Claudio A. P. Anderson, Kenneth C. Hunter, Tony TI Proteasome inhibitor drugs on the rise SO CANCER RESEARCH LA English DT Article ID PANCREATIC-CANCER CELLS; BORTEZOMIB; APOPTOSIS; MYELOMA; SITES AB In May 2003, the U.S. Food and Drug Administration granted the proteasome inhibitor bortezomib (Velcade) fast-track status for the treatment of multiple myeloma. This landmark represented the first approval of a drug targeting the ubiquitin-proteasome system (UPS) for any indication. More recently, at the AACR Special Conference "Ubiquitin and Cancer: From Molecular Targets and Mechanisms to the Clinic" (Orlando, FL, January 18-22, 2006), it became evident that drug discovery in the UPS is experiencing another round of great excitement. The reason-new clinical applications found for bortezomih, along with the promised success of new types of proteasome inhibitors reaching the clinic. C1 Novartis Fdn, Genom Inst, San Diego, CA 92121 USA. Scripps Res Inst, San Diego, CA USA. Salk Inst Biol Studies, San Diego, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Joazeiro, CAP (reprint author), Novartis Fdn, Genom Inst, 10675 John J Hopkins Dr, San Diego, CA 92121 USA. EM cjoazeiro@hotmail.com NR 8 TC 47 Z9 48 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2006 VL 66 IS 16 BP 7840 EP 7842 DI 10.1158/0008-5472.CAN-06-2033 PG 3 WC Oncology SC Oncology GA 074QZ UT WOS:000239828200003 PM 16861477 ER PT J AU Das, S Ongusaha, PP Yang, YS Park, JM Aaronson, SA Lee, SW AF Das, Sanjeev Ongusaha, Pat P. Yang, Yoon Sun Park, Jin-Mo Aaronson, Stuart A. Lee, Sam W. TI Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance through nuclear factor-kappa B pathway activation SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL-CELLS; CANCER PREVENTION; ANTICANCER AGENTS; INDUCED APOPTOSIS; DOMAIN; INHIBITION; INDUCTION; COX-2; ADHESION; PROTEIN AB Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by various types of collagens and is known to play a role in cell attachment, migration, survival, and proliferation. However, little is known about the molecular mechanism(s) underlying the role of DDR1 in cancer. We report here that DDR1 induces cyclooxygenase-2 (Cox-2) expression resulting in enhanced chemoresistance. Depletion of DDR1-mediated Cox-2 induction using short hairpin RNA (shRNA) results in increased chemosensitivity. We also show that DDR1 activates the nuclear factor-kappa B (NF-kappa B) pathway and blocking this activation by an I kappa B superrepressor mutant results in the ablation of DDR1-induced Cox-2, leading to enhanced chemosensitivity, indicating that DDR1-mediated Cox-2 induction is NF-kappa B dependent. We identify the upstream activating kinases of the NF-kappa B pathway, IKK beta and IKK gamma, as essential for DDR1-mediated NF-kappa B activation, whereas IKK alpha seems to be dispensable. Finally, shRNA-mediated inhibition of DDR1 expression significantly enhanced chemosensitivity to genotoxic drugs in breast cancer cells. Thus, DDR1 signaling provides a novel target for therapeutic intervention with the prosurvival/antiapoptotic machinery of tumor cells. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Curonix Inc, Seoul, South Korea. Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM sam.lee@cbTc2.mgh.harvard.edu FU NCI NIH HHS [CA085214, CA080058, CA097216] NR 46 TC 31 Z9 33 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2006 VL 66 IS 16 BP 8123 EP 8130 DI 10.1158/0008-5472.CAN-06-1215 PG 8 WC Oncology SC Oncology GA 074QZ UT WOS:000239828200039 PM 16912190 ER PT J AU Geiger, GA Parker, SE Beothy, AP Tucker, JA Mullins, MC Kao, GD AF Geiger, Geoffrey A. Parker, Sharon E. Beothy, Andrew P. Tucker, Jennifer A. Mullins, Mary C. Kao, Gary D. TI Zebrafish as a "biosensor"? Effects of ionizing radiation and amifostine on embryonic viability and development SO CANCER RESEARCH LA English DT Article ID DNA FRAGMENTATION; NERVOUS-SYSTEM; APOPTOSIS; PROTECTION; STAUROSPORINE; INDUCTION; TOXICITY; DAMAGE; MODEL AB The zebrafish (Danio rerio) has emerged as a popular vertebrate model system for cancer and treatment-related research. Benefits include ease of care, rapid development, optical clarity of embryos, which allows visualization of major organ systems, and opportunities for genetic manipulation. However, specific parameters of radiation sensitivity have not been systematically documented. We investigated the effects of radiation and a radiomodifier on zebrafish viability and embryonic development. Embryos were exposed toy-radiation (5, 10, or 20 Gy) at sequential times postfertilization and serially assessed for viability and morphologic abnormalities. As expected, lethality and morphologic perturbations were more pronounced earlier in embryogenesis and with higher radiation doses and were partially reversed by amifostine. The effects of radiation and concurrent treatment with amifostine on the developmental organization of the eye and brain were striking. Radiation resulted in hypocellularity and disorganization of the cellular layers of the retina, effects partially reversed by arnifostine, as well as lens opacification. Radiation strikingly reduced the volume of brain, but the volume loss was substantially blocked by amifostine. Increased terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling signal was noted in both the irradiated eye and brain, but reduced by amifostine. Finally, irradiating embryos resulted in caspase activation detectable in 96-well microplates, which was proportional to the number of embryos and radiation dose; the degree of activation was markedly reduced by arnifostine. These results together suggest the power and versatility of the zebrafish in assessing the effects of radiation and radiomodifiers on organ and tissue development. C1 Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. RP Kao, GD (reprint author), John Morgan 180 H,Hamilton Walk, Philadelphia, PA 19104 USA. EM Kao@xyt.upenn.edu FU NCI NIH HHS [CA107956, P01CA075138, C5T32CA009677] NR 30 TC 59 Z9 61 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2006 VL 66 IS 16 BP 8172 EP 8181 DI 10.1158/0008-5472.CAN-06-0466 PG 10 WC Oncology SC Oncology GA 074QZ UT WOS:000239828200045 PM 16912196 ER PT J AU Moy, B Goss, PE AF Moy, Beverly Goss, Paul E. TI Estrogen receptor pathway: Resistance to endocrine therapy and new therapeutic approaches SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; BREAST-CANCER CELLS; TAMOXIFEN RESISTANCE; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; INDUCED APOPTOSIS; CROSS-TALK; DEPRIVATION; ALPHA; ANTIESTROGEN AB Endocrine therapy is widely accepted as the most important treatment for all patients with hormone receptor - positive breast cancer. However, despite the positive effect of endocrine therapy on clinical outcome, resistance to these drugs inevitably develops. This article reviews the problem of resistance to hormonal therapy and addresses potential approaches to overcome intrinsic or acquired mechanisms of resistance. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Moy, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,YAW 9A, Boston, MA 02114 USA. EM bmoy@partners.org NR 32 TC 38 Z9 39 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2006 VL 12 IS 16 BP 4790 EP 4793 DI 10.1158/1078-0432.CCR-06-1535 PG 4 WC Oncology SC Oncology GA 074TJ UT WOS:000239834400002 PM 16914563 ER PT J AU Wen, PY Yung, WKA Lamborn, KR Dahia, PL Wang, YF Peng, B Abrey, LE Raizer, J Cloughesy, TF Fink, K Gilbert, M Chang, S Junck, L Schiff, D Lieberman, F Fine, HA Mehta, M Robins, HI DeAngelis, LM Groves, MD Puduvalli, VK Levin, V Conrad, C Maher, EA Aldape, K Hayes, M Letvak, L Egorin, MJ Capdeville, R Kaplan, R Murgo, AJ Stiles, C Prados, MD AF Wen, Patrick Y. Yung, W. K. Alfred Lamborn, Kathleen R. Dahia, Patricia L. Wang, Yanfeng Peng, Bin Abrey, Lauren E. Raizer, Jeffrey Cloughesy, Timothy F. Fink, Karen Gilbert, Mark Chang, Susan Junck, Larry Schiff, David Lieberman, Frank Fine, Howard A. Mehta, Minesh Robins, H. Ian DeAngelis, Lisa M. Groves, Morris D. Puduvalli, Vinay K. Levin, Victor Conrad, Charles Maher, Elizabeth A. Aldape, Kenneth Hayes, Michael Letvak, Laurie Egorin, Merrill J. Capdeville, Renaud Kaplan, Richard Murgo, Anthony J. Stiles, Charles Prados, Michael D. TI Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08 SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR EXPRESSION; PDGF-RECEPTOR GENES; TRANSFORMED PHENOTYPE; HUMAN ASTROCYTOMAS; HUMAN MENINGIOMAS; KINASE INHIBITOR; TYROSINE KINASE; CELL-GROWTH; DRUG; GLIOBLASTOMA AB Purpose: Phase I: To determine the maximum tolerated doses, toxicities, and pharmacokinetics of imatinib mesylate (Gleevec) in patients with malignant gliomas taking enzyme-inducing antiepileptic drugs (EIAED) or not taking EIAED. Phase II: To determine the therapeutic efficacy of imatinib. Experimental Design: Phase I component used an interpatient dose escalation scheme. End points of the phase II component were 6-month progression-free survival and response. Results: Fifty patients enrolled in the phase I component (27 EIAED and 23 non-EIAED). The maximum tolerated dose for non-EIAED patients was 800 mg/d. Dose-limiting toxicities were neutropenia, rash, and elevated alanine aminotransferase. EIAED patients received up to 1,200 mg/d imatinib without developing dose-limiting toxicity. Plasma exposure of imatinib was reduced by similar to 68% in EIAED patients compared with non-EIAED patients. Fifty-five non-EIAED patients (34 glioblastoma multiforme and 21 anaplastic glioma) enrolled in the phase II component. Patients initially received 800 mg/d imatinib; 15 anaplastic glioma patients received 600 mg/d after hemorrhages were observed. There were 2 partial response and 6 stable disease among glioblastoma multiforme patients and 0 partial response and 5 stable disease among anaplastic glioma patients. Six-month progression-free survival was 3% for glioblastoma multiforme and 10% for anaplastic glioma patients. Five phase II patients developed intratumoral hemorrhages. Conclusions: Single-agent imatinib has minimal activity in malignant gliomas. CYP3A4 inducers, such as EIAEDs, substantially decreased plasma exposure of imatinib and should be avoided in patients receiving imatinib for chronic myelogenous leukemia and gastrointestinal stromal tumors. The evaluation of the activity of combination regimens incorporating imatinib is under way in phase II trials. C1 Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Novartis Pharmaceut, Florham Pk, NJ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIH, Neurooncol Branch, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org RI Puduvalli, Vinay/A-2411-2016; OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [R03CA102974-02] NR 42 TC 270 Z9 274 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2006 VL 12 IS 16 BP 4899 EP 4907 DI 10.1158/1078-0432.CCR-06-0773 PG 9 WC Oncology SC Oncology GA 074TJ UT WOS:000239834400017 PM 16914578 ER PT J AU Louie, TJ Peppe, J Watt, CK Johnson, D Mohammed, R Dow, G Weiss, K Simon, S John, JF Garber, G Chasan-Taber, S Davidson, DM AF Louie, Thomas J. Peppe, Jennifer Watt, C. Kevin Johnson, David Mohammed, Rasheed Dow, Gordon Weiss, Karl Simon, Stuart John, Joseph F., Jr. Garber, Gary Chasan-Taber, Scott Davidson, David M. CA Tolevamer Study Investigator Grp TI Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile - Associated diarrhea SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1st International Clostridium Difficile Symposium CY MAY 05-07, 2004 CL Kranjska Gora, SLOVENIA ID ANTIBIOTIC-ASSOCIATED DIARRHEA; ANTIBODY-RESPONSE; TOXIN BINDING; COLITIS; METRONIDAZOLE; INFECTION; DISEASE; MANAGEMENT; DIAGNOSIS; STRAIN AB Background. Current antibiotic therapies for Clostridium difficile - associated diarrhea have limitations, including progression to severe disease, recurrent C. difficile - associated diarrhea, and selection for nosocomial pathogens. Tolevamer, a soluble, high - molecular weight, anionic polymer that binds C. difficile toxins A and B is a unique nonantibiotic treatment option. Methods. In this 3-arm, multicenter, randomized, double-blind, active-controlled, parallel-design phase II study, patients with mild to moderately severe C. difficile - associated diarrhea were randomized to receive 3 g of tolevamer per day (n = 97), 6 g of tolevamer per day (n = 95), or 500 mg of vancomycin per day (n = 97). The primary efficacy parameter was time to resolution of diarrhea, defined as the first day of 2 consecutive days when the patient had hard or formed stools (any number) or <= 2 stools of loose or watery consistency. Results. In the per-protocol study population, resolution of diarrhea was achieved in 48 (67%) of 72 patients receiving 3 g of tolevamer per day (median time to resolution of diarrhea, 4.0 days; 95% confidence interval, 2.0-6.0 days), in 58 (83%) of 70 patients receiving 6 g of tolevamer per day ( median time to resolution of diarrhea, 2.5 days; 95% confidence interval, 2.0-3.0 days), and in 73 (91%) of 80 patients receiving vancomycin (median time to resolution of diarrhea, 2.0 days; 95% confidence interval, 1.0-3.0 days). Tolevamer administered at a dosage of 6 g per day was found to be noninferior to vancomycin administered at a dosage of 500 mg per day with regard to time to resolution of diarrhea (P = .02) and was associated with a trend toward a lower recurrence rate. Tolevamer was well tolerated but was associated with an increased risk of hypokalemia. Conclusions. Tolevamer, a novel polystyrene binder of C. difficile toxins A and B, effectively treats mild to moderate C. difficile diarrhea and merits further clinical development. C1 Univ Calgary, Calgary, AB, Canada. Moncton Hosp, Moncton, NB, Canada. Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. Univ Ottawa, Ottawa, ON K1N 6N5, Canada. Genzyme Corp, Cambridge, MA USA. Bio Test Clin, Springfield, MO USA. Bay Pines Vet Affairs Med Ctr, Bay Pines, FL USA. Radiant Res, Austell, GA USA. Georgia Lung Associates, Austell, GA USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Louie, TJ (reprint author), Foothills Med Ctr, AGW5,1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM louie@ucalgary.ca NR 36 TC 112 Z9 116 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 15 PY 2006 VL 43 IS 4 BP 411 EP 420 DI 10.1086/506349 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 063XN UT WOS:000239053300004 PM 16838228 ER PT J AU Korves, CT Goldie, SJ Murray, MB AF Korves, Caroline T. Goldie, Sue J. Murray, Megan B. TI Blood screening for West Nile virus: The cost-effectiveness of a real-time, trigger-based strategy SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB Previous studies have demonstrated that universal blood screening for West Nile virus is not cost-effective. A newly proposed, real-time, trigger-based screening strategy was analyzed and was also shown to be not cost-effective. These results were highly sensitive to pricing of screening assays. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Columbia Univ, Earth Inst, New York, NY USA. RP Korves, CT (reprint author), Mailman Sch Publ Hlth, ICAP Rm 1201,722 W 168th St, New York, NY 10032 USA. EM ck2187@columbia.edu FU NIAID NIH HHS [R01 AI052284-02, T32 AI007535] NR 6 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 15 PY 2006 VL 43 IS 4 BP 490 EP 493 DI 10.1086/506570 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 063XN UT WOS:000239053300015 PM 16838239 ER PT J AU Mably, JD Chuang, LP Serluca, FC Mohideen, MAPK Chen, JN Fishman, MC AF Mably, John D. Chuang, Lesley P. Serluca, Fabrizio C. Mohideen, Manzoor-Ali P. K. Chen, Jau-Nian Fishman, Mark C. TI santa and valentine pattern concentric growth of cardiac myocardium in the zebrafish SO DEVELOPMENT LA English DT Article DE santa; valentine; myocardial growth; cerebral cavernous malformations; CCM ID CEREBRAL CAVERNOUS MALFORMATIONS; CYTOPLASMIC DOMAIN; CARDIOVASCULAR-SYSTEM; BINDING-PROTEIN; GENE CLOCHE; HEART TUBE; MUTATIONS; INTEGRIN; EMBRYOS; CCM1 AB During embryogenesis, the myocardial layer of the primitive heart tube grows outward from the endocardial-lined lumen, with new cells added to generate concentric thickness to the wall. This is a key evolutionary step, demarcating vertebrates from more primitive chordates, and is essential for normal cardiac function. Zebrafish embryos with the recessive lethal mutations santa (san) and valentine (vtn) do not thicken, but do add the proper number of cells to the myocardium. Consequently, the heart chambers are huge, constituted of a monolayered myocardium lined by endocardium. This phenotype is similar to that of the heart of glass (heg) mutation, which we described previously as a novel endocardial expressed gene. By positional cloning, we here identify san as the zebrafish homolog of human CCM1, and vtn as the homolog of human CCM2. Dominant mutations of either in humans cause vascular anomalies in the brain, known as cerebral cavernous malformations. The synergistic effects of morpholino pairs indicate that san, vtn and heg are in a genetic pathway, and san and vtn contain protein motifs, NPxY and PTB domain, respectively, known to interact. This suggests that concentric growth of the myocardium, crucial for blood pressure generation, is dictated by a heg-san-vtn signaling pathway. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Mably, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM jmably@partners.org; mark.fishman@novartis.com OI Chen, Jau-Nian/0000-0001-8807-3607 FU NHLBI NIH HHS [5R01HL49579, 5R01HL63206-04]; NIDDK NIH HHS [5R01DK55383] NR 44 TC 76 Z9 79 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG 15 PY 2006 VL 133 IS 16 BP 3139 EP 3146 DI 10.1242/dev.02469 PG 8 WC Developmental Biology SC Developmental Biology GA 073QV UT WOS:000239758600010 PM 16873582 ER PT J AU Mirchandani, KD D'Andrea, AD AF Mirchandani, Kanchan D. D'Andrea, Alan D. TI The Fanconi anemia/BRCA pathway: A coordinator of cross-link repair SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE Fanconi anemia; DNA cross-links; mitomycin C; translesion DNA synthesis ID DOUBLE-STRAND BREAKS; DNA-REPAIR; HOMOLOGOUS RECOMBINATION; FANCD2 FUNCTIONS; CORE COMPLEX; PROTEIN; DAMAGE; BRCA2; UBIQUITIN; RAD51 AB Fanconi anemia (FA) is a rare inherited disease characterized by genomic instability and markedly increased cancer risk. Efforts to elucidate the molecular basis of FA have unearthed a novel DNA damage response pathway, the integrity of which is critical for cellular resistance to DNA cross-linking agents. Despite significant progress in uncovering the molecular events underlying FA, the precise function of this pathway in DNA repair is unknown. This article will review evidence implicating FA proteins in multiple aspects of DNA cross-link repair and propose a model to explain the selectivity of the FA pathway toward DNA cross-linking agents. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu NR 50 TC 54 Z9 56 U1 0 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 15 PY 2006 VL 312 IS 14 BP 2647 EP 2653 DI 10.1016/j.yexcr.2006.06.014 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 075DT UT WOS:000239864100003 PM 16859679 ER PT J AU Chin, L Garraway, LA Fisher, DE AF Chin, Lynda Garraway, Levi A. Fisher, David E. TI Malignant melanoma: genetics and therapeutics in the genomic era SO GENES & DEVELOPMENT LA English DT Review DE development; genetics; genomics; melanoma; therapeutics ID GROWTH-FACTOR RECEPTOR; TRANSCRIPTION FACTOR MITF; STIMULATING HORMONE-RECEPTOR; PRIMARY CUTANEOUS MELANOMA; CLEAR-CELL SARCOMA; BCL-2 ANTISENSE OLIGONUCLEOTIDE; SINGLE-NUCLEOTIDE POLYMORPHISM; RESPONSE MODIFIER IMIQUIMOD; T-LYMPHOCYTE ANTIGEN-4; CULTURED MAST-CELLS AB Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future. C1 Dana Farber Canc Inst, Melanoma Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Melanoma Program, Boston, MA 02115 USA. EM lynda_chin@dfci.harvard.edu; david_fisher@dfci.harvard.edu FU NCI NIH HHS [K08 CA115927-01, CA102309, CA102369, P50 CA936831, R01 CA93947, U01 CA84313]; NIAMS NIH HHS [AR045662, AR43369] NR 386 TC 296 Z9 300 U1 1 U2 34 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 2006 VL 20 IS 16 BP 2149 EP 2182 DI 10.1101/gad.1437206 PG 34 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 074CR UT WOS:000239790600001 PM 16912270 ER PT J AU Kritikou, EA Milstein, S Vidalain, PO Lettre, G Bogan, E Doukoumetzidis, K Gray, P Chappell, TG Vidal, M Hengartner, MO AF Kritikou, Ekaterini A. Milstein, Stuart Vidalain, Pierre-Olivier Lettre, Guillaume Bogan, Erica Doukoumetzidis, Kimon Gray, Phillip Chappell, Thomas G. Vidal, Marc Hengartner, Michael O. TI C. elegans GLA-3 is a novel component of the MAP kinase MPK-1 signaling pathway required for germ cell survival SO GENES & DEVELOPMENT LA English DT Article DE apoptosis; GLA-3; MAPK signaling; germline development; C. elegans ID ACTIVATED PROTEIN-KINASE; ZINC-FINGER PROTEINS; ALPHA MESSENGER-RNA; DAMAGE CHECKPOINT PROTEIN; AU-RICH ELEMENTS; CAENORHABDITIS-ELEGANS; MUSCLE-CELLS; TRANSCRIPTION FACTOR; OOCYTE MATURATION; PHOSPHATASE LIP-1 AB During oocyte development in Caenorhabditis elegans, approximately half of all developing germ cells undergo apoptosis. While this process is evolutionarily conserved from worms to humans, the regulators of germ cell death are still largely unknown. In a genetic screen for novel genes involved in germline apoptosis in Caenorhabditis elegans, we identified and cloned gla-3. Loss of gla-3 function results in increased germline apoptosis and reduced brood size due to defective pachytene exit from meiosis I. gla-3 encodes a TIS11-like zinc-finger-containing protein that is expressed in the germline, from the L4 larval stage to adulthood. Biochemical evidence and genetic epistasis analysis revealed that GLA-3 participates in the MAPK signaling cascade and directly interacts with the C. elegans MAPK MPK-1, an essential meiotic regulator. Our results show that GLA-3 is a new component of the MAPK cascade that controls meiotic progression and apoptosis in the C. elegans germline and functions as a negative regulator of the MAPK signaling pathway during vulval development and in muscle cells. C1 Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland. Univ Zurich, PhD Program Mol Life Sci, CH-8057 Zurich, Switzerland. Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Invitrogen Corp, Carlsbad, CA 92008 USA. RP Hengartner, MO (reprint author), Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland. EM michael.hengartner@molbio.unizh.ch RI Hengartner, Michael/E-6235-2011; OI Hengartner, Michael/0000-0002-7584-596X FU NCI NIH HHS [1 R33 CA105405-01, 5 T32 CA09361-25, R33 CA105405, T32 CA009361]; NHGRI NIH HHS [5 R01 HG01715-07, R01 HG001715] NR 70 TC 33 Z9 33 U1 1 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 AUG 15 PY 2006 VL 20 IS 16 BP 2279 EP 2292 DI 10.1101/gad.384506 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 074CR UT WOS:000239790600011 PM 16912277 ER PT J AU Schwarze-Zander, C Blackard, JT Zheng, H Addo, MM Lin, W Robbins, GK Sherman, KE Zdunek, D Hess, G Chung, RT AF Schwarze-Zander, Carolynne Blackard, Jason T. Zheng, Hui Addo, Marylyn M. Lin, Wenyu Robbins, Gregory K. Sherman, Kenneth E. Zdunek, Dietmar Hess, Georg Chung, Raymond T. CA AIDS Clinical Trial Grp A5071 Stu TI GB virus C (GBV-C) infection in hepatitis C virus (HCV)/HIV-coinfected patients receiving HCV treatment: Importance of the GBV-C genotype SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1st International Conference on HIV and Hepatitis Co-Infection CY DEC 02-04, 2004 CL Amsterdam, NETHERLANDS SP Natl Inst Allergy & Infect Dis, AIDS Clin Trials Grp, Ctr AIDS Res, Natl Inst Hlth ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; PHYLOGENETIC ANALYSIS; ANTIRETROVIRAL THERAPY; NUCLEOTIDE-SEQUENCES; DISEASE PROGRESSION; COINFECTED PERSONS; INTERFERON-ALPHA; HIV-1 INFECTION; LIVER FIBROSIS AB Background. Persistent GB virus C (GBV-C) coinfection leads to slower human immunodeficiency virus (HIV) progression. Despite the existence of multiple GBV-C genotypes, their relevance to the progression of HIV disease is unknown. We therefore investigated (1) the prevalence and genotype of GBV-C in hepatitis C virus (HCV)/HIV-coinfected patients and (2) the impact of HCV treatment on GBV-C RNA clearance. Methods. We retrospectively studied 130 HCV/HIV-coinfected patients initiating HCV therapy. Anti-E2 enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction (PCR), and real-time PCR were used to detect and quantify GBV-C infection. GBV-C genotype was determined by sequencing the 5' untranslated region. Results. GBV-C infection (past or current) was identified in 111 (85%) of the patients. Ongoing GBV-C replication was detected in 40 patients. Coinfection with GBV-C genotype 2 was associated with significantly higher CD4(+) cell counts. After 24 weeks of HCV therapy, GBV-C RNA clearance was observed in 50% of patients, although this was not associated with changes in HIV load or with CD4(+) cell counts. Sustained GBV-C RNA clearance was observed in 31% of patients with GBV-C RNA detected at baseline. Conclusions. GBV-C coinfection was extremely common. GBV-C RNA clearance with HCV therapy was associated with neither short-term loss of HIV control nor impaired immune status. The association of GBV-C genotype 2 with higher CD4(+) cell counts merits further study. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Roche Diagnost, Mannheim, Germany. Roche Diagnost, Penzberg, Germany. Univ Bonn, Dept Internal Med 1, D-5300 Bonn, Germany. Harvard Univ, Sch Med, Harvard Ctr AIDS Res, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org RI Robbins, Gregory/F-7988-2011 FU NIAID NIH HHS [AI38855, AI38858, P30-AI42851] NR 52 TC 32 Z9 32 U1 2 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2006 VL 194 IS 4 BP 410 EP 419 DI 10.1086/505713 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 064WO UT WOS:000239121000002 PM 16845623 ER PT J AU Smyk-Pearson, S Tester, IA Lezotte, D Sasaki, AW Lewinsohn, DM Rosen, HR AF Smyk-Pearson, Susan Tester, Ian A. Lezotte, Dennis Sasaki, Anna W. Lewinsohn, David M. Rosen, Hugo R. TI Differential antigenic hierarchy associated with spontaneous recovery from hepatitis C virus infection: Implications for vaccine design SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL RESPONSES; IMMUNE-RESPONSES; EFFECTOR FUNCTION; DENDRITIC CELLS; VIRAL CLEARANCE; HCV INFECTION; CD4(+); PERSISTENCE; EVASION; HELP AB Background. Cellular immune responses play a central role in the control of hepatitis C virus (HCV) infection, and in some individuals the adaptive immune response can spontaneously eradicate HCV infection. The development of vaccine candidates to prevent the spread of this infection remains a top priority; however, understanding the correlates of effective immunological containment is an important prerequisite. Methods. Using 750 overlapping peptides, we directly characterized ex vivo total and subgenomic HCV-specific CD4(+) and CD8(+) T cell responses in a large cohort of participants with either chronic infection or spontaneously resolved infection. Results. In chronic infection, the frequency of total CD4(+) T cells specific for HCV averaged 0.06%, compared with 0.38% in resolved infection. Total HCV-specific CD4(+) and CD8(+) T cell responses were strongly correlated in the setting of spontaneous resolution but not in the setting of viral persistence. NS3 protein-specific responses comprised a significantly greater proportion of the total response in resolved infection than in chronic infection, whereas responses to different regions comprised a larger proportion of responses in chronic infection. Conclusion. Because these data comprehensively define the breadth, specificity, and threshold of the T cell response associated with spontaneous recovery from HCV infection, they have important implications in the development of multigenic vaccine candidates for this common infection. C1 Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Hepatitis C Ctr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Integrated Program, Denver, CO 80262 USA. Univ Colorado, Natl Jewish Hosp, Denver, CO 80202 USA. Univ Colorado, Dept Prevent Med, Denver, CO 80202 USA. Portland Vet Affairs Med Ctr, Div Pulm & Crit Care Med, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Rosen, HR (reprint author), Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Hepatitis C Ctr, 4200 E 9th Ave,No B-158, Denver, CO 80262 USA. EM Hugo.Rosen@UCHSC.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NIDDK NIH HHS [R01 DK060590] NR 40 TC 46 Z9 48 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2006 VL 194 IS 4 BP 454 EP 463 DI 10.1086/505714 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 064WO UT WOS:000239121000007 PM 16845628 ER PT J AU Prasad, R Giri, S Nath, N Singh, I Singh, AK AF Prasad, Ratna Giri, Shailendra Nath, Narender Singh, Inderjit Singh, Avtar K. TI 5-aminoimidazole-4-carboxamide-1-beta4-ribofurano side attenuates experimental autoimmune encephalomyelitis via modulation of endothelial-monocyte interaction SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE EAE; AICAR; endothelial; monocyte; cell adhesion molecules ID ACTIVATED PROTEIN-KINASE; CENTRAL-NERVOUS-SYSTEM; NF-KAPPA-B; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NITRIC-OXIDE SYNTHASE; ADHESION MOLECULE EXPRESSION; DEVELOPING RAT-BRAIN; MULTIPLE-SCLEROSIS; TRANSCRIPTIONAL REGULATION; INDUCED APOPTOSIS AB Experimental autoimmune encephalomyelitis (EAE) is a model for studying multiple sclerosis (MS), a chronic demyelinating disorder of the CNS. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), an activator of AMP-activated protein kinase (AMPK), has been reported to show antiinflammatory and immunomodulatory effects in various models of inflammation. Recently, we have reported AICAR-mediated attenuation of active and passive EAE in mouse model [Nath et al. (2005) J. Immunol. 175:566-574]. Here we used a rat model of acute EAE to show anti inflammatory effects of AICAR after daily treatment starting at onset of the disease. By maintaining the blood-brain barrier (BBB), AICAR-administered animals showed lower clinical scores compared with untreated EAE animals. AICAR inhibited the infiltration of inflammatory cells across the BBB, resulting in lowered expression of proinflammatory mediators in the CNS and protection from severe demyelination. By using in vitro model of endothelial-leukocyte interaction, we showed that AICAR inhibited adhesion of monocytes to tumor necrosis factor-alpha-activated endothelial cells. One of the mechanisms of this action is through down-regulation of expression of endothelial cell adhesion molecules via modulation of nuclear factor kappa B activation. The data suggest that AICAR attenuates EAE progression by limiting infiltration of leukocytes across the BBB, thereby controlling the consequent inflammatory reaction in the CNS. (c) 2006 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Pathol & Lab Med, Ralph Johnson Vet Affairs Med Ctr, Childrens Res Inst 505, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, Ralph Johnson Vet Affairs Med Ctr, Childrens Res Inst 505, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, NS-37766, NS-40144, NS-40810, NS-34741] NR 55 TC 37 Z9 38 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 15 PY 2006 VL 84 IS 3 BP 614 EP 625 DI 10.1002/jnr.20953 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 071FR UT WOS:000239584700015 PM 16770773 ER PT J AU Moran-Gates, T Massari, C Graulich, A Liegeois, JF Tarazi, FI AF Moran-Gates, Taylor Massari, Carla Graulich, Amaury Liegeois, Jean-Francois Tarazi, Frank I. TI Long-term effects of JL 13, a potential atypical antipsychotic, on rat dopamine and serotonin receptor subtypes SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE autoradiography; antipsychotic drugs; caudate-putamen; dopamine receptors; frontal cortex; JL 13; serotonin receptors ID PYRIDOBENZOXAZEPINE COMPOUND; D-4 RECEPTOR; SCHIZOPHRENIA; CLOZAPINE; INCREASES; DRUGS; JL13; RISPERIDONE; OLANZAPINE; QUETIAPINE AB Changes in dopamine (DA) D-1, D-2, D-3, and D-4 receptors and serotonin 5-HT1A and 5-HT2A receptors in rat forebrain regions were autoradiographically quantified after continuous infusion of JL 13 [(5-(4-methylpiperazin-1-yl)8-chloro-pyrido[2,3-b][1,5]benzoxazepine fumarate] for 28 days with osmotic minipumps and compared with the effects of other typical (fluphenazine) and atypical (clozapine, olanzapine, and risperidone) antipsychotic drugs from previous studies. Similar to other typical and atypical antipsychotics, JL 13 increased labeling of D2 receptors in medial prefrontal cortex (MPC) and hippocampus (HIP) and D-4 receptors in nucleus accumbens (NAc), caudate-putamen (CPu), and HIP In addition, JL 13 increased 5-HT1A and decreased 5-HT2A receptors in MPC and dorsolateral frontal cortex (DFC), an effect shared by atypical antipsychotics, and may contribute to their psychopharmacological properties. Clozapine and JL 13, but not other antipsychotics, spared D2 receptors in CPu, which may reflect their ability to induce minimal extrapyramidal side effects. In addition, JL 13 but not other typical and atypical antipsychotic drugs increased abundance of D, receptors in CPu and NAc. JL 13 as well as other antipsychotic agents did not alter levels of forebrain D3 receptors. An atypical-like profile of JL 13 on DA and 5-HT receptor subtypes should encourage further development of this compound as a novel atypical anti psychotic drug. (c) 2006Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA. Univ Liege, Drugs Res Ctr, Med Chem Lab, Liege, Belgium. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, Lab Psychiat Neurosci, McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM ftarazi@hms.harvard.edu FU NIMH NIH HHS [MH-068359] NR 33 TC 6 Z9 6 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 15 PY 2006 VL 84 IS 3 BP 675 EP 682 DI 10.1002/jnr.20972 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 071FR UT WOS:000239584700022 PM 16810690 ER PT J AU Triantafyllou, C Hoge, RD Wald, LL AF Triantafyllou, Christina Hoge, Richard D. Wald, Lawrence L. TI Effect of spatial smoothing on physiological noise in high-resolution fMRI SO NEUROIMAGE LA English DT Article DE physiological noise; fMRI; high field; spatial resolution; SNR; magnetic field strength; 7 Tesla ID MRI AB Physiological noise dominates the SNR of the fMRI time-course at commonly. used spatial resolutions at field strengths of 3 T and above. Operating in this physiological noise dominated regime limits some benefits of high field acquisition since increases in image SNR produce only modest increases in time-course SNR. Although previous studies have shown that the physiological noise dominance can be mitigated by using higher spatial resolutions, not all functional studies require voxel sizes smaller than the thickness of the human cortex. In this study, we examine the effect of acquiring high spatial resolution, thermal noise dominated time-courses and spatially smoothing the images to lower resolutions, which would otherwise be physiological noise dominated. At high field strengths, where physiological noise is most problematic, this strategy lowered the overall time-course variance compared to direct acquisition at commonly used spatial resolution. At 7 T for example, 5 x 5 x 3 mm(3) resolution images derived from smoothing 1.5 x 1.5 x 3 mm(3) data improved time-course SNR by a factor of 1.89 compared to a time-series acquired at 5 x 5 x 3 mm(3). Presumably, this effect was derived from the reduced physiological-to-thermal noise ratio in the high spatial resolution data followed by a smoothing operation that improves SNR without adding physiological noise. Our findings demonstrate that in contrast to conventional SNR penalties associated with spatially smoothing Fourier data, the time-course SNR of smoothed high-resolution data can be improved compared to direct acquisition at the desired resolution. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, MIT, HMS, AA Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. RP Wald, LL (reprint author), Massachusetts Gen Hosp, MIT, HMS, AA Martinos Ctr Biomed Imaging,Dept Radiol, Mailcode 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM wald@nmr.mgh.harvard.edu RI Triantafyllou, Christina/E-7724-2011; Wald, Lawrence/D-4151-2009 FU NCRR NIH HHS [P41RR14075, R01RR1453A01] NR 11 TC 63 Z9 64 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2006 VL 32 IS 2 BP 551 EP 557 DI 10.1016/j.neuroimage.2006.04.182 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 074YO UT WOS:000239848700008 PM 16815038 ER PT J AU Bohland, JW Guenther, FH AF Bohland, Jason W. Guenther, Frank H. TI An fMRI investigation of syllable sequence production SO NEUROIMAGE LA English DT Review DE speech production; sequencing; fMRI; language; motor control ID SUPPLEMENTARY MOTOR AREA; VERBAL WORKING-MEMORY; EVENT-RELATED FMRI; POSITRON-EMISSION-TOMOGRAPHY; BASAL GANGLIA CIRCUITS; NEURAL-NETWORK MODEL; FALSE DISCOVERY RATE; SPEECH PRODUCTION; FRONTAL-CORTEX; PREFRONTAL CORTEX AB Fluent speech comprises sequences that are composed from a finite alphabet of learned words, syllables, and phonemes. The sequencing of discrete motor behaviors has received much attention in the motor control literature, but relatively little has been focused directly on speech production. In this paper, we investigate the cortical and subcortical regions involved in organizing and enacting sequences of simple speech sounds. Sparse event-triggered functional magnetic resonance imaging (fMRI) was used to measure responses to preparation and overt production of non-lexical three-syllable utterances, parameterized by two factors: syllable complexity and sequence complexity. The comparison of overt production trials to preparation only trials revealed a network related to the initiation of a speech plan, control of the articulators, and to hearing one's own voice. This network included the primary, motor and somatosensory cortices, auditory cortical areas, supplementary motor area (SMA), the precentral gyrus of the insula, and portions of the thalamus, basal ganglia, and cerebellum. Additional stimulus complexity led to increased engagement of the basic speech network and recruitment of additional areas known to be involved in sequencing non-speech motor acts. In particular, the left hemisphere inferior frontal sulcus and posterior parietal cortex, and bilateral regions at the junction of the anterior insula and frontal operculum, the SMA and pre-SMA, the basal ganglia, anterior thalamus, and the cerebellum showed increased activity for more complex stimuli. We hypothesize mechanistic roles for the extended speech production network in the organization and execution of sequences of speech sounds. (c) 2006 Elsevier Inc. All rights reserved. C1 Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Bohland, JW (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM jbohland@cns.bu.edu RI Bohland, Jason/L-4807-2016 OI Bohland, Jason/0000-0002-6305-5848 FU NCRR NIH HHS [P41RR14075]; NIDCD NIH HHS [R01 DC02852] NR 152 TC 219 Z9 223 U1 3 U2 26 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2006 VL 32 IS 2 BP 821 EP 841 DI 10.1016/j.neuroimage.2006.04.173 PG 21 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 074YO UT WOS:000239848700035 PM 16730195 ER PT J AU Fleming, HE Scadden, DT AF Fleming, Heather E. Scadden, David T. TI Embryonic stem cells make human T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID IN-VITRO; DIFFERENTIATION; GENERATION; EXPRESSION C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu NR 15 TC 3 Z9 3 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 AUG 15 PY 2006 VL 103 IS 33 BP 12213 EP 12214 DI 10.1073/pnas.0605344103 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075EW UT WOS:000239867500001 PM 16894150 ER PT J AU Overholtzer, M Zhang, J Smolen, GA Muir, B Li, W Sgroi, DC Deng, CX Brugge, JS Haber, DA AF Overholtzer, Michael Zhang, Jianmin Smolen, Gromoslaw A. Muir, Beth Li, Wenmei Sgroi, Dennis C. Deng, Chu-Xia Brugge, Joan S. Haber, Daniel A. TI Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast; mammary; transformation; Yorkie ID YES-ASSOCIATED PROTEIN; COMPARATIVE GENOMIC HYBRIDIZATION; SQUAMOUS-CELL CARCINOMA; MAMMARY EPITHELIAL-CELLS; AMINO-ACID CHANGE; TUMOR-SUPPRESSOR; PROMOTES APOPTOSIS; BREAST-CANCER; TRANSCRIPTIONAL COACTIVATOR; PROLIFERATION ARREST AB In a screen for gene copy-number changes in mouse mammary tumors, we identified a tumor with a small 350-kb amplicon from a region that is syntenic to a much larger locus amplified in human cancers at chromosome 11c122. The mouse amplicon contains only one known gene, Yap, encoding the mammalian ortholog of Drosophila Yorkie (Yki), a downstream effector of the Hippo(Hpo)Salvador(Sav)-Warts(Wts) signaling cascade, recently identified in flies as a critical regulator of cellular proliferation and apoptosis. In nontransformed mammary epithelial cells, overexpression of human YAP induces epithelial-to-mesenchymal transition, suppression of apoptosis, growth factor-independent proliferation, and anchorage-independent growth in soft agar. Together, these observations point to a potential oncogenic role for YAP in 11q22amplified human cancers, and they suggest that this highly conserved signaling pathway identified in Drosophila regulates both cellular proliferation and apoptosis in mammalian epithelial cells. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Pathol Res Unit,Dept Pathol, Charlestown, MA 02129 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM joan_brugge@hms.harvard.edu RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [F32 CA117737, CA080111, CA089393, P01 CA080111, P01 CA95281, P50 CA089393, T32 CA009361, T32CA09361] NR 54 TC 423 Z9 439 U1 4 U2 46 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 AUG 15 PY 2006 VL 103 IS 33 BP 12405 EP 12410 DI 10.1073/pnas.0605579103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075EW UT WOS:000239867500038 PM 16894141 ER PT J AU Johnson, WE Li, W Meyer, CA Gottardo, R Carroll, JS Brown, M Liu, XS AF Johnson, W. Evan Li, Wei Meyer, Clifford A. Gottardo, Raphael Carroll, Jason S. Brown, Myles Liu, X. Shirley TI Model-based analysis of tiling-arrays for ChIP-chip SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional genomics; genome tiling microarrays; model-based probe analysis; transcription regulation ID BINDING-SITES; GENOME AB We propose a fast and powerful analysis algorithm, titled Modelbased Analysis of Tiling-arrays (MAT), to reliably detect regions enriched by transcription factor chromatin immunoprecipitation (ChIP) on Affymetrix tiling arrays (ChIP-chip). MAT models the baseline probe behavior by considering probe sequence and copy number on each array. It standardizes the probe value through the probe model, eliminating the need for sample normalization. MAT uses an innovative function to score regions for ChIP enrichment, which allows robust P value and false discovery rate calculations. MAT can detect ChIP regions from a single ChIP sample, multiple ChIP samples, or multiple ChIP samples with controls with increasing accuracy. The single-array ChIP region detection feature minimizes the time and monetary costs for laboratories newly adopting ChIP-chip to test their protocols and antibodies and allows established ChIP-chip laboratories to identify samples with questionable quality that might contaminate their data. MAT is developed in open-source Python and is available at http://chip. dfci.harvard.edu/-wli/MAT. The general framework presented here can be extended to other oligonucleoticle microarrays and tiling array platforms. C1 Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ British Columbia, Dept Stat, Vancouver, BC V6T 1Z2, Canada. RP Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM xsliu@jimmy.harvard.edu RI Li, Wei/A-8544-2009; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [T32 CA009337]; NHGRI NIH HHS [R01 HG004069, R01 HG004069-01]; NIDDK NIH HHS [T90 DK070078, T90 DK070078-01] NR 14 TC 314 Z9 319 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 2006 VL 103 IS 33 BP 12457 EP 12462 DI 10.1073/pnas.0601180103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075EW UT WOS:000239867500047 PM 16895995 ER PT J AU Georgieva, L Moskvina, V Peirce, T Norton, N Bray, NJ Jones, L Holmans, P MacGregor, S Zammit, S Wilkinson, J Williams, H Nikolov, I Williams, N Ivanov, D Davis, KL Haroutunian, V Buxbaum, JD Craddock, N Kirov, G Owen, MJ O'Donovan, MC AF Georgieva, Lyudmila Moskvina, Valentina Peirce, Tim Norton, Nadine Bray, Nicholas J. Jones, Lesley Holmans, Peter MacGregor, Stuart Zammit, Stanley Wilkinson, Jennifer Williams, Hywel Nikolov, Ivan Williams, Nigel Ivanov, Dobril Davis, Kenneth L. Haroutunian, Vahram Buxbaum, Joseph D. Craddock, Nick Kirov, George Owen, Michael J. O'Donovan, Michael C. TI Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE association; oligodentrocyte/myelin-related genes ID MULTIPLE TESTING CORRECTION; NYHOLTS PROCEDURE; PROBE LEVEL; EXPRESSION; MYELIN; PROTEIN; DYSFUNCTION; CORTEX; BRAIN; DISEQUILIBRIUM AB Abnormal oligodendrocyte function has been postulated as a primary etiological event in schizophrenia. Oligodendrocyte lineage transcription factor 2 (OLIG2) encodes a transcription factor central to oligodendrocyte development. Analysis of OLIG2 in a case-control sample (n = approximate to 1,400) in the U.K. revealed several SNPs to be associated with schizophrenia (minimum P = 0.0001, genewide P = 0.0009). To obtain independent support for this association, we sought evidence for genetic interaction between OLIG2 and three genes of relevance to oligodendrocyte function for which we have reported evidence for association with schizophrenia: CNP, NRG1, and ERBB4. We found interaction effects on disease risk between OLIG2 and CNP (minimum P = 0.0001, corrected P = 0.008) for interaction with ERBB4 (minimum P = 0.002, corrected P = 0.04) but no evidence for interaction with NRG1. To investigate the biological plausibility of the interactions, we sought correlations between the expression of the genes. The results were similar to those of the genetic interaction analysis. OLIG2 expression significantly correlated in cerebral cortex with CNP (P < 10(-7)) and ERBB4 (P = 0.002, corrected P = 0.038) but not NRG1. In mouse striatum, O1ig2 and Cnp expression also was correlated, and linkage analysis for trans-effects on gene expression suggests that each locus regulates the other's expression. Our data provide strong convergent evidence that variation in OLIG2 confers susceptibility to schizophrenia alone and as part of a network of genes implicated in oligodendrocyte function. C1 Univ Cardiff Wales, Sch Med, Dept Psychol Med, Cardiff CF14 4XN, Wales. Univ Cardiff Wales, Sch Med, Biostat & Bioinformat Unit, Cardiff CF14 4XN, Wales. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10021 USA. Bronx Vet Affairs Med Ctr, Mental Illness Res Ctr, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Educ Ctr, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Ctr Clin, Bronx, NY 10468 USA. RP Owen, MJ (reprint author), Univ Cardiff Wales, Sch Med, Dept Psychol Med, Heath Pk, Cardiff CF14 4XN, Wales. EM owenmj@cf.ac.uk; odonovanmc@cf.ac.uk RI Macgregor, Stuart/C-6442-2009; turton, miranda/F-4682-2011; Holmans, Peter/F-4518-2015; OI Macgregor, Stuart/0000-0001-6731-8142; Holmans, Peter/0000-0003-0870-9412; Zammit, Stanley/0000-0002-2647-9211; O'Donovan, Michael/0000-0001-7073-2379; Ivanov, Dobril/0000-0001-6271-6301; Buxbaum, Joseph/0000-0001-8898-8313; Escott-Price, Valentina/0000-0003-1784-5483 FU Medical Research Council [G9309834, G9810900] NR 54 TC 69 Z9 70 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 AUG 15 PY 2006 VL 103 IS 33 BP 12469 EP 12474 DI 10.1073/pnas.0603029103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075EW UT WOS:000239867500049 PM 16891421 ER PT J AU Xia, SH Wang, JD He, CW Hong, S Serhan, CN Kang, JX AF Xia, Shuhua Wang, Jingdong He, Chengwei Hong, Song Serhan, Charles N. Kang, Jing X. TI Melanoma growth is reduced in fat-1 transgenic mice: Impact of omega-6/omega-3 essential fatty acids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE prostaglandin E-3; eicosapentaenoic acid; tumorigenesis ID LUNG-CANCER CELLS; BREAST-CANCER; TUMOR ANGIOGENESIS; ADIPOSE-TISSUE; N-3; PTEN; EICOSANOIDS; GENE; METASTASIS; OMEGA-3 AB An important nutritional question as to whether the ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids plays a role in tumorigenesis remains to be clarified in well qualified experimental models. The recently engineered fat-1 mice, which can convert n-6 to n-3 fatty acids and have a balanced ratio of n-6 to n-3 fatty acids in their tissues and organs independent of diet, allow carefully controlled studies to be performed in the absence of potential confounding factors of diet and therefore are a useful model for elucidating the role of n-6/n-3 fatty acid ratio in tumorigenesis. We implanted mouse melanoma B16 cells into transgenic and WT littermates and examined the incidence of tumor formation and tumor growth rate. The results showed a dramatic reduction of melanoma formation and growth in fat-1 transgenic mice. The level of n-3 fatty acids and their metabolite prostaglandin E3 (IRGEA were much higher (but the n-6/n-3 ratio is much lower) in the tumor and surrounding tissues of fat-1 mice than that of WT animals. The phosphatase and tensin homologue deleted on the chromosome 10 (PTEN) gene was significantly up-regulated in the fat-1 mice. In vitro experiments showed that addition of the n-3 fatty acid eicosapentaenoic acid or PGE(3) inhibited the growth of B16 cell line and increased the expression of PTEN, which could be partially attenuated by inhibition of PGE(3) production, suggesting that PGE(3) may act as an antitumor mediator. These data demonstrate an anticancer (antimelanoma) effect of n-3 fatty acids through, at least in part, activation of PTEN pathway mediated by PGE(3). C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM jxkang@partners.org FU NIDCR NIH HHS [P50 DE016191, P50-DE016191]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11]; NIGMS NIH HHS [R37-GM038675] NR 30 TC 87 Z9 92 U1 2 U2 12 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 AUG 15 PY 2006 VL 103 IS 33 BP 12499 EP 12504 DI 10.1073/pnas.0605394103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075EW UT WOS:000239867500054 PM 16888035 ER PT J AU Wong, BS Yamada, K Okumi, M Weiner, J O'Malley, PE Tseng, YL Dor, FJMF Cooper, DKC Saidman, SL Griesemer, A Sachs, DH AF Wong, Banny S. Yamada, Kazuhiko Okumi, Masayoshi Weiner, Joshua O'Malley, Patricia E. Tseng, Yau-Lin Dor, Frank J. M. F. Cooper, David K. C. Saidman, Susan L. Griesemer, Adam Sachs, David H. TI Allosensitization does not increase the risk of xenoreactivity to alpha 1,3-galactosyltransferase gene-knockout miniature swine in patients on transplantation waiting lists SO TRANSPLANTATION LA English DT Article DE panel reactive antibodies; xenotransplantation; sensitization; HLA antibodies ID ANTI-GAL ANTIBODIES; HLA-SPECIFIC ANTIBODIES; POSITIVE CROSS-MATCH; KIDNEY-TRANSPLANTATION; SENSITIZED PATIENTS; NATURAL ANTIBODIES; LEUKOCYTE ANTIGENS; NUCLEAR TRANSFER; IGM ANTIBODIES; BABOONS AB Background. The recent availability of alpha 1,3-galactosyltransferase knockout (GalT-KO) miniature swine has eliminated anti-Gal antibodies as the major barrier to xenotransplantation, potentially bringing this modality closer to clinical application. Highly-allosensitized patients, who have poor prospects of receiving a suitable cross-match negative human organ, might be the first patients to benefit from xenotransplantation of porcine organs. However, concerns exist regarding crossreactivity of alloreactive anti-human leukocyte antigen (HLA) antibodies against xenogeneic swine leukocyte antigen (SLA) antigens. We have investigated this question using sera from such patients on GalT-KO target cells. Methods. Using flow cytometry and complement- dependent cytotoxicity (CDC) assays, we have tested a panel of 88 human serum samples from patients awaiting cadaveric renal allotransplantation for reactivity against: 1) human; 2) standard miniature swine; and 3) GalT-KO peripheral blood lymphocytes (PBL) and cultured endothelial cells. Results. Anti-swine IgM and IgG antibody binding, as well as CDC, were significantly attenuated on GalT-KO versus standard swine. No correlation was found between the degree of anti-human panel reactive antibodies (PRA) and xenoreactivity against either standard or GalT-KO miniature swine. Treatment of sera with dithiothreitol (DTT) showed that the majority of remaining lymphocytotoxicity against GalT-KO swine was mediated by preformed IgM antibodies. Patients with high alloreactivity but low anti-GalT-KO xenoreactivity were readily identified. Conclusions. Highly allosensitized patients awaiting renal transplants appear to be at no increased risk of xenosensitization over their non-sensitized cohorts, and could therefore be candidates for xenotransplantation using GalT-KO swine donors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E Bldg 149-9019,13th St, Boston, MA 02129 USA. EM sachs@helix.mgh.harvard.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NIAID NIH HHS [5P01-AI39755, 5P01-AI45897] NR 28 TC 39 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 15 PY 2006 VL 82 IS 3 BP 314 EP 319 DI 10.1097/01.tp.0000228907.12073.0b PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 075KV UT WOS:000239884800005 PM 16906027 ER PT J AU Szomolanyi-Tsuda, E Seedhom, MO Carroll, MC Garcea, RL AF Szomolanyi-Tsuda, Eva Seedhom, Mina O. Carroll, Michael C. Garcea, Robert L. TI T cell-independent and T cell-dependent immunoglobulin G responses to polyomavirus infection are impaired in complement receptor 2-deficient mice SO VIROLOGY LA English DT Article DE complement receptor; TI antiviral antibody responses; polyomavirus infection ID ANTIBODY-RESPONSES; B-CELLS; COMPLEMENT RECEPTORS; IN-VIVO; AFFINITY MATURATION; ADAPTIVE IMMUNITY; HUMORAL IMMUNITY; CR2(-/-) MICE; VIRUS; INDUCTION AB Polyomavirus (PyV) infection induces protective T cell-independent (TI) IgM and IgG antibody responses in T cell-deficient mice, but these responses are not generated by immunization with viral proteins or virus like particles. We hypothesized that innate signals contribute to the generation of isotype-switched antiviral antibody responses. We studied the role of complement receptor (CR2) engagement in TI and T cell-dependent (TD) antibody responses to PyV using CR2-deficient mice. Antiviral IgG responses were reduced by 80-40% in CP2-/- mice compared to wild type. Adoptive transfer experiments demonstrated the need for CR2 not only in TD, but also in TI IgG responses to PyV. Transfer of CR2-/- B lymphocytes to SCID mice resulted in TI antiviral IgG responses that corresponded to 10% of that seen in wild-type B cell-reconstituted mice. Thus, our studies revealed a profound dependence of TI and TD antiviral antibody responses on CR2-mediated signals in PyVinfected mice, where the viral antigen is abundant and persistent. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pediat, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. RP Szomolanyi-Tsuda, E (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. EM Eva.Szomolanyi-Tsuda@umassmed.edu FU NCI NIH HHS [R01 CA066644-05, CA37667, CA66644, R01 CA037667, R01 CA066644, R01 CA066644-06, R01 CA066644-07, R01 CA066644-08]; NIAID NIH HHS [AI39246, R01 AI039246] NR 38 TC 12 Z9 12 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 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 2006 VL 352 IS 1 BP 52 EP 60 DI 10.1016/j.virol.2006.04.018 PG 9 WC Virology SC Virology GA 074IV UT WOS:000239806800006 PM 16733062 ER PT J AU Smith, AK Ries, AP Zhang, BH Tulsky, JA Prigerson, HG Block, SD AF Smith, Alexander K. Ries, Angela Poppe Zhang, Baohui Tulsky, James A. Prigerson, Holly G. Block, Susan D. TI Resident approaches to advance care planning on the day of hospital admission SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID COMMUNICATION-SKILLS; LIFE; END; DIRECTIVES; PATIENT; RESUSCITATION; PREFERENCES; PHYSICIANS; SUPPORT AB Background: Advance care planning is the process of establishing a patient's goals and preferences for future care. Previous research has demonstrated a need to improve patient-physician communication around advance care planning. A critical time for advance care planning conversations is the day of admission to the hospital. Methods: A survey of internal medicine residents was administered at Duke University Medical Center and the Brigham and Women's Hospital, 2 major academic teaching centers. Residents were questioned about their approaches to advance care planning on their last on-call admitting day. Results: Of 347 residents solicited, 292 ( 84.1%) participated in the survey. Residents reported that they established preferences for cardiopulmonary resuscitation ( CPR) with 70.5% of patients, established a health care proxy with 33.7% of patients, discussed goals and values concerning end-of-life care with 32.0% of patients, and asked 35.6% of patients if they had an advance directive. Although 89.0% of residents had observed an advance care planning discussion model, only 66.4% had received teaching and 36.6% had received feedback about advance care planning conversations. In multivariable analysis, having received feedback about advance care planning conversations was associated with a higher percentage of conversations about health care proxy and goals and values related to the end of life. Conclusions: Residents discuss patient preferences for CPR on the day of admission with most patients. Preparing residents, particularly through feedback, may improve communication around other elements of advance care planning. C1 Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Vet Affairs Med Ctr, Ctr Palliat Care, Durham, NC USA. Vet Affairs Med Ctr, Dept Med, Durham, NC USA. RP Smith, AK (reprint author), Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, 44 Binney St, Boston, MA 02115 USA. EM asmith17@partners.org NR 20 TC 23 Z9 23 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 14 PY 2006 VL 166 IS 15 BP 1597 EP 1602 DI 10.1001/archinte.166.15.1597 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 073QM UT WOS:000239757700007 PM 16908792 ER PT J AU Shores, MM Matsumoto, AM Sloan, KL Kivlahan, DR AF Shores, Molly M. Matsumoto, Alvin M. Sloan, Kevin L. Kivlahan, Daniel R. TI Low serum testosterone and mortality in male veterans SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HORMONE-BINDING GLOBULIN; CORONARY-ARTERY-DISEASE; MIDDLE-AGED MEN; OLDER MEN; CARDIOVASCULAR-DISEASE; PREMATURE MORTALITY; CRITICAL ILLNESS; HEART-DISEASE; POPULATION; HYPOPITUITARISM AB Background: Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance. This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans. Methods: We used a clinical database to identify men older than 40 years with repeated testosterone levels obtained from October 1, 1994, to December 31, 1999, and without diagnosed prostate cancer. A low testosterone level was a total testosterone level of less than 250 ng/dL (< 8.7 nmol/L) or a free testosterone level of less than 0.75 ng/dL (< 0.03 nmol/L). Men were classified as having a low testosterone level ( 166 [ 19.3%]), an equivocal testosterone level ( equal number of low and normal levels) ( 240 [ 28.0%]), or a normal testosterone level ( 452 [ 52.7%]). The risk for all-cause mortality was estimated using Cox proportional hazards regression models, adjusting for demographic and clinical covariates over a follow-up of up to 8 years. Results: Mortality in men with normal testosterone levels was 20.1%( 95% confidence interval [ CI], 16.2%-24.1%) vs 24.6%( 95% CI, 19.2%-30.0%) in men with equivocal testosterone levels and 34.9% ( 95% CI, 28.5%-41.4%) in men with low testosterone levels. After adjusting for age, medical morbidity, and other clinical covariates, low testosterone levels continued to be associated with increased mortality ( hazard ratio, 1.88; 95% CI, 1.34-2.63; P < . 001) while equivocal testosterone levels were not significantly different from normal testosterone levels ( hazard ratio, 1.38; 95% CI, 0.99%-1.92%; P=.06). In a sensitivity analysis, men who died within the first year( 50[ 5.8%]) were excluded to minimize the effect of acute illness, and low testosterone levels continued to be associated with elevated mortality. Conclusions: Low testosterone levels were associated with increased mortality in male veterans. Further prospective studies are needed to examine the association between low testosterone levels and mortality. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Shores, MM (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Geriatr Res Educ & Clin Ctr, 1660 S Columbian Way,Mailstop S-182GRECC, Seattle, WA 98108 USA. EM mxs@u.washington.edu NR 47 TC 277 Z9 282 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 14 PY 2006 VL 166 IS 15 BP 1660 EP 1665 DI 10.1001/archinte.166.15.1660 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 073QM UT WOS:000239757700018 PM 16908801 ER PT J AU Aharon, I Becerra, L Chabris, CF Borsook, D AF Aharon, I. Becerra, L. Chabris, C. F. Borsook, D. TI Noxious heat induces fMRI activation in two anatomically distinct clusters within the nucleus accumbens (vol 392, pg 159, 2006) SO NEUROSCIENCE LETTERS LA English DT Correction C1 Massachusetts Gen Hosp, Athinoula Martinos NMR Ctr Med Imaging, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. McLean Hosp, PAIN Grp, Brain Imaging Ctr, Belmont, MA 02478 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp, Athinoula Martinos NMR Ctr Med Imaging, Boston, MA 02114 USA. EM dborsook@mclean.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 14 PY 2006 VL 404 IS 1-2 BP 247 EP 247 DI 10.1016/j.neulet.2005.12.086 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 073SZ UT WOS:000239764200050 ER PT J AU Lin, SS Bassik, MC Suh, H Nishino, M Arroyo, JD Hahn, WC Korsmeyer, SJ Roberts, TM AF Lin, Stephen S. Bassik, Michael C. Suh, Heikyung Nishino, Mari Arroyo, Jason D. Hahn, William C. Korsmeyer, Stanley J. Roberts, Thomas M. TI PP2A regulates BCL-2 phosphorylation and proteasome-mediated degradation at the endoplasmic reticulum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN PHOSPHATASE 2A; SERINE/THREONINE PHOSPHATASES; PROAPOPTOTIC BAX; APOPTOSIS; CA2+; DEPHOSPHORYLATION; IDENTIFICATION; MITOCHONDRIA; SUBUNIT; DISEASE AB Anti-apoptotic activity of BCL-2 is mediated by phosphorylation at the endoplasmic reticulum (ER), but how this phosphorylation is regulated and the mechanism(s) by which it regulates apoptosis are unknown. We purified macromolecular complexes containing BCL-2 from ER membranes and found that BCL-2 co-purified with the main two subunits of the serine/threonine phosphatase, PP2A. The association of endogenous PP2A and BCL-2 at the ER was verified by co-immunoprecipitation and microcystin affinity purification. Knock down or pharmacological inhibition of PP2A caused degradation of phosphorylated BCL-2 and led to an overall reduction in BCL-2 levels. We found that this degradation was due to the action of the proteasome acting selectively at the ER. Conversely, overexpression of PP2A caused elevation in endogenous BCL-2. Most importantly, we found that PP2A knock down sensitized cells to several classes of death stimuli (including ER stress), but this effect was abolished in a genetic background featuring knock in of a non-phosphorylatable BCL-2 allele. These studies support the hypothesis that PP2A-mediated dephosphorylation of BCL-2 is required to protect BCL-2 from proteasome-dependent degradation, affecting resistance to ER stress. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Howard Hughes Med Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM thomas_roberts@dfci.harvard.edu NR 31 TC 64 Z9 66 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 11 PY 2006 VL 281 IS 32 BP 23003 EP 23012 DI 10.1074/jbc.M602648200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 070RY UT WOS:000239542600062 PM 16717086 ER PT J AU Febbo, PG Kantoff, PW AF Febbo, Phillip G. Kantoff, Philip W. TI Noise and bias in microarray analysis of tumor specimens SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; PROSTATE-CANCER; RADICAL PROSTATECTOMY; SIGNATURE; SURVIVAL C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol,Div Med Oncol, Duke Inst Genome Sci & Policy, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Febbo, PG (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. NR 16 TC 13 Z9 15 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 AUG 10 PY 2006 VL 24 IS 23 BP 3719 EP 3721 DI 10.1200/JCO.2006.06.7942 PG 3 WC Oncology SC Oncology GA 075TG UT WOS:000239907500002 PM 16822841 ER PT J AU Kennedy, RD D'Andrea, AD AF Kennedy, Richard D. D'Andrea, Alan D. TI DNA repair pathways in clinical practice: Lessons from pediatric cancer susceptibility syndromes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID ACUTE MYELOID-LEUKEMIA; BASE EXCISION-REPAIR; ANEMIA-BRCA PATHWAY; DEPENDENT PROTEIN-KINASE; DOUBLE-STRAND BREAKS; GERM-CELL TUMORS; FANCONI-ANEMIA; MISMATCH REPAIR; LUNG-CANCER; DAMAGE RESPONSE AB Human cancers exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair. Cancer cells are often defective in one of six major DNA repair pathways, namely: mismatch repair, base excision repair, nucleotide excision repair, homologous recombination, nonhomologous endjoining and translesion synthesis. The specific DNA repair pathway affected is predictive of the kinds of mutations, the tumor drug sensitivity, and the treatment outcome. The study of rare inherited DNA repair disorders, such as Fanconi anemia, has yielded new insights to drug sensitivity and treatment of sporadic cancers, such as breast or ovarian epithelial tumors, in the general population. The Fanconi anemia pathway is an example of how DNA repair pathways can be deregulated in cancer cells and how biomarkers of the integrity of these pathways could be useful as a guide to cancer management and may be used in the development of novel therapeutic agents. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Kennedy, Richard/J-3489-2012; Mendez, Pedro /J-8955-2016 OI Kennedy, Richard/0000-0003-4737-6163; Mendez, Pedro /0000-0001-6713-7907 FU NCI NIH HHS [P50 CA105009-01]; NHLBI NIH HHS [P01HL54785, R01HL52725]; NIDDK NIH HHS [R01 DK43889]; PHS HHS [P0150654] NR 108 TC 161 Z9 163 U1 0 U2 10 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 AUG 10 PY 2006 VL 24 IS 23 BP 3799 EP 3808 DI 10.1200/JCO.2005.05.4171 PG 10 WC Oncology SC Oncology GA 075TG UT WOS:000239907500012 PM 16896009 ER PT J AU Husain, SS Nirthanan, S Ruesch, D Solt, K Cheng, Q Li, GD Arevalo, E Olsen, RW Raines, DE Forman, SA Cohen, JB Miller, KW AF Husain, S. Shaukat Nirthanan, Selvanayagam Ruesch, Dirk Solt, Ken Cheng, Qi Li, Guo-Dong Arevalo, Enrique Olsen, Richard W. Raines, Douglas E. Forman, Stuart A. Cohen, Jonathan B. Miller, Keith W. TI Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; ALPHA(1)BETA(2)GAMMA(2L) GABA(A) RECEPTORS; BINDING-SITE; A RECEPTOR; AMINO-ACID; GAMMA; IDENTIFICATION; SUBUNIT; ANTAGONIST; RESIDUES AB To locate the binding sites of general anesthetics on ligand-gated ion channels, two derivatives of the intravenous general anesthetic etomidate (2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate), in which the 2-ethyl group has been replaced by photoactivable groups based on either aryl diazirine or benzophenone chemistry, have been synthesized and characterized pharmacologically. TDBzl-etomidate (4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate) and BzBzl-etomidate (4-benzoylbenzyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate are both potent general anesthetics with half-effective anesthetic concentrations of 700 and 220 nM, respectively. Both agents resembled etomidate in enhancing currents elicited by low concentrations of GABA on heterologously expressed GABA(A) receptors and in shifting the GABA concentration-response curve to lower concentrations. They also allosterically enhanced the binding of flunitrazepam to mammalian brain GABAA receptors. Both agents were also effective and selective photolabels, photoincorporating into some, but not all, subunits of the Torpedo nicotinic acetylcholine receptor to a degree that was allosterically regulated by an agonist or a noncompetitive inhibitor. Thus, they have the necessary pharmacological and photochemical properties to be useful in identifying the site of etomidate-induced anesthesia. C1 Harvard Med Sch, Dept Neurobiol, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Miller, KW (reprint author), Harvard Med Sch, Dept Neurobiol, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM k_miller@helix.mgh.harvard.edu OI Solt, Ken/0000-0001-5328-2062 FU NIGMS NIH HHS [GM58448, T32 GM07592] NR 36 TC 27 Z9 27 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 10 PY 2006 VL 49 IS 16 BP 4818 EP 4825 DI 10.1021/jm051207b PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 069PD UT WOS:000239459800005 PM 16884293 ER PT J AU Yang, FJ Vought, BW Satterlee, JS Walker, AK Sun, ZYJ Watts, JL DeBeaumont, R Saito, RM Hyberts, SG Yang, S Macol, C Iyer, L Tjian, R van den Heuvel, S Hart, AC Wagner, G Naar, AM AF Yang, Fajun Vought, Bryan W. Satterlee, John S. Walker, Amy K. Sun, Z. -Y. Jim Watts, Jennifer L. DeBeaumont, Rosalie Saito, R. Mako Hyberts, Sven G. Yang, Shaosong Macol, Christine Iyer, Lakshmanan Tjian, Robert van den Heuvel, Sander Hart, Anne C. Wagner, Gerhard Naar, Anders M. TI An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis SO NATURE LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; CAENORHABDITIS-ELEGANS; KIX DOMAIN; TRANSACTIVATION DOMAIN; SECONDARY STRUCTURE; PROTEIN CBP; C-ELEGANS; COACTIVATOR; ACTIVATION; CREB AB The sterol regulatory element binding protein ( SREBP) family of transcription activators are critical regulators of cholesterol and fatty acid homeostasis(1,2). We previously demonstrated that human SREBPs bind the CREB- binding protein ( CBP)/ p300 acetyltransferase KIX domain and recruit activator- recruited co- factor ( ARC)/ Mediator co- activator complexes through unknown mechanisms(3-5). Here we show that SREBPs use the evolutionarily conserved ARC105 ( also called MED15) subunit to activate target genes. Structural analysis of the SREBP- binding domain in ARC105 by NMR revealed a three- helix bundle with marked similarity to the CBP/ p300 KIX domain. In contrast to SREBPs, the CREB and c- Myb activators do not bind the ARC105 KIX domain, although they interact with the CBP KIX domain, revealing a surprising specificity among structurally related activator- binding domains. The Caenorhabditis elegans SREBP homologue SBP- 1 promotes fatty acid homeostasis by regulating the expression of lipogenic enzymes(6,7). We found that, like SBP- 1, the C. elegans ARC105 homologue MDT- 15 is required for fatty acid homeostasis, and show that both SBP- 1 and MDT- 15 control transcription of genes governing desaturation of stearic acid to oleic acid. Notably, dietary addition of oleic acid significantly rescued various defects of nematodes targeted with RNA interference against sbp- 1 and mdt- 15, including impaired intestinal fat storage, infertility, decreased size and slow locomotion, suggesting that regulation of oleic acid levels represents a physiologically critical function of SBP- 1 and MDT- 15. Taken together, our findings demonstrate that ARC105 is a key effector of SREBP-dependent gene regulation and control of lipid homeostasis in metazoans. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Washington State Univ, Inst Biol Chem, Pullman, WA 99164 USA. Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Naar, AM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM naar@helix.mgh.harvard.edu RI van den Heuvel, Sander/B-8892-2011; OI Iyer, Lakshmanan/0000-0001-9167-6396 FU NCI NIH HHS [R01 CA127990]; NIDDK NIH HHS [R01 DK074114, R01 DK074114-01] NR 30 TC 172 Z9 209 U1 3 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 10 PY 2006 VL 442 IS 7103 BP 700 EP 704 DI 10.1038/nature04942 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071UU UT WOS:000239630200049 PM 16799563 ER PT J AU Harris, NS AF Harris, N. Stuart TI A woman with hypotension after an overdose of amlodipine - Massive overdose of amlodipine (calcium-channel blocker) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INTENSIVE INSULIN THERAPY; VERAPAMIL OVERDOSE; NIFEDIPINE; DILTIAZEM; TOXICITY; ANTAGONISTS; GLUCAGON; AMRINONE C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. RP Harris, NS (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 37 TC 26 Z9 28 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 10 PY 2006 VL 355 IS 6 BP 602 EP 611 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 071QM UT WOS:000239616700012 PM 16899781 ER PT J AU Giri, S Rattan, R Haq, E Khan, M Yasmin, R Won, JS Key, L Singh, AK Singh, I AF Giri, Shailendra Rattan, Ramandeep Haq, Ehtishamul Khan, Mushfiquddin Yasmin, Rifat Won, Je-song Key, Lyndon Singh, Avtar K. Singh, Inderjit TI AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model SO NUTRITION & METABOLISM LA English DT Article ID ACTIVATED PROTEIN-KINASE; ENHANCER-BINDING-PROTEIN; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; GENE-EXPRESSION; ADIPOSE-TISSUE; MITOCHONDRIAL BIOGENESIS; SKELETAL-MUSCLE; TRANSCRIPTIONAL COACTIVATOR; 3T3-L1 ADIPOCYTES AB Background: Obesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase ( AMPK) is an energy sensor that regulates cellular metabolism. The role of AMP-activated protein kinase in adipocyte differentiation is not completely understood, therefore, we examined the effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside ( AICAR), a pharmacological activator of AMP-activated protein kinase ( AMPK) on adipocyte differentiation in 3T3L1 cells and in a mouse Diet induced obesity (DIO) model. Methods: To examine the effect of AICAR on adipocyte differentiation in 3T3L1 cells and in a mouse Diet induced obesity ( DIO) model, 3T3L1 cells were differentiatied in the presence or absence of different concentration of AICAR and neutral lipid content and expression of various adipocyte-specific transcription factors were examined. In vivo study, treated and untreated mice with AICAR (0.1 - 0.5 mg/g body weight) were fed high-fat diet (60% kcal% fat) to induce DIO and several parameters were studied. Results: AICAR blocked adipogenic conversion in 3T3L1 cells along with significant decrease in the neutral lipid content by downregulating several adipocyte-specific transcription factors including peroxisome proliferators-activated receptor gamma (PPAR gamma), C/EBP alpha and ADD1/ SREBP1, which are critical for adipogenesis in vitro. Moreover, intraperitoneal administration of AICAR ( 0.5 mg g/body weight) to mice fed with high-fat diet ( 60% kcal% fat) to induce DIO, significantly blocked the body weight gain and total content of epididymal fat in these mice over a period of 6 weeks. AICAR treatment also restored normal adipokine levels and resulted in significant improvement in glucose tolerance and insulin sensitivity. The reduction in adipose tissue content in AICAR treated DIO mice was due to reduction in lipid accumulation in the pre-existing adipocytes. However, no change was observed in the expression of PPAR gamma, C/EBP alpha and ADD1/ SREBP1 transcription factors in vivo though PGC1 alpha expression was significantly induced. Conclusion: This study suggests that AICAR inhibits adipocyte differentiation via downregulation of expression of adipogenic factors in vitro and reduces adipose tissue content in DIO mice by activating expression of PGC1a without inhibiting adipocyte-specific transcription factors in DIO mice. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN 55905 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, 171 Ashley Ave, Charleston, SC 29425 USA. EM giris@musc.edu; rattanr@musc.edu; shahe@musc.edu; khanm@musc.edu; yasmin@musc.edu; wonj@musc.edu; keyl@musc.edu; singhak@musc.edu; singhi@musc.edu OI Haq, Ehtishamul/0000-0002-4195-0606 FU NCRR NIH HHS [C06 RR015455, C06 RR018823]; NINDS NIH HHS [R01 NS034741, R01 NS022576, R01 NS037766, R01 NS040144, R01 NS040810, R37 NS022576] NR 62 TC 91 Z9 93 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-7075 J9 NUTR METABOLISM JI Nutr. Metab. PD AUG 10 PY 2006 VL 3 AR 31 DI 10.1186/1743-7075-3-31 PG 20 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 083UN UT WOS:000240483800001 PM 16901342 ER PT J AU Xia, T Kovochich, M Brant, J Hotze, M Sempf, J Oberley, T Sioutas, C Yeh, JI Wiesner, MR Nel, AE AF Xia, Tian Kovochich, Michael Brant, Jonathan Hotze, Matt Sempf, Joan Oberley, Terry Sioutas, Constantinos Yeh, Joanne I. Wiesner, Mark R. Nel, Andre E. TI Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm SO NANO LETTERS LA English DT Article ID DIESEL EXHAUST PARTICLES; DIRECT ELECTRON-TRANSFER; ULTRAFINE PARTICLES; CARBON-NANOTUBES; FULLERENE DERIVATIVES; EPITHELIAL-CELLS; STATE PROPERTIES; AQUEOUS-SOLUTION; GLUCOSE-OXIDASE; IN-VIVO AB Nanomaterial properties differ from those bulk materials of the same composition, allowing them to execute novel activities. A possible downside of these capabilities is harmful interactions with biological systems, with the potential to generate toxicity. An approach to assess the safety of nanomaterials is urgently required. We compared the cellular effects of ambient ultrafine particles with manufactured titanium dioxide (TiO2), carbon black, fullerol, and polystyrene (PS) nanoparticles (NPs). The study was conducted in a phagocytic cell line ( RAW 264.7) that is representative of a lung target for NPs. Physicochemical characterization of the NPs showed a dramatic change in their state of aggregation, dispersibility, and charge during transfer from a buffered aqueous solution to cell culture medium. Particles differed with respect to cellular uptake, subcellular localization, and ability to catalyze the production of reactive oxygen species (ROS) under biotic and abiotic conditions. Spontaneous ROS production was compared by using an ROS quencher (furfuryl alcohol) as well as an NADPH peroxidase bioelectrode platform. Among the particles tested, ambient ultrafine particles (UFPs) and cationic PS nanospheres were capable of inducing cellular ROS production, GSH depletion, and toxic oxidative stress. This toxicity involves mitochondrial injury through increased calcium uptake and structural organellar damage. Although active under abiotic conditions, TiO2 and fullerol did not induce toxic oxidative stress. While increased TNF-alpha production could be seen to accompany UFP-induced oxidant injury, cationic PS nanospheres induced mitochondrial damage and cell death without inflammation. In summary, we demonstrate that ROS generation and oxidative stress are a valid test paradigm to compare NP toxicity. Although not all materials have electronic configurations or surface properties to allow spontaneous ROS generation, particle interactions with cellular components are capable of generating oxidative stress. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Div Clin Immunol & Allergy, Los Angeles, CA 90095 USA. Duke Univ, Dept Civil & Environm Engn, Durham, NC 27708 USA. William S Middleton Mem Vet Adm Med Ctr, Pathol Serv, Madison, WI 53792 USA. Univ So Calif, Dept Civil & Environm Engn, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, So Calif Particle Ctr, Los Angeles, CA 90095 USA. Univ Pittsburgh, Sch Med, Dept Bioengn, Dept Biol Struct, Pittsburgh, PA 15260 USA. RP Nel, AE (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Div Clin Immunol & Allergy, 52-175 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM anel@mednet.ucla.edu RI Nel, Andre/J-2808-2012; xia, tian/C-3158-2013 OI xia, tian/0000-0003-0123-1305 FU NIAID NIH HHS [GM/AI66466]; NIEHS NIH HHS [R01 ES015498, R01 ES10253, R01 ES10553, R01 ES13432]; PHS HHS [U19 A1070453] NR 53 TC 894 Z9 934 U1 33 U2 340 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD AUG 9 PY 2006 VL 6 IS 8 BP 1794 EP 1807 DI 10.1021/nl061025k PG 14 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 071SY UT WOS:000239623900039 PM 16895376 ER PT J AU Tengs, T Lee, JC Paez, JG Zhao, XJ LaFramboise, T Giannoukos, G Thomas, RK AF Tengs, Torstein Lee, Jeff C. Paez, J. Guillermo Zhao, Xiaojun LaFramboise, Thomas Giannoukos, Georgia Thomas, Roman K. TI A transforming MET mutation discovered in non-small cell lung cancer using microarray-based resequencing SO CANCER LETTERS LA English DT Article DE oncogene; tumor suppressor gene; gene mutation; microarray; dideoxy sequencing; resequencing ID BRAF GENE; C-MET; GENOME; KINASE AB We have designed resequencing microarrays to test the performance of this platform when interrogating a large number of exons (164 total) from genes associated with cancer. To evaluate false positive and negative rates, dideoxy sequencing was done for 335,420 bases interrogated by the arrays. From the array data, calls could be made for similar to 97.5% of the bases, and false positive rates were very low with only a single mutation reported from the array dataset for which the corresponding dideoxy trace had a clean wildtype sequence. For the nucleotide positions where array calls were made, false negative rates were 1.41% for heterozygous mutations. All the homozygous mutations were detected, but 8.11% were erroneously reported as heterozygous changes from the reference sequence by the array analysis software. In addition, 20 non-small cell lung cancer (NSCLC) samples were analyzed using the arrays, and both somatic and germline mutations were found. The most interesting findings were two MET mutations that have recently been implemented in NSCLC. Large scale MALDI-TOF genotyping indicated that one of these mutations (T1010I) might represent a true cancer-causing genotype, whereas the other (N375S) appears to be a common gem-dine polymorphism. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. Merck & Co Inc, Boston, MA 02115 USA. RP Tengs, T (reprint author), Natl Vet Inst, Ullevaalsveien 68, N-0454 Oslo, Norway. EM torstein.tengs@vetinst.no; rthomas@broad.mit.edu NR 15 TC 18 Z9 19 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 8 PY 2006 VL 239 IS 2 BP 227 EP 233 DI 10.1016/j.canlet.2005.08.007 PG 7 WC Oncology SC Oncology GA 073PF UT WOS:000239754400008 PM 16171945 ER PT J AU O'Donoghue, M de Lemos, JA Morrow, DA Murphy, SA Buros, JL Cannon, CP Sabatine, MS AF O'Donoghue, Michelle de Lemos, James A. Morrow, David A. Murphy, Sabina A. Buros, Jacqueline L. Cannon, Christopher P. Sabatine, Marc S. TI Prognostic utility of heart-type fatty acid binding protein in patients with acute coronary syndromes SO CIRCULATION LA English DT Article DE fatty acid-binding proteins; angina, unstable; mortality; myocardial infarction ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC TROPONIN-T; C-REACTIVE PROTEIN; RISK STRATIFICATION; NATRIURETIC PEPTIDE; AMERICAN-COLLEGE; UNSTABLE ANGINA; MYOGLOBIN; PLASMA; THROMBOLYSIS AB Background - Heart-type fatty acid binding protein (H-FABP) is a cytosolic protein that is released rapidly from the cardiomyocyte in response to myocardial injury. Although it has been investigated as an early marker of acute myocardial infarction, its prognostic utility in acute coronary syndromes has not been established. Methods and Results - We measured H-FABP in 2287 patients with acute coronary syndromes from the OPUS-TIMI 16 trial. H-FABP was elevated (> 8 ng/mL) in 332 patients (14.5%). Patients with an elevated H-FABP were more likely to suffer death (hazard ratio [HR], 4.1; 95% CI, 2.6 to 6.5), recurrent myocardial infarction (HR, 1.6; 95% CI, 1.0 to 2.5), congestive heart failure (HR, 4.5; 95% CI, 2.6 to 7.8), or the composite of these end points (HR, 2.6; 95% CI, 1.9 to 3.5) through the 10-month follow-up period. H-FABP predicted the risk of the composite end point both in patients who were troponin I negative (HR, 2.1; 95% CI, 1.3 to 3.4) and in those who were troponin I positive (HR, 3.3; 95% CI, 2.0 to 5.3). In a Cox proportional-hazards model that adjusted for baseline variables, including demographics, clinical characteristics, creatinine clearance, ST deviation, index diagnosis, and troponin I, elevated H-FABP remained a significant predictor of the composite end point (HR, 1.9; 95% CI, 1.3 to 2.7), as well as the individual end points of death (HR, 2.7; 95% CI, 1.5 to 4.9) and CHF (HR, 2.4; 95% CI, 1.2 to 5.0). In a multimarker approach, H-FABP, troponin I, and B-type natriuretic peptide provided complementary information. Conclusions - Elevation of H-FABP is associated with an increased risk of death and major cardiac events in patients presenting across the spectrum of acute coronary syndromes and is independent of other established clinical risk predictors and biomarkers. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Cardiol, Dallas, TX 75230 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM msabatine@partners.org OI Buros, Jacqueline/0000-0001-9588-4889 FU NHLBI NIH HHS [U01 HL083-1341] NR 33 TC 82 Z9 85 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 AUG 8 PY 2006 VL 114 IS 6 BP 550 EP 557 DI 10.1161/CIRCULATIONAHA.106.641936 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 071LJ UT WOS:000239603400009 PM 16880323 ER PT J AU Shioda, T Chesnes, J Coser, KR Zou, LH Hur, J Dean, KL Sonnenschein, C Soto, AM Isselbacher, KJ AF Shioda, Toshi Chesnes, Jessica Coser, Kathryn R. Zou, Lihua Hur, Jingyung Dean, Kathleen L. Sonnenschein, Carlos Soto, Ana M. Isselbacher, Kurt J. TI Importance of dosage standardization for interpreting transcriptomal signature profiles: Evidence from studies of xenoestrogens SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast cancer; estrogen; pharmacogenomics; toxicogenomics; transcriptome ID BREAST-CANCER CELLS; ESTROGEN-RESPONSIVE GENES; EXPRESSION PATTERNS; REGULATED GENES; DNA MICROARRAY; TARGET GENES; IDENTIFICATION; PROLIFERATION; MECHANISMS; GENOMICS AB To obtain insights into similarities and differences in the biological actions of related drugs or toxic agents, their transcriptomal signature profiles (TSPs) have been examined in a large number of studies. However, many such reports did not provide proper justification for the dosage criteria of each agent. Using a well characterized cell culture model of estrogen-dependent proliferation of MCF7 human breast cancer cells, we demonstrate how different approaches to dosage standardization exert critical influences on TSPs, leading to different and even conflicting conclusions. Using quantitative cellular response (QCR)-based dosage criteria, TSPs were determined by Affymetrix microarray when cells were proliferating at comparable rates in the presence of various estrogens. We observed that TSPs of the xenoestrogens (e.g., genistein or bisphenol A) were clearly different from the TSP of 17 beta-estradiol; namely, the former strongly enhanced expression of genes involved in mitochondrial oxidative phosphorylation, whereas the latter showed minimal effects. In contrast, TSPs for genistein and 17 beta-estradiol were indistinguishable by using the marker gene expression-based dosage criteria, conditions in which there was comparable expression of the mRNA transcripts for the estrogen-inducible WISP2 gene. Our findings indicate that determination and interpretation of TSPs in pharmacogenomic and toxicogenomic studies that examine the transcriptomal actions of related agents by microarray require a clear rationale for the dosage standardization method to be used. We suggest that future studies involving TSP analyses use quantitative and objective dosage standardization methods, such as those with quantitative cellular response or marker gene expression-based dosage criteria. C1 Massachusetts Gen Hosp, Ctr Canc Res, Dept Tumor Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Profiling Lab, Charlestown, MA 02129 USA. Harvard Bauer Ctr Genom Res, Div Computat Biol, Cambridge, MA 02138 USA. Tufts Univ, Sch Med, Dept Anat & Cell Biol, Boston, MA 02111 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Dept Tumor Biol, Charlestown, MA 02129 USA. EM tshioda@partners.org; kisselbacher@partners.org RI Zou, Lihua/E-6748-2010 FU NCI NIH HHS [R01 CA82230, R01 CA082230]; NIEHS NIH HHS [R21 ES012301, ES012301] NR 28 TC 36 Z9 37 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 8 PY 2006 VL 103 IS 32 BP 12033 EP 12038 DI 10.1073/pnas.0605341103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072VU UT WOS:000239701900039 PM 16882715 ER PT J AU Taniguchi, CM Tran, TT Kondo, T Luo, J Ueki, K Cantley, LC Kahn, CR AF Taniguchi, Cullen M. Tran, Thien T. Kondo, Tatsuya Luo, Ji Ueki, Kohjiro Cantley, Lewis C. Kahn, C. Ronald TI Phosphoinositide 3-kinase regulatory subunit p85 alpha suppresses insulin action via positive regulation of PTEN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE conditional gene knockout; diabetes; insulin resistance ID MICE LACKING; PHOSPHATIDYLINOSITOL 3'-KINASE; GLUCOSE-PRODUCTION; SKELETAL-MUSCLE; HEPATIC GLUCOSE; RESISTANCE; SENSITIVITY; EXPRESSION; IRS-2; HYPOGLYCEMIA AB The phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on liver. Here, we show that mice with a liver-specific deletion of the p85 alpha regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity. Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. This increased Akt activity correlates with increased phosphatidylinositol (3,4,5)-trisphosphate levels which are due, at least in part, to diminished activity of the (3,4,5)-trisphosphate phosphatase PTEN. Thus, the regulatory subunit p85 alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Kumamoto Univ, Grad Sch Med Sci, Dept Metab Med, Kumamoto 8608555, Japan. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02116 USA. Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo 1130033, Japan. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM lcantley@hms.harvard.edu; c.ronald.kahn@joslin.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA089021, P01 CA089021]; NIDDK NIH HHS [DK34834, DK33201, DK55545, R01 DK033201, R01 DK055545]; NIGMS NIH HHS [GM41890, R01 GM041890, R37 GM041890] NR 32 TC 93 Z9 93 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 8 PY 2006 VL 103 IS 32 BP 12093 EP 12097 DI 10.1073/pnas.0604628103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072VU UT WOS:000239701900049 PM 16880400 ER PT J AU Sun, YL Jiang, XF Chen, SJ Price, BD AF Sun, Yingli Jiang, Xiaofeng Chen, Shujuan Price, Brendan D. TI Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation SO FEBS LETTERS LA English DT Article DE ATM; anacardic acid; Tip60; HAT; radiosensitivity; DNA repair ID DOUBLE-STRAND BREAKS; DEACETYLASE INHIBITORS; ACETYLATION; ATM; REPAIR; TIP60; P300; ACTIVATION; PROTEINS; PCAF AB Histone acetyltransferases (HATs) regulate transcription, chromatin structure and DNA repair. Here, we utilized a novel HAT inhibitor, anacardic acid, to examine the role of HATs in the DNA damage response. Anacardic acid inhibits the Tip60 HAT in vitro, and blocks the Tip60-dependent activation of the ATM and DNA-PKcs protein kinases by DNA damage in vivo. Further, anacardic acid sensitizes human tumor cells to the cytotoxic effects of ionizing radiation. These results demonstrate a central role for HATs such as Tip60 in regulating the DNA damage response. HAT inhibitors provide a novel therapeutic approach for increasing the sensitivity of tumors to radiation therapy. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Div Gen Stabil & DNA Repair, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Div Gen Stabil & DNA Repair, Dept Radiat Oncol,Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu FU NINDS NIH HHS [R21 NS061669] NR 21 TC 113 Z9 118 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 7 PY 2006 VL 580 IS 18 BP 4353 EP 4356 DI 10.1016/j.febslet.2006.06.092 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 072JF UT WOS:000239669000009 PM 16844118 ER PT J AU Tang, E Dai, YM Zhang, J Li, ZJ Yao, YG Zhang, J Huang, XD AF Tang, En Dai, Yu-Mei Zhang, Jian Li, Zhao-Ji Yao, Yuan-Gen Zhang, Jie Huang, Xu-Dong TI Two cobalt(II) 5-aminoisophthalate complexes and their stable supramolecular microporous frameworks SO INORGANIC CHEMISTRY LA English DT Article ID INDUCED MAGNETIC TRANSITIONS; COORDINATION POLYMERS; ORDERING TEMPERATURE; DIAMOND FRAMEWORK; CRYSTAL-STRUCTURE; 3D ARCHITECTURE; POROUS SOLIDS; NETWORKS; MOLECULES; DESIGN AB Two stable supramolecular microporous cobalt(II) polymers, namely [Co(HAIP)(2)](n)center dot 3nH(2)O (1) and [Co(AIP)(H2O)](n) (2), AIP = 5-aminoisophthalate, were hydrothermally synthesized and characterized by single-crystal X-ray diffraction, IR spectra, thermogravimetric analyses, and variable-temperature magnetic susceptibility measurements. The two complexes are constructed from the same Co-2(CO2)(2) SBU, which is extended into a 1D chain in 1 and a 2D layer in 2. As a result, 1 and 2 are 2D and 3D coordination polymers, respectively. The 3D supramolecular network of complex 1 is held up by strong hydrogen bonds formed between carboxylate groups and shows very high stability when the free H2O molecules are removed, indicating an extraordinarily stable H-bonding system. Upon water ligands being liberated, complex 2 becomes a stable microporous solid with coordination-unsaturated Co centers. The behavior of the susceptibility curve of 1 suggests the occurrence of an interesting intrachain antiferromagnetic coupling between the Co(II) ions and the presence of a significant orbital contribution, whereas the features of 2 indicate an antiferromagnetic coupling with T-N = 3.5 K and a long-range antiferromagnetic order with a field-induced magnetic transition. C1 Chinese Acad Sci, Fujian Inst Res Struct Matter, State Key Lab Struct Chem, Fujian 350002, Peoples R China. Fujian Normal Univ, Coll Chem & Mat Sci, Fuzhou 350007, Fujian, Peoples R China. Massachusetts Gen Hosp, Genet & Aging Res Unit, Massachusetts Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Yao, YG (reprint author), Chinese Acad Sci, Fujian Inst Res Struct Matter, State Key Lab Struct Chem, Fujian 350002, Peoples R China. EM yyg@fjirsm.ac.cn RI zhang, Jie/B-8067-2011; Zhang, Jian/B-5056-2011 OI Zhang, Jian/0000-0003-3373-9621 NR 40 TC 32 Z9 32 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD AUG 7 PY 2006 VL 45 IS 16 BP 6276 EP 6281 DI 10.1021/ic0602244 PG 6 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 068SI UT WOS:000239394300030 PM 16878937 ER PT J AU Krueger, A Garbe, AI von Boehmer, H AF Krueger, Andreas Garbe, Annette I. von Boehmer, Harald TI Phenotypic plasticity of T cell progenitors upon exposure to Notch ligands SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COMMON LYMPHOID PROGENITORS; MOUSE BONE-MARROW; LINEAGE COMMITMENT; IN-VITRO; HEMATOPOIETIC PROGENITORS; PRECURSOR CELLS; STEM-CELLS; THYMUS; DIFFERENTIATION; IDENTIFICATION AB Despite many efforts, the nature of thymic immigrants that give rise to T cells has remained obscure, especially since it became known that extrathymic lineage-negative, Sca-1-positive, c-kit high progenitor cells differ from intrathymic early T cell progenitors (ETPs) by functional potential and dependence on Notch signaling. After our observation that intrathymic T cell precursors expressing a human CD25 reporter under control of pre-TCR alpha regulatory elements almost exclusively have the ETP phenotype, we have analyzed the phenotypic changes of reporter-expressing common lymphoid progenitor (CLP) cells in the bone marrow when cultured on Delta-like 1-expressing stromal cells. We note that these quickly adopt the phenotype of double negative (DN)2 thymocytes with little display of the ETP phenotype. Our data suggest that common lymphoid progenitor (CLP) cells could be responsible for the rapid reconstitution of thymus function after bone marrow transplantation since CLP cells in the blood have the capacity to rapidly enter the thymus and become DN2 thymocytes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krueger, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Andreas_Krueger@dfci.harvard.edu RI Krueger, Andreas/B-9427-2009; Garbe, Annette/A-4824-2014 OI Krueger, Andreas/0000-0001-7873-7334; FU NIAID NIH HHS [R01 AI045846, AI45846] NR 25 TC 40 Z9 40 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 7 PY 2006 VL 203 IS 8 BP 1977 EP 1984 DI 10.1084/jem.20060731 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 071LL UT WOS:000239603600017 PM 16847069 ER PT J AU Chakraverty, R Cote, D Buchli, J Cotter, P Hsu, R Zhao, GL Sachs, T Pitsillides, CM Bronson, R Means, T Lin, C Sykes, M AF Chakraverty, Ronjon Cote, Daniel Buchli, Jennifer Cotter, Pete Hsu, Richard Zhao, Guiling Sachs, Teviah Pitsillides, Costas M. Bronson, Roderick Means, Terry Lin, Charles Sykes, Megan TI An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ANTIGEN-PRESENTING CELLS; TOTAL-BODY IRRADIATION; TUMOR-NECROSIS-FACTOR; DENDRITIC CELLS; IN-VIVO; AUTOIMMUNE-DISEASE; ALLOGENEIC CHIMERAS; TARGET ORGANS; CUTTING EDGE AB Transfer of T cells to freshly irradiated allogeneic recipients leads to their rapid recruitment to nonlymphoid tissues, where they induce graft-versus-host disease (GVHD). In contrast, when donor T cells are transferred to established mixed chimeras (MCs), GVHD is not induced despite a robust graft-versus-host (GVH) reaction that eliminates normal and malignant host hematopoietic cells. We demonstrate here that donor GVH-reactive T cells transferred to MCs or freshly irradiated mice undergo similar expansion and activation, with similar up-regulation of homing molecules required for entry to nonlymphoid tissues. Using dynamic two-photon in vivo microscopy, we show that these activated T cells do not enter GVHD target tissues in established MCs, contrary to the dogma that activated T cells inevitably traffic to nonlymphoid tissues. Instead, we show that the presence of inflammation within a nonlymphoid tissue is a prerequisite for the trafficking of activated T cells to that site. Our studies help to explain the paradox whereby GVH-reactive T cells can mediate graft-versus-leukemia responses without inducing GVHD in established MCs. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu RI Cote, Daniel/D-5185-2011 FU NCI NIH HHS [R01 CA079989, R01 CA79989]; NIBIB NIH HHS [R01 EB000664] NR 59 TC 116 Z9 119 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 7 PY 2006 VL 203 IS 8 BP 2021 EP 2031 DI 10.1084/jem.20060376 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 071LL UT WOS:000239603600021 PM 16880259 ER PT J AU Nakazawa, T Matsubara, A Noda, K Hisatomi, T She, H Skondra, D Miyahara, S Sobrin, L Thomas, KL Chen, DF Grosskreutz, CL Hafezi-Moghadam, A Miller, JW AF Nakazawa, Toru Matsubara, Akihisa Noda, Kousuke Hisatomi, Toshio She, Haicheng Skondra, Dimitra Miyahara, Shinsuke Sobrin, Lucia Thomas, Kennard L. Chen, Dong F. Grosskreutz, Cynthia L. Hafezi-Moghadam, Ali Miller, Joan W. TI Characterization of cytokine responses to retinal detachment in rats SO MOLECULAR VISION LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; NECROSIS-FACTOR-ALPHA; PROLIFERATIVE VITREORETINOPATHY; NEUROTROPHIC FACTOR; UP-REGULATION; CELL-DEATH; PHOTORECEPTOR APOPTOSIS; CHEMOTACTIC PROTEIN-1; LEUKOCYTE RECRUITMENT AB Purpose: Photoreceptor apoptosis is associated with retinal detachment (RD) induced photoreceptor degeneration. Previously, we demonstrated the importance of caspase activation for RD-induced photoreceptor death in a rat model of RD. However, extracellular signals that precede the activation of caspases and photoreceptor degeneration remain unclear. The aim of this study is to characterize the molecular and cellular responses that occur after RD. The expression of cytokines, chemokines, and growth factors were examined in a rat model of RD. Methods: RD was induced in adult rats by subretinal injection of sodium hyaluronate. Retinal tissues were collected at various times (1, 3, 6, 24, and 72 h) after the induction of detachment. To screen for expressional changes in response to RD, major candidates for cytokines, chemokines, and growth factors were broadly examined by quantitative real time polymerase chain reaction (QPCR). To identify the cellular sources of the expressed genes, cells from various layers of the retina were obtained using laser capture microdissection (LCM), and their mRNAs were isolated. Protein expression was quantified by immunohistochemistry and Enzyme Linked-Immuno-Sorbent Assay (ELISA). To assess the potential of early response genes after RD to induce photoreceptor degeneration, exogenous recombinant proteins were subretinally injected and the photoreceptor cell death was assessed using a TdT-dUTP terminal nick-end labeling (TUNEL) assay at 24 h after RD. Results: At 72 h after RD a significant increase in mRNA levels for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), monocyte chemotactic protein-1 (MCP-1), and basic fibroblast growth factor (bFGF) were detected in the neural retina. LCM revealed increased expression of mRNA for bFGF and MCP-1 in all retinal layers, though bFGF was especially evident in the outer nuclear layer (ONL) and MCP-1 in the inner nuclear layer (INL). TNF-alpha was increased in the ONL and the INL, and IL-1 beta was increased in the ganglion cell layer. Time course experiments showed that TNF-alpha, IL-1 beta and MCP-1 increased within 1 h after RD, while bFGF was increased by 24 h. Increased protein expression for TNF-alpha, IL-1 beta, and MCP-1 was demonstrated by ELISA at 6 h after RD. Immunohistochemistry showed TNF-alpha and bFGF expression in the whole retina, with IL-1 beta specifically expressed in astrocytes and MCP-1 in MUller cells. Subretinal administration of MCP-1 significantly increased TUNEL-positive cells in the ONL 24 h after RD, while injection of vehicle control, TNF-alpha, or IL-1 beta showed no effect. Conclusions: Retinal glial cells, including astrocytes and MUller cells, are a major source of cytokine induction after RD. The increased expression and release of MCP-1 may be an important cause of photoreceptor degeneration associated with RD. This study helps to understand the mechanisms of RD-induced photoreceptor degeneration. Our results may provide new therapeutic targets to prevent photoreceptor degeneration following RD. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol,Program Neu, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, 325 Cambridge St, Boston, MA 02114 USA. EM Joan_Miller@meei.harvard.edu NR 56 TC 93 Z9 95 U1 1 U2 5 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD AUG 7 PY 2006 VL 12 IS 97-98 BP 867 EP 878 PG 12 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 074NO UT WOS:000239819300002 PM 16917487 ER PT J AU Bilenca, A Ozcan, A Bouma, B Tearney, G AF Bilenca, A. Ozcan, A. Bouma, B. Tearney, G. TI Fluorescence coherence tomography SO OPTICS EXPRESS LA English DT Article ID MICROSCOPY; RESOLUTION; INTERFERENCE; ILLUMINATION; MEDIA; EYE AB In this paper, we introduce a new form of cross-sectional, coherence-gated fluorescence imaging, which we term 'spectral-domain fluorescence coherence tomography' (SD-FCT). SD-FCT is accomplished by spectrally detecting self-interference of the spontaneous emission of fluorophores located along the axial (depth) dimension of the sample. We have built a first generation SD-FCT system that utilizes two opposing low numerical-aperture objective lenses in an interferometer and an imaging spectrometer for detecting self-interference of fluorescence emitted from a sample. Here, in proof-of-principle experiments we demonstrate cross-sectional profiling of layered fluorescence phantoms. Narrow (a few micrometers FWHM) axial point-spread functions, large ranging depths (a few hundreds of micrometers) and wide fields of view (> 1 mm) were measured. Initial results suggest that SD-FCT may be a viable tool for the investigation of semi-transparent and selectively labeled fluorescent samples. (c) 2006 Optical Society of America C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Bilenca, A (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 7, Boston, MA 02114 USA. EM abilenca@partners.org RI Ozcan, Aydogan/I-2608-2013 OI Ozcan, Aydogan/0000-0002-0717-683X NR 17 TC 17 Z9 17 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD AUG 7 PY 2006 VL 14 IS 16 BP 7134 EP 7143 DI 10.1364/OE.14.007134 PG 10 WC Optics SC Optics GA 075CU UT WOS:000239861100017 PM 19529084 ER PT J AU Halabi, T Craft, D Bortfeld, T AF Halabi, Tarek Craft, David Bortfeld, Thomas TI Dose-volume objectives in multi-criteria optimization SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; FLUENCE MAP OPTIMIZATION AB Unlike conventional optimization with dose-volume (DV) constraints, multicriteria optimization (MCO) with DV objectives provides tradeoff information which we believe is necessary for choosing better treatment plans. We show that the MCO formulation with DV objectives is better suited to convex approximation than conventional formulations with DV constraints. We provide a relaxation of the integer programming formulation which reduces the computation time for a single plan from over 5 h to about 2 min, without significantly compromising the results. We also derive a heuristic to improve on the relaxed solutions, adding only a few additional minutes of computation time. We apply these techniques to a skull based tumour case and a paraspinal tumour case. Based on a careful examination of the driving terms in the relaxed formulation and the heuristic, we argue that our techniques should apply more generally for DV objectives in multi-objective IMRT treatment planning. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Halabi, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. EM thalabi@partners.org FU NCI NIH HHS [1 R01 CA103904-01A1] NR 18 TC 24 Z9 28 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 7 PY 2006 VL 51 IS 15 BP 3809 EP 3818 DI 10.1088/0031-9155/51/15/014 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 078CM UT WOS:000240078800015 PM 16861782 ER PT J AU Blasiole, JA Shinkunas, L LaBrecque, DR Arnold, RM Zickmund, SL AF Blasiole, Julie A. Shinkunas, Laura LaBrecque, Douglas R. Arnold, Robert M. Zickmund, Susan L. TI Mental and physical symptoms associated with lower social support for patients with hepatitis C SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE hepatitis C; social support; depression; anxiety; quality of life; stigmatization ID QUALITY-OF-LIFE; PEGINTERFERON ALPHA-2A; INTERFERON-ALPHA; RECEIVING INTERFERON-ALPHA-2B; DEPRESSIVE SYMPTOMS; ANTIVIRAL THERAPY; INFECTED PATIENTS; VIRUS-INFECTION; PLUS RIBAVIRIN; DISEASE AB AIM: To systematically examine the impact of the hepatitis C virus (HCV) diagnosis on patients' level of social support in a large-scale study. METHODS: Patients evaluated and treated for HCV in a tertiary referral center were enrolled in a cross-sectional study. Demographic data, functional and emotional status as measured by the Hospital Anxiety and Depression Scale (HAD) and the Sickness Impact Profile (SIP), severity of liver disease, mode of acquisition, and physical and psychiatric comorbidities were collected from patients or abstracted from the medical record. All participants completed a semi-structured interview, addressing questions of social support. RESULTS: A total of 342 patients (mean age 45.2 years; 37% women) were enrolled. Ninety-two (27%) patients described lower levels of support by family and friends. Nearly half of the participants (45%) noted the loss of at least one relationship due to the disease. Fears related to transmitting the disease (25%) were common and often associated with ignorance or even discrimination by others (19%). Nearly one fifth of the patients did not share information about their disease with others to avoid being stigmatized. Lower levels of social support were significantly associated with living alone, being unemployed, being excluded from antiviral therapy, having psychiatric comorbidities, contracting HCV through intravenous drug use, having high levels of anxiety and depression as measured by the HAD and negative mood state as measured by the SIR Patients reporting lower levels of social support also noted more physical symptoms as measured by the SIP. CONCLUSION: Patients with hepatitis C often face significant social problems, ranging from social isolation to familial stress. The most common concerns reflect a limited insight of patients and their relatives and friends about the disease, the risk factors for its spread, and about potential consequences. Our data suggest that educational interventions targeting support persons and the stressors identified in our findings may lessen or alleviate the social strains patients with hepatitis C experience. (c) 2006 The WJG Press. All rights reserved. C1 Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot,Dept Med, Pittsburgh, PA 15240 USA. Univ Iowa, Sch Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Univ Iowa Hosp & Clin, Dept Internal Med, Iowa City, IA 52242 USA. RP Zickmund, SL (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot,Dept Med, 151C-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM susan.zickmund@med.va.gov FU NHLBI NIH HHS [HL07121, T32 HL007121] NR 53 TC 28 Z9 29 U1 3 U2 4 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD AUG 7 PY 2006 VL 12 IS 29 BP 4665 EP 4672 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 076IH UT WOS:000239949900010 PM 16937437 ER PT J AU O'Day, DH Suhre, K Myre, MA Chatterjee-Chakraborty, M Chavez, SE AF O'Day, Danton H. Suhre, Karsten Myre, Michael A. Chatterjee-Chakraborty, Munmun Chavez, Sara E. TI Isolation, characterization, and bioinformatic analysis of calmodulin-binding protein cmbB reveals a novel tandem IP22 repeat common to many Dictyostelium and Mimivirus proteins SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE calmodulin-binding protein; CaMBOT; Dictyostelium; FNIP repeat; leucine rich repeat; Mimivirus; YopM ID REGULATES NUCLEAR NUMBER; LEUCINE-RICH REPEAT; MYOSIN-I; GIANT VIRUS; NUCLEOMORPHIN; DOMAIN; SEQUENCE; CYTOKINESIS; RECOGNITION; EXPRESSION AB A novel calmodulin-binding protein cmbB from Dictyostelium discoideum is encoded in a single gene. Northern analysis reveals two cmbB transcripts first detectable at 4 h during multicellular development. Western blotting detects an similar to 46.6 kDa protein. Sequence analysis and calmodulin-agarose binding studies identified a "classic" calcium-dependent calmodulin-binding domain ((179)IPKSLRSLFLGKGYNQPLEF(198)) but structural analyses suggest binding may not involve classic alpha-helical calmodulin-binding. The cmbB protein is comprised of tandem repeats of a newly identified IP22 motif ([I,L]Pxxhxxhxhxxxhxxxhxxxx; where h = any hydrophobic amino acid) that is highly conserved and a more precise representation of the FNIP repeat. At least eight Acanthamoeba polyphaga Mimivirus proteins and over 100 Dictyostelium proteins contain tandem arrays of the IP22 motif and its variants. cmbB also shares structural homology to YopM, from the plague bacterium Yersenia pestis. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada. CNRS, Struct & Genom Informat Lab, UPR 2589, Inst Struct Biol & Microbiol, F-13288 Marseille 09, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP O'Day, DH (reprint author), Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada. EM doday@utm.utoronto.ca OI Suhre, Karsten/0000-0001-9638-3912 NR 33 TC 10 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 4 PY 2006 VL 346 IS 3 BP 879 EP 888 DI 10.1016/j.bbrc.2006.05.204 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 061IT UT WOS:000238865900034 PM 16777069 ER PT J AU Jeong, D Cha, H Kim, E Kang, M Yang, DK Kim, JM Yoon, PO Oh, JG Bernecker, OY Sakata, S Thu, LT Cui, L Lee, YH Kim, DH Woo, SH Liao, R Hajjar, RJ Park, WJ AF Jeong, Dongtak Cha, Hyeseon Kim, Eunyoung Kang, Misuk Yang, Dong Kwon Kim, Ji Myoung Yoon, Pyoung Oh Oh, Jae Gyun Bernecker, Oliver Y. Sakata, Susumu Thu, Le Thi Cui, Lei Lee, Young-Hoon Kim, Do Han Woo, Sun-Hee Liao, Ronglih Hajjar, Roger J. Park, Woo Jin TI PICOT inhibits cardiac hypertrophy and enhances ventricular function and cardiomyocyte contractility SO CIRCULATION RESEARCH LA English DT Article DE cardiac hypertrophy; protein kinase C; PICOT; contractility ID CONGESTIVE-HEART-FAILURE; KINASE-C-EPSILON; INTERACTING PROTEIN; SIGNALING PATHWAYS; PRESSURE-OVERLOAD; RAT-HEART; IN-VIVO; THIOREDOXIN; MICE; EXPRESSION AB Multiple signaling pathways involving protein kinase C (PKC) have been implicated in the development of cardiac hypertrophy. We observed that a putative PKC inhibitor, PICOT ((P) under bar KC-(I) under bar nteracting (C) under bar ousin (O) under barf (T) under bar hioredoxin) was upregulated in response to hypertrophic stimuli both in vitro and in vivo. This suggested that PICOT may act as an endogenous negative feedback regulator of cardiac hypertrophy through its ability to inhibit PKC activity, which is elevated during cardiac hypertrophy. Adenovirus-mediated gene transfer of PICOT completely blocked the hypertrophic response of neonatal rat cardiomyocytes to enthothelin-1 and phenylephrine, as demonstrated by cell size, sarcomere rearrangement, atrial natriuretic factor expression, and rates of protein synthesis. Transgenic mice with cardiac-specific overexpression of PICOT showed that PICOT is a potent inhibitor of cardiac hypertrophy induced by pressure overload. In addition, PICOT overexpression dramatically increased the ventricular function and cardiomyocyte contractility as measured by ejection fraction and end-systolic pressure of transgenic hearts and peak shortening of isolated cardiomyocytes, respectively. Intracellular Ca2+ handing analysis revealed that increases in myofilament Ca2+ responsiveness, together with increased rate of sarcoplasmic reticulum Ca2+ reuptake, are associated with the enhanced contractility in PICOT-overexpressing cardiomyocytes. The inhibition of cardiac remodeling by of PICOT with a concomitant increase in ventricular function and cardiomyocyte contractility suggests that PICOT may provide an efficient modality for treatment of cardiac hypertrophy and heart failure. C1 Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. Gwangju Inst Sci & Technol, Global Res Lab Cardiovasc Gene Therapy, Kwangju 500712, South Korea. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Chungnam Natl Univ, Coll Pharm, Taejon, South Korea. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Chonbuk Natl Univ, Sch Dent, Dept Oral Anat, Jeonju, South Korea. RP Park, WJ (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, 1 Oryong Dong, Kwangju 500712, South Korea. EM wjpark@gist.ac.kr FU NHLBI NIH HHS [HL-080498-01] NR 37 TC 49 Z9 55 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG 4 PY 2006 VL 99 IS 3 BP 307 EP 314 DI 10.1161/01.RES.0000234780.06115.2c PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 070DT UT WOS:000239501200015 PM 16809552 ER PT J AU Rottbauer, W Wessels, G Dahme, T Just, S Trano, N Hassel, D Burns, CG Katus, HA Fishman, MC AF Rottbauer, Wolfgang Wessels, Georgia Dahme, Tillman Just, Steffen Trano, Nicole Hassel, David Burns, Charles Geoffrey Katus, Hugo A. Fishman, Mark C. TI Cardiac myosin light chain-2 - A novel essential component of thick- myofilament assembly and contractility of the heart SO CIRCULATION RESEARCH LA English DT Article DE cardiac myosin light chain-2; myofibrillogenesis; zebrafish heart ID MYOSIN LIGHT CHAIN-2; EMBRYONIC HEART; TRANSCRIPTIONAL REGULATION; DANIO-RERIO; ZEBRAFISH; EXPRESSION; MUTATION; MUSCLE; GROWTH; CARDIOMYOPATHY AB Although it is well known that mutations in the cardiac regulatory myosin light chain-2 (mlc-2) gene cause hypertrophic cardiomyopathy, the precise in vivo structural and functional roles of MLC-2 in the heart are only poorly understood. We have isolated a mutation in zebrafish, tell tale heart (tel(m225)), which selectively perturbs contractility of the embryonic heart. By positional cloning, we identified tel to encode the zebrafish mlc-2 gene. In contrast to mammals, zebrafish have only 1 cardiac-specific mlc-2 gene, which we find to be expressed in atrial and ventricular cardiomyocytes during early embryonic development, but also in the adult heart. Accordingly, loss of zMLC-2 function cannot be compensated for by upregulation of another mlc-2 gene. Surprisingly, ultrastructural analysis of tel cardiomyocytes reveals complete absence of organized thick myofilaments. Thus, our findings provide the first in vivo evidence that cardiac MLC-2 is required for thick-filament stabilization and contractility in the vertebrate heart. C1 Univ Heidelberg, Dept Med 3, D-69120 Heidelberg, Germany. Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Novartis Inst Biomed Res, Cambridge, MA USA. RP Rottbauer, W (reprint author), Univ Heidelberg, Dept Med 3, INF 410, D-69120 Heidelberg, Germany. EM wolfgang.rottbauer@med.uni-heidelberg.de RI Katus, Hugo/P-1712-2016 FU NHLBI NIH HHS [1R01HL63206, 5R01HL49579]; NIA NIH HHS [K01 AG023562]; NIDDK NIH HHS [5R01DK55383] NR 31 TC 80 Z9 81 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG 4 PY 2006 VL 99 IS 3 BP 323 EP 331 DI 10.1161/01.RES.0000234807.16034.fe PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 070DT UT WOS:000239501200017 PM 16809551 ER PT J AU Qin, WP Yang, TL Ho, L Zhao, Z Wang, J Chen, LH Zhao, W Thiyagarajan, M MacGrogan, D Rodgers, JT Puigserver, P Sadoshima, J Deng, HT Pedrini, S Gandy, S Sauve, AA Pasinetti, GM AF Qin, Weiping Yang, Tianle Ho, Lap Zhao, Zhong Wang, Jun Chen, Linghong Zhao, Wei Thiyagarajan, Meenakshisundaram MacGrogan, Donal Rodgers, Joseph T. Puigserver, Pere Sadoshima, Junichi Deng, Haiteng Pedrini, Steven Gandy, Samuel Sauve, Anthony A. Pasinetti, Giulio M. TI Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT HISTONE DEACETYLASE; TRANSGENIC MICE; PROTEIN; FAMILY; LONGEVITY; NICOTINAMIDE; INHIBITION; REGULATOR AB Nicotinamide adenine dinucleotide(NAD)(+)-dependent sirtuins have been identified to be key regulators in the lifespan extending effects of calorie restriction (CR) in a number of species. In this study we report for the first time that promotion of the NAD(+)-dependent sirtuin, SIRT1-mediated deacetylase activity, may be a mechanism by which CR influences Alzheimer disease (AD)-type amyloid neuropathology. Most importantly, were port that the predicted attenuation of beta-amyloid content in the brain during CR can be reproduced in mouse neurons in vitro by manipulating cellular SIRT1 expression/activity through mechanisms involving the regulation of the serine/threonine Rho kinase ROCK1, known in part for its role in the inhibition of the non-amyloidogenic alpha-secretase processing of the amyloid precursor protein. Conversely, we found that the expression of constitutively active ROCK1 in vitro cultures significantly prevented SIRT1-mediated response, suggesting that alpha-secretase activity is required for SIRT1-mediated prevention of AD-type amyloid neuropathology. Consistently we found that the expression of exogenous human ( h) SIRT1 in the brain of hSIRT1 transgenics also resulted in decreased ROCK1 expression and elevated alpha-secretase activity in vivo. These results demonstrate for the first time a role for SIRT1 activation in the brain as a novel mechanism through which CR may influence AD amyloid neuropathology. The study provides a potentially novel pharmacological strategy for AD prevention and/or treatment. C1 Cornell Univ, Weill Med Coll, Dept Pharmacol, Tri Inst Program Chem Biol, New York, NY 10021 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Geriatr Res & Clin Ctr, Bronx, NY 10468 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Cardiovasc Res Inst, Newark, NJ 07103 USA. Rockefeller Univ, Proteom Resource Ctr, New York, NY 10021 USA. Thomas Jefferson Univ, Farber Inst Neurosci, Philadelphia, PA 19107 USA. RP Pasinetti, GM (reprint author), Cornell Univ, Weill Med Coll, Dept Pharmacol, Tri Inst Program Chem Biol, New York, NY 10021 USA. EM as2004@med.cornell.edu; giulio.pasinetti@mssm.edu RI Zhao, Wei/B-3220-2010; Zhao, Wei/A-2206-2010 FU NIA NIH HHS [P01 AG010491-14, P01 AG010491] NR 31 TC 329 Z9 339 U1 3 U2 28 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 4 PY 2006 VL 281 IS 31 BP 21745 EP 21754 DI 10.1074/jbc.M602909200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 068PO UT WOS:000239387100020 PM 16751189 ER PT J AU Hung, KE Kho, AT Sarracino, D Richard, LG Krastins, B Forrester, S Haab, BB Kohane, IS Kucherlapati, R AF Hung, Kenneth E. Kho, Alvin T. Sarracino, David Richard, Larissa Georgeon Krastins, Bryan Forrester, Sara Haab, Brian B. Kohane, Isaac S. Kucherlapati, Raju TI Mass spectrometry-based study of the plasma proteome in a mouse intestinal tumor model SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE colon cancer; mouse; plasma biomarker; proteomics; mass spectrometry ID ROLLING-CIRCLE AMPLIFICATION; COLORECTAL-CANCER; GENE-EXPRESSION; PLASMINOGEN-ACTIVATOR; PROSTATE-CANCER; IDENTIFICATION TECHNOLOGY; OVARIAN-CANCER; STROMAL CELLS; COLON-CANCER; IN-VITRO AB Early detection of cancer can greatly improve prognosis. Identification of proteins or peptides in the circulation, at different stages of cancer, would greatly enhance treatment decisions. Mass spectrometry ( MS) is emerging as a powerful tool to identify proteins from complex mixtures such as plasma that may help identify novel sets of markers that may be associated with the presence of tumors. To examine this feature we have used a genetically modified mouse model, Apc(Min), which develops intestinal tumors with 100% penetrance. Utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified total plasma proteome (TPP) and plasma glycoproteome (PGP) profiles in tumor-bearing mice. Principal component analysis (PCA) and agglomerative hierarchial clustering analysis revealed that these protein profiles can be used to distinguish between tumor-bearing ApcMin and wild-type control mice. Leave-one-out cross-validation analysis established that global TPP and global PGP profiles can be used to correctly predict tumor-bearing animals in 17/19 (89%) and 19/19 (100%) of cases, respectively. Furthermore, leave-one-out cross-validation analysis confirmed that the significant differentially expressed proteins from both the TPP and the PGP were able to correctly predict tumor-bearing animals in 19/19 (100%) of cases. A subset of these proteins was independently validated by antibody microarrays using detection by two color rolling circle amplification (TC-RCA). Analysis of the significant differentially expressed proteins indicated that some might derive from the stroma or the host response. These studies suggest that mass spectrometry-based approaches to examine the plasma proteome may prove to be a valuable method for determining the presence of intestinal tumors. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA 02115 USA. Van Andel Res Inst, Grand Rapids, MI 49503 USA. RP Kucherlapati, R (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM rkucherlapati@partners.org RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NCI NIH HHS [CA 084301, F012596]; NIDDK NIH HHS [K08 DK078033]; NIEHS NIH HHS [ES 11040]; NINDS NIH HHS [P01 NS40828, R01 NS047527, R21 NS052498]; PHS HHS [2596] NR 65 TC 29 Z9 30 U1 1 U2 5 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 AUG 4 PY 2006 VL 5 IS 8 BP 1866 EP 1878 DI 10.1021/pr060120r PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 070AW UT WOS:000239493700006 PM 16889408 ER PT J AU Wang, X Zou, L Lu, T Bao, S Hurov, KE Hittelman, WN Elledge, SJ Li, L AF Wang, Xin Zou, Lee Lu, Tao Bao, Shilai Hurov, Kristen E. Hittelman, Walter N. Elledge, Stephen J. Li, Lei TI Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress SO MOLECULAR CELL LA English DT Article ID DNA-DAMAGE CHECKPOINT; CELL-CYCLE; GENOMIC INSTABILITY; GENOTOXIC STRESS; ATR; COMPLEXES; CHROMATIN; PROTEINS; BINDING; CANCER AB The ATR-mediated checkpoint is not only critical for responding to genotoxic stress but also essential for cell proliferation. The RFC-related checkpoint protein Rad17, a phosphorylation substrate of ATR, is critical for ATR-mediated checkpoint signaling and cell survival. Here, we show that phosphorylation of Rad17 by ATR is important for genomic stability and restraint of S phase but is not essential for cell survival. The phosphomutant Rad17AA exhibits distinct defects in hydroxyurea- (HU) and ultraviolet-(UV) induced Chk1 activation, indicating that separate Rad17 functions are required differently in response to different types of replication interference. Although cells expressing Rad17AA can initiate Chk1 phosphorylation after HU treatment, they fail to sustain Chk1 phosphorylation after withdrawal of HU and are profoundly sensitive to HU. Importantly, we found that phosphorylated Rad17 interacts with Claspin and regulates its phosphorylation. These findings reveal a phosphorylation-dependent function of Rad17 in an ATR-Rad17-Claspin-Chk1 -signaling cascade that responds to specific replication stress. C1 Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Canc Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Dept Genet, Boston, MA 02115 USA. RP Elledge, SJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM selledge@genetics.med.harvard.edu; leili@mdanderson.org FU NCI NIH HHS [CA76172]; NIGMS NIH HHS [GM44664] NR 29 TC 77 Z9 78 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG 4 PY 2006 VL 23 IS 3 BP 331 EP 341 DI 10.1016/j.molcel.2006.06.022 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 074IK UT WOS:000239805700005 PM 16885023 ER PT J AU Ellinor, PT Petrov-Kondratov, VI Zakharova, E Nam, EG MacRae, CA AF Ellinor, Patrick T. Petrov-Kondratov, Vadim I. Zakharova, Elena Nam, Edwin G. MacRae, Calum A. TI Potassium channel gene mutations rarely cause atrial fibrillation SO BMC MEDICAL GENETICS LA English DT Article ID OF-FUNCTION MUTATION; LONG-QT SYNDROME; KCNQ1; LOCUS; IDENTIFICATION; POLYMORPHISMS; KCNE1; DEATH; RISK AB Background: Mutations in several potassium channel subunits have been associated with rare forms of atrial fibrillation. In order to explore the role of potassium channels in inherited typical forms of the arrhythmia, we have screened a cohort of patients from a referral clinic for mutations in the channel subunit genes implicated in the arrhythmia. We sought to determine if mutations in KCNJ2 and KCNE1-5 are a common cause of atrial fibrillation. Methods: Serial patients with lone atrial fibrillation or atrial fibrillation with hypertension were enrolled between June 1, 2001 and January 6, 2005. Each patient underwent a standardized interview and physical examination. An electrocardiogram, echocardiogram and blood sample for genetic analysis were also obtained. Patients with a family history of AF were screened for mutations in KCNJ2 and KCNE1-5 using automated sequencing. Results: 96 patients with familial atrial fibrillation were enrolled. Eighty-three patients had lone atrial fibrillation and 13 had atrial fibrillation and hypertension. Patients had a mean age of 56 years at enrollment and 46 years at onset of atrial fibrillation. Eighty-one percent of patients had paroxysmal atrial fibrillation at enrollment. Unlike patients with an activating mutation in KCNQ1, the patients had a normal QT(c) interval with a mean of 412 +/- 42 ms. Echocardiography revealed a normal mean ejection fraction of 62.0 +/- 7.2 % and mean left atrial dimension of 39.9 +/- 7.0 mm. A number of common polymorphisms in KCNJ2 and KCNE1-5 were identified, but no mutations were detected. Conclusion: Mutations in KCNJ2 and KCNE1-5 rarely cause typical atrial fibrillation in a referral clinic population. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM pellinor@partners.org; vadimpetrov@comcast.net; ezakharova@partners.org; enam@partners.org; cmacrae@partners.org FU NHLBI NIH HHS [K23 HL071632, R01 HL075431, HL75431, HL71632] NR 21 TC 43 Z9 44 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD AUG 3 PY 2006 VL 7 AR 70 DI 10.1186/1471-2350-7-70 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 083JI UT WOS:000240451800002 PM 16887036 ER PT J AU McEwen, JM Madison, JM Dybbs, M Kaplan, JM AF McEwen, Jason M. Madison, Jon M. Dybbs, Michael Kaplan, Joshua M. TI Antagonistic regulation of synaptic vesicle priming by tomosyn and UNC-13 SO NEURON LA English DT Article ID GLR-1 GLUTAMATE RECEPTORS; C-ELEGANS; CAENORHABDITIS-ELEGANS; TRANSMITTER RELEASE; DROSOPHILA UNC-13; AXONAL-TRANSPORT; EXOCYTOSIS; SYNTAXIN; PROTEIN; FUSION AB Priming of synaptic vesicles (SVs) is essential for synaptic transmission. UNC-13 proteins are required for priming. Current models propose that UNC-13 stabilizes the open conformation of Syntaxin, in which the SNARE helix is available for interactions with Synaptobrevin and SNAP-25. Here we show that Tomosyn inhibits SV priming. Tomosyn contains a SNARE motif, which forms an inhibitory SNARE complex with Syntaxin and SNAP-25. Mutants lacking Tomosyn have increased synaptic transmission, an increased pool of primed vesicles, and increased abundance of UNC-13 at synapses. Behavioral, imaging, and electrophysiological studies suggest that SV priming was reconstituted in unc-13 mutants by expressing a constitutively open mutant Syntaxin, or by mutations eliminating Tomosyn. Thus, priming is modulated by the balance between Tomosyn and UNC-13, perhaps by regulating the availability of open-Syntaxin. Even when priming was restored, synaptic transmission remained defective in unc-13 mutants, suggesting that UNC-13 is also required for other aspects of secretion. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg,7th Floor,185 Cambridge St, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU NIGMS NIH HHS [GM54728]; NINDS NIH HHS [1F32NS10310] NR 43 TC 71 Z9 84 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD AUG 3 PY 2006 VL 51 IS 3 BP 303 EP 315 DI 10.1016/j.neuron.2006.06.025 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 075TT UT WOS:000239908800006 PM 16880125 ER PT J AU Goldsmith, KC Liu, X Dam, V Morgan, BT Shabbout, M Cnaan, A Letai, A Korsmeyer, SJ Hogarty, MD AF Goldsmith, K. C. Liu, X. Dam, V. Morgan, B. T. Shabbout, M. Cnaan, A. Letai, A. Korsmeyer, S. J. Hogarty, M. D. TI BH3 peptidomimetics potently activate apoptosis and demonstrate single agent efficacy in neuroblastoma SO ONCOGENE LA English DT Article DE apoptosis; neuroblastoma; Bcl-2 homologues; programmed cell death; MYCN ID HUMAN NEURO-BLASTOMA; CELL-LINES; CANCER-CELLS; IN-VIVO; P53; PROTEINS; DOMAINS; TUMOR; RESISTANCE; MUTATIONS AB The major impediment to cure for many malignancies is the development of therapy resistance with resultant tumor progression. Genetic alterations leading to subversion of inherent apoptosis pathways are common themes in therapy resistance. Bcl-2 family proteins play a critical role in regulating mitochondrial apoptosis that governs chemotherapeutic effects, and defective engagement of these pathways contributes to treatment failure. We have studied the efficacy of BH3 peptidomimetics consisting of the minimal death, or BH3, domains of the proapoptotic BH3-only proteins Bid and Bad to induce apoptosis using neuroblastoma (NB) as a model system. We demonstrate that BH3 peptides, modified with an arginine homopolymer for membrane transduction (called r8-BidBH3 and r8-BadBH3, respectively), potently induce apoptosis in NB cells, including those with MYCN amplification. Cell death is caspase 9 dependent, consistent with a requirement for the intrinsic mitochondrial pathway. Substitutions at highly conserved residues within the r8-BidBH3 peptide abolish apoptotic efficacy supporting activity through specific BH domain interactions. Concomitant exposure to r8-BadBH3 and r8-BidBH3 at sublethal monotherapy doses revealed potent synergy consistent with a competitive displacement model, whereby BH3 peptides displace sequestered BH3 proteins to induce cell death. Further, BH3 peptides demonstrate antitumor efficacy in a xenograft model of NB in the absence of additional genotoxic or trophic stressors. These data provide proof of principle that targeted re-engagement of apoptosis pathways may be of therapeutic utility, and BH3-like compounds are attractive lead agents to re-establish therapy-induced apoptosis in refractory malignancies. C1 Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Hogarty, MD (reprint author), Childrens Hosp Philadelphia, Div Oncol, 9 N ARC,Suite 902C,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM hogartym@email.chop.edu FU NCI NIH HHS [CA97323] NR 39 TC 37 Z9 37 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 3 PY 2006 VL 25 IS 33 BP 4525 EP 4533 DI 10.1038/sj.onc.1209489 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 069OG UT WOS:000239457500003 PM 16568093 ER PT J AU Hur, C Wittenberg, E Nishioka, NS Gazelle, GS AF Hur, Chin Wittenberg, Eve Nishioka, Norman S. Gazelle, G. Scott TI Quality of life in patients with various Barrett's esophagus associated health states SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article ID HIGH-GRADE DYSPLASIA; PAPER STANDARD GAMBLE; GASTROESOPHAGEAL-REFLUX; PHOTODYNAMIC THERAPY; COST-EFFECTIVENESS; LASER-ABLATION; FOLLOW-UP; ESOPHAGECTOMY; MANAGEMENT; SURVEILLANCE AB Background: The management of Barrett's esophagus ( BE), particularly high grade dysplasia (HGD), is an area of much debate and controversy. Surgical esophagectomy, intensive endoscopic surveillance and mucosal ablative techniques, especially photodynamic therapy (PDT), have been proposed as possible management strategies. The purpose of this study was to determine the health related quality of life associated with Barrett's esophagus and many of the pivotal health states associated with Barrett's HGD management. Methods: 20 patients with Barrett's esophagus were enrolled in a pilot survey study at a large urban hospital. The utility of Barrett's esophagus without dysplasia ( current health state) as well as various health states associated with HGD management ( hypothetical states as the subject did not have HGD) were measured using a validated health utility instrument ( Paper Standard Gamble). These specific health states were chosen for the study because they are considered pivotal in Barrett's HGD decision making. Information regarding Barrett's HGD was presented to the subject in a standardized format that was designed to be easily comprehendible. Results: The average utility scores ( 0 - 1 with 0 = death and 1 = perfect health) for the various Barrett's esophagus associated states were: BE without dysplasia- 0.95; Post-esophagectomy for HGD with dysphagia-0.92; Post-PDT for HGD with recurrence uncertainty-0.93; Post-PDT for HGD with recurrence uncertainty and dysphagia-0.91; Intensive endoscopic surveillance for HGD-0.90. Conclusion: We present the scores for utilities associated with Barrett's esophagus as well as various states associated with the management of HGD. The results of our study may be useful in advising patients and providers regarding expected outcomes of the various HGD management strategies as well as providing utility scores for future cost-effectiveness analyses. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management GSG, Boston, MA 02115 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM chur@mgh-ita.org; eve@mgh-ita.org; nnishioka@partners.org; scott@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 FU NCI NIH HHS [1K07 CA107060, K07 CA107060] NR 34 TC 10 Z9 10 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD AUG 2 PY 2006 VL 4 AR 45 DI 10.1186/1477-7525-4-45 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 091MU UT WOS:000241033800001 PM 16884539 ER PT J AU Vasterling, JJ Proctor, SP Amoroso, P Kane, R Heeren, T White, RF AF Vasterling, Jennifer J. Proctor, Susan P. Amoroso, Paul Kane, Robert Heeren, Timothy White, Roberta F. TI Neuropsychological outcomes of army personnel following deployment to the Iraq War SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TRAUMATIC BRAIN-INJURY; MENTAL-HEALTH PROBLEMS; PERSIAN-GULF-WAR; DEPRESSION; IMPAIRMENT; VETERANS; STRESS; MEMORY; AFGHANISTAN; EMPLOYMENT AB Context The effects of war-zone deployment on neuropsychological health remain poorly understood. Neuropsychological performance deficits serve as sensitive measures of neural dysfunction and are often associated with psychosocial and occupational problems. Previous studies have not conducted objective neuropsychological assessments both before and after a major war-zone deployment. \ Objective To examine objective neuropsychological outcomes of Iraq War deployment in a large military cohort. Design, Setting, and Participants The Neurocognition Deployment Health Study, a prospective, cohort-controlled study conducted at military installations. This report centers on 961 male and female active-duty Army soldiers drawn from the larger cohort. Deploying Army soldiers (n = 654) were examined prior to deployment to Iraq (April-December 2003) and shortly after return (within a mean of 73 days [median, 75 days]; January-May 2005) from Iraq deployment. A comparison group of soldiers (n=307) similar in military characteristics but not deploying overseas during the study was assessed in sessions timed to be as close as possible to the assessment of deployers. Military unit sampling procedures facilitated representation of combat, combat support, and combat service support functions among both deployers and nondeployers. Main Outcome Measures Individually administered, performance-based neuropsychological tasks. Estimates (P; the unstandardized parameter estimate) for the absolute differences in adjusted mean outcome scores between deployed and nondeployed groups were determined using generalized estimating equations. Results Multiple linear regression analyses adjusted for battalion membership revealed that Iraq deployment, compared with nondeployment, was associated with neuropsychological compromise on tasks of sustained attention (beta =0.11; P<.001), verbal learning (beta =-1.51; P=.003), and visual-spatial memory (beta=-3.82; P<.001). Iraq deployment was also associated with increased negative state affect on measures of confusion (beta = 1.40; P<.001) and tension (beta= 1.24; P<.001). In contrast, deployment was associated with improved simple reaction time (beta=4.30; P=.003). Deployment effects remained statistically significant after taking into account deployment-related head injury and stress and depression symptoms. Conclusions Deployment to Iraq is associated with increased risk of neuropsychological compromise. Findings point to the need to investigate further the impact of deployment on neural functioning. Public health implications include consideration of neuropsychological compromise in health prevention and postdeployment clinical and occupational management. C1 SE Louisiana Vet Hlth Care Syst, Res Serv COSF, New Orleans, LA 70112 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. USA, Environm Med Res Inst, Natick, MA 01760 USA. Madigan Army Med Ctr, Ft Lewis, WA USA. VA Maryland Hlth Care Syst, Baltimore, MD USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Vasterling, JJ (reprint author), SE Louisiana Vet Hlth Care Syst, Res Serv COSF, 1601 Perdido St, New Orleans, LA 70112 USA. EM jvaster@tulane.edu NR 48 TC 210 Z9 211 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 2 PY 2006 VL 296 IS 5 BP 519 EP 529 DI 10.1001/jama.296.5.519 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 069YW UT WOS:000239486900016 PM 16882958 ER PT J AU Pines, JM Hollander, JE Localio, AR Metlay, JP AF Pines, Jesse M. Hollander, Judd E. Localio, A. Russell Metlay, Joshua P. TI The association between emergency department crowding and hospital performance on antibiotic timing for pneumonia and percutaneous intervention for myocardial infarction SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE pneumonia; emergency department crowding; acute myocardial infarction; quality; timing ID OUTCOMES; QUALITY; CARE AB Background: Antibiotics within four hours of arrival for patients with pneumonia and percutaneous intervention (PCI) within two hours for patients with acute myocardial infarction (AMI) are standard measures of emergency department (ED) quality. Objectives: To assess the institutional-level association between measures of ED crowding and process measures for pneumonia and AMI. Methods: The authors used summary data from 24 academic hospitals in the University Health Consortium. Analysis included the 2004 ED cycle time survey and performance data from January to December 2004 regarding the Joint Commission for Accreditation of Healthcare Organizations' PN-5b (initial antibiotic administration within four hours) for pneumonia and AMI-8a (PCI received within 120 minutes). Spearman correlation coefficients were used to determine associations between crowding and performance measures. Results: Across all institutions, 59% (range 43%-77%) of pneumonia patients received antibiotics within four hours, and 57% (range 22%-95%) of AMI patients received PCI within two hours. An increase in overall ED length of stay (-0.44, p = 0.04) and for admitted patients (-0.37, p = 0.08) was associated with a decrease in the proportion of pneumonia patients receiving antibiotics within four hours. An increase in chest x-ray turnaround time (-0.83, p < 0.001) and an increase in the left-without-being-seen rate (-0.51, p = 0.01) were also associated with a decrease in the proportion of pneumonia patients receiving antibiotics within four hours. No measures of crowding exhibited an association with time to PCI for AMI patients. Conclusions: Administrative measures of ED crowding showed an association with poorer performance on pneumonia quality of care measures but not with AMI quality of care measures. Hospitals might consider improving ED throughput, reducing boarding times for admitted patients, and reducing chest x-ray turnaround times to improve pneumonia care. C1 Hosp Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Pines, JM (reprint author), 3400 Spruce St,Ground Ravdin, Philadelphia, PA 19104 USA. EM pinesjes@uphs.upenn.edu OI Hollander, Judd/0000-0002-1318-2785 NR 21 TC 120 Z9 121 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD AUG PY 2006 VL 13 IS 8 BP 873 EP 878 DI 10.1197/j.aem.2006.03.568 PG 6 WC Emergency Medicine SC Emergency Medicine GA 118UK UT WOS:000242967300010 PM 16766743 ER PT J AU Demissie, S Levy, D Benjamin, EJ Cupples, LA Gardner, JP Herbert, A Kimura, M Larson, MG Meigs, JB Keaney, JF Aviv, A AF Demissie, S. Levy, D. Benjamin, E. J. Cupples, L. A. Gardner, J. P. Herbert, A. Kimura, M. Larson, M. G. Meigs, J. B. Keaney, J. F. Aviv, A. TI Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study SO AGING CELL LA English DT Article DE accelerated aging; disease; insulin/IGF-1 signalling; life span; oxidative stress; telomeres ID HOMEOSTASIS MODEL ASSESSMENT; CARDIOVASCULAR-DISEASE; GLUCOSE-TOLERANCE; HUMAN FIBROBLASTS; PULSE PRESSURE; BLOOD-PRESSURE; INFLAMMATION; ATHEROSCLEROSIS; ASSOCIATION; SENSITIVITY AB Insulin resistance and oxidative stress are associated with accelerated telomere attrition in leukocytes. Both are also implicated in the biology of aging and in aging-related disorders, including hypertension. We explored the relations of leukocyte telomere length, expressed by terminal restriction fragment (TRF) length, with insulin resistance, oxidative stress and hypertension. We measured leukocyte TRF length in 327 Caucasian men with a mean age of 62.2 years (range 40-89 years) from the Offspring cohort of the Framingham Heart Study. TRF length was inversely correlated with age (r = -0.41, P < 0.0001) and age-adjusted TRF length was inversely correlated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r = -0.16, P = 0.007) and urinary 8-epi-PGF(2 alpha) (r = -0.16, P = 0.005) - an index of systemic oxidative stress. Compared with their normotensive peers, hypertensive subjects exhibited shorter age-adjusted TRF length (hypertensives = 5.93 +/- 0.042 kb, normotensives = 6.07 +/- 0.040 kb, P = 0.025). Collectively, these observations suggest that hypertension, increased insulin resistance and oxidative stress are associated with shorter leukocyte telomere length and that shorter leukocyte telomere length in hypertensives is largely due to insulin resistance. C1 Univ Med & Dent New Jersey, Ctr Human Dev & Aging, MSB, Newark, NJ 07103 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. Evans Mem Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Aviv, A (reprint author), Univ Med & Dent New Jersey, Ctr Human Dev & Aging, MSB, Room F-464,185 S Orange Ave, Newark, NJ 07103 USA. EM avivab@umdnj.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01 HL64753, N01-HC 25195, R01 HL076784]; NIA NIH HHS [AG021593] NR 37 TC 247 Z9 261 U1 0 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD AUG PY 2006 VL 5 IS 4 BP 325 EP 330 DI 10.1111/j.1474-9726.2006.00224.x PG 6 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 064WP UT WOS:000239121100006 PM 16913878 ER PT J AU Kemppainen, JK Eller, LS Bunch, E Hamilton, MJ Dole, P Holzemer, W Kirksey, K Nicholas, PK Corless, IB Coleman, C Nokes, KM Reynolds, N Sefcik, L Wantland, D Tsai, YF AF Kemppainen, J. K. Eller, L. S. Bunch, E. Hamilton, M. J. Dole, P. Holzemer, W. Kirksey, K. Nicholas, P. K. Corless, I. B. Coleman, C. Nokes, K. M. Reynolds, N. Sefcik, L. Wantland, D. Tsai, Y-F TI Strategies for self-management of HIV-related anxiety SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; PSYCHIATRIC-DISORDERS; INFECTED ADULTS; NATIONAL SAMPLE; DRUG-USE; PREVALENCE; WOMEN; CARE; MEN AB This study examines the frequency and effectiveness of commonly used strategies for self management of anxiety in an international sample of 502 participants from Norway (n = 42, 8%), Taiwan ( n = 35, 7%), and the US (n = 426, 85%). An activities checklist summarized into five categories of self-care behaviours including activities/thoughts, exercise, medications, complementary therapies, and substance use determined self-care behaviours. Ratings of frequency and effectiveness for each self-care activity were also included. Praying received the highest overall rating of effectiveness of any self-management strategies included in this study at 8.10 ( scale 1 to 10), followed by meditation (7.37), exercising (7.32), using relaxation techniques (7.22), cooking (6.98), and walking (6.90). An analysis of effectiveness scores for each self-care strategy by country reflected a wide variation. The three most effective anxiety self-care strategies reported by participants from Norway included exercise (7.31), walking (6.96), and reading (6.44). Highest ratings of effectiveness by participants from Taiwan included talking with others with HIV (6.0), attending support groups ( 6.0), and exercising ( 6.0). US participants allocated highest ratings of effectiveness to complementary/alternative therapies, including praying ( 8.10), meditating ( 7.43), and using relaxation techniques (7.35). Regardless of the country, watching television and talking with family and friends were the two most frequently reported strategies. These strategies for self-management of HIV-related anxiety are important for clinicians to be aware of in the care of persons with HIV/AIDS. C1 Univ N Carolina, Wilmington, NC 28401 USA. Rutgers State Univ, Coll Nursing, Piscataway, NJ 08855 USA. Univ Oslo, N-0316 Oslo, Norway. Texas A&M Univ, Corpus Christi, TX USA. St Vincents Hosp & Med Ctr, New York, NY 10011 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Harris Cty Hosp, Houston, TX USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. CUNY Hunter Coll, New York, NY 10021 USA. Ohio State Univ, Columbus, OH 43210 USA. Chang Gung Univ, Taoyuan, Taiwan. RP Kemppainen, JK (reprint author), 1080 St Joseph,Apt 3B, Carolina Beach, NC 28428 USA. EM kemppainenj@uncw.edu OI Corless, Inge/0000-0003-0438-2037 NR 29 TC 20 Z9 22 U1 4 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD AUG PY 2006 VL 18 IS 6 BP 597 EP 607 DI 10.1080/09540120500275726 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 062WR UT WOS:000238977300011 PM 16831788 ER PT J AU Safren, SA Martin, C Menon, S Greer, J Solomon, S Mimiaga, MJ Mayer, KH AF Safren, Steven A. Martin, Clifford Menon, Sunil Greer, Joseph Solomon, Suniti Mimiaga, Matthew J. Mayer, Kenneth H. TI A survey of MSM HIV prevention outreach workers in Chennai, India SO AIDS EDUCATION AND PREVENTION LA English DT Article ID MEN; SEX; RISK AB The present formative study sought to describe issues relevant to HIV prevention among men who have sex with men (MSM) in South India by surveying 62 MSM outreach workers from three nongovernmental organizations in Chennai. Although 92% reported having sex with men, only 74% identified as gay and 27% were married. Only half of these men reported having been tested for HIV. More than half of the sample reported that they would rather not know they had HIV until they were sick, and almost half indicated that they would rather end their life than live with the disease. Eighty-five percent of the sample reported having experienced varying levels of harassment from police, and 86% reported varying levels of harassment from others. These data point to several important barriers to HIV prevention among MSM in South India and lay the groundwork for enhancing the use of outreach workers to play a role in HIV prevention in this population. C1 Brown Univ, Miriam Hosp, Sch Med, Providence, RI 02906 USA. Brown Univ, Fenway Community Hlth, Res & Evaluat Dept, Providence, RI 02906 USA. Brown Univ, Fenway Community Hlth, Res & Evaluat Dept, Providence, RI 02906 USA. Fenway Community Hlth, Res & Evaluat Dept, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NYU, Sch Med, New York, NY 10012 USA. Sahodaran, Madras, Tamil Nadu, India. YR Gaitonete Ctr AIDS Res & Educ, Madras, Tamil Nadu, India. Harvard Univ, Sch Publ Hlth, Res & Evaluat Dept, Cambridge, MA 02138 USA. RP Mayer, KH (reprint author), Brown Univ, Miriam Hosp, Sch Med, 164 Summit Ave, Providence, RI 02906 USA. EM Kenneth_Mayer@brown.edu FU NIAID NIH HHS [AI48040-03, U01 AI048040] NR 16 TC 29 Z9 30 U1 1 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD AUG PY 2006 VL 18 IS 4 BP 323 EP 332 DI 10.1521/aeap.2006.18.4.323 PG 10 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 077FH UT WOS:000240013000004 PM 16961449 ER PT J AU Wang, SY Zhuang, Y Zhai, S Zhao, SG Kang, WZ Li, XH Yu, XG Walker, BD Altfeldi, MA Sun, YT AF Wang, Shaoyang Zhuang, Yan Zhai, Song Zhao, Shuguang Kang, Whenzhen Li, Xinhong Yu, Xu G. Walker, Bruce D. Altfeldi, Marcus A. Sun, Yongtao TI Association between HIV type 1-specific T cell responses and CD4(+) T cell counts or CD4(+): CD8(+) T cell ratios in HIV type 1 subtype B infection in China SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; HIV-1-INFECTED INDIVIDUALS; LYMPHOCYTE RECOGNITION; PERIPHERAL-BLOOD; VACCINE DESIGN; NEF PROTEIN; VIRAL LOAD; VIREMIA; TAT AB CD4(+) T cell counts and CD4(+):CD8(+) T cell ratios represent key determinants of HIV disease progression and infectivity. However, the relationship between the HIV-1-specific cytotoxic T lymphocyte (CTL) response and these determinants has not been elucidated for all HIV-1B and HIV-1C proteins. In the present study, virus-specific T cell responses to HIV-1B and HIV-1C proteins were analyzed with interferon gamma (IFN-gamma) enzyme-linked immunospot (ELISpot) assays using synthetic overlapping peptides corresponding to naturally occurring HIV-1B and HIV-1C consensus sequences. For Gag/Gag p24/Gag p17, a correlation between T cell responses and CD4(+) T cell count in HIV-1 clade B and clade C was seen: elevated T cell response resulted in higher CD4(+) T cell production. A statistically significant correlation between the Pol-specific T cell response and CD4(+) T cell counts was also found in HIV-1 subtype C. For all HIV-1B and HIV-1C proteins, a correlation between the HIV-1-specific T cell response and CD4(+):CD8(+) T cell ratios was found for Tat and Pol proteins. CD4(+) T cell counts in patients with Tat and/or Rev T cell response were higher than in patients without Tat and/or Rev T cell response. We suggest that this correlation within HIV-1B and HIV-1C Gag p24/Gag p17 responses makes the Gag p24/Gag p17 region a potential vaccine candidate and that HIV-1-specific CTL epitopes toward Pol are important in controlling HIV-1 infection; we emphasize that future vaccination strategies should include these early antigens, Tat and Rev. C1 Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, Xian 710038, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA 02129 USA. RP Sun, YT (reprint author), Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, Xian 710038, Peoples R China. EM yongtaos@hotmail.com NR 40 TC 4 Z9 5 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 2006 VL 22 IS 8 BP 780 EP 787 DI 10.1089/aid.2006.22.780 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 078GI UT WOS:000240090100010 PM 16910834 ER PT J AU Kelly, JF Stout, R Zywiak, W Schneider, R AF Kelly, John F. Stout, Robert Zywiak, William Schneider, Robert TI A 3-year study of addiction mutual-help group participation following intensive outpatient treatment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE mutual-help groups; self-help; Alcoholics Anonymous; Narcotics Anonymous; SMART recovery; Women for Sobriety ID SUBSTANCE-USE DISORDERS; ALCOHOLICS-ANONYMOUS INVOLVEMENT; COCAINE-DEPENDENT PATIENTS; SELF-HELP; CONTINUING CARE; GROUP ATTENDANCE; UNTREATED INDIVIDUALS; TREATMENT OUTCOMES; SOCIAL NETWORKS; ABUSE TREATMENT AB Addiction-focused mutual-help group participation is associated with better substance use disorder (SUD) treatment outcomes. However, little has been documented regarding which types of mutual-help organizations patients attend, what levels of participation may be beneficial, and which patients, in particular, are more or less likely to participate. Furthermore, much of the evidence supporting the use of these organizations comes from studies examining participation and outcomes concurrently, raising doubts about cause-effect connections, and little is known about influences that may moderate the degree of any general benefit. Alcohol-dependent outpatients (N=227; 27% female; M age=42) enrolled in a randomized-controlled telephone case monitoring trial were assessed at treatment intake and at 1, 2, and 3 years postdischarge. Lagged-panel, hierarchical linear models tested whether mutual-help group participation in the first and second year following treatment predicted subsequent outcomes and whether these effects were moderated by gender, concurrent axis I diagnosis, religious preference, and prior mutual-help experience. Robust regression curve analysis was used to examine dose-response relationships between mutual-help and outcomes. Mutual-help participation was associated with both greater abstinence and fewer drinks per drinking day and this relationship was not found to be influenced by gender, Axis I diagnosis, religious preference, or prior mutual-help participation. Mutual-help participants attended predominantly Alcoholics Anonymous and tended to be Caucasian, be more educated, have prior mutual-help experience, and have more severe alcohol involvement. Dose-response curve analyses suggested that even small amounts of participation may be helpful in increasing abstinence, whereas higher doses may be needed to reduce relapse intensity. Use of mutual-help groups following intensive outpatient SUD treatment appears to be beneficial for many different types of patients and even modest levels of participation may be helpful. Future emphasis should be placed on ways to engage individuals with these cost-effective resources over time and to gather and disseminate evidence regarding additional mutual-help organizations. C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Decis Sci Inst, Providence, RI USA. Brown Univ, Providence, RI 02912 USA. Harvard Univ, Pilgrim Healthcare, Boston, MA 02115 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Addict Res Program, 5 Emerson Pl, Boston, MA 02114 USA. EM jkelly11@partners.org NR 86 TC 58 Z9 59 U1 3 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2006 VL 30 IS 8 BP 1381 EP 1392 DI 10.1111/j.1530-0277.2006.00165.x PG 12 WC Substance Abuse SC Substance Abuse GA 065VA UT WOS:000239186800013 PM 16899041 ER PT J AU Cannon, CP Curtis, SP Bolognese, JA Laine, L AF Cannon, Christopher P. Curtis, Sean P. Bolognese, James A. Laine, Loren CA MEDAL Steering Committee TI Clinical trial design and patient demographics of the multinational etoricoxib and diclofenac arthritis long-term (MEDAL) study program: Cardiovascular outcomes with etoricoxib versus diclofenac in patients with osteoarthritis and rheumatoid arthritis SO AMERICAN HEART JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; GASTROINTESTINAL TOXICITY; GASTRODUODENAL ULCERS; PREVENTION; MANAGEMENT; CELECOXIB; NAPROXEN; INHIBITOR; ROFECOXIB; ASPIRIN AB Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently needed for the treatment of patients with arthritis.. However, long-term use of such drugs that are cyclooxygenase-2 (COX-2) selective inhibitors has been reported to increase cardiovascular risk as compared with placebo, whereas long-term, randomized controlled trials assessing the risk of traditional NSAIDs versus placebo are lacking. The MEDAL program is designed to provide a precise estimate of the relative cardiovascular event rates with the COX-2 selective inhibitor etoricoxib in comparison to the traditional NSAID diclofenac in patients with osteoarthritis and rheumatoid arthritis. The MEDAL program consists of 3 multinational, randomized, double-blind trials in patients with osteoarthritis and rheumatoid arthritis comparing etoricoxib (60 or 90 mg daily) to diclofenac (150 mg daily). All investigator-reported thrombotic cardiovascular events will be adjudicated by an independent panel of experts blinded to treatment assignment. The primary analysis is a noninferiority comparison of etoricoxib versus diclofenac for confirmed thrombotic cardiovascular events, defined as an upper bound of the 95% CI for a hazard ratio of < 1.30. With the planned 635 observed events from approximately 40000 patient-years of exposure, using an estimated annual event rate of 1.30% in the control arm, the maximum annual event rate for etoricoxib that would meet the noninferiority criteria would be approximately 1.46%, yielding a hazard ratio of 1.12. A total of 34 701 patients have been enrolled in the MEDAL program. Roughly 13 000 and 10000 patients will, respectively, have had >= 18 or >= 24 months of exposure, with maximum exposure of similar to 40 months. The MEDAL program will help to better define the risk-to-benefit ratio of 2 NSAIDs, that differ in their selectivity for COX-2, notably diclofenac and etoricoxib. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. Merck Res Labs, Rahway, NJ USA. Univ So Calif, Sch Med, Dept Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. RP Cannon, CP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div,TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 38 TC 49 Z9 51 U1 0 U2 4 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 AUG PY 2006 VL 152 IS 2 BP 237 EP 245 DI 10.1016/j.ahj.2006.05.024 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071BU UT WOS:000239573000008 PM 16875903 ER PT J AU Peacock, F Morris, DL Anwaruddin, S Christenson, RH Collinson, PO Goodacre, SW Januzzi, JL Jesse, RL Kaski, JC Kontos, MC Lefevre, G Mutrie, D Sinha, MK Uettwiller-Geiger, D Pollack, CV AF Peacock, Frank Morris, Deborah L. Anwaruddin, Saif Christenson, Robert H. Collinson, Paul O. Goodacre, Steve W. Januzzi, James L. Jesse, Robert L. Kaski, Juan C. Kontos, Michael C. Lefevre, Guillaume Mutrie, Dave Sinha, Manas K. Uettwiller-Geiger, Denise Pollack, Charles V. TI Acute ischemic heart disease - Meta-analysis of ischemia-modified albumin to rule out acute coronary syndromes in the emergency department SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC TROPONIN-T; CREATINE KINASE-MB; CHEST-PAIN; EARLY-DIAGNOSIS; RISK STRATIFICATION; MISSED DIAGNOSES; COBALT BINDING; MARKER; UNIT AB Background Because of possible adverse outcomes, many of the > 6 million annual emergency department (ED) patients with suspected acute coronary syndromes (ACS) undergo extensive evaluations. To minimize medica I errors, chest pain evaluations are structured to identify accurately nearly 100% of patients with ACS. This is at a cost of negative evaluation rates that can exceed 90%. Ischemia-modified albumin (IMA), a serum biomarker with a high negative predictive value (NPV) at ED presentation, may exclude ACS. Our objective was to perform a meta-analysis of IMA use for ACS risk stratification. Methods By computer literature search and communication with authors of unpublished information, all IMA data were considered. This analysis included studies if they reported IMA results from an ED presentation for suspected ACS. We defined a negative triple prediction test (TPT) as a nondiagnostic electrocardiogram, negative troponin, and negative IMA. Results Eight studies of > 1800 patients met the entry criteria. The TPT sensitivity and NPV for acute ACS were 94.4% and 97.1% and, for longer-term outcomes, were 89.2% and 94.5%, respectively. Conclusions A negative TPT of a nondiagnostic electrocardiogram, negative troponin, and negative IMA has a high NPV for excluding ACS in the ED. C1 Cleveland Clin Fdn, Dept Emergency Med, Cleveland, OH 44195 USA. Ischemia Technol, Denver, CO USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. St Georges Healthcare NHS Trust, London, England. Sheffield Teaching Hosp Trust, Sheffield, S Yorkshire, England. Hunter Holmes McGuire Vet Adm Med Ctr, Med Coll Virginia, Richmond, VA USA. Univ London St Georges Hosp, Coronary Artery Dis Res Unit, London, England. Virginia Commonwealth Univ, Dept Internal Med Cardiol, Richmond, VA USA. Virginia Commonwealth Univ, Dept Emergency Med, Richmond, VA USA. Virginia Commonwealth Univ, Dept Radiol, Richmond, VA USA. Hop Tenon, Serv Biochim & Hormonol, F-75970 Paris, France. Thunder Bay Reg Hosp, Thunder Bay, ON, Canada. John T Mather Hosp, Dept Clin Labs, Port Jefferson, NY USA. Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. RP Peacock, F (reprint author), Cleveland Clin Fdn, Dept Emergency Med, Desk E-19,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 31 TC 96 Z9 113 U1 1 U2 11 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 AUG PY 2006 VL 152 IS 2 BP 253 EP 262 DI 10.1016/j.ahj.2005.12.024 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071BU UT WOS:000239573000010 PM 16875905 ER PT J AU Deswal, A Petersen, NJ Urbauer, DL Wright, SM Beyth, R AF Deswal, Anita Petersen, Nancy J. Urbauer, Diana L. Wright, Steven M. Beyth, Rebecca TI Racial variations in quality of care and outcomes in an ambulatory heart failure cohort SO AMERICAN HEART JOURNAL LA English DT Article ID HEALTH-CARE; VETERANS-AFFAIRS; RACE; AMERICAN; HOSPITALIZATIONS; RACE/ETHNICITY; DISPARITIES; DYSFUNCTION; MANAGEMENT; COMMITTEE AB Background Few recent studies have demonstrated similar quality of care for hospitalized black and white patients with heart failure (HF). However, systematic evaluation of racial differences in both the quality of care and outcomes is needed in the outpatient setting, where most patients with HF are treated and where care may be more fragmented. Methods We examined racial differences in quality-of-care measures and outcomes of 1-year mortality and hospitalization in a national cohort of 18 611 ambulatory patients with HF treated at Veterans Affairs medical centers between October 2000 and September 2002. Results Black patients were more likely to have left ventricular ejection fraction assessment than whites (risk-adjusted OR 1.29, 95% CI 1.11-1.49). In patients with left ventricular ejection fraction < 40%, blacks were as likely as whites to be on treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (risk-adjusted OR 1.06, 95% CI 0.85-1.33) and beta-blockers (risk-adjusted OR 0.92, 95% CI 0.79-1.07). However, black patients more frequently had uncontrolled hypertension and were more likely to be hospitalized for any cause (OR 1.20, 95% CI 1.08-1.33) or for HF (OR 1.43, 95% CI 1.23-1.66), although 1-year mortality did not differ by race (OR 1.03, 95% CI 0.89-1.20). Conclusions In a financially "equal access" health care system, the quality of outpatient HF care assessed by select quality measures and 1-year mortality was similar in black compared to white patients. However, blacks were more likely to be hospitalized, especially with HF. Identifying and targeting potentially modifiable factors such as uncontrolled hypertension in black patients may narrow the racial gap in hospitalizations. C1 Baylor Coll Med, Michael E DeBakey Vet Affaris Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affaris Med Ctr, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Vet Hlth Adm, Off Qual & Performance, Washington, DC USA. Univ Florida, Coll Med Geriatr, Rehabil Outcomes Res Ctr, NF SG Vet Hlth Syst, Gainesville, FL USA. RP Deswal, A (reprint author), VA Med Ctr, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM adeswal@bcm.tmc.edu NR 27 TC 40 Z9 40 U1 0 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 AUG PY 2006 VL 152 IS 2 BP 348 EP 354 DI 10.1016/j.ahj.2005.12.004 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071BU UT WOS:000239573000027 PM 16875921 ER PT J AU Morrow, DA Scirica, BM Karwatowska-Prokopczuk, E Skene, A McCabe, CH Braunwald, E AF Morrow, David A. Scirica, Benjamin M. Karwatowska-Prokopczuk, Ewa Skene, Allan McCabe, Carolyn H. Braunwald, Eugene CA MERLIN TIMI 36 Investigators TI Evaluation of a novel anti-ischemic agent in acute coronary syndromes: Design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial SO AMERICAN HEART JOURNAL LA English DT Article ID CHRONIC HEART-FAILURE; VENTRICULAR MYOCYTES; AMERICAN-COLLEGE; UNSTABLE ANGINA; TASK-FORCE; OXIDATION; INJURY; REPERFUSION; MANAGEMENT; INHIBITOR AB Background Despite advances in antithrombotic therapies and invasive technology, the risk of recurrent ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) remains substantial. Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload and has been shown to reduce ischemia in patients with chronic stable angina. Study Design MERLIN-TIMI 36 is a phase III, randomized, double-blind, parallel-group, placebo-controlled, multinational clinical trial to evaluate the efficacy and safety of ranolazine during long-term treatment of patients with NSTE-ACS receiving standard therapy (N = 6500). Eligible patients are randomized. 1: 1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 hour, followed by an 80-mg/h infusion (40 mg/h for patients with severe renal insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched placebo until the end of study. The primary end point is the time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction, or recurrent ischemia. Secondary end points include ischemia on Halter monitoring, hospitalization for new or worsening heart failure, quality of life measures, and exercise performance. The evaluation of long-term safety will include death from any cause and symptomatic documented arrhythmia. Recruitment began in October 2004. The trial will continue until 730 major cardiovascular events and 3 10 deaths are recorded with expected completion in 24 to 28 months. Conclusions MERLIN-TIMI 36 will evaluate the role of ranolazine in the acute and chronic management of patients presenting with NSTE-ACS. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. CV Therapeut Inc, Palo Alto, CA USA. Nottingham Clin Res Ltd, Nottingham, England. RP Morrow, DA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 27 TC 6 Z9 6 U1 0 U2 2 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 AUG PY 2006 VL 152 IS 2 BP 400 EP 406 DI 10.1016/j.ahj.2006.06.016 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071BU UT WOS:000239573000036 ER PT J AU Foo, SY Everett, BM Yeh, RW Criss, D Laposata, M Van Cott, EM Jang, IK AF Foo, Shi Yin Everett, Brendan M. Yeh, Robert W. Criss, David Laposata, Michael Van Cott, Elizabeth M. Jang, Ik-Kyung TI Prevalence of heparin-induced thrombocytopenia in patients undergoing cardiac catheterization SO AMERICAN HEART JOURNAL LA English DT Article ID THROMBOSIS; RISK AB Background Heparin is ubiquitously used in cardiac catheterization but predisposes to the development of heparin-induced thrombocytopenia. The objective was to examine prospectively the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies and heparin-induced thrombocytopenia in the population undergoing cardiac catheterization. Methods This is a prospective study of 500 consecutive patients presenting for cardiac catheterization at our institution who were enrolled over the course of 1 year. Anti-PF4/heparin antibodies and concurrent platelet counts were measured at catheterization and 5 days thereafter. Thrombotic complications were assessed 30 days after the procedure via telephone interview. All patients presenting for cardiac catheterization at our institution were screened. Inclusion criteria were (a) males and nonpregnant females with age > 18 years and (b) patients scheduled to undergo cardiac catheterization. Patients with a known history of heparin-induced thrombocytopenia, with documented bleeding or hypercoagulability, and those at high risk for bleeding were excluded. Results Of 500 patients, 15 (3%) had anti-PF4/heparin antibodies before catheterization. After catheterization, the prevalence of anti-PF4/heparin antibodies increased to 10.1% (36 of 357) of the patients. Overall rates of thrombotic complications were low (4 of 445, 0.9%) and did not correlate with anti-PF4/heparin antibody status. Patients with an initial positive test for anti-PF4/heparin antibodies were more likely to have prior coronary disease (73.3% vs 45.2%; P <.05). Patients who developed anti-PF4/heparin antibodies after catheterization were more likely to have increased length of stay (3.7 vs 2,4 days; P =.02). The platelet count at the time of catheterization was lower in the cohort of patients who developed the second positive anti-PF4/heparin antibody test versus patients without a second positive antibody test (mean values of 191,800/mu L vs 222,300/mu l; P =.008). Conclusions The prevalence of antibodies to PF4/heparin is low in the population presenting for cardiac catheterization. However, a significant proportion of patients develop antibodies to PF4/heparin after a small exposure to heparin during catheterization. Clinically significant thrombotic complications were rare and did not correlate with antibody status. C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 12 TC 4 Z9 4 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 AUG PY 2006 VL 152 IS 2 AR 290.e7 DI 10.1016/j.ahj.2006.04.028 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071BU UT WOS:000239573000016 ER PT J AU Spertus, JA Dawson, J Masoudi, FA Krumholz, HM Reid, KJ Peterson, ED Rumsfeld, JS AF Spertus, John A. Dawson, Jill Masoudi, Frederick A. Krumholz, Harlan M. Reid, Kimberly J. Peterson, Eric D. Rumsfeld, John S. CA Cardiovascular Outcomes Res Consor TI Prevalence and predictors of angina pectoris one month after myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID QUALITY-OF-LIFE; CORONARY-ARTERY-DISEASE; HEALTH-STATUS; FUNCTIONAL STATUS; SURGERY TRIAL; ANGIOPLASTY; INTERVENTION; OUTCOMES; IMPACT; COLLEGE AB Angina pectoris (AP) is a treatable symptom that is associated with mortality and decreased quality of life. The prevalence and predictors of AP 1 month after a myocardial infarction (MI), a time when additional treatments might be offered, have not been described. We prospectively enrolled 2,094 patients with MI from 19 centers in the United States and evaluated angina symptoms 1 month after discharge with the Seattle Angina Questionnaire. Multivariable logistic regression analysis was performed to identify patient and treatment characteristics associated with 1-month AP. At 1 month, 571 patients, (27.3%) had AP. Women (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.09 to 1.74), younger patients (OR 1.33 per 10-year increment, 95% CI 1.20 to 1.47), those with previous coronary artery bypass (OR 1.47, 95% CI 1.05 to 2.05), smokers (OR 1.35, 95% CI 1.09 to 1.77), and those who developed postinfarct AP during the index hospitalization (OR 1.85, 95% CI 1.20 to 2.65) were more likely to have AP at follow-up. In contrast, patients who were treated with coronary artery bypass surgery during their index admission were less likely to have AP at 1 month (OR 0.5, 95% CI 0.33 to 0.77). The strongest correlate was the frequency of AP before patients' MI., Compared with those without AP before MI, those with AP < 1 time per week (OR 1.86, 95% CI 1.45 to 2.41), weekly (OR 4.24, 95% CI 3.09 to 5.82), and daily (OR 6.12, 95% CI 3.62 to 10.3) were more likely to have AP I month later. In conclusion, > 1 in 4 patients reported AP 1 month after an MI. (c) 2006 Elsevier Inc. All rights reserved. C1 Mid Amer Heart Inst, Kansas City, MO USA. Univ Missouri, Kansas City, MO 64110 USA. Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80202 USA. Denver Hlth Med Syst, Denver, CO USA. Yale Univ, New Haven, CT USA. Duke Univ, Durham, NC USA. RP Spertus, JA (reprint author), Mid Amer Heart Inst, Kansas City, MO USA. EM spertusj@umkc.edu NR 20 TC 21 Z9 21 U1 0 U2 1 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2006 VL 98 IS 3 BP 282 EP 288 DI 10.1016/j.amjcard.2006.01.099 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 069VT UT WOS:000239477600002 PM 16860010 ER PT J AU Nieman, K Cury, RC Ferencik, M Nomura, CH Abbara, S Hoffmann, U Gold, HK Jang, IK Brady, TJ AF Nieman, Koen Cury, Ricardo C. Ferencik, Maros Nomura, Cesar H. Abbara, Suhny Hoffmann, Udo Gold, Herman K. Jang, Ik-Kyung Brady, Thomas J. TI Differentiation of recent and chronic myocardial infarction by cardiac computed tomography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MULTIDETECTOR-ROW CT; RIGHT-VENTRICULAR DYSPLASIA; CORONARY-ANGIOGRAPHY; TRANSMISSION TOMOGRAPHY; LIPOMATOUS METAPLASIA; PREDICTION; VIABILITY; SIZE; FEASIBILITY; EXPERIENCE AB Clinical use of cardiac computed tomography is rapidly expanding, and its purpose may reach beyond noninvasive coronary angiography. We investigated the ability of 64-slice multidetector computed tomography to differentiate between recent and long-standing myocardial infarction (MI). Contrast-enhanced coronary computed tomographic (CT) scans (Siemens Sensation 64) of patients with a recent MI (< 7 days, n = 16), long-standing MI (> 12 months, n = 13), and no MI (n = 13) were retrospectively evaluated. To anticipate transmural variation of myocardial perfusion and to neutralize image noise, a series of thin, overlapping slices was created in parallel alignment to the myocardial wall. Within each of these slices, a small region of interest was placed at a constant in-plane position to measure the CT attenuation (Hounsfield units [HU]) at consecutive transmural locations of injured and normal remote myocardium. In addition, wall thickness and the myocardial cavity were measured. Significantly lower CT attenuation values were found in patients With long-standing MI (-13 +/- 37 HU) than in those with acute MI (26 +/- 26HU) and normal controls (73 +/- 14 HU, p < 0.001). The attenuation difference between infarcted and remote myocardia was larger in patients with long-standing MI than in patients with recent MI (89 41 and 55 33 HU, respectively, p < 0.001). In addition, long-standing MI was associated with wall thinning (p < 0.01), and ventricular dilation (p < 0.05), whereas recent MI was not (p > 0.05). In conclusion, recent and long-standing MIs may be differentiated by computed tomography based on myocardial CT attenuation values and ventricular dimensions. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Erasmus Med Ctr, Dept Cardiol, Rotterdam, Netherlands. RP Nieman, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM koennieman@hotmail.com RI Nomura, Cesar/H-1636-2012 FU NHLBI NIH HHS [1T32 HL076136-02] NR 30 TC 53 Z9 56 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2006 VL 98 IS 3 BP 303 EP 308 DI 10.1016/j.amjcard.2006.01.101 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 069VT UT WOS:000239477600005 PM 16860013 ER PT J AU Huffman, JC Smith, FA Blais, MA Beiser, ME Januzzi, JL Fricchione, GL AF Huffman, Jeff C. Smith, Felicia A. Blais, Mark A. Beiser, Marguerite E. Januzzi, James L. Fricchione, Gregory L. TI Recognition and treatment of depression and anxiety in patients with acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID QUALITY-OF-LIFE; PROGNOSIS; EVENTS; OUTPATIENTS; INVENTORY; MORTALITY; IMPACT; CARE AB The objective of this study was to determine the ability of providers (medical residents and nurse practitioners) on inpatient cardiac units to recognize and appropriately treat patients with clinically significant depression and anxiety among a cohort admitted with acute myocardial infarction. Patients within 72 hours of acute myocardial infarction underwent screening with the Standardized Clinical Instrument for Diagnostic and,Statistical Manual of Mental Disorders, Fourth Edition module for major depressive disorder (MDD), the Beck Depression Inventory (BDI-II), and the Beck Anxiety Inventory (BAI). In addition, the study psychiatrist and a treatment team clinician independently assessed whether they believed that patients had clinically significant depression or anxiety. Prescription of antidepressants and benzodiazepines during hospitalization was recorded by chart review. Assessments were completed for 74 patients. Providers identified < 15% of patients with current MDD or with a BDI score >= 10; 11% of patients with current MDD had appropriate treatment with antidepressants. There was no significant correlation of providers' assessment of depression with current MDD, BDI scores, or psychiatrists' clinical assessment of depression. In contrast, providers identified 31% of patients with a BAI score >= 10 and 50% of patients who were assessed by psychiatrists as anxious; > 80% of patients with high anxiety received benzodiazepines. Providers' assessments of anxiety were significantly correlated with BAI scores and with psychiatrists' clinical assessments. In conclusion, medical residents and nurse practitioners routinely under-recognize and undertreat depression among patients with acute myocardial infarction on inpatient cardiac units. Recognition and treatment of anxiety is substantially better, up to 50% of patients who are found to be anxious by psychiatrists after acute myocardial infarction remain unrecognized. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Columbia Univ, Sch Nursing, New York, NY USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM jhuffman@partners.org NR 26 TC 45 Z9 49 U1 1 U2 5 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2006 VL 98 IS 3 BP 319 EP 324 DI 10.1016/j.amjcard.2006.02.033 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 069VT UT WOS:000239477600008 PM 16860016 ER PT J AU van Kimmenade, RRJ Pinto, YM Bayes-Genis, A Lainchbury, JG Richards, AM Januzzi, JL AF van Kimmenade, Roland R. J. Pinto, Yigal M. Bayes-Genis, Antoni Lainchbury, John G. Richards, A. Mark Januzzi, James L., Jr. TI Usefulness of intermediate amino-terminal pro-brain natriuretic peptide concentrations for diagnosis and prognosis of acute heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NT-PROBNP; PREDICTORS; MORTALITY; DYSPNEA AB Age-stratified cutpoints for aminoterminal pro-brain natriuretic peptide (NT-pro-BNP) concentrations are diagnostic in 83% of all subjects with acute dyspnea. This study analyzed subjects with NT-pro-BNP concentrations between the "rule-out" and "rule-in" cutpoints, the so-called natriuretic peptide gray zone. NT-pro-BNP concentrations, clinical characteristics, and 60-day mortality were studied in 1,256 acutely dyspneic patients from an international multicenter study. Of all subjects, 215 had gray-zone NT-pro-BNP concentrations, 116 of whom (54%) were diagnosed with heart failure (HF). Among these subjects, patients with HF were more likely to be older, to have a history of HF, to be in atrial fibrillation, and to have elevated troponin T concentrations compared with those without HF. In multivariate analysis, the use of loop diuretics on presentation (odds ratio [OR] 3.99, 95% confidence interval [CI] 1.58 to 10.1, p = 0.003), paroxysmal nocturnal dyspnea (OR 4.50, 95% CI 1.31 to 15.4, p = 0.02), jugular venous distention (OR 3.05, 95% Cl = 1.06 to 8.79, p = 0.04), and the absence of cough (OR 0.18, 95% CI 0.06 to 0.52, p = 0.001) were associated with a diagnosis of acute HF in gray-zone patients. Subjects with HF and diagnostically elevated NT-pro-BNP concentrations had the highest mortality rates, subjects without HF and NT-pro-BNP concentrations < 300 ng/L had the lowest mortality rates, and subjects with gray-zone NT-pro-BNP had intermediate outcomes, irrespective of their final diagnoses. Adding specific clinical information to NT-pro-BNP improves diagnostic accuracy in subjects with intermediate NT-pro-BNP concentrations. Mortality rates in subjects with intermediate NT-pro-BNP concentrations are lower than in those with NT-pro-BNP concentrations diagnostic for HF but are higher than in subjects with NT-pro-BNP concentrations less than the gray zone. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. Hosp Santa Creu i Sant Pau, ICCC, Dept Cardiol, Barcelona, Spain. Christchurch Sch Med & Hlth Sci, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand. RP Januzzi, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. EM jjanuzzi@partners.org RI Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X; NR 9 TC 47 Z9 51 U1 0 U2 2 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2006 VL 98 IS 3 BP 386 EP 390 DI 10.1016/j.amjcard.2006.02.043 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 069VT UT WOS:000239477600021 PM 16860029 ER PT J AU Yeh, RW Everett, BM Foo, SY Dorer, DJ Laposata, M Van Cott, EM Jang, IK AF Yeh, Robert W. Everett, Brendan M. Foo, Shi-Yin Dorer, David J. Laposata, Michael Van Cott, Elizabeth M. Jang, Ik-Kyung TI Predictors for the development of elevated anti-heparin/platelet factor 4 antibody titers in patients undergoing cardiac catheterization SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEPARIN-INDUCED THROMBOCYTOPENIA AB A substantial proportion of patients who undergo cardiac catheterization develop antibodies directed against the heparin/platelet factor 4 (PF4) complex after the procedure, which have been implicated in the pathogenesis of heparin-induced thrombocytopenia. This study attempted to identify factors that predicted the development of these antibodies in a prospective cohort study. Antiheparin/PF4 antibody titers were measured at baseline and again 5 +/- 2 days after cardiac catheterization by enzyme-linked immunosorbent assay. A total of 311 patients who underwent cardiac catheterization were included in the analysis. Of these, 25 (8.0%) developed positive antibody levels after catheterization. Patients who had positive antibody test results after catheterization had significantly greater baseline antiheparin/PF4 antibody titers compared with those whose titers remained low (optical density 0.227 vs 0.158, p < 0.001). In a logistic regression model, greater baseline antibody titers, a history of heparin exposure, and a lower platelet count at enrollment were the strongest predictors of conversion to positive, antiheparin/PF4 antibody titers after cardiac catheterization. It is possible to identify patients at high risk for developing elevated titers of antiheparin/PF4 antibodies on the basis of their baseline clinical characteristics. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM ijang@partners.org NR 9 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2006 VL 98 IS 3 BP 419 EP 421 DI 10.1016/j.amjcard.2006.02.048 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 069VT UT WOS:000239477600028 PM 16860036 ER PT J AU Mantzoros, CS Williams, CJ Manson, JE Meigs, JB Hu, FB AF Mantzoros, Christos S. Williams, Catherine J. Manson, JoAnn E. Meigs, James B. Hu, Frank B. TI Adherence to the Mediterranean dietary pattern is positively associated with plasma adiponectin concentrations in diabetic women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE Mediterranean diet; adiponectin; cardiovascular disease risk ID SOLUBLE LEPTIN RECEPTOR; FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; INSULIN SENSITIVITY; CIRCULATING ADIPONECTIN; MYOCARDIAL-INFARCTION; ALCOHOL-CONSUMPTION; METABOLIC SYNDROME; SERUM ADIPONECTIN; PHYSICAL-ACTIVITY AB Background: Although the typical diet of the Mediterranean region has received much recognition over the past several years for its association with substantial health benefits, it remains unknown whether its favorable effects are mediated through changes in adiponectin concentrations. Objective: The objective was to determine whether adherence to a Mediterranean-type diet is associated with higher plasma adiponectin concentrations. Design: This study was a prospective and cross-sectional evaluation of plasma adiponectin concentrations and dietary data from 987 diabetic women from the Nurses' Health Study who had no history of cardiovascular disease at the time blood was drawn in 1990. Results: Women who scored highest on a 9-point scale that measures adherence to a Mediterranean-type dietary pattern tended to be older, were less likely to be current smokers, had lower body mass indexes and waist circumferences, and had higher total energy intakes, physical activities, and plasma adiponectin concentrations than did women with the lowest scores. Median plasma adiponectin concentrations were 23% higher in women who most closely followed a Mediterranean-type diet than in low adherers after adjustment for age and energy intake (P < 0.01). Body composition, lifestyle, and medical history explained some, but not all, of the observed association between diet and adiponectin concentrations because high adherers tended to have greater adiponectin concentrations than did moderate or low adherers, even after adjustment for these variables. Conclusions: Our data suggest that, of the several components of the Mediterranean dietary pattern score, alcohol, nuts, and whole grains show the strongest association with adiponectin concentrations. Close adherence to a Mediterranean-type diet is associated with higher adiponectin concentrations. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM frank.hu@channing.harvard.edu FU NHLBI NIH HHS [HL60712, HL34594, HL65582]; NIDDK NIH HHS [DK58845, P30 DK040561, P30 DK040561-11] NR 42 TC 133 Z9 135 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 AUG PY 2006 VL 84 IS 2 BP 328 EP 335 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 072LG UT WOS:000239674300009 PM 16895879 ER PT J AU Plebani, M Laposata, M AF Plebani, Mario Laposata, Michael TI Translational research involving new biomarkers of disease - A leading role for pathologists SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID LABORATORY MEDICINE; PROTEOMIC PATTERNS; CLINICAL-RESEARCH; PROSTATE-CANCER; FUTURE; SERUM; DIAGNOSTICS C1 Univ Hosp Padova, Dept Lab Med, Padua, Italy. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Plebani, M (reprint author), Univ Hosp Padova, Dept Lab Med, Padua, Italy. NR 25 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2006 VL 126 IS 2 BP 169 EP 171 DI 10.1309/5GHY0VCWBUY58EFX PG 3 WC Pathology SC Pathology GA 066FV UT WOS:000239216000001 PM 16891189 ER PT J AU Saenz, AJ Lee-Lewandrowski, E Wood, MJ Neilan, TG Siegel, AJ Januzzi, JL Lewandrowski, KB AF Saenz, Adam J. Lee-Lewandrowski, Elizabeth Wood, Malissa J. Neilan, Tomas G. Siegel, Arthur J. Januzzi, James L. Lewandrowski, Kent B. TI Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon runners before and after the 2005 Boston Marathon SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE troponin; TnT; matrix metalloproteinase-9; S-100 beta; stroke panel; marathon; sports medicine ID MARKERS AB We report changes in cardiac troponin-T (TnT) and a new plasma stroke biomarker panel (D dimer, B-natriuretic peptide [BNP], matrix metalloproteinase-9 [MMP-9], S-100 beta, Biosite Diagnostics, San Diego, CA) in 30 nonprofessional marathon runners before and immediately after the 2005 Boston Marathon. Following competition, there was a statistically significant increase in MMP-9 (P <.001) and D dimer (P <.001). Nonsignificant changes in S-100 P and BNP were observed. Premarathon and postmarathon values for a multimarker stroke index increased from 0.97 (normal) to 3.5 (low risk or more; P <.001). Two subjects had index values more than the high-risk cutoff value. Mean TnT premarathon and postmarathon levels increased (from < 0.01 to 0.03 ng/mL; P <.0001). After the marathon, with a cutoff value of 0.05 ng/mL, 7 runners (23%) had values above the manufacturer's recommended cutoff for myocardial damage. Although biochemical evidence of myocardial damage following strenuous exercise may reflect myocardial stunning or subclinical ischemia, the changes in the stroke index and values for individual stroke markers may reflect a systemic inflammatory response to exertional rhabdomyolysis which is common, but the possibility of subclinical central nervous system damage cannot be excluded. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. McLean Hosp, Dept Med, Belmont, MA 02178 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, 55 Fruit St,GRB5, Boston, MA 02114 USA. NR 14 TC 37 Z9 38 U1 0 U2 5 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2006 VL 126 IS 2 BP 185 EP 189 DI 10.1039/D7QUF0HJMCYYYY5A PG 5 WC Pathology SC Pathology GA 066FV UT WOS:000239216000003 PM 16891191 ER PT J AU Lum, G AF Lum, Gifford TI Evaluation of a protocol to control utilization of B-type natriuretic peptide testing SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE B-type natriuretic peptide; BNP; congestive heart failure; CHF; utilization protocol; serial BNP ID CHRONIC HEART-FAILURE; EMERGENCY DIAGNOSIS; MANAGEMENT; GUIDELINES; DISEASE; UPDATE AB The Veterans Affairs (VA) Boston Healthcare System, Boston, MA, instituted a protocol limiting the number of B-type natriuretic peptide (BNP) assays to I per hospitalization or outpatient visit and requiring approval of the cardiology service for more than 1 because of a 3-fold monthly increase in BNP testing. Effectiveness of this protocol was assessed by studying BNP utilization for 6-month periods before and after institution of the protocol. Before: 1, 886 assays in 752 patients; mean BNP assays per patient, 2.5; direct reagent cost, $33,948; 1 BNP assay in 57.3% (431) of patients; 321 patients with multiple and 204 patients with serial BNP requests. After: 782 assays (-58.5%) in 593 patients (-21.1%); mean BNP assays per patient, 1.3 (-48.0%); direct reagent cost, $14,076 (-58.5%); 1 BNP assay in 81.1% (481) of patients; 112 patients with multiple and 24 patients with serial BNP requests (-88.2%). The emergency department was the source of BNP assays in 15.4% of requests before compared with 58.1% after introduction of the protocol. The protocol with slight modifications has been adopted by other VA medical centers in New England and may serve as a model for other medical facilities seeking to control BNP utilization. C1 VA Boston Healthcare Syst, Dept Pathol & Lab Med, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Dept Pathol & Lab Med, 1400 VFW Pkwy, Boston, MA 02132 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2006 VL 126 IS 2 BP 190 EP 194 DI 10.1309/4X8HVJFKPHXJYMFK PG 5 WC Pathology SC Pathology GA 066FV UT WOS:000239216000004 PM 16891192 ER PT J AU Blechner, M Kish, J Chadaga, V Dighe, AS AF Blechner, Michael Kish, Joshua Chadaga, Vivek Dighe, Anand S. TI Analysis of search in an online clinical laboratory manual SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE informatics; management; administration; clinical chemistry AB Online laboratory manuals have developed into an important gateway to the laboratory. Clinicians increasingly expect up-to-date laboratory test information to be readily available online. During the past decade, sophisticated Internet search technology has developed, permitting rapid and accurate retrieval of a wide variety of content. We studied the role of search in an online laboratory manual. We surveyed the utilization of search technology in publicly available online manuals and examined how users interact with the search feature of a laboratory handbook. We show how a laboratory can improve its online handbook through insights gained by collecting information about each user's activity. We also discuss future applications for search-related technologies and the potential role of the online laboratory manual as the primary laboratory information portal. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Decis Syst Grp, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Dighe, AS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bigelow Bldg,Room 510, Boston, MA 02114 USA. FU NLM NIH HHS [T15 LM0007092] NR 9 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2006 VL 126 IS 2 BP 208 EP 214 DI 10.1309/PHAMDT8NN44WMBDF PG 7 WC Pathology SC Pathology GA 066FV UT WOS:000239216000007 PM 16891195 ER PT J AU Branda, JA Kratz, A AF Branda, John A. Kratz, Alexander TI Effects of yeast on automated cell counting SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE cell counters; fungemia; Candida; yeast; hematology analyzers; ADVIA 120/2120; automated cell analysis; flow cytometry ID QUANTITATIVE BLOOD CULTURES; ELEVATED PLATELET COUNTS; LYSIS-CENTRIFUGATION; HEMOGLOBIN CONCENTRATION; CLINICAL-EVALUATION; STREAM INFECTIONS; LIGHT-SCATTERING; SURVEILLANCE; SYSTEM; VOLUME AB We studied the effects of yeast in peripheral blood samples on results reported by an ADVIA 120/2120 Hematology System (Bayer HealthCare, Diagnostics Division, Tarrytown, NY). In a simulated candidemia model, very high concentrations (1-5 x 10(8) colony-forming units [CFU]/mL) of Candida glabrata and Candida parapsilosis caused a spuriously elevated platelet count. No such effect was observed with Candida albicans. All 3 yeast species, when present at a concentration of 1-5 x 10(6) CFU/mL or greater, increased the automated WBC counts significantly and in a dose-dependent manner The yeast cells were mainly misidentified as lymphocytes. All spurious results were flagged by the cell counter for microscopic review. We conclude that although the presence of yeast in a blood sample can interfere with the ADVIA 120/2120 Hematology System, compromised results are appropriately flagged by the instrument and are seen only when the yeast concentration is very high. C1 Massachusetts Gen Hosp, Div Lab Med, Clin Hematol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kratz, A (reprint author), Massachusetts Gen Hosp, Div Lab Med, Clin Hematol Lab, 55 Fruit St,GRJ 235, Boston, MA 02114 USA. NR 21 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2006 VL 126 IS 2 BP 248 EP 254 DI 10.1039/1G5HB7PAK8V0KAR7 PG 7 WC Pathology SC Pathology GA 066FV UT WOS:000239216000013 PM 16891201 ER PT J AU Yu, CL Wang, SF Pan, PC Wu, MT Ho, CK Smith, TJ Li, Y Pothier, L Christiani, DC Grp, KLR AF Yu, Chu-Ling Wang, Su-Fen Pan, Pi-Chen Wu, Ming-Tsang Ho, Chi-Kung Smith, Thomas J. Li, Yi Pothier, Lucille Christiani, David C. Grp, Kaohsiung Leukemia Res TI Residential exposure to petrochemicals and the risk of leukemia: Using geographic information system tools to estimate individual-level residential exposure SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE environmental exposure; environmental pollution; leukemia ID AIR-POLLUTION; CANCER MORTALITY; SOUTH WALES; BAGLAN BAY; TAIWAN; AREA; INDUSTRIES; CHILDREN; HEALTH; PLANT AB The authors conducted a population-based, case-control study in Kaohsiung, southern Taiwan, Republic of China, to investigate the association between residential petrochemical exposure and leukemia risk among subjects 29 years of age and younger. Between November 1997 and June 2003,171 cases and 410 controls matched for age and sex were recruited. Since assessment of petrochemical impacts depends on accurate exposure estimates, the authors developed a procedure using geographic information system tools to assign subjects' exposure. The resulting individual-level exposure estimates (the exposure opportunity score) are an integrated exposure measure that accounts for subjects' mobility, length of stay at each residence, distance to petrochemical plant(s), monthly prevailing wind direction, and multiple petrochemical pollution sources. Different conditional logistic regression models were fitted for subjects aged 0-19 and 20-29 years to evaluate separately childhood versus adulthood leukemia. No overall association was observed for the younger age group. However, residential petrochemical exposure was a significant risk factor for leukemia for the older age group. For one unit of increase in the log-transformed exposure opportunity score, the adjusted odds ratio was 1.54 (95 percent confidence interval: 1.14, 2.09). This study illustrates the utility of geographic information system tools for providing refined exposure estimates for residential exposure to petrochemical pollution. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Natl Changhua Univ Educ, Dept Geog, Changhua, Taiwan. Kaohsiung Med Univ, Sch Publ Hlth, Kaohsiung, Taiwan. Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Wu, Ming-Tsang/D-2385-2009; Ho, Chi-Kung/D-4587-2009 FU NIEHS NIH HHS [ES00002, ES09723] NR 33 TC 49 Z9 50 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 2006 VL 164 IS 3 BP 200 EP 207 DI 10.1093/aje/kwj182 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 068QX UT WOS:000239390600002 PM 16754633 ER PT J AU El-Serag, HB AF El-Serag, Hashem B. TI Temporal trends in new and recurrent esophageal strictures in department of veterans affairs SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL-REFLUX-DISEASE; EOSINOPHILIC ESOPHAGITIS; CONCEPTUAL-FRAMEWORK; TIME TRENDS; OMEPRAZOLE; ADULTS AB BACKGROUND: Anecdotal experience suggests that gastroenterologists are encountering fewer patients with esophageal strictures; however, the temporal trends of esophageal strictures have not been well examined in large studies. METHODS: We examined the incidence rates of new esophageal strictures as well as esophageal dilations among patients presenting to VA facilities between 1998 and 2003 as a proportion of the annual frequency of all endoscopic procedures and/or imaging procedures. Recurrent strictures were defined as those recorded at least 3 months after the index date of a new stricture or the date of the preceding recurrent stricture. Stricture was defined only in the presence of an upper endoscopy or upper gastrointestinal (UGI) contrast imaging within 30 days before or after the date of diagnosis. This algorithm was validated by manually reviewing the medical records of 180 patients; the positive predictive value was approximately 84%. The risk of recurrent strictures was examined using Cox proportional hazards model for multiple failures. RESULTS: There were 19,157 patients identified between fiscal year (FY) 1998 and FY 2003 with new esophageal strictures. New strictures comprised a constant annual proportion of total EGD and UGI imaging studies. New strictures declined by 11.6% as a proportion of all upper endoscopies (not including UGI imaging). However, esophageal dilations associated with new stricture diagnoses declined among patients with new esophageal strictures, 16.8% had at least one episode of recurrence. The 1-yr incidence rate of recurrent strictures declined significantly (-36.0%) from 13.9 per 100 person-years for patients diagnosed with new strictures in 1998 to 8.9 per 100 person-years in patients diagnosed with new strictures in 2003. In the full multivarlable model, new strictures diagnoses during 2001-2003 were associated with a reduced risk of having recurrent strictures (19% in the first year and 13% throughout follow-up) independent of age, gender, race, geographic region, or the presence of Barrett's esophagus. CONCLUSION: The incidence of recurrent strictures has declined between 1998 and 2003 by approximately one-third. Although there has been only a small decline in the incidence of new esophageal strictures among patients undergoing endoscopy, the use of esophageal dilations has declined considerably among these patients. The role of proton pump inhibitors needs to be examined. C1 Houston Dept Vet Affairs Med Ctr, Sect Gastroenterol & Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Dept Vet Affairs Med Ctr, Sect Gastroenterol & Hlth Serv Res, Houston, TX USA. NR 16 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2006 VL 101 IS 8 BP 1727 EP 1733 DI 10.1111/j.1572-0241.2006.00618.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 076MI UT WOS:000239962000006 PM 16817844 ER PT J AU Peskind, ER Potkin, SG Pomara, N Ott, BR Graham, SM Olin, JT McDonald, S AF Peskind, Elaine R. Potkin, Steven G. Pomara, Nunzio Ott, Brian R. Graham, Stephen M. Olin, Jason T. McDonald, Scott CA MEM-MD-10 Study Grp TI Memantine treatment in mild to moderate Alzheimer disease: A 24-week randomized, controlled trial SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the International-College-of-Geriatric-Psychoneuropharmacology CY NOV 02-05, 2005 CL Pittsburg, PA SP Int Coll Geriatr Psychoneuropharmacol DE memantine; Alzheimer disease; dementia ID VASCULAR DEMENTIA; INVENTORY; DONEPEZIL; EFFICACY; SCALE AB Objective: The objective of this study was to compare the efficacy and safety of the moderate-affinity, uncompetitive N-methyl-d-aspartate receptor antagonist, memantine, versus placebo in patients with mild to moderate Alzheimer disease ( AD). Method: This was a randomized, double-blind, placebo-controlled clinical trial conducted at 42 U. S. sites. Participants were 403 outpatients with mild to moderate AD and Mini-Mental State Examination scores of 10 - 22 randomized to memantine (20 mg/day; N = 201) or placebo (N = 202) for 24 weeks. Primary outcomes were change from baseline at 24 weeks on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog), a measure of cognition, and on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), a global measure. Secondary outcomes included change on the Neuropsychiatric Inventory (NPI) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL(23)), measures of behavior and function, respectively. Results: Most (82.4%) participants completed the trial. Memantine resulted in significantly better outcomes than placebo on measures of cognition, global status, and behavior when based on the protocol-specified primary last observation carried forward imputation as well as a mixed-models repeated-measures approach applied to the continuous outcomes. Treatment discontinuations because of adverse events for memantine versus placebo were 19 (9.5%) and 10 (5.0%), respectively. Conclusions: These results support the safety and efficacy of memantine for the treatment of mild to moderate AD. C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs NW Network, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. Nathan S Kline Inst Psychiat Res, Jersey City, NJ USA. Brown Univ, Dept Clin Neurosci, Jersey City, NJ USA. Forest Res Inst, Jersey City, NJ USA. RP Peskind, ER (reprint author), VA Puget Sound Hlth Care Syst, S-1166 E,1660 So Columbian Way, Seattle, WA 98108 USA. EM peskind@u.washington.edu RI Potkin, Steven/A-2021-2013 NR 22 TC 166 Z9 177 U1 2 U2 38 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD AUG PY 2006 VL 14 IS 8 BP 704 EP 715 DI 10.1097/01.JGP.0000224350.82719.83 PG 12 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 066BV UT WOS:000239205500009 PM 16861375 ER PT J AU Carr, LS AF Salomone Carr, Laura TI Teaching as a new practitioner SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Pharm Dept GRB 005, Boston, MA 02114 USA. RP Carr, LS (reprint author), Massachusetts Gen Hosp, Pharm Dept GRB 005, 55 Fruit St, Boston, MA 02114 USA. EM LauraCCarr@gmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD AUG 1 PY 2006 VL 63 IS 15 BP 1400 EP + DI 10.2146/ajhp050445 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 071FM UT WOS:000239584100004 PM 16849703 ER PT J AU Locke, DP Sharp, AJ McCarroll, SA McGrath, SD Newman, TL Cheng, Z Schwartz, S Albertson, DG Pinkel, D Altshuler, DM Eichler, EE AF Locke, Devin P. Sharp, Andrew J. McCarroll, Steven A. McGrath, Sean D. Newman, Tera L. Cheng, Ze Schwartz, Stuart Albertson, Donna G. Pinkel, Daniel Altshuler, David M. Eichler, Evan E. TI Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECENT SEGMENTAL DUPLICATIONS; DELETION POLYMORPHISMS; IDENTIFICATION; GENES AB Studies of copy-number variation and linkage disequilibrium (LD) have typically excluded complex regions of the genome that are rich in duplications and prone to rearrangement. In an attempt to assess the heritability and LD of copy-number polymorphisms (CNPs) in duplication-rich regions of the genome, we profiled copy-number variation in 130 putative "rearrangement hotspot regions" among 269 individuals of European, Yoruba, Chinese, and Japanese ancestry analyzed by the International HapMap Consortium. Eighty-four hotspot regions, corresponding to 257 bacterial artificial chromosome (BAC) probes, showed evidence of copy-number differences. Despite a predisposing genetic architecture, no polymorphism was ever observed in the remaining 46 "rearrangement hotspots," and we suggest these represent excellent candidate sites for pathogenic rearrangements. We used a combination of BAC-based and high-density customized oligonucleotide arrays to resolve the molecular basis of structural rearrangements. For common variants (frequency > 10%), we observed a distinct bias against copy-number losses, suggesting that deletions are subject to purifying selection. Heritability estimates did not differ significantly from 1.0 among the majority (30 of 34) of loci analyzed, consistent with normal Mendelian inheritance. Some of the CNPs in duplication-rich regions showed strong LD with nearby single-nucleotide polymorphisms (SNPs) and were observed to segregate on ancestral SNP haplotypes. However, LD with the best available SNP markers was weaker than has been reported for deletion polymorphisms in less complex regions of the genome. These observations may be accounted for by a low density of SNP data in duplicated regions, challenges in mapping and typing the CNPs, and the possibility that CNPs in these regions have rearranged on multiple haplotype backgrounds. Our results underscore the need for complete maps of genetic variation in duplication-rich regions of the genome. C1 Univ Washington, Dept Gen Sci, Sch Med, Seattle, WA 98195 USA. Howard Hughes Med Inst, Seattle, WA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. Univ Chicago, Dept Genet, Chicago, IL 60637 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Eichler, EE (reprint author), Univ Washington, Dept Gen Sci, Sch Med, 1705 NE Pacific St, Seattle, WA 98195 USA. EM eee@gs.washington.edu RI Sharp, Andrew/A-5783-2008; McCarroll, Steven/A-8433-2009; Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NHGRI NIH HHS [HG002385, R01 HG002385]; NICHD NIH HHS [HD043569, R01 HD043569] NR 20 TC 229 Z9 232 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 2006 VL 79 IS 2 BP 275 EP 290 DI 10.1086/505653 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 063SR UT WOS:000239040400009 PM 16826518 ER PT J AU Oschatz, E Benesch, T Kodras, K Hoffmann, U Haas, M AF Oschatz, Elisabeth Benesch, Thomas Kodras, Katharina Hoffmann, Udo Haas, Martin TI Changes of coronary calcification after kidney transplantation SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE coronary calcification; mineral metabolism; transplantation ID STAGE RENAL-DISEASE; VASCULAR CALCIFICATION; ARTERY CALCIFICATION; DIALYSIS PATIENTS; HEMODIALYSIS-PATIENTS; COMPUTED-TOMOGRAPHY; YOUNG-ADULTS; CALCIUM; PATHOGENESIS; ANGIOGRAPHY AB Background: Coronary artery calcification (CAC) in patients with end-stage renal disease is driven by uremia and increased serum calcium and phosphate levels. Improvement in calcium-phosphate homeostasis and uremia by kidney transplantation therefore might favorably influence CAC. Methods: We measured the extent of CAC by using multidetector computed tomography in 31 patients immediately after transplantation and at 6 and 12 months' follow-up. Baseline and follow-up measurements were compared, and the effect of atherogenic factors on CAC progression was determined by means of multivariate regression analysis. Results: Mean total Agatston score increased significantly from baseline to 6 months (716 +/- 980 [SD] versus 916 +/- 1,307; P < 0.001), but remained unchanged at 12 months' follow-up (890 +/- 1,263; P = not significant). Progression of calcification was present only in patients with a baseline total Agatston score higher than 10. In these patients, the score increased from 964 +/- 1,028 to 1,234 +/- 1,385 (P < 0.001) at 6 months and remained stable thereafter (1,199 +/- 1,338; P = not significant). Duration of pretransplantation dialysis treatment and smoking were identified as independent predictors of posttransplantation CAC progression. Conversely, changes in calcium and phosphate levels were not associated with calcification. Conclusion. This study shows that CAC progresses during the early posttransplantation course, but slows between 6 and 12 months after transplantation. The extent of early calcification is influenced mainly by dialysis treatment duration and smoking. C1 Univ Hosp Vienna, Div Nephrol & Dialysis, Dept Internal Med 3, A-1090 Vienna, Austria. Univ Hosp Vienna, Inst Med Stat, Dept Radiol, A-1090 Vienna, Austria. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Haas, M (reprint author), Univ Hosp Vienna, Div Nephrol & Dialysis, Dept Internal Med 3, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM martin.haas@meduniwien.ac.at NR 21 TC 35 Z9 36 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2006 VL 48 IS 2 BP 307 EP 313 DI 10.1053/j.ajkd.200604.066 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 071UP UT WOS:000239629700016 PM 16860198 ER PT J AU Dicianno, BE Spaeth, DM Cooper, RA Fitzgerald, SG Boninger, ML AF Dicianno, Brad E. Spaeth, Donald M. Cooper, Rory A. Fitzgerald, Shirley G. Boninger, Michael L. TI Advancements in power wheelchair joystick technology: Effects of isometric joysticks and signal conditioning on driving performance SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE assistive technology; isometric; joystick; movement disorders; rehabilitation; wheelchairs ID POSITION; TREMOR; SUPPRESSION AB Objective: An estimated 125 000 Americans with movement disorders; that preclude independent mobility in a power wheelchair could benefit from improved control devices. We developed variable gain algorithm (VGA) software for our isometric Joystick OX that allows it to emulate a commercially available motion-sensing joystick (MSX 'in performance but retain the unique customizable features of an isometric control. Force sensing algorithm (FSA) software allowed the IJ to function as a simple isometric device. Design: Using a Fitts' Law paradigm, we compared driving performance with floor targets using a standard MSJ and an U with both FSA and VGA software in 11 electric power wheelchair users with a variety of impairments. Outcome measures were reaction time (RT), movement time (MT), and driving accuracy (DA). Results: The IJ with FSA had a significantly shorter RT than the MSJ (P < 0.0020). The IJ with FSA had a significantly longer MT than the MSJ to far targets (P < 0.0159). No differences were found between the IJ with VGA and the MSJ with respect to RT or MT. No differences in DA were found among any of the joysticks. Conclusions: VGA software allowed the IJ to function similarly to the MSJ with respect to RT, MT, and DA. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Associated Rehabil E, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Human Engn Res Labs, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Associated Rehabil E, 7180 Highland Dr,Bldg 4,2nd Floor E,151R1-H, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X; Dicianno, Brad/0000-0003-0738-0192 FU NICHD NIH HHS [K12HD01097] NR 26 TC 18 Z9 18 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2006 VL 85 IS 8 BP 631 EP 639 DI 10.1097/01.phm.0000228519.54763.b4 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 073AK UT WOS:000239714400001 PM 16865017 ER PT J AU Wermemer, HK Borg-Stein, J Comba, L Delaney, B Rothmund, A Barlow, D Breeze, G Thompson, A AF Wermemer, Heidi K. Borg-Stein, Joanne Comba, Lorraine Delaney, Bobbi Rothmund, Astrid Barlow, David Breeze, Gail Thompson, Anita TI Functionally oriented rehabilitation program for patients with fibromyalgia - Preliminary results SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE fibromyalgia; exercise; pain; rehabilitation; treatment ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; EXERCISE; QUESTIONNAIRE; FATIGUE AB Objective: To evaluate function and disability in patients with fibromyalgia before and after participation in a functionally oriented, multidisciplinary, 8-wk treatment program. Design: A total of 23 patients who met American College of Rheumatology criteria for the diagnosis of fibromyalgia were enrolled in the study. Outcome measures included: range of motion, 6-min walk test, a modified Fibromyalgia Impact Questionnaire, a modified SF-36 Physical Functioning Scale, and the Fibromyalgia Health Assessment Questionnaire. Pretreatment and posttreatment scores were analyzed using paired t tests. Results: All subjects completed the program, and there were no reported injuries. Three subjects failed to complete the survey instruments at the conclusion of the study. Intention to treat analysis including these subjects was carried out but did not significantly change results. For the remaining subjects (n = 20), a significant improvement was found on the Physical Functioning Scale (P 0.0 1). Trends toward improvement on the Fibromyalgia Impact Questionnaire (P = 0.40) and Fibromyalgia Health Assessment Questionnaire (P = 0.14) were seen but did not achieve statistical significance. Range of motion testing revealed significant improvements in lumbar spine extension (P < 0.001), straight-leg raise (P < 0.001), cervical spine flexion (P < 0.01), cervical spine rotation (P < 0.05), and cervical spine side bending (P < 0.05). Distance traveled during the 6-min walk test increased significantly (P < 0.01), whereas perceived exertion as measured by the Borg scale did not change. There were no injuries or other adverse consequences of the program. Conclusions: This study utilized multiple functional outcome measures to demonstrate improved function and decreased disability in patients with fibromyalgia. Our patients reported significantly improved physical function after participation in the 8-wk intensive multidisciplinary treatment program. This progressive, functionally based exercise training program was well tolerated by all participants and outlines an effective exercise prescription for patients with fibromyalgia. Fibromyalgia patients in this study responded favorably to a treatment program that focused on function instead of pain. C1 VA Boston Hlth Care Syst, W Roxbury Div, Spinal Cord Injury Unit 128, W Roxbury, MA 02132 USA. Spaulding Wellesley Rehabil Hosp, Wellesley, MA USA. RP Wermemer, HK (reprint author), VA Boston Hlth Care Syst, W Roxbury Div, Spinal Cord Injury Unit 128, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 19 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2006 VL 85 IS 8 BP 659 EP 666 DI 10.1097/phm.0000228677.46845.b2 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 073AK UT WOS:000239714400004 ER PT J AU Neilan, TG Doherty, GA Chen, G Deflandre, C McAllister, H Butler, RK McClelland, SE Kay, E Ballou, LR Fitzgerald, DJ AF Neilan, Tomas G. Doherty, Glen A. Chen, Gang Deflandre, Catherine McAllister, Hester Butler, Ryan K. McClelland, Sarah E. Kay, Elaine Ballou, Leslie R. Fitzgerald, Desmond J. TI Disruption of COX-2 modulates gene expression and the cardiac injury response to doxorubicin SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE apoptosis; cyclooxygenase ID METASTATIC BREAST-CANCER; PROSTAGLANDIN-E RECEPTOR; INDUCED APOPTOSIS; CYCLOOXYGENASE-2-DEFICIENT MICE; ISCHEMIA/REPERFUSION INJURY; INDUCED CARDIOMYOPATHY; ENDOTHELIAL-CELLS; PPAR-ALPHA; INHIBITION; PROTECTS AB Disruption of COX-2 modulates gene expression and the cardiac injury response to doxorubicin. Am J Physiol Heart To determine the role of cyclooxygenase (COX)-2 in anthracycline-induced cardiac toxicity, we administered doxorubicin (Dox) to mice with genetic disruption of COX-2 (COX-2(-/-)). After treatment with Dox, COX-2(-/-) mice had increased cardiac dysfunction and cardiac cell apoptosis compared with Dox-treated wild-type mice. The expression of the death-associated protein kinase- related apoptosis-inducing protein kinase-2 was also increased in Dox-treated COX-2(-/-) animals. The altered gene expression, cardiac injury, and dysfunction after Dox treatment in COX-2(-/-) mice was attenuated by a stable prostacyclin analog, iloprost. Wild-type mice treated with Dox developed cardiac fibrosis that was absent in COX-2(-/-) mice and unaffected by iloprost. These results suggest that genetic disruption of COX-2 increases the cardiac dysfunction after treatment with Dox by an increase in cardiac cell apoptosis. This Dox-induced cardiotoxicity in COX-2(-/-) mice was attenuated by a prostacyclin analog, suggesting a protective role for prostaglandins in this setting. C1 Royal Coll Surgeons Ireland, Dept Clin Pharmacol, Inst Pharmaceut Sci, Dublin 2, Ireland. Beaumont Hosp, Dept Surg, Dublin 9, Ireland. Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. Univ Coll Dublin, Dept Vet Med, Dublin 2, Ireland. Univ Tennessee, Dept Vet Affairs Med Ctr, Memphis, TN USA. Univ Tennessee, Dept Med, Memphis, TN USA. Univ Tennessee, Dept Mol Sci, Memphis, TN USA. RP Neilan, TG (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM tneilan@partners.org NR 34 TC 18 Z9 20 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 2006 VL 291 IS 2 BP H532 EP H536 DI 10.1152/ajpheart.00863.2005 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 063LS UT WOS:000239020300006 PM 16617129 ER PT J AU Soberman, RJ Christmas, P AF Soberman, Roy J. Christmas, Peter TI Revisiting prostacyclin: new directions in pulmonary fibrosis and inflammation SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Editorial Material ID FIBROBLAST PROLIFERATION; ARTERIAL-HYPERTENSION; PROSTAGLANDIN-E-2; MICE C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Soberman, RJ (reprint author), Massachusetts Gen Hosp, Renal Unit, CNY8,Bldg 149,Navy Yard,13th St, Charlestown, MA 02129 USA. EM soberman@helix.mgh.harvard.edu FU NIAID NIH HHS [1R56 AI068871-01]; NIGMS NIH HHS [5R01GM-68123-04] NR 12 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2006 VL 291 IS 2 BP L142 EP L143 DI 10.1152/ajplung.00102.2006 PG 2 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 060ZL UT WOS:000238840900002 PM 16581828 ER PT J AU Chang, L Mayer, EA Labus, JS Schmulson, M Lee, OY Olivas, TI Stains, J Naliboff, BD AF Chang, Lin Mayer, Emeran A. Labus, Jennifer S. Schmulson, Max Lee, Oh Young Olivas, Teresa I. Stains, Jean Naliboff, Bruce D. TI Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE visceral perception; gender ID GENDER-RELATED DIFFERENCES; QUALITY-OF-LIFE; TEMPORAL SUMMATION; COLONIC TRANSIT; FIBROMYALGIA SYNDROME; RECTAL DISTENSION; PRIMARY-CARE; IBS PATIENTS; WIND-UP; PAIN AB In irritable bowel syndrome (IBS) patients, the relationship between sex and sensitivity to visceral stimuli is incompletely understood. Our aim was to evaluate the effect of sex on perceptual responses to visceral stimulation in IBS. Fifty-eight IBS patients (mean age 42 +/- 1 yr; 34 men, 24 women) and 26 healthy controls (mean age 38 +/- 3 yr; 9 men, 17 women) underwent barostat-assisted distensions of the rectum and sigmoid colon. Rectal discomfort thresholds were measured using a randomized, phasic distension paradigm before and after repeated noxious sigmoid stimulation (SIG, 60-mmHg pulses). Sex had a significant effect on rectal discomfort thresholds. Women with IBS were the most sensitive ( lower thresholds [27 +/- 2.7 mmHg] and higher ratings), with significantly lower rectal discomfort thresholds compared with men with IBS (38 +/- 2.3 mmHg) and healthy women who were the least sensitive (41.9 +/- 3.2 mmHg; both P < 0.01). There were no significant differences in rectal discomfort thresholds between healthy men (34 +/- 4.3 mmHg) and men with IBS. Across both IBS and control groups, women demonstrated a significant lowering of discomfort thresholds after noxious sigmoid stimulation (P < 0.01), while men did not. Sex significantly influences perceptual sensitivity to rectosigmoid distension. Women show greater perceptual responses to this paradigm. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Nacl Autonoma Mexico, Sch Med, Dept Expt Med, Mexico City 04510, DF, Mexico. Hanyang Univ, Coll Med, Dept Internal Med, Seoul 133791, South Korea. RP Chang, L (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,RM 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM linchang@ucla.edu FU NCCIH NIH HHS [R24 AT-002681]; NIAMS NIH HHS [AR-41622]; NIDDK NIH HHS [P50 DK-64539, DK-48351] NR 60 TC 53 Z9 54 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD AUG PY 2006 VL 291 IS 2 BP R277 EP R284 DI 10.1152/ajpregu.00729.2005 PG 8 WC Physiology SC Physiology GA 060LF UT WOS:000238803000005 PM 16574882 ER PT J AU Kagay, CR Quale, C Smith-Bindman, R AF Kagay, Christopher R. Quale, Christopher Smith-Bindman, Rebecca TI Screening mammography in the American elderly SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID BREAST-CANCER SURVIVAL; BILLING CLAIMS DATA; MEDICARE BENEFICIARIES; OLDER WOMEN; PREVENTIVE SERVICES; ADMINISTRATIVE DATA; RACIAL-DIFFERENCES; STAGE; HISPANICS; ETHNICITY AB Background: Substantial differences exist in estimates of the proportion of elderly women who undergo screening mammography and the impact of race and ethnicity on mammography usage. Methods: A representative 5% sample of elderly women living in 11 Surveillance, Epidemiology, and End Results areas from 1991 to 2001 was constructed using Medicare data. Biennial rates of screening mammography (at least one mammogram within each 2-year period) were calculated for overlapping 2-year periods, adjusting to a 2000-2001 age and race distribution. Multivariate repeated-measures logistic regression was used to examine predictors of screening usage. Results: The sample included 146,669 women. Between 1991 and 2001 the age- and race-adjusted proportion of women aged 65 years and older who underwent at least biennial screening mammography increased from 35.8% to 47.9%. Mammography screening increased for all racial and ethnic groups, but remained significantly higher for non-Hispanic white women as compared with all other groups. The biennial screening rate in 2000-2001 was 50.6% for non-Hispanic white, 40.5% for African-American, 34.7% for Asian-American, 36.3% for Hispanic, and 12.5% for Native-American women. After controlling for age, site, physician access, comorbidities, education, and income, African Americans (odds ratio [OR] = 0.80, 95% confidence interval [CI] = 0.78-0.83), Asian Americans (OR = 0.53, CI = 0.51-0.55), Hispanics (OR = 0.70, CI = 0.67-0.74), and Native Americans (OR = 0.37, CI = 0.29-0.46) were still all less likely than non-Hispanic white women to undergo screening. Conclusions: Elderly women undergo significantly less mammography screening than is suggested by self-reported surveys. All groups of non-white women undergo less screening than do white women. The magnitude of the difference in screening rates comparing Asian-American and Hispanic women with white women is especially large; however, other studies have questioned the sensitivity of Medicare data for identifying people of Asian and Hispanic ethnicity. For African-American women, the magnitude of the gap is smaller, but it is of concern that the gap in screening as compared with white women has grown over time. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Smith-Bindman, R (reprint author), 1600 Divisadero St,Rm C-250, San Francisco, CA 94115 USA. EM ckagay@partners.org; Rebecca.smith-bindman@radiology.ucsf.edu FU NCI NIH HHS [K07 CA86032] NR 51 TC 49 Z9 49 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD AUG PY 2006 VL 31 IS 2 BP 142 EP 149 DI 10.1016/j.amepre.2006.03.029 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 065UP UT WOS:000239185600005 PM 16829331 ER PT J AU Matthews, AM Fireman, M Zucker, B Sobel, M Hauser, P AF Matthews, Annette M. Fireman, Marian Zucker, Betsy Sobel, Michelle Hauser, Peter TI Relapse to opioid use after treatment of chronic hepatitis C with pegylated interferon and ribavirin SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID INJECTION-DRUG USERS; METHADONE-MAINTENANCE; VIRUS-INFECTION; SUBSTANCE USE; DISORDERS; THERAPY C1 Portland VA Med Ctr, NW Hepatitis Resource Ctr C, JENS Lab, Gastroenterol Sect, Portland, OR 97202 USA. Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97202 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97202 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97202 USA. RP Matthews, AM (reprint author), Portland VA Med Ctr, NW Hepatitis Resource Ctr C, JENS Lab, Gastroenterol Sect, 3710 SW US Vet Hosp Rd,POB 1035 V3MHC, Portland, OR 97202 USA. EM annette.matthews@med.va.gov NR 22 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2006 VL 163 IS 8 BP 1342 EP 1347 DI 10.1176/appi.ajp.163.8.1342 PG 6 WC Psychiatry SC Psychiatry GA 068FT UT WOS:000239358800009 PM 16877644 ER PT J AU Viswanath, K Steele, WR Finnegan, JR AF Viswanath, Kasisomayajula Steele, Whitney Randolph Finnegan, John R., Jr. TI Social capital and health: Civic engagement, community size, and recall of health messages SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SELF-RATED HEALTH; INCOME INEQUALITY; CARDIOVASCULAR-DISEASE; WIDE PREVENTION; PUBLIC-HEALTH; COMMUNICATION; STRATEGIES; PROGRAM; DISCRIMINATION; INFORMATION AB Objectives. We explored the effects of community integration and pluralism on recall of cardiovascular disease health information messages. Methods. With 1980-1983 data from the Minnesota Heart Health Program, we examined whether ties to community groups were associated with recall of health messages, and whether this relation was modified by size and degree of differentiation of the community. Results. A higher level of civic engagement through ties to community groups was associated with better recall of health messages. Ties to community groups independently contributed to better message recall even after control for gender, education, and other variables. The moderating role of community size was nonsignificant but intriguing. Conclusions. Community group membership could increase exposure to health messages, providing a critical pathway for social capital to influence health promotion and, thus, public health outcomes. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Viswanath, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, SM 251,44 Binney St, Boston, MA 02115 USA. EM vish_viswanath@dfci.harvard.edu NR 51 TC 61 Z9 61 U1 0 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2006 VL 96 IS 8 BP 1456 EP 1461 DI 10.2105/AJPH.2003.029793 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 070NR UT WOS:000239530000026 PM 16809608 ER PT J AU Tindle, HA Rigotti, NA Davis, RB Barbeau, EM Kawachi, I Shiffman, S AF Tindle, Hilary A. Rigotti, Nancy A. Davis, Roger B. Barbeau, Elizabeth M. Kawachi, Ichiro Shiffman, Saul TI Cessation among smokers of "light" cigarettes: Results from the 2000 National Health Interview Survey SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID YIELD CIGARETTES; HARM REDUCTION; LUNG-CANCER; NICOTINE; BELIEFS; SMOKING; BRAND; RISK AB Objectives. A large proportion of smokers erroneously believe that low-nicotine/low-tar cigarettes, also called "light cigarettes" or "lights," reduce health risks and are a rational alternative to smoking cessation. However, the availability of light cigarettes may deter smoking cessation. Methods. We analyzed the 32374 responses to the US 2000 National Health Interview Survey. Current and former smokers ("ever-smokers") were asked if they had ever used a lower tar. and nicotine cigarette to reduce health risks. Multi-variable logistic regression identified determinants of lights use and smoking cessation. Results were weighted to reflect the national population. Results. Of 12285 ever-smokers, 37% (N=4414) reported having used light cigarettes to reduce health risks. Current abstinence was less often reported by eversmokers who had previously used light cigarettes than by ever-smokers who had never used lights (37% vs 53%, P <.01). Adjusted odds of cessation among eversmokers who had used light cigarettes relative to those who had never used lights were reduced by 54% (adjusted odds ratio=0.46, 95% confidence interval = 0.41, 0.51). Conclusions. Use of light cigarettes Was common and was associated with lower odds of current smoking cessation, validating the concern that smokers may use lights as an alternative to cessation. C1 Univ Pittsburgh, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Osher Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA. RP Tindle, HA (reprint author), Univ Pittsburgh, Parkvale Bldg,200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM tindleha@upmc.edu RI Shiffman, Saul/K-7337-2012 NR 32 TC 25 Z9 26 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2006 VL 96 IS 8 BP 1498 EP 1504 DI 10.2105/AJPH.2005.072785 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 070NR UT WOS:000239530000032 PM 16809583 ER PT J AU Harris, RS Winkler, T Tgavalekos, N Musch, G Melo, MFV Schroeder, T Chang, YC Venegas, JG AF Harris, R. Scott Winkler, Tilo Tgavalekos, Nora Musch, Guido Melo, Marcos F. Vidal Schroeder, Tobias Chang, Yuchiao Venegas, Jose G. TI Regional pulmonary perfusion, inflation, and ventilation defects in bronchoconstricted patients with asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE emission computed tomography; pulmonary gas exchange; vascular resistance; vasoconstriction; ventilation-perfusion ratio ID METHACHOLINE-INDUCED BRONCHOCONSTRICTION; BLOOD-FLOW DISTRIBUTION; THIN-SECTION CT; BIMODAL VENTILATION; EXERCISE CHALLENGE; BRONCHIAL-ASTHMA; AIRWAY-CLOSURE; LUNG-FUNCTION; GAS-EXCHANGE; PET AB Rationale: Bronchoconstriction in asthma leads to heterogeneous ventilation and the formation of large and contiguous ventilation defects in the lungs. However, the regional adaptations of pulmonary perfusion (Q) to such ventilation defects have not been well studied. Methods: We used positron emission tomography to assess the intrapulmonary kinetics of intravenously infused tracer nitrogen-13 ((NN)-N-13), and measured the regional distributions of ventilation and perfusion in 11 patients with mild asthma. For each subject, the regional washout kinetics of (NN)-N-13 before and during methacholine-induced bronchoconstriction were analyzed. Two regions of interest (ROIs) were defined: one over a spatially contiguous area of high tracer retention (TR) during bronchoconstriction and a second one covering an area of similar size, showing minimal tracer retention (NR). Results: Both ROIs demonstrated heterogeneous washout kinetics, which could be described by a two-compartment model with fast and slow washout rates. We found a systematic reduction in regional Q to the TR ROI during bronchoconstriction and a variable and nonsignificant change in relative Q for NR regions. The reduction in regional Q was associated with an increase in regional gas content of the TR ROI, but its magnitude was greater than that anticipated solely by the change in regional lung inflation. Conclusion: During methacholine-induced bronchoconstriction, perfusion to ventilation defects are systematically reduced by a relative increase in regional pulmonary vascular resistance. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Harris, RS (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM rharris@partners.org RI Winkler, Tilo/B-5337-2009; OI Winkler, Tilo/0000-0002-7276-5550; Schroeder, Tobias/0000-0002-4439-8060 FU NHLBI NIH HHS [HL-04501, HL-68011] NR 43 TC 59 Z9 60 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2006 VL 174 IS 3 BP 245 EP 253 DI 10.1164/rccm.200510-1634OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 068ZW UT WOS:000239415200007 PM 16690973 ER PT J AU Borges, JB Okamoto, VN Matos, GFJ Caramez, MPR Arantes, PR Barros, F Souza, CE Victorino, JA Kacmarek, RM Barbas, CSV Carvalho, CRR Amato, MBP AF Borges, Joao B. Okamoto, Valdelis N. Matos, Gustavo F. J. Caramez, Maria P. R. Arantes, Paula R. Barros, Fabio Souza, Ciro E. Victorino, Josue A. Kacmarek, Robert M. Barbas, Carmen S. V. Carvalho, Carlos R. R. Amato, Marcelo B. P. TI Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; mechanical ventilation; positive end-expiratory pressure; pulmonary shunt; recruitment strategy ID END-EXPIRATORY PRESSURE; GAS-EXCHANGE IMPAIRMENT; VENOUS OXYGEN-SATURATION; ARTERIAL PULSE PRESSURE; RECRUITMENT MANEUVERS; ALVEOLAR RECRUITMENT; PROTECTIVE-VENTILATION; FLUID-RESPONSIVENESS; COMPUTED-TOMOGRAPHY; GENERAL-ANESTHESIA AB Rationale: The hypothesis that lung collapse is detrimental during the acute respiratory distress syndrome is still debatable. One of the difficulties is the lack of an efficient maneuver to minimize it. Objectives: To test if a bedside recruitment strategy, capable of reversing hypoxemia and collapse in > 95% of lung units, is clinically applicable in early acute respiratory distress syndrome. Methods: Prospective assessment of a stepwise maximum-recruitment strategy using multislice computed tomography and continuous blood-gas hemodynamic monitoring. Measurements and Main Results: Twenty-six patients received sequential increments in inspiratory airway pressures, in 5 cm H2O steps, until the detection of Pa-O2 + Pa-CO2 >= 400 mm Hg. Whenever this primary target was not met, despite inspiratory pressures reaching 60 cm H2O, the maneuver was considered incomplete. If there was hemodynamic deterioration or barotrauma, the maneuver was to be interrupted. Late assessment of recruitment efficacy was performed by computed tomography (9 patients) or by online continuous monitoring in the intensive care unit (15 patients) up to 6 h. It was possible to open the lung and to keep the lung open in the majority (24/26) of patients, at the expense of transient hemodynamic effects and hypercapnia but without major clinical consequences. No barotrauma directly associated with the maneuver was detected. there was a strong and inverse relationship between arterial oxygenation and percentage of collapsed lung mass (R - 0.91; P < 0.0001). Conclusions: It is often possible to reverse hypoxemia and fully recruit the lung in early acute respiratory distress syndrome. Due to transient side effects, the required maneuver still awaits further evaluation before routine clinical application. C1 Univ Sao Paulo, Hosp Clin, Resp Intens Care Unit, Dept Pulm, Sao Paulo, Brazil. Univ Sao Paulo, Hosp Clin, Gen Intens Care Unit, Emergency Clin Div, Sao Paulo, Brazil. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Amato, MBP (reprint author), Univ Sao Paulo, Lab Pneumol LIM09, Fac Med, Av Dr Arnaldo 455,Sala 2206,2nd Floor, BR-01246903 Sao Paulo, Brazil. EM armato@unisys.com.br RI Carvalho, Carlos/H-2161-2011 NR 79 TC 233 Z9 269 U1 1 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2006 VL 174 IS 3 BP 268 EP 278 DI 10.1164/rccm.200506-97OC PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 068ZW UT WOS:000239415200010 PM 16690982 ER PT J AU Burman, WJ Goldberg, S Johnson, JL Muzanye, G Eagle, M Mosher, AW Choudhri, S Daley, CL Munsiff, SS Zhao, Z Vernon, A Chaisson, RE AF Burman, William J. Goldberg, Stefan Johnson, John L. Muzanye, Grace Eagle, Melissa Mosher, Ann W. Choudhri, Shurjeel Daley, Charles L. Munsiff, Sonal S. Zhao, Zhen Vernon, Andrew Chaisson, Richard E. CA Tuberculosis Trials Consortium TI Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE efficacy; moxifloxacin; randomized trial; toxicity; tuberculosis ID EARLY BACTERICIDAL ACTIVITY; MYCOBACTERIUM-TUBERCULOSIS; MURINE TUBERCULOSIS; CONTAINING REGIMENS; WEEKLY RIFAPENTINE; GATIFLOXACIN; OFLOXACIN; DURATION; THERAPY; CULTURE AB Rationale: Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans. Objective: To compare the impact of moxifloxacin versus ethambutol, both in combination with isoniazid, rifampin, and pyrazinamide, on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens. Methods: Adults with smear-positive pulmonary tuberculosis were randomized in a factorial design to receive moxifloxacin (400 mg) versus ethambutol given 5 d/wk versus 3 d/wk (after 2 wk of daily therapy). All doses were directly observed. Measurements: The primary endpoint was sputum culture status at 2 mo of treatment. Results: Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy. Conclusions: The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points. C1 Denver Publ Hlth, Denver, CO USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. Case Western Reserve Univ, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Uganda Case Western Res Univ Res Collobarat, Kampala, Uganda. S Tex Vet Hlth Care Syst, San Antonio, TX USA. Duke Univ, Med Ctr, Durham, NC USA. Bayer Inc, West Haven, CT USA. New York City Dept Hlth & Mental Hyg, New York, NY USA. Johns Hopkins Univ, Ctr TB Res, Baltimore, MD USA. RP Burman, WJ (reprint author), 605 Bannock St, Denver, CO 80204 USA. EM bburman@dhha.org NR 34 TC 184 Z9 196 U1 1 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2006 VL 174 IS 3 BP 331 EP 338 DI 10.1164/rccm.200603-360OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 068ZW UT WOS:000239415200018 PM 16675781 ER PT J AU McLoud, TC AF McLoud, Theresa C. TI "A system for the clinical staging of lung cancer" - A commentary SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE cancer; cardiopulmonary imaging; chest imaging; lung disease ID BRONCHOGENIC-CARCINOMA; CT; TOMOGRAPHY; PET C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders 216,Fruit St, Boston, MA 02114 USA. NR 14 TC 2 Z9 2 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 AUG PY 2006 VL 187 IS 2 BP 269 EP 270 DI 10.2214/AJR.05.1968 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 068FX UT WOS:000239359200004 PM 16861526 ER PT J AU DeFrate, LE Papannagari, R Gill, TJ Moses, JM Pathare, NP Li, G AF DeFrate, Louis E. Papannagari, Ramprasad Gill, Thomas J. Moses, Jeremy M. Pathare, Neil P. Li, Guoan TI The 6 degrees of freedom kinematics of the knee after anterior cruciate ligament deficiency - An in vivo imaging analysis SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anterior cruciate ligament (ACL); knee kinematics; ACL reconstruction; imaging ID JOINT KINEMATICS; BIOMECHANICAL CONSEQUENCES; TIBIOFEMORAL KINEMATICS; CARTILAGE CONTACT; FLEXION; ACL; GRAFT; OSTEOARTHRITIS; RECONSTRUCTION; WEIGHTBEARING AB Background: Previous studies of knee joint function after anterior cruciate ligament deficiency have focused on measuring anterior-posterior translation and internal-external rotation. Few studies have measured the effects of anterior cruciate ligament deficiency on 6 degrees of freedom knee kinematics in vivo. Objective: To measure the 6 degrees of freedom knee kinematics of patients with anterior cruciate ligament deficiency. Study Design: Controlled laboratory study. Methods: The knee joint kinematics of 8 patients with unilateral anterior cruciate ligament rupture was measured during a quasistatic lunge. Kinematics was measured from full extension to 90 degrees of flexion using imaging and 3-dimensional modeling techniques. The healthy, contralateral knee of each patient served as a control. Results: Anterior cruciate ligament deficiency caused a statistically significant anterior shift (approximately 3 mm) and internal rotation of the tibia (approximately 20) at low flexion angles. However, ligament deficiency also caused a medial translation of the tibia (approximately 1 mm) between 151 and 900 of flexion. Conclusion: The medial shift of the tibia after anterior cruciate ligament deficiency might alter contact stress distributions in the tibiofemoral cartilage near the medial tibial spine. These findings correlate with the observation that osteoarthritis in patients with anterior cruciate ligament injuries is likely to occur in this region. Clinical Relevance: The data from this study suggest that future anterior cruciate ligament reconstruction techniques should reproduce not only anterior stability but also medial-lateral stability. C1 Harvard Univ, Bioengn Lab, Sch Med, Massachusetts Gen Hosp,Dept Orthopaed Surg, Boston, MA 02114 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Li, G (reprint author), Harvard Univ, Bioengn Lab, Sch Med, Massachusetts Gen Hosp,Dept Orthopaed Surg, GRJ 1215,55 Fruit St, Boston, MA 02114 USA. EM gli1@partners.org FU NIAMS NIH HHS [R01 AR052408] NR 31 TC 131 Z9 137 U1 0 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD AUG PY 2006 VL 34 IS 8 BP 1240 EP 1246 DI 10.1177/0363546506287299 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 065OG UT WOS:000239168600004 PM 16636348 ER PT J AU Finan, KR Leeth, RR Whitley, BM Klapow, JC Hawn, MT AF Finan, Kelly R. Leeth, Ruth R. Whitley, Bryan M. Klapow, Joshua C. Hawn, Mary T. TI Improvement in gastrointestinal symptoms and quality of life after cholecystectomy SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE laparoscopic cholecystectomy; symptom improvement; biliary symptom; quality of life; effectiveness ID LAPAROSCOPIC CHOLECYSTECTOMY; ABDOMINAL SYMPTOMS; ACUTE CHOLECYSTITIS; RANDOMIZED-TRIAL; IMPACT; GALLSTONES; SURGERY; PATTERNS; OUTCOMES; DISEASE AB Background: Laparoscopic cholecystectomy (LC) is the accepted treatment for symptomatic cholelithiasis but has been criticized as an over-used procedure. This study assesses the effectiveness of LC on reduction in gastrointestinal (GI) symptoms and the impact on quality of life (QOL). Methods: A prospective cohort of subjects evaluated for gallstone disease between August 2001 and July 2004 completed preoperative and postoperative GI gallbladder symptom surveys (GISS) and SF36 QOL surveys. The GISS was developed to quantify the magnitude, severity, and distressfulness of 16 GI symptoms. Surveys were scored and evaluated using paired t tests. Results: Fifty-five subjects were included in the final analysis. The GISS revealed significant improvement in biliary type symptoms but not reflux or irritable bowel symptoms after LC (P > .05). Significant improvement was seen in QOL (P < .01). Conclusion: This study supports the utility of LC by showing not only a significant reduction of GI symptoms but also marked improvement in patients' general QOL. (c) 2006 Excerpta Medica Inc. All rights reserved. C1 Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL 35294 USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. RP Hawn, MT (reprint author), Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, KB 429,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mhawn@uab.edu NR 37 TC 18 Z9 18 U1 1 U2 4 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD AUG PY 2006 VL 192 IS 2 BP 196 EP 202 DI 10.1016/j.amjsurg.2006.01.020 PG 7 WC Surgery SC Surgery GA 071EK UT WOS:000239580900010 PM 16860629 ER PT J AU Irving, JA Alkushi, A Young, RH Clement, PB AF Irving, Julie A. Alkushi, Abdulmohsen Young, Robert H. Clement, Philip B. TI Cellular fibromas of the ovary: A study of 75 cases including 40 mitotically active tumors emphasizing their distinction from fibrosarcoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; cellular fibroma; fibrosarcoma ID SEX CORD ELEMENTS; FEMALE GENITAL-TRACT; OF-THE-LITERATURE; STROMAL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; FIBROTHECOMATOUS TUMOR; LUTEINIZED THECOMAS; CD10 EXPRESSION; CARCINOMA; SURVIVAL AB Cellular fibroblastic tumors of the ovary are currently classified as either cellular fibroma (CF) or fibrosarcoma. The former are characterized by bland nuclei, 3 or fewer mitotic figures per 10 high-power fields (MFs/10 HPFs), and a low malignant potential, whereas fibrosarcomas usually have severe nuclear atypia, 4 MFs/10 HPFs, and an aggressive clinical course. The prognosis of cellular fibromatous tumors with >= 4 MFs/10 HPFs and low-grade cytology is not established and it is the purpose of this study to investigate that aspect. It has been our anecdotal experience that otherwise typical CFs with >= 4 MFs/10 HPFs usually have a benign clinical course, suggesting that such tumors should be regarded as "mitotically active cellular fibroma" (MACF) rather than fibrosarcoma. Seventy-five cellular fibromatous neoplasms were analyzed to determine their clinicopathologic features and the appropriateness of "MACF" as a designation for otherwise typical CFs with >= 4 MFs/10 HPFs. The mean age of patients with CF (n = 35, 0 to 3 MFs/10 HPFs) and MACF (n = 40, >= 4 MFs/10 HPFs) was 51 and 41 years, respectively. Patients most commonly presented with symptoms related to a pelvic mass. All tumors were unilateral. The mean tumor size of CFs was 8.0cm and 9.4cm for MACFs. The majority of the tumors were solid; approximately one-third of them had a cystic component. Ovarian surface adhesions, involvement of the ovarian surface, or both, was present in 6% of CFs and 10% of MACFs. Eleven percent of CFs and 13% of MACFs were associated with extraovarian involvement. All tumors consisted of cellular, intersecting bundles of spindle cells with bland nuclear features. The mean highest mitotic count for MACFs was 6.7 MFs/10 HPFs (range 4 to 19 MFs/10 HPFs). Follow-up of 3 months to 12 years (mean 4.75 y) was available in 18 of the 40 patients with MACFs and was uneventful in all cases. We conclude that cellular fibromatous neoplasms with bland cytology and elevated mitotic counts are associated with favorable patient outcome and should be diagnosed as MACF rather than fibrosarcoma, which usually have moderate to severe atypia and elevated mitotic rates. As prior observations have shown that even typical CFs can occasionally recur locally, particularly if they are associated with rupture or adherence, long-term follow-up for patients with CFs and MACFs is appropriate. C1 Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. King Fahad Natl Guard Hosp, Dept Pathol & Lab Med, Riyadh, Saudi Arabia. Massachusetts Gen Hosp, James Horner Wright Pathol Labs, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Irving, JA (reprint author), Vancouver Gen Hosp, Dept Pathol, 855 W 12th Ave,1st Floor JPPN, Vancouver, BC V5Z 1M9, Canada. EM Julie.Irving@vch.ca NR 35 TC 38 Z9 44 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 AUG PY 2006 VL 30 IS 8 BP 929 EP 938 DI 10.1097/00000478-200608000-00001 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 068ZO UT WOS:000239414400001 PM 16861962 ER PT J AU Smith, RN Kawai, T Boskovic, S Nadazdin, O Sachs, DH Cosimi, AB Colvin, RB AF Smith, R. N. Kawai, T. Boskovic, S. Nadazdin, O. Sachs, D. H. Cosimi, A. B. Colvin, R. B. TI Chronic antibody mediated rejection of renal allografts: Pathological, serological and immunologic features in nonhuman primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE alloantibodies; chronic rejection; primate ID ACUTE HUMORAL REJECTION; CHRONIC VASCULAR REJECTION; CLASS-I MOLECULES; CYNOMOLGUS MONKEYS; KIDNEY-TRANSPLANTATION; PERITUBULAR CAPILLARIES; ENDOTHELIAL-CELLS; MIXED CHIMERISM; C4D DEPOSITION; HLA ANTIBODIES AB The pathogenesis of late renal allograft loss is heterogeneous and difficult to diagnose. We have analyzed renal allografts in nonhuman primates to determine the relationship between alloantibodies and the graft pathology of late graft loss. Seventeen Cynomolgus monkeys were chosen from among those on several protocols for renal allotransplantation with mixed chimerism induction so that animals with and without alloantibodies were included. All animals received transient CD154 blockade and short-term cyclosporine treatment until day 28. Serial blood samples were tested for alloantibodies. Protocol biopsies and autopsy kidneys were scored for pathology and C4d deposition. Group 1, defined by complete lack of C4d deposition (24 tissue samples; 8 recipients), had no detectable alloantibodies (33 serum samples; 1-7 samples per recipient) and no evidence of chronic rejection. Three survived greater than 2 years with normal function and histology. Group 2, defined as having C4d deposition in peritubular capillaries, all made alloantibodies (100%), and most grafts later showed chronic allograft glomerulopathy (89%), and/or arteriopathy (89%). All grafts in Group 2 failed (3-27 months). Pathologic lesions of typical of chronic rejection in humans develop in monkeys, correlate with antecedent alloantibodies/C4d deposition and predict chronic rejection rather than durable accommodation. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Smith, RN (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM smith.rex@mgh.harvard.edu FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [R01 AI037692, R01 AI037692-09, R21 AI037692, R21 AI037692-06, R01 AI037692-10] NR 51 TC 42 Z9 44 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD AUG PY 2006 VL 6 IS 8 BP 1790 EP 1798 DI 10.1111/j.1600-6143.2006.01351.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 061NQ UT WOS:000238879700009 PM 16780551 ER PT J AU Saab, S Shpaner, A Zhao, Y Brito, I Durazo, F Han, S Farmer, DG Ghobrial, RM Yersiz, H Goldstein, LI Tong, MJ Busuttil, RW AF Saab, S. Shpaner, A. Zhao, Y. Brito, I. Durazo, F. Han, S. Farmer, D. G. Ghobrial, R. M. Yersiz, H. Goldstein, L. I. Tong, M. J. Busuttil, R. W. TI Prevalence and risk factors for diabetes mellitus in moderate term survivors of liver transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE diabetes mellitus; liver transplantation ID HEPATITIS-C; RECIPIENTS; DISEASE; IMPACT; COMPLICATIONS; METABOLISM; MANAGEMENT; INFECTION; CIRRHOSIS; THERAPY AB The prevalence and risk factors for diabetes mellitus after liver transplantation are not well understood. Thus, we sought to identify independent risk factors for the development of diabetes after liver transplantation using currently accepted medical criteria. We studied the prevalence and risk factors in 253 adult recipients transplanted at UCLA between January 1998 and December 2002. Analysis of the retrospective data was performed using demographic, immunosuppression and liver disease variables. Factors found to be significant on a univariate analysis were further studied in a multivariate analysis. There were 158 men and 95 women in our study. The mean age was 51.4 +/- 11.0 years. The mean [+/- standard deviation (SD) pretransplant body mass index was 26.7 (+/- 5.1). Most patients were transplanted for hepatitis C (HCV). The prevalence of diabetes after transplantation was 17.8%. In a multivariate analysis only gender [odds ratio (OR) = 0.37; p = 0.02] was independently predictive of the development of diabetes. This study in a large liver transplant recipient population identifies male gender as an independent risk factor for the development of diabetes. Follow-up studies are needed to assess the impact of diabetes, and its intervention on post-transplant morbidity and mortality. C1 Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Liver Transplant Ctr, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. Huntington Med Res Inst, Pasadena, CA USA. RP Saab, S (reprint author), Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA 90024 USA. EM Ssaab@mednet.ucla.edu NR 42 TC 37 Z9 40 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD AUG PY 2006 VL 6 IS 8 BP 1890 EP 1895 DI 10.1111/j.1600-6143.2006.01385.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 061NQ UT WOS:000238879700020 PM 16889544 ER PT J AU Beffa, DC Carter, EA Lu, XM Yu, YM Prelack, K Sheridan, RL Young, VR Fischman, AJ Tompkins, RG AF Beffa, David C. Carter, Edward A. Lu, Xiao-Ming Yu, Yong-Ming Prelack, Kathrina Sheridan, Robert L. Young, Vernon R. Fischman, Alan J. Tompkins, Ronald G. TI Negative chemical ionization gas chromatography/mass spectrometry to quantify urinary 3-methylhistidine: Application to burn injury SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE 3-methylhistidine; 3MH; burns; burn injury; negative chemical ionization; NCI; rat; human; method; gas chromatography; mass spectrometry.; GC/MS ID RABBIT SKELETAL-MUSCLE; N-TAU-METHYLHISTIDINE; AMINO-ACID SEQUENCE; PROTEIN-METABOLISM; THERMAL-INJURY; CHILDREN; NITROGEN; GLUCOSE; ACTIN AB A rapid method for measuring 3 -methylhistidine (3MH) in rat and human urine with higher sensitivity and precision than any previously reported method is described using internal standard [1-C-13]3MH (M + 1) and negative chemical ionization (NCI) gas chromatography/mass spectrometry (GUMS). Internal standard [1-C-13]3MH (M + 1) was added to rat and human urine samples, hydrolyzed, and absorbed onto cation exchange columns. The column eluent was dried and derivatized for GUMS analysis. Quantification of 3MH levels was accomplished by monitoring the m/z 204 fragment. The m/z 204 fragment was chosen due to the fragment's abundance and stability as determined by analysis of [methyl-H-2(3), O-18(2)]3MH (M + 7) and [methyl-C-13]3MH (M + 1) fragmentation patterns under NCI conditions. This method shows excellent linearity (0.9989) over the range studied (0-0.5 mol), high recovery (95.9%), and low coefficient of variation (4.7%). The described method is sensitive enough to detect 6.8 pmol amount of urinary 3MH with a precision of 9.1%. The in vivo utility of this method to quantify urinary 3MH was tested in a burn injury rat model and on urine specimens from pediatric burn patients. Data obtained from the urine of burn-injured rats and pediatric burn patients match previously reported trends and validate the in vivo utility of this method. (c) 2006 Elsevier Inc. All rights reserved. C1 Shriners Burn Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Burns & Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Illinois, Dept Emergency Med, Chicago, IL 60607 USA. MIT, Dept Nutr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. RP Beffa, DC (reprint author), Shriners Burn Hosp, Boston, MA 02114 USA. EM dbeffa@uic.edu FU NIDDK NIH HHS [P30 DK040561-11, P30 DK040561] NR 17 TC 8 Z9 8 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 1 PY 2006 VL 355 IS 1 BP 95 EP 101 DI 10.1016/j.ab.2006.03.057 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 067UB UT WOS:000239327000011 PM 16762308 ER PT J AU Sethu, P Moldawer, LL Mindrinos, MN Scumpia, PO Tannahill, CL Wilhelmy, J Efron, PA Brownstein, BH Tompkins, RG Toner, M AF Sethu, Palaniappan Moldawer, Lyle L. Mindrinos, Michael N. Scumpia, Philip O. Tannahill, Cynthia L. Wilhelmy, Julie Efron, Philip A. Brownstein, Bernard H. Tompkins, Ronald G. Toner, Mehmet TI Microfluidic isolation of leukocytes from whole blood for phenotype and gene expression analysis SO ANALYTICAL CHEMISTRY LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-B; FUNCTIONAL GENOMICS; L-SELECTIN; CD11B/CD18; ACTIVATION; MONOCYTES; PLATELETS AB Technologies that enable the isolation of cell subtypes from small samples of complex populations will greatly facilitate the implementation of proteomics and genomics to human diseases. Transcriptome analysis of blood requires the depletion of contaminating erythrocytes. We report an automated microfluidic device to rapidly deplete erythrocytes from whole blood via deionized water lysis and to collect enriched leukocytes for phenotype and genomic analyses. Starting with blood from healthy subjects, we demonstrate the utility of this microfluidic cassette and lysis protocol to prepare unstimulated leukocytes, and leukocytes stimulated ex vivo with Staphylococcal enterotoxin B, which mimics some of the cellular effects seen in patients with severe bacterial infections. Microarrays are used to assess the global gene expression response to enterotoxin B. The results demonstrate that this system can isolate unactivated leukocytes from small blood samples without any significant loss, which permits more information to be obtained from subsequent analysis, and will be readily applicable to clinical settings. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Washington Univ, Sch Med, St Louis, MO 63101 USA. Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM mtoner@hms.harvard.edu FU NIBIB NIH HHS [P41 EB-002503, P41 EB002503]; NIGMS NIH HHS [T32 GM-008721, U54 GM-062119, U54 GM062119] NR 24 TC 58 Z9 60 U1 1 U2 12 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 AUG 1 PY 2006 VL 78 IS 15 BP 5453 EP 5461 DI 10.1021/ac060140c PG 9 WC Chemistry, Analytical SC Chemistry GA 068RW UT WOS:000239393100037 PM 16878882 ER PT J AU Jiang, YD Wain, JC Chang, AW Zapol, WM Xie, ZC AF Jiang, Yandong Wain, John C. Chang, August W. Zapol, Warren M. Xie, Zhongcong TI Differential changes of alveolar gas concentrations during anesthetic induction of a patient with an absent right pulmonary artery SO ANESTHESIA AND ANALGESIA LA English DT Article ID COMPUTER-SIMULATION PROGRAM; INHALATION ANESTHESIA; INHALED ANESTHETICS; SYSTEM MODEL; HALOTHANE AB A 38-yr-old man with congenital right pulmonary artery agenesis, whose right lung was perfused with collateral systemic arterial blood, presented for right pneumonectomy. Because of a likely difference in gas exchange between the two lungs, we sampled end-tidal gases from each lung individually, as well as from the common gas outlet of a double-lumen endobronchial tube. Our results indicated a higher end-tidal CO, from the left, normally perfused, lung than from the right, systemically perfused, lung. We also determined uptake of sevoflurane from each lung, demonstrating a more rapid uptake in the left lung than in the right. In conclusion, we report the rare case of unilateral pulmonary artery agenesis with systemic arterial collateralization and characterize the differences in gas exchange. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Xie, ZC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St,CLN 309, Boston, MA 02114 USA. EM zxie@partners.org FU NHLBI NIH HHS [HL 42397]; NIA NIH HHS [AG008812-15, AG 000294-17]; NINDS NIH HHS [NS048140-01] NR 13 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 2006 VL 103 IS 2 BP 312 EP 315 DI 10.1213/01.ane.0000226089.53300.7a PG 4 WC Anesthesiology SC Anesthesiology GA 065SA UT WOS:000239178400011 PM 16861410 ER PT J AU Seim, A Andersen, B Sandberg, WS AF Seim, Andreas Andersen, Bjorn Sandberg, Warren S. TI Statistical process control as a tool for monitoring nonoperative time SO ANESTHESIOLOGY LA English DT Article ID ANESTHESIA; CARE; IMPROVEMENT; OUTCOMES; SURGERY AB Background: Administrators need simple tools to quickly identify even small changes in the performance of perioperative systems. This applies both to established systems and to impact assessments of deliberate perioperative system design changes. Methods: Statistical process control was originally developed to detect nonrandom variation in manufacturing processes by continuous comparison to previous performance. The authors applied the technique to assess the nonoperative time performance between successive cases for same surgeon following themselves in a redesigned operating room. This operating room specifically implemented a new patient care pathway that improves throughput by reducing the nonoperative time. The authors tested how quickly statistical process control detected reductions in nonoperative time. They also tested the ability of statistical process control to detect successively smaller performance changes and investigated its utility for longitudinal process monitoring. Results. Statistical process control detected a clear reduction in nonoperative time after the new operating room had been used for only 2 days. The method could detect nonoperative time changes of between 5 and 10 min per case for a single operating room within one fiscal quarter. Nonoperative time for the new process was globally stable over the 31 months analyzed, but late in the analysis period, the authors detected small performance decrements, mostly attributable to factors external to the new operating room. Conclusions: Statistical process control is useful for detecting changes in perioperative system performance, represented in this study by nonopcrative time. The technique is able to detect changes quickly and to detect small changes over time. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, 55 Fruit St, Boston, MA 02114 USA. EM wsandberg@partners.org NR 16 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 2006 VL 105 IS 2 BP 370 EP 380 DI 10.1097/00000542-200608000-00021 PG 11 WC Anesthesiology SC Anesthesiology GA 068YP UT WOS:000239411600020 PM 16871072 ER PT J AU Quackenbush, J AF Quackenbush, J. TI From 'omes to biology SO ANIMAL GENETICS LA English DT Article; Proceedings Paper CT Symposium on Integration of Structural and Functional Genomics CY SEP 22-25, 2005 CL Iowa State Univ, Ames, IA HO Iowa State Univ DE genomics; integration; microarray data; review; systems biology ID TIGR GENE INDEXES; MICROARRAY DATA; EUKARYOTIC GENOMES; ALZHEIMERS-DISEASE; EXPRESSION; PLATFORMS; STANDARDS; SYSTEM; TOOL; EST AB Technologies that have emerged from the genome project have dramatically increased our ability to generate data on the way in which organisms respond to their environments, how they execute their programmes of development and growth, and how these are altered in the development of disease states. However, our ability to analyse these large datasets has not kept pace with our ability to generate them and consequently new strategies must be developed to address the issues associated with their analysis. One approach that we have employed quite successfully is to look at data from microarrays (or proteomics or metabolomics experiments) not as independent datasets, but rather as elements of a much larger body of biological information across various scales that must be integrated with, and interpreted within, the context of such ancillary data. Here we outline the general approach and provide three examples from published studies of the way in which we have applied this strategy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu NR 32 TC 8 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0268-9146 J9 ANIM GENET JI Anim. Genet. PD AUG PY 2006 VL 37 SU 1 BP 48 EP 56 DI 10.1111/j.1365-2052.2006.01476.x PG 9 WC Agriculture, Dairy & Animal Science; Genetics & Heredity SC Agriculture; Genetics & Heredity GA 086QT UT WOS:000240688800009 PM 16887002 ER PT J AU Cochran, DM Fukumura, D Ancukiewicz, M Carmeliet, P Jain, RK AF Cochran, David M. Fukumura, Dai Ancukiewicz, Marek Carmeliet, Peter Jain, Rakesh K. TI Evolution of oxygen and glucose concentration profiles in a tissue-mimetic culture system of embryonic stem cells SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE mathematical modeling; cancer; hypoxia; stem cell; biology; tissue-mimetic culture ID MULTICELLULAR TUMOR SPHEROIDS; GROWTH; METABOLISM; NECROSIS; DEVICE; RATES; PH AB A tissue-mimetic culture system (TMCS) in which cells are sandwiched between two glass slides provides an ideal microenvironment for studying the effects of oxygen and nutrient gradients on cells in culture. A mathematical model was utilized to predict the time course of the development of oxygen and glucose concentration gradients within the TMCS. Oxygen and glucose consumption rates of mouse embryonic stem cells were measured its parameters for the model. The model predicts oxygen and glucose concentration profiles, directly using a single experimentally controlled variable, the seeding density of cells within the system. The model predicts that the time required for the gradients to reach steady state is inversely related to the cell density, and the penetration depth of the gradients into the TMCS is inversely related to the square root of the cell density. Experimental oxygen concentration measurements were performed at a cell density of 9.1 X 10(6) cells cm(-3), and the gradient was found to develop to it steady-state profile within 20 min and penetrate approximately 2 mm into the TMCS, consistent with the theoretical predictions. This model and the TMCS provide useful tools for investigating the effect of the metabolic microenvironment on cells in culture. C1 Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Katholieke Univ Leuven VIB, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvad.edu NR 30 TC 33 Z9 34 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD AUG PY 2006 VL 34 IS 8 BP 1247 EP 1258 DI 10.1007/s10439-006-9134-4 PG 12 WC Engineering, Biomedical SC Engineering GA 075PO UT WOS:000239897900002 PM 16832606 ER PT J AU Arnlov, J Pencina, MJ Amin, S Nam, BH Benjamin, EJ Murabito, JM Wang, TJ Knapp, PE D'Agostino, RB Bhasin, S Vasan, RS AF Arnlov, Johan Pencina, Michael J. Amin, Shreyasee Nam, Byung-Ho Benjamin, Emelia J. Murabito, Joanne M. Wang, Thomas J. Knapp, Philip E. D'Agostino, Ralph B., Sr. Bhasin, Shalendar Vasan, Ramachandran S. TI Endogenous sex hormones and cardiovascular disease incidence in men SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; ISCHEMIC-HEART-DISEASE; ALPHA GENE VARIATION; MIDDLE-AGED MEN; DEHYDROEPIANDROSTERONE-SULFATE; MYOCARDIAL-INFARCTION; ELDERLY-MEN; RISK-FACTORS; FREE TESTOSTERONE; ESTROGEN AB Background: Data suggest that endogenous sex hormones (testosterone, dehydroepiandrosterone sulfate [DHEA-S], and estradiol) influence cardiovascular disease (CVD) risk factors and vascular function. Yet, prospective studies relating sex hormones to CVD incidence in men have yielded inconsistent results. Objective: To examine the association of circulating sex hormone levels and CVD risk in men. Design: Prospective cohort study. Setting: Community-based study in Framingham, Massachusetts. Participants: 2084 middle-aged white men without CVD at baseline. Measurements: The authors used multivariable Cox regression to relate baseline levels of testosterone, DHEA-S, and estradiol to the incidence of CVD (coronary, cerebrovascular, or peripheral vascular disease or heart failure) during 10 years of follow-up. Results: During follow-up, 386 men (18.5%) experienced a first CVD event. After adjustment for baseline standard CVD risk factors, higher estradiol level was associated with lower risk for CVD (hazard ratio per SD increment in log estradiol, 0.90 [95% Cl, 0.82 to 0.99]; P = 0.035). The authors observed effect modification by age: Higher estradiol levels were associated with lower CVD risk in older (median age > 56 years) men (hazard ratio per SD increment, 0.86 [Cl, 0.78 to 0.96]; P = 0.005) but not in younger (median age <= 56 years) men (hazard ratio per SD increment, 1.11 [Cl, 0.89 to 1.38]; P = 0.36). The association of higher estradiol level with lower CVD incidence remained robust in time-dependent Cox models (updating standard CVD risk factors during follow-up). Serum testosterone and DHEA-S levels were not statistically significantly associated with incident CVD. Limitations: Sex hormone levels were measured only at baseline, and the findings may not be generalizable to women and nonwhite people. Conclusions: In the community-based sample, a higher serum estradiol level was associated with lower risk for CVD events in older men. The findings are consistent with the hypothesis that endogenous estrogen has vasculoprotective influences in men. C1 Boston Univ, Sch Med, Framingham Heart Study, Massachusetts Gen Hosp, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin, Coll Med, Rochester, MN USA. Uppsala Univ, Uppsala, Sweden. NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Boston Univ, Sch Med, Framingham Heart Study, Massachusetts Gen Hosp, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Arnlov, Johan/N-9886-2013; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K23 HL074077, N01-HC-25195, 2K24 HL04334]; NINDS NIH HHS [6R01-NS 17950] NR 60 TC 119 Z9 123 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 1 PY 2006 VL 145 IS 3 BP 176 EP 184 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 070MN UT WOS:000239526800003 PM 16880459 ER PT J AU Ascherio, A Chen, HP Weisskopf, MG O'Reilly, E McCullough, ML Calle, EE Schwarzschild, MA Thun, MJ AF Ascherio, Alberto Chen, HonPei Weisskopf, Marc G. O'Reilly, Eilis McCullough, Marjorie L. Calle, Eugenia E. Schwarzschild, Michael A. Thun, Michael J. TI Pesticide exposure and risk for Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID AMERICAN-CANCER-SOCIETY; DOPAMINERGIC NEUROTOXICITY; SUBSTANTIA-NIGRA; PARAQUAT; POPULATION; ETIOLOGY; MANEB; ONSET; DEGENERATION; PREVALENCE AB Objective: Chronic, low-dose exposure to pesticides is suspected to increase the risk for Parkinson's disease (PD), but data are inconclusive. Methods: We prospectively examined whether individuals exposed to pesticides have higher risk for PD than those not exposed. The study population comprised participants in the Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation of US men and women initiated in 1992 by the American Cancer Society. Follow-up surveys were conducted in 1997, 1999, and 2001. The 143,325 individuals who returned the 2001 survey and did not have a diagnosis or symptoms of PD at baseline (1992) were included in the analyses. Results: Exposure to pesticides was reported by 7,864 participants (5.7%), including 1,956 farmers, ranchers, or fishermen. Individuals exposed to pesticides had a 70% higher incidence of PD than those not exposed (adjusted relative risk, 1.7; 95% confidence interval, 1.2-2.3; p = 0.002). The relative risk for pesticide exposure was similar in farmers and nonfarmers. No relation was found between risk for PD and exposure to asbestos, chemical/acids/solvents, coal or stone dust, or eight other occupational exposures. Interpretation: These data support the hypothesis that exposure to pesticides may increase risk for PD. Future studies should seek to identify the specific chemicals responsible for this association. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02215 USA. EM aascheri@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU NIEHS NIH HHS [ES10804] NR 51 TC 191 Z9 195 U1 1 U2 17 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 AUG PY 2006 VL 60 IS 2 BP 197 EP 203 DI 10.1002/ana.20904 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 070PX UT WOS:000239536600008 PM 16802290 ER PT J AU Tournilhac, O Santos, DD Xu, L Kutok, J Tai, YT Le Gouill, S Catley, L Hunter, Z Branagan, AR Boyce, JA Munshi, N Anderson, KC Treon, SP AF Tournilhac, O. Santos, D. D. Xu, L. Kutok, J. Tai, Y. -T. Le Gouill, S. Catley, L. Hunter, Z. Branagan, A. R. Boyce, J. A. Munshi, N. Anderson, K. C. Treon, S. P. TI Mast cells in Waldenstrom's macroglobulinemia support lymphoplasmacytic cell growth through CD154/CD40 signaling SO ANNALS OF ONCOLOGY LA English DT Article DE mast cells; Waldenstrom's; macroglobulinemia; cd154; cd40; lymphoplasmacytic cells ID IGE SYNTHESIS; B-CELLS; LYMPHOMA AB Bone marrow (BM) mast cells (MC) are commonly found in association with lymphoplasmacytic cells (LPC) in patients with Waldenstrom's macroglobulinemia (WM). We therefore sought to clarify the role of MC in WM. Co-culture of sublethally irradiated HMC-1 MC, KU812 basophilic cells, or autologous BM MC along with BM LPC from WM patients resulted in MC dose-dependent tumor colony formation and/or proliferation as assessed by H-3-thymidine uptake studies. Furthermore, by immunohistochemistry, multicolor flow cytometry and/or RT-PCR analysis, CD40 ligand (CD154), a potent inducer of B-cell expansion, was expressed on BM MC from 32 of 34 (94%), 11 of 13 (85%), and 7 of 9 (78%) patients, respectively. In contrast, MC from five healthy donors did not express CD154. By multicolor flow cytometry, CD154 was expressed on BM LPC from 35 of 38 (92%) patients and functionality was confirmed by CD154 and CD40 agonistic antibody stimulation, which induced proliferation, support survival and/or pERK phosphorylation of LPC. Moreover, MC induced expansion of LPC from 3 of 5 patients was blocked in a dose dependent manner by use of a CD154 blocking protein. These studies demonstrate that in WM, MC may support tumor cell expansion through constitutive CD154-CD40 signaling and therefore provide the framework for therapeutic targeting of MC and MC-WM cell interactions in WM. C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, D1B07,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013; Catley, Laurence/E-5313-2013 OI Hunter, Zachary/0000-0002-1689-1691; FU NCI NIH HHS [K-23CA087977-03] NR 18 TC 58 Z9 59 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2006 VL 17 IS 8 BP 1275 EP 1282 DI 10.1093/annonc/mdl109 PG 8 WC Oncology SC Oncology GA 075QA UT WOS:000239899100014 PM 16788002 ER PT J AU Zeitels, SM Akst, LM Burns, JA Hillman, RE Broadhurst, MS Anderson, RR AF Zeitels, Steven M. Akst, Lee M. Burns, James A. Hillman, Robert E. Broadhurst, Matthew S. Anderson, R. Rox TI Pulsed angiolytic laser treatment of ectasias and varices in singers SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Laryngological-Association CY MAY 19-20, 2006 CL Chicago, IL SP Amer Laryngol Assoc DE dysphonia; ectasia; glottis; hoarseness; laryngoscopy; laser; singer; varix; vocal cord; vocal fold; voice ID VOCAL FOLD; DYE-LASER; CLINICAL EXPERIENCE; GLOTTAL DYSPLASIA; SURGERY; PAPILLOMATOSIS; MANAGEMENT; CO2-LASER; LARYNX; CORDS AB Objectives: Varices and ectasias in singers are typically the result of phonotraumatic shearing stresses and/or collision forces on the microcirculation within the superficial lamina propria. These lesions can be debilitating in performing vocalists because of the effect of recurrent hemorrhage and/or as a contributing factor to the morbidity of other mass lesions such as polyps, nodules, and cysts. Phonomicrosurgical treatment of performers is understandably approached with great trepidation, as the vocal liability of surgically disturbing the superficial lamina propria and epithelium must be balanced with the inherent detrimental vocal effect(s) of the lesion(s). Pulsed angiolytic lasers that emit radiation at high absorbance peaks of oxyhemoglobin were examined to determine whether they were an efficacious treatment approach for ectasias and varices based on these lasers' mechanisms of action and prior experience in phonomicrosurgery. Methods: A prospective trial was done in 39 patients (40 procedures in 54 vocal folds) without complication to evaluate the effectiveness of a 585-nm pulsed dye laser (PDL; 25 cases) and a 532-nm pulsed KTP laser (15 cases) in a noncontact mode to treat 65 varices and 43 ectasias. Twenty-nine of 39 patients had varices and ectasias associated with other phonotraumatic mass lesions that required resection. Results: All patients have resumed full vocal activities, and no patient has had a subsequent hemorrhage or vocal deterioration. Conclusions: Both the 585-nm PDL and the 532-nm pulsed KTP laser were found to be efficacious and relatively safe treatment modalities for vascular abnormalities of the vocal folds in singers. Noncontact selective photoangiolysis of the aberrant vessels prevented future bleeding without substantial photothermal trauma to the overlying epithelium and surrounding delicate superficial lamina propria, thereby allowing for optimal postoperative mucosal pliability and glottal sound production. However, the pulsed KTP laser was substantially easier to use because of its enhanced hemostasis due to its longer pulse width. Vessel wall rupture was commonplace during use of the 585-nm PDL, but rarely occurred during photoangiolysis with the 532-nm pulsed KTP laser. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, 1 Bowdoin Sq, Boston, MA 02114 USA. NR 33 TC 46 Z9 46 U1 1 U2 3 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 2006 VL 115 IS 8 BP 571 EP 580 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 073WS UT WOS:000239774000002 PM 16944655 ER PT J AU Khan, AM Levine, SR Nadol, JB AF Khan, Aayesha M. Levine, Stephen R. Nadol, Joseph B., Jr. TI The widely patent cochleovestibular communication of Edward Cock is a distinct inner ear malformation: Implications for cochlear implantation SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE cochlear implant; Edward Cock; inner ear malformation; widely patent cochleovestibular communication ID CONGENITAL-MALFORMATIONS; MONDINI-DYSPLASIA; HUMAN EMBRYO; MENINGITIS; RECONSTRUCTION; CHILDREN; POPULATIONS; LABYRINTH; DEAFNESS; CT AB Objectives: In 1838, Edward Cock described the anatomic findings in 4 inner ears with a widely patent communication between the cochlea and the vestibule that is now frequently referred to as the "common cavity deformity" and is often confused with Michel's "otocyst deformity." Little is known about the anatomic characteristics, including the presence of neural elements in this malformation. Methods: Light microscopy and 2-dimensional and computerized 3-dimensional reconstructions were used to determine the histopathology and spiral ganglion cell counts in 7 temporal bones with a widely patent cochleovestibular communication. Results: In all 7 specimens, the cochlea, vestibule, and semicircular canals were distinguishable and a bony defect resulting in an abnormal communication of perilymphatic space between the cochlea and vestibule was present. The ductus reuniens was abnormally wide in all. The cochlear duct varied from less than 1 turn to up to 2 turns. The mean spiral ganglion cells were estimated as a percentage of age-matched normal controls at 2.3%, 16.5%, and 26.8% when the cochlea was approximately 1, 1(1/2), and 2 turns, respectively (p = .007). The cribrose area consisted of a thin membrane in 2 specimens, and Rosenthal's canal openly communicated with the cerebrospinal fluid space in 3 specimens. The stapes footplate was abnormal in all 7 specimens and consisted of a central defect bridged by a thin membrane in 4 specimens. The facial nerve was dehiscent in 5 specimens (71%) and also followed an anomalous course in 2 specimens (28%). Conclusions: The widely patent cochleovestibular communication is a distinct inner ear malformation, recognition of which may have important clinical implications. Estimates of spiral ganglion cells can be predicted from the number of cochlear turns. Although cochlear implantation is feasible in patients with this malformation, a higher risk of cerebrospinal fluid gushers, facial nerve injuries, meningitis, and poor performance would be predicted. A better understanding of the anatomy will allow more effective surgical planning and techniques and may have a significant impact in improving outcomes. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Temporal Bone Fdn, Boston, MA USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [5-R01 DC00152-23] NR 43 TC 5 Z9 8 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 2006 VL 115 IS 8 BP 595 EP 606 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA 073WS UT WOS:000239774000005 PM 16944658 ER PT J AU Bhattacharyya, N Chien, W AF Bhattacharyya, Neil Chien, Wade TI Risk of second primary malignancy after radioactive iodine treatment for differentiated thyroid carcinoma SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE differentiated thyroid carcinoma; radioactive iodine; second primary malignancy ID CANCER PATIENTS; I-131 THERAPY; RADIOIODINE; SURVIVAL; OUTCOMES AB Objectives: The association between second primary malignancy (SPM) and radioactive iodine (RAI) is controversial. We examined the association between RAI and SPM after treatment of differentiated thyroid carcinoma (DTC) using a large cohort from a national cancer database. Methods: From the Surveillance, Epidemiology and End Results (SEER) database, all index cases of DTC (papillary or follicular) were extracted for the years 1988 to 2001. Two cohorts were constructed: 1) patients with DTC who were not treated with RAI, and 2) patients with DTC who were treated with RAI. For each cohort, we tabulated all subsequent malignancies for each patient, identifying patients in each group with 1 of more SPMs. Results: According to inclusion criteria, 18,882 cases of DTC treated without RAI (mean follow-up, 55.5 months) and 10,349 cases treated with RAI (mean follow-up, 61.8 months) were identified. The most common SPM sites were breast or prostate followed by colon or lung for both groups. On univariate analysis, SPMs developed in 6.7% of patients without RAI versus 4.8% of those with RAI (p < .001, univariate chi(2)). However, on multivariate analysis, only age and male gender had statistically significant hazard ratios (1.052 and 1.438, respectively; p < .001); follicular carcinoma histology and use of RAI did not influence occurrence of SPM after DTC (p = .180 and p = .789, respectively). Conclusions: Use of RAI does not elevate the risk of SPM. Concern about SPM induction should not adversely affect the decision to administer RAI for DTC. C1 Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Div Otolaryngol, 45 Francis St, Boston, MA 02115 USA. NR 19 TC 27 Z9 29 U1 1 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 2006 VL 115 IS 8 BP 607 EP 610 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 073WS UT WOS:000239774000006 PM 16944659 ER PT J AU Halpern, SD Asch, DA Shaked, A Stock, P Blumberg, EA AF Halpern, Scott D. Asch, David A. Shaked, Abraham Stock, Peter Blumberg, Emily A. TI Inadequate hepatitis B vaccination and post-exposure evaluation among transplant surgeons - Prevalence, correlates, and implications SO ANNALS OF SURGERY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE WORKERS; OCCUPATIONAL EXPOSURES; BLOODBORNE PATHOGENS; RISK; TRANSMISSION; INFECTION; HIV; PROPHYLAXIS; PREVENTION AB Objectives: To identify the proportion of U.S. transplant surgeons who are adequately vaccinated against hepatitis B virus (HBV), identify characteristics associated with inadequate vaccination, and assess the proportion who had been evaluated for immunization following potential HBV exposures. Summary Background Data: It is unknown what proportion of transplant surgeons are appropriately vaccinated against HBV or evaluated for immunization following operative exposures. Methods: We mailed questionnaires and to all active U.S. transplant surgeons. We compared demographic characteristics of responders and nonresponders to evaluate the potential for nonresponse bias. Results: Of 619 eligible respondents, 347 (56.1%) returned completed questionnaires. Of the 311 surgeons for whom HBV vaccination was indicated (all surgeons with neither a prior history of HBV infection nor a prior adverse reaction to the vaccine itself), 70 (22.5%; 95% confidence interval [CI], 18.0-27.6%) received fewer than the recommended 3 injections. Surgeon characteristics associated with inadequate vaccination included length of clinical practice (odds ratio [OR], 1.5 per 10-year increment in duration of practice; 95% Cl 1.1-2.2), increased fear of infection (OR, 1.2 for each unit increase in fear out of 10; 95% Cl, 1.1-1.4), and lack of recent testing for HBV infection (OR, 2.0; 95% Cl, 1.1-3.8). Of the 94 surgeons (27.3%) reporting at least one needle-stick exposure while operating on an HBV-infected patient, 14 (14.9%) were inadequately vaccinated; of these 14, only 5 (35.7%) sought appropriate serologic testing and counseling for active immunization. Surgeons underestimated both the risks of percutaneous exposure while operating, and of becoming infected with HBV if exposed. Conclusions: Many transplant surgeons are inadequately vaccinated against HBV and fail to seek evaluation following possible exposures. Underestimation of the risks of HBV exposure and transmission may relate to these failures. Requiring documentation of HBV vaccination and immunity to maintain operating room privileges may protect surgeons, their patients, and operating room staff. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Halpern, SD (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 115 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM scott.halpern@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU AHRQ HHS [HS10399, U18 HS010399] NR 27 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 2006 VL 244 IS 2 BP 305 EP 309 DI 10.1097/01.sla.0000217641.53330.e8 PG 5 WC Surgery SC Surgery GA 068FS UT WOS:000239358700019 PM 16858195 ER PT J AU Zabicki, K Colbert, JA Dominguez, FJ Gadd, MA Hughes, KS Jones, JL Specht, MC Michaelson, JS Smith, BL AF Zabicki, Katherina Colbert, James A. Dominguez, Francisco J. Gadd, Michele A. Hughes, Kevin S. Jones, Julie L. Specht, Michelle C. Michaelson, James S. Smith, Barbara L. TI Breast cancer diagnosis in women <= 40 versus 50 to 60 years: Increasing size and stage disparity compared with older women over time SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE early-onset breast cancer; diagnosis; young women; screening; high risk ID DEATH RATES; TUMOR SIZE; MAMMOGRAPHY; AGE; CARCINOMA; TRIAL; SURVIVAL; MUTATION; CARRIERS; YOUNGER AB Background: Women <= 40 years account for 5% of new breast cancer diagnoses. Although there is increased awareness of genetic and other breast cancer risk factors, it is not clear whether this has resulted in earlier diagnosis in young women. Methods: A database review identified 8892 women treated for breast cancer from 1980 to 2002. We compared 925 women aged <= 40 years with 2362 women aged 50 to 60 years. The mean and median tumor size and lymph node status were determined for each group. Results: There were significant differences in tumor size and lymph node status in younger versus older women. From 1980 to the mid 1990s, tumor size and nodal status did not differ. Since the mid 1990s, tumor size has decreased more rapidly for women aged 50 to 60 years than for those <= 40 years. In 1998 to 2002, the mean tumor size reached a plateau of 1.8 cm in women 50 to 60 years, compared with a plateau of 2.4 cm in women <= 40 years (P < .001). The median tumor size in 1998 to 2002 was 1.4 cm in women 50 to 60 years compared with 1.9 cm in women <= 40 years (P <.001). Lymph node status was also significantly different during 1998 to 2002: 23.9% positive in women 50 to 60 years versus 35.2% in women <= 40 years (P < .001). Conclusions: Since the 1980s, women aged 50 to 60 years have enjoyed a greater decrease in tumor size and percentage with positive nodes. These data could be the result of ineffective screening of younger women or of more aggressive tumor biology. Further study is required to determine whether more effective identification and screening of young, high-risk women can result in earlier detection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, 55 Fruit St,Yawkey 9, Boston, MA 02114 USA. EM blsmith1@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 37 TC 40 Z9 41 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD AUG PY 2006 VL 13 IS 8 BP 1072 EP 1077 DI 10.1245/ASO.2006.03.055 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 085OY UT WOS:000240614600007 PM 16865599 ER PT J AU Chou, RC Henson, JW Tian, D Hedley-Whyte, ET Reginato, AM AF Chou, R. C. Henson, J. W. Tian, D. Hedley-Whyte, E. T. Reginato, A. M. TI Successful treatment of rheumatoid meningitis with cyclophosphamide but not infliximab SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Editorial Material ID ARTHRITIS; RITUXIMAB; THERAPY; LYMPHOMAS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Div Neuropathol, Boston, MA 02114 USA. RP Reginato, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol, 55 Fruit St, Boston, MA 02114 USA. EM areginato@partners.org NR 12 TC 16 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 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD AUG PY 2006 VL 65 IS 8 BP 1114 EP 1116 DI 10.1136/ard.2005.042093 PG 5 WC Rheumatology SC Rheumatology GA 063GJ UT WOS:000239006000026 PM 16837495 ER PT J AU Jassal, DS Neilan, TG Pradhan, AD Lynch, KE Vlahakes, G Agnihotri, AK Picard, MH AF Jassal, Davinder S. Neilan, Tomas G. Pradhan, Aruna D. Lynch, Karen E. Vlahakes, Gus Agnihotri, Arvind K. Picard, Michael H. TI Surgical management of infective endocarditis: Early predictors of short-term morbidity and mortality SO ANNALS OF THORACIC SURGERY LA English DT Article ID MITRAL-VALVE ENDOCARDITIS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; EMBOLIC EVENTS; DIAGNOSIS; RISK; DEATH; COMPLICATIONS; DETERMINANTS; REPLACEMENT; SURVIVAL AB Background. Infective endocarditis is a diagnostic and therapeutic challenge that ultimately requires surgical intervention in 20% of all cases. Early determinants of morbidity and mortality in this high risk population are not well described. Methods. The aim of this study was to determine preoperative clinical, microbiological, electrocardiographic, and echocardiographic variables that predicted the need for permanent pacemaker implantation and in-hospital death in a surgical cohort of patients with active infective endocarditis. Results. We identified 91 patients (61 males and 30 females, mean age 58 +/- 16 years) who underwent surgical intervention for active culture-positive infective endocarditis as defined by the Duke criteria. Native valve infective endocarditis was present in 78 (85.7%) and prosthetic valve endocarditis in 13 (14.3%) of cases. The aortic valve was infected in 61 (67.0%), the mitral in 35 (38.5%), and multiple valves in 8 patients (8.8%). The most common indication for surgical intervention was intractable heart failure. Twenty-two patients (24.2%) required pacemakers, while there were 14 (15.4%) in-hospital deaths. In age-adjusted and gender-adjusted analyses, the presence of left bundle branch block on preoperative electrocardiogram (ECG) and presence of depressed left ventricular systolic function (ejection fraction [EF] < 50%) predicted the need for a permanent pacemaker implantation, while the presence of depressed left ventricular function predicted in-hospital mortality. Conclusions. Preoperative ECG findings of left bundle branch block and reduced left ventricular function may allow for early risk stratification of this high risk population. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med, Cardiac Ultrasound Lab,Dept Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cardiac Surg Div, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jassal, DS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med, Cardiac Ultrasound Lab,Dept Cardiol, VBK 508,55 Fruit St, Boston, MA 02114 USA. EM djassal@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 31 TC 22 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2006 VL 82 IS 2 BP 524 EP 529 DI 10.1016/j.athoracsur.2006.02.023 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 070UM UT WOS:000239550600021 PM 16863755 ER PT J AU Apple, KA McLean, JE Squires, CE Schaeffer, B Sample, JA Murphy, RL Deschamps, AM Leonardi, AH Allen, CM Hendrick, JW Stroud, RE Mukherjee, R Spinale, FG AF Apple, Kimberly A. McLean, Julie E. Squires, Christina E. Schaeffer, Brooke Sample, Jeffrey A. Murphy, Rebecca L. Deschamps, Anne M. Leonardi, Amy H. Allen, Claire M. Hendrick, Jennifer W. Stroud, Robert E. Mukherjee, Rupak Spinale, Francis G. TI Differential effects of protein kinase C isoform activation in endothelin-mediated myocyte contractile dysfunction with cardioplegic arrest SO ANNALS OF THORACIC SURGERY LA English DT Article ID CARDIAC TROPONIN-I; CARDIOPULMONARY BYPASS; VENTRICULAR MYOCYTES; REPERFUSION; ISCHEMIA; EPSILON; PHOSPHORYLATION; ANTAGONISM; EXPRESSION; ISOZYMES AB Background. Increased myocardial interstitial levels of endothelin (ET) occur during cardioplegic arrest (CA) and may contribute to contractile dysfunction. Endothelin receptor transduction involves the protein kinase-C (PKC) family comprised of multiple isoforms with diverse functions. Which PKC isoforms may be involved in ET-induced contractile dysfunction after CA remains unknown. Methods. Shortening velocity was measured in isolated left ventricular porcine myocytes and randomized (minimum of 30 per group): normothermia (cell culture media for 2 hours at 37 degrees C); CA (2 hours in CA solution [4 degrees C, 24 mEq K+] followed by reperfusion in cell media); ET/CA (100 pM ET incubated during CA and reperfusion). These studies were carried out in the presence and absence of PKC inhibitors (500 nM) and directed against members of the classical PKC subfamily (beta I, beta II, gamma) and the novel subfamily (epsilon, eta). Results. Cardiac arrest reduced shortening velocity by approximately 50%, which was further reduced in the presence of ET. Inhibition of either the beta II or gamma PKC isoform significantly increased shortening velocity from ET/CA as well as CA only values. In separate studies (n = 3), total beta II and phosphorylated beta II increased by over 150% with ET/CA (p < 0.05). Taken together, these results suggest that a predominant intracellular effector for the negative contractile effects mediated by ET in the context of CA is the PKC isoform beta II. Conclusions. Targeted inhibition of specific PKC isoforms relieves the negative inotropic effects of ET after simulated CA. These findings provide important mechanistic support for the development of targeted inhibitory strategies with respect to ET signaling and myocyte contractile dysfunction in the context of CA and reperfusion. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Room 625,Strom Thurmond Res Bldg,770 MUSC Complex, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [HL57952, HL56603] NR 26 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2006 VL 82 IS 2 BP 664 EP 671 DI 10.1016/j.athoracsur.2006.03.021 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 070UM UT WOS:000239550600043 PM 16863782 ER PT J AU Robicsek, A Strahilevitz, J Sahm, DF Jacoby, GA Hooper, DC AF Robicsek, A. Strahilevitz, J. Sahm, D. F. Jacoby, G. A. Hooper, D. C. TI qnr Prevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID QUINOLONE RESISTANCE; TRANSFERABLE PLASMID; GENE AB We screened 313 ceftazidime-resistant Enterobacteriaceae isolates obtained in the United States from 1999 to 2004 for all three known qnr genes. A qnr gene was present in 20% of Klebsiella pneumoniae isolates, 31% of Enterobacter sp. isolates, and 4% of Escherichia coli isolates. qnrA and qnrB occurred with equivalent frequencies and, except for qnrB in enterobacters, were stable over time. qnrS was absent. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Focus BioInova, Herndon, VA USA. Lahey Clin Fdn, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI043312, AI43312, AI57576, R01 AI057576] NR 9 TC 289 Z9 329 U1 6 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2006 VL 50 IS 8 BP 2872 EP 2874 DI 10.1128/AAC.01647-05 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 071YS UT WOS:000239640400045 PM 16870791 ER PT J AU Marra, DE Yip, D Fincher, EF Moy, RL AF Marra, Diego E. Yip, Darwin Fincher, Edgar F. Moy, Ronald L. TI Systemic toxicity from topically applied lidocaine in conjunction with fractional photothermolysis SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ANESTHESIA; PHARMACOKINETICS AB Background: Topical anesthetics, unlike injectable anesthetics, can be applied painlessly and can provide sufficient pain control to maintain patient comfort throughout a variety of laser procedures. Although the use of topical lidocaine is considered relatively safe, instances of cardiotoxic and neurotoxic adverse events have been reported to occur. Observations: A 52-year-old woman underwent fractional photo thermolysis for management of severe hypopigmentation and scarring of several years' duration. Shortly after termination of treatment to her face and neck, which required prolonged exposure to a 30% lidocaine gel compound both before and during surgery, she developed clinical signs and symptoms consistent with systemic lidocaine toxicity. The results of laboratory studies confirmed serum lidocaine levels within the toxic range. We postulate that the combination of the high concentration of topical lidocaine required to achieve sufficient anesthesia, together with the laser-induced disruption in epidermal barrier function, may have been responsible for this phenomenon. Conclusions: Application of a 30% topical lidocaine gel to a limited area in conjunction with fractional photothermolysis may generate serum lidocaine levels high enough to elicit systemic toxicity. Laser surgeons should be alert to this phenomenon, particularly in patients with underlying hepatic, endocrine, cardiac, or central nervous system/ psychiatric dysfunction; in patients with a low body mass index; and in patients who are taking medications that may interfere with hepatic lidocaine metabolism. C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Moy, RL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. EM rmoy@ucla.edu NR 16 TC 45 Z9 47 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 2006 VL 142 IS 8 BP 1024 EP 1026 DI 10.1001/archderm.142.8.1024 PG 3 WC Dermatology SC Dermatology GA 073SK UT WOS:000239762700010 PM 16924052 ER PT J AU Brauner, SC Chen, TC Hutchinson, T Chang, MA Pasquale, LR Grosskreutz, CL AF Brauner, Stacey C. Chen, Teresa C. Hutchinson, Thomas Chang, Michael A. Pasquale, Louis R. Grosskreutz, Cynthia L. TI The course of glaucoma during pregnancy - A retrospective case series SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-PRESSURE; ANTIGLAUCOMA THERAPY AB Objective: To better understand the course of glaucoma during pregnancy in women with preexisting disease. Methods: Retrospective case series of 28 eyes of 15 women with glaucoma followed up during pregnancy. Data were analyzed for age, race/ethnicity, medications, glaucoma type, intraocular pressure (IOP), and visual fields before, during, and after pregnancy. Results: In 16 (57.1%) of 28 eyes, IOP was stable during pregnancy, with no progression of visual field loss. In 5 eyes (17.9%), visual field loss progressed during pregnancy, while IOP remained stable or increased. In 5 eyes (17.9%), IOP increased during pregnancy, but there was no progression of visual field loss. In 2 eyes (7.1%), data were inconclusive because of medication noncompliance and preexisting severe visual field loss. Glaucoma medications were used by 13 of 15 patients to control glaucoma during pregnancy. The classes of medications used most frequently were beta-blockers, alpha(2)-adrenergic agents, cholinergic agents, and topical carbonic anhydrase inhibitors. Conclusions: The course of glaucoma during pregnancy is variable, and women must be monitored closely during pregnancy. Medications may be necessary to control IOP and to prevent vision loss during pregnancy. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu NR 27 TC 18 Z9 19 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2006 VL 124 IS 8 BP 1089 EP 1094 DI 10.1001/archopht.124.8.1089 PG 6 WC Ophthalmology SC Ophthalmology GA 073QQ UT WOS:000239758100001 PM 16908810 ER PT J AU Young, NA T Moriarty, A Walsh, MK Wang, E Wilbur, DC AF Young, Nancy A. T Moriarty, Ann Walsh, Molly K. Wang, Edward Wilbur, David C. TI The potential for failure in gynecologic regulatory proficiency testing with current slide validation criteria - Results from the College of American Pathologists Interlaboratory Comparison in Gynecologic Cytology Program SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Society-of-Cytopathology CY NOV 04-09, 2005 CL San Diego, CA SP Amer Soc Cytopathol ID SQUAMOUS INTRAEPITHELIAL LESION; CERVICOVAGINAL CYTOLOGY; PAPANICOLAOU SMEARS; INTEROBSERVER VARIABILITY; CERVICAL SMEARS; PERFORMANCE; FEATURES; WELL AB Context-Current regulatory proficiency testing scoring results in an automatic failure for identifying high-grade squamous intraepithelial lesion (HSIL) as negative. Objective.-The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology data from January 2004 to April 2005 were analyzed to estimate the percentage of failure based on negative responses for HSIL and validation criteria. Design.-More than 15 000 participants received field-validated and educational slide sets for conventional, ThinPrep, and SurePath modules. Educational sets fulfilled the validation criteria of the Center for Medicare and Medicaid Services, which required the consensus diagnosis of biopsy-proven HSIL (not field-validated) after review by 3 pathologists. The College of American Pathologists field validation required at least 20 responses to the HSIL+ series, with 70% matched to HSIL+ (standard error <= 0.05). Minimum regulatory proficiency testing failure estimates were based on incorrect negative responses for the reference category of HSIL. Results.-For both cytotechnologists and pathologists, there was a statistically significant higher failure rate for slides that were not field-validated versus those that were field-validated. In conventional modules, 5.3% of the slides that were not field-validated were called negative, versus 1.2% of the field-validated slides. In all liquid-based preparations, 4.0% of the non-field-validated versus 2.2% field-validated slides were called negative. Pathologists would have failed more often than cytotechnologists for the slides that were not field-validated, whereas there was no statistical difference in failure performance with field-validated slides. Conclusions.-Failures were significantly greater with the slides that were not field-validated for both conventional and liquid-based preparations (ThinPrep only) and have implications for both regulatory proficiency testing and expert legal review. Poor performance of pathologists relative to that of cytotechnologists may reflect a lack of prescreening of slides or scope of practice issues. C1 Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. AmeriPath Indiana, Indianapolis, IN USA. Coll Amer Pathologists, Dept Biostat, Northfield, IL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Young, NA (reprint author), Fox Chase Canc Ctr, Dept Pathol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM na-young@fccc.edu NR 16 TC 8 Z9 8 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 2006 VL 130 IS 8 BP 1114 EP 1118 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 069UE UT WOS:000239473000005 ER PT J AU Turner, AP Williams, RM Bowen, JD Kivlahan, DR Haselkorn, JK AF Turner, Aaron P. Williams, Rhonda M. Bowen, James D. Kivlahan, Daniel R. Haselkorn, Jodie K. TI Suicidal ideation in multiple sclerosis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE depression; multiple sclerosis; rehabilitation; suicide ID COGNITIVE-BEHAVIOR THERAPY; RISK-FACTORS; PRIMARY-CARE; UNITED-STATES; DEPRESSION; PREVALENCE; MS; HOPELESSNESS; VALIDITY; LIFE AB Objective: To examine risk factors for suicidal ideation among people with multiple sclerosis (MS). Design: Cohort study linking computerized medical records with a mailed self-report survey. Setting: Veteran's Health Administration (VHA) region covering the northwestern United States. Participants: VHA patients with MS (N=445) who returned mailed surveys. Interventions: Not applicable. Main Outcome Measure: Suicidal ideation is assessed by the Patient Health Questionnaire (PHQ) suicide item with suicidal ideation more than half the days considered persistent. Results: One hundred thirty-one (29.4%) of 445 respondents (95% confidence interval [CI], 25.4%-33.9%) endorsed suicidal ideation, and 35 (7.9%; 95% CI, 5.7%-10.8%) endorsed persistent suicidal ideation over the last 2 weeks. In bivariate analyses, suicidal ideation was associated with younger age, earlier disease course, progressive disease subtype, lower income, not being married, lower social support, not driving, higher levels of physical disability (mobility, bowel, bladder), and depression. Analyses on persistent suicidal ideation yielded similar results. In fully adjusted multivariate logistic regression, only depression severity and bowel disability were independently associated with suicidal ideation. Only depression severity was independently associated with persistent suicidal ideation. By using the 2-question depression screen (U.S. Preventive Services Task Force) consisting of the depression and anhedonia items from the PHQ-9, sensitivity and specificity were marginal for suicidal ideation (65.6% and 79.9%) but acceptable for persistent suicidal ideation (88.6% and 71.2%). Conclusions: Suicidal ideation is common among VHA patients with MS, and depression severity is the best risk marker. Brief screening for depression in MS should include the assessment of suicidal ideation. C1 VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@med.va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 50 TC 36 Z9 37 U1 4 U2 10 PU W B SAUNDERS CO-ELSEVIER INC 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 AUG PY 2006 VL 87 IS 8 BP 1073 EP 1078 DI 10.1016/j.apmr.2006.04.021 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 072KW UT WOS:000239673300008 PM 16876552 ER PT J AU Shen, WT Lee, J Kebebew, E Clark, OH Duh, QY AF Shen, Wen T. Lee, James Kebebew, Electron Clark, Orlo H. Duh, Quan-Yang TI Selective use of steroid replacement after adrenalectomy - Lessons from 331 consecutive cases SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 17-20, 2006 CL San Francisco, CA SP Pacific Coast Surg Assoc ID SUBCLINICAL CUSHINGS-SYNDROME; BILATERAL ADRENALECTOMY; INSUFFICIENCY; INCIDENTALOMAS; MANAGEMENT; TUMORS AB Hypothesis: Only selected patients require steroid replacement therapy following adrenalectomy. Design: Retrospective review. Settings: University tertiary care center and veterans' hospital. Patients: A total of 331 patients who underwent adrenalectomy by 1 surgeon (Q.-Y.D.) between April 1, 1993, and August 31, 2005. Interventions: Laparoscopic, open, and hand-assisted adrenalectomy. Steroid replacement therapy was administered using a standardized hydrocortisone taper protocol. Main Outcome Measures: Indications for adrenalectomy, operative approach, requirement for postoperative steroid replacement, and episodes of acute adrenocortical insufficiency. Results: Of the 331 adrenalectomies, 304 were laparoscopic, 23 were open, and 4 were hand assisted. There were 299 unilateral adrenalectomies and 32 bilateral adrenalectomies performed. Fifty-seven (17%) of the 331 patients required steroid replacement after adrenalectomy. Of the 57 patients requiring steroid replacement, 52 had Cushing syndrome and 5 had bilateral pheochromocytomas. The 52 patients with Cushing syndrome included 16 with pituitary tumors who had failed pituitary resection and/or medical therapy, 14 with unilateral adrenal adenomas, 9 with ectopic corticotropin-secreting tumors who had failed resection and/or medical therapy, 7 with incidentalomas and subclinical Cushing syndrome, 4 with macronodular hyperplasia, and 2 with adrenocortical carcinoma. No patients undergoing unilateral adrenalectomy for non-Cushing adrenal disease required steroid replacement. Four (7%) of the 57 patients receiving steroid replacement had episodes of acute adrenocortical insufficiency following operation and required increased steroid supplementation. There were no cases of acute adrenocortical insufficiency in the 274 patients who did not receive steroid replacement. Conclusions: Steroid replacement therapy after adrenalectomy should be reserved for patients with Cushing syndrome (overt or subclinical) and patients undergoing bilateral adrenalectomy. Patients undergoing aldrenalectomy for unilateral non-Cushing adrenal tumors do not require postoperative steroid replacement. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Duh, QY (reprint author), San Francisco Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM quan-yang.duh@med.va.gov NR 19 TC 29 Z9 35 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD AUG PY 2006 VL 141 IS 8 BP 771 EP 774 DI 10.1001/archsurg.141.8.771 PG 4 WC Surgery SC Surgery GA 072FB UT WOS:000239657600010 PM 16924084 ER PT J AU Leonardi, MJ McGory, ML Ko, CY AF Leonardi, Michael J. McGory, Marcia L. Ko, Clifford Y. TI The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis - A systematic review of 33 randomized controlled trials SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 17-20, 2006 CL San Francisco, CA SP Pacific Coast Surg Assoc ID LOW-MOLECULAR-WEIGHT; LOW-DOSE HEPARIN; VEIN THROMBOSIS; GENERAL-SURGERY; STANDARD HEPARIN; UNFRACTIONATED HEPARIN; ABDOMINAL-SURGERY; MULTICENTER TRIAL; POSTOPERATIVE THROMBOEMBOLISM; KABI 2165 AB Hypothesis: Major bleeding complications from pharmacologic deep venous thrombosis (DVT) prophylaxis are infrequent. Design: Systematic review of the MEDLINE database from 1965 to August 2005, using the terms DVT, prophylaxis, general surgery, and heparin. Setting and Patients: Randomized controlled trials evaluating pharmacologic DVT prophylaxis in patients undergoing general surgery. Main Outcome Measures: Eight complication categories: injection site bruising, wound hematoma, drain site bleeding, hematuria, gastrointestinal tract bleeding, retroperitoneal bleeding, discontinuation of prophylaxis, and subsequent operation. Results: Fifty-two randomized controlled trials studied DVT prophylaxis; 33 randomized controlled trials with 33 813 patients undergoing general surgery evaluated pharmacologic prophylaxis and quantified bleeding complications. Of the minor complications, injection site bruising (6.9%), wound hematoma (5.7%), drain site bleeding (2.0%), and hematuria (1.6%) were most common. Major bleeding complications, such as gastrointestinal tract (0.2%) or retroperitoneal (< 0.1%) bleeding, were infrequent. Discontinuation of prophylaxis occurred in 2.0% of patients and subsequent operation in less than 1% of patients. When analyzed by high-vs low-dose unfractionated heparin, the lower dose had a smaller rate of discontinuation of prophylaxis (P=.02) and subsequent operation (P=.06). Conclusions: Knowledge of bleeding complication rates is important for surgeons because DVT prophylaxis may soon be implemented by Medicare as a quality measure. This level 1 evidence report shows that bleeding complications requiring a change in care occur less than 3% of the time and seem reduced with lower-dose prophylaxis. Given these findings, most patients undergoing general surgery could receive pharmacologic prophylaxis safely. C1 Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ctr Hlth Sci 72 215, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Surg Outcomes & Qual, David Geffen Sch Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Leonardi, MJ (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ctr Hlth Sci 72 215, 10833 Le Conte Ave,POB 956904, Los Angeles, CA 90095 USA. EM mjleonardi@mednet.ucla.edu NR 39 TC 59 Z9 65 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0004-0010 EI 1538-3644 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD AUG PY 2006 VL 141 IS 8 BP 790 EP 797 DI 10.1001/archsurg.141.8.790 PG 8 WC Surgery SC Surgery GA 072FB UT WOS:000239657600016 PM 16924087 ER PT J AU Moore, KJ Freeman, MW AF Moore, Kathryn J. Freeman, Mason W. TI Scavenger receptors in atherosclerosis: Beyond lipid uptake SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; B TYPE-I; MARROW-DERIVED CELLS; E-DEFICIENT MICE; FALCIPARUM-PARASITIZED ERYTHROCYTES; MACROPHAGE-SPECIFIC EXPRESSION; CLASS-A OVEREXPRESSION; SR-BI; OXIDIZED PHOSPHOLIPIDS; APOLIPOPROTEIN-E AB Atherosclerotic vascular disease arises as a consequence of the deposition and retention of serum lipoproteins in the artery wall. Macrophages in lesions have been shown to express >= 6 structurally different scavenger receptors for uptake of modified forms of low-density lipoproteins (LDLs) that promote the cellular accumulation of cholesterol. Because cholesterol-laden macrophage foam cells are the primary component of the fatty streak, the earliest atherosclerotic lesion, lipid uptake by these pathways has long been considered a requisite and initiating event in the pathogenesis of atherosclerosis. Although the removal of proinflammatory modified LDLs from the artery wall via scavenger receptors would seem beneficial, the pathways distal to scavenger receptor uptake that metabolize the modified lipoproteins appear to become overwhelmed, leading to the accumulation of cholesterol-laden macrophages and establishment of a chronic inflammatory setting. These observations have led to the current dogma concerning scavenger receptors, which is that they are proatherogenic molecules. However, recent studies suggest that the effects of scavenger receptors on atherogenesis may be more complex. In addition to modified lipoprotein uptake, these proteins are now known to regulate apoptotic cell clearance, initiate signal transduction, and serve as pattern recognition receptors for pathogens, activities that may contribute both to proinflammatory and anti-inflammatory forces regulating atherogenesis. In this review, we focus on recent advances in our knowledge of scavenger receptor regulation and signal transduction, their roles in sterile inflammation and infection, and the potential impact of these pathways in regulating the balance of lipid accumulation and inflammation in the artery wall. C1 Harvard Univ, Lipid Metab Unit, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Moore, KJ (reprint author), Harvard Univ, Lipid Metab Unit, Sch Med, Massachusetts Gen Hosp, GRJ1328,55 Fruit St, Boston, MA 02114 USA. EM kmoore@molbio.mgh.harvard.edu OI Moore, kathryn/0000-0003-2505-2547 NR 92 TC 254 Z9 266 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2006 VL 26 IS 8 BP 1702 EP 1711 DI 10.1161/01.ATV.0000229218.97976.43 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 068RF UT WOS:000239391400006 PM 16728653 ER PT J AU Chan, ESL Fernandez, P Merchant, AA Montesinos, MC Trzaska, S Desai, A Tung, CF Khoa, DN Pillinger, MH Reiss, AB Tomic-Canic, M Chen, JF Schwarzschild, MA Cronstein, BN AF Chan, E. S. L. Fernandez, P. Merchant, A. A. Montesinos, M. C. Trzaska, S. Desai, A. Tung, C. F. Khoa, D. N. Pillinger, M. H. Reiss, A. B. Tomic-Canic, M. Chen, J. F. Schwarzschild, M. A. Cronstein, B. N. TI Adenosine A(2A) receptors in diffuse dermal fibrosis pathogenic role in human dermal fibroblasts and in a murine model of scleroderma SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SUPEROXIDE ANION GENERATION; ADENOSINE-DEAMINASE; SYSTEMIC-SCLEROSIS; HUMAN-NEUTROPHILS; ALVEOLAR MACROPHAGES; CARDIAC FIBROBLASTS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; A(2B) RECEPTORS; A(2A) RECEPTOR AB Objective. Adenosine regulates inflammation and tissue repair, and adenosine A(2A) receptors promote wound healing by stimulating collagen matrix production. We therefore examined whether adenosine A(2A) receptors contribute to the pathogenesis of dermal fibrosis. Methods. Collagen production by primary human dermal fibroblasts was analyzed by real-time polymerase chain reaction, C-14-proline incorporation, and Sircol assay. Intracellular signaling for dermal collagen production was investigated using inhibitors of MEK-1 and by demonstration of ERK phosphorylation. In vivo effects were studied in a bleomycin-induced dermal fibrosis model using adenosine A(2A) receptor-deficient wild-type littermate mice, C57BL/6 mice, and mice treated with adenosine A(2A) receptor antagonist. Morphometric features and levels of hydroxyproline were determined as measures of dermal fibrosis. Results. Adenosine A(2A) receptor occupancy promoted collagen production by primary human dermal fibroblasts, which was blocked by adenosine A(2A), but not A(1) or A(2B), receptor antagonism. Adenosine A(2A) receptor ligation stimulated ERK phosphorylation, and A(2A) receptor-mediated collagen production by dermal fibroblasts was blocked by MEK-1 inhibitors. Adenosine A(2A) receptor-deficient and A(2A) receptor antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis. Conclusion. These results demonstrate that adenosine A(2A) receptors play an active role in the pathogenesis of dermal fibrosis and suggest a novel therapeutic target in the treatment and prevention of dermal fibrosis in diseases such as scleroderma. C1 NYU, Sch Med, Div Clin Pharmacol, New York, NY 10016 USA. NYU, Sch Med, New York, NY USA. Univ Valencia, Valencia, Spain. Winthrop Univ Hosp, Mineola, NY 11501 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Cronstein, BN (reprint author), NYU, Sch Med, Div Clin Pharmacol, 550 1St Ave,NBV16N1, New York, NY 10016 USA. EM Bruce.Cronstein@nyumc.org RI Montesinos, M. Carmen/G-8852-2015; OI Montesinos, M. Carmen/0000-0003-1801-311X; Reiss, Allison B/0000-0002-4478-2441; Pillinger, Michael/0000-0003-3168-1542 FU NCRR NIH HHS [M01-RR00096]; NIAAA NIH HHS [AA-13336]; NIAMS NIH HHS [AR-41911]; NIGMS NIH HHS [GM-56268] NR 46 TC 63 Z9 67 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2006 VL 54 IS 8 BP 2632 EP 2642 DI 10.1002/art.21974 PG 11 WC Rheumatology SC Rheumatology GA 071ZC UT WOS:000239641400034 PM 16871530 ER PT J AU Deckersbach, T Rauch, S Buhlmann, U Wilhelm, S AF Deckersbach, Thilo Rauch, Scott Buhlmann, Ulrike Wilhelm, Sabine TI Habit reversal versus supportive psychotherapy in Tourette's disorder: A randomized controlled trial and predictors of treatment response SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Tourette's disorder; tics; habit reversal; treatment outcome; predictors of treatment response ID OBSESSIVE-COMPULSIVE-DISORDER; TIC SUPPRESSION; INHIBITION; SCALE; HALOPERIDOL; SEVERITY; PIMOZIDE; CHILDREN; PLACEBO AB Tourette syndrome (TS) is characterized by chronic motor and vocal tics. Habit reversal therapy (HR) is a behavioral treatment for tics which has received recent empirical support. The present study compared the efficacy of HRT in reducing tics, improving life-satisfaction and psychosocial functioning in comparison with supportive psychotherapy (SP) in outpatients with TS. In addition, we investigated whether impairments in response inhibition in patients with TS predict response to HR treatment which specifically aims to inhibit tics. Thirty adult outpatients with DSM-IV TS were randomized to 14 individual sessions of HR (n = 15); or SP (n = 15). HR but not SP reduced tic severity over the course of the treatment. Both groups improved in life-satisfaction and psychosocial functioning during active treatment. Reductions in tic severity (HR) and improvements in life-satisfaction and psychosocial functioning (HR and SP) remained stable at the 6-month follow-up. The extent of pre-treatment response inhibition impairment in the HR group predicted reductions in tic-severity from pre- to post-treatment. Our results suggest that HR has specific tic-reducing effects although SP is effective in improving life-satisfaction and psychosocial functioning. Assessments of response inhibition may be of value for predicting treatment response to HR. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, OCD Clin, Dept Psychiat, Psychiat Neurosci Div, Charlestown, MA 02129 USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, OCD Clin, Dept Psychiat, Psychiat Neurosci Div, 149-2611,Bldg 149,13th St, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org NR 36 TC 64 Z9 64 U1 4 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD AUG PY 2006 VL 44 IS 8 BP 1079 EP 1090 DI 10.1016/j.brat.2005.08.007 PG 12 WC Psychology, Clinical SC Psychology GA 064ZX UT WOS:000239130300002 PM 16259942 ER PT J AU Levin, J Werth, VP AF Levin, Joshua Werth, Victoria P. TI Skin disorders with arthritis SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Review DE skin; joints; arthritis; arthralgias ID FEBRILE NEUTROPHILIC DERMATOSIS; ERYTHEMA-ELEVATUM-DIUTINUM; HYPEROSTOSIS-OSTEITIS SAPHO; INTERSTITIAL LUNG-DISEASE; PLACEBO-CONTROLLED TRIAL; PSORIATIC-ARTHRITIS; PYODERMA-GANGRENOSUM; SWEETS-SYNDROME; MULTICENTRIC RETICULOHISTIOCYTOSIS; ACNE FULMINANS AB Many inflammatory, metabolic and infectious diseases affect the skin and joints. Most of these, such as rheumatoid arthritis and systemic lupus erythaematosus, are considered to be rheumatic conditions with secondary skin involvement. However, several primary cutaneous diseases are associated with arthritis and may even present with joint symptoms prior to cutaneous lesions. Common skin disorders, such as acne and psoriasis, have well-known musculoskeletal manifestations. Other less common conditions, such as dermatomyositis, multicentric reticulohistiocytosis, pyoderma gangrenosum, Sweet's syndrome and various cutaneous vasculitides, also have frequent joint involvement. This review will discuss the clinical presentation, both cutaneous and musculoskeletal, diagnosis and management of these disorders. C1 Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Werth, VP (reprint author), Hosp Univ Penn, 2 Rhoads Pavil,36th & Spruce St, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu NR 146 TC 19 Z9 20 U1 0 U2 3 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6942 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD AUG PY 2006 VL 20 IS 4 BP 809 EP 826 DI 10.1016/j.berh.2006.05.001 PG 18 WC Rheumatology SC Rheumatology GA 095BK UT WOS:000241283000013 PM 16979539 ER PT J AU Da Silva, N Pietrement, C Brown, D Breton, S AF Da Silva, Nicolas Pietrement, Christine Brown, Dennis Breton, Sylvie TI Segmental and cellular expression of aquaporins in the male excurrent duct SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article; Proceedings Paper CT 4th International Conference on Aquaporins CY SEP 10-13, 2005 CL Genval, BELGIUM DE water channel; fluid reabsorption; fluid secretion; male fertility ID TRANSMEMBRANE CONDUCTANCE REGULATOR; ESTROGEN-RECEPTOR-ALPHA; MALE REPRODUCTIVE-TRACT; NEPHROGENIC DIABETES-INSIPIDUS; RAT CAUDA-EPIDIDYMIDIS; ADULT MALE-RAT; WATER CHANNEL; EFFERENT DUCTULES; FLUID REABSORPTION; INITIAL SEGMENT AB The male reproductive tract and accessory glands comprise a complex but interrelated system of tissues that are composed of many distinct cell types, all of which contribute to the ability of spermatozoa to carry out their ultimate function of fertilizing an oocyte. Spermatozoa undergo their final steps of maturation as they pass through the male excurrent duct, which includes efferent ducts, the epididymis and the vas deferens. The composition of the luminal environment in these organs is tightly regulated. Major fluid reabsorption occurs in efferent ducts and in the epididymis, and leads to a significant increase in sperm concentration. In the distal epididymis and vas deferens, fluid secretion controls the final fluidity of the luminal content. Therefore, the process of water movement in the excurrent duct is a crucial step for the establishment of male fertility. Aquaporins contribute to transepithelial water transport in many tissues, including the kidney, the brain, the eye and the respiratory tract. The present article reviews our current knowledge regarding the distribution and function of aquaporins in the male excurrent duct. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Program Membrane Biol, Div Nephrol,Sch Med, Massachusetts Gen Hosp,Dept Med, Boston, MA 02114 USA. RP Breton, S (reprint author), Harvard Univ, Program Membrane Biol, Div Nephrol,Sch Med, Massachusetts Gen Hosp,Dept Med, CPZN 8150,185 Cambridge St, Boston, MA 02114 USA. EM sbreton@partners.org FU NIDDK NIH HHS [DK38452, DK43351, DK57521] NR 73 TC 29 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD AUG PY 2006 VL 1758 IS 8 BP 1025 EP 1033 DI 10.1016/j.bbamem.2006.06.026 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 094XP UT WOS:000241272900008 PM 16935257 ER PT J AU Sebastian, S Settleman, J Reshkin, SJ Azzariti, A Bellizzi, A Paradiso, A AF Sebastian, Sinto Settleman, Jeffrey Reshkin, Stephan J. Azzariti, Amalia Bellizzi, Antonia Paradiso, Angelo TI The complexity of targeting EGFR signalling in cancer: From expression to turnover SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE cancer; EGER; cell signalling; trafficking; turnover; EGER inhibitors ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR GENE; TYROSINE KINASE INHIBITOR; METASTATIC BREAST-CANCER; SQUAMOUS-CELL CARCINOMA; CLATHRIN-COATED PITS; DOWN-REGULATION; ZD1839 IRESSA; LUNG-CANCER; MONOCLONAL-ANTIBODY AB The epidermal growth factor receptor (ErbB1 or EGFR) has been found to be altered in a variety of human cancers. A number of agents targeting these receptors, including specific antibodies directed against the ligand-binding domain of the receptor and small molecules that inhibit kinase activity are either in clinical trials or are already approved for clinical treatment. However, identifying patients that are likely to respond to such treatments has been challenging. As a consequence, it still remains important to identify additional alterations of the tumor cell that contribute to the response to EGFR-targeted agents. While EGFR-mediated signalling pathways have been well established, there is still a rather limited understanding of how intracellular protein-protein interactions, ubiquitination, endocytosis and subsequent degradation of EGFR contribute to the determination of sensitivity to EGFR targeting agents and are emerging areas of investigation. This review primarily focuses on the basic signal transduction pathways mediated through activated membrane bound and/or endosomal EGFR and emphasizes the need to co-target additional proteins that function either upstream or downstream of EGFR to improve cancer therapy. (c) 2006 Elsevier B.V. All rights reserved. C1 Natl Canc Inst, Clin Expt Oncol Lab, I-70126 Bari, Italy. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Bari, Dept Gen & Environm Physiol, Bari, Italy. RP Paradiso, A (reprint author), Natl Canc Inst, Clin Expt Oncol Lab, Via Amendola 209, I-70126 Bari, Italy. EM a.paradiso@oncologico.bari.it OI Reshkin, Stephan/0000-0001-9757-5908 NR 245 TC 152 Z9 171 U1 6 U2 35 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD AUG PY 2006 VL 1766 IS 1 BP 120 EP 139 DI 10.1016/j.bbcan.2006.06.001 PG 20 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 080JM UT WOS:000240243800009 PM 16889899 ER PT J AU Fraguas, R Papakostas, GI Mischoulon, D Bottiglieri, T Alpert, J Fava, M AF Fraguas, Renerio, Jr. Papakostas, George I. Mischoulon, David Bottiglieri, Teodoro Alpert, Jonathan Fava, Maurizio TI Anger attacks in major depressive disorder and serum levels of homocysteine SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anger; depression; homocysteine; hostility; major depressive disorder; moderator ID PLASMA HOMOCYSTEINE; UNIPOLAR DEPRESSION; PSYCHOLOGICAL STRESS; MONOAMINE METABOLISM; FLUOXETINE TREATMENT; FOLATE; VITAMIN-B-12; POPULATION; RISK; METHYLATION AB Background: increased levels of homocysteine have been associated with anger and depression separately. We investigated the association of anger attacks in major depressive disorder (MDD) with serum levels of homocysteine. Methods: Homocysteine serum levels were measured in 192 outpatients with nonpsycbotic MDD, mean age 39.9 +/- 10.7 (range 19-65), 53% women, at baseline of an open-trial antidepressant treatment. We used the Massachusetts General Hospital Anger Attacks Questionnaire to evaluate anger attacks, the Structured Clinical Interview for DSM-IITR Axis I Disorders-Patient Edition (SCID-I/P) to diagnose MDD and the 17-item Hamilton Rating Scale for Depression to measure depression severity. Results: In the multiple regression analysis split by anger attacks adjusted for parameters of depression, creatinine, vitamin B-12, folate, age, smoking, and alcohol consumption, serum levels of homocysteine were positively correlated with length of current major depressive episode (t value, 3.01; 95% confidence interval [CI], .09 to .43; p =.004) and HAM-D-17 scores (t value, 2.48; 95% CI, .07 to 0.64; p =.016) in patients with anger attacks but not in those without anger attacks. Conclusions: Anger attacks in MDD may moderate the relationship of homocysteine serum levels with the severity and length of the depressive episode. Future studies are warranted to confirm and clarify the nature of this moderating effect. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program,Med Sch, Boston, MA 02114 USA. Baylor Univ, Med Ctr, Inst Metabol Dis, Dallas, TX USA. RP Fraguas, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program,Med Sch, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM rfraguas@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01MH48483-05] NR 44 TC 14 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 2006 VL 60 IS 3 BP 270 EP 274 DI 10.1016/j.biopsych.2005.08.026 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 070SI UT WOS:000239543800008 PM 16325154 ER PT J AU Anagnostopoulos, A Hari, PN Perez, WS Ballen, K Bashey, A Bredeson, CN Freytes, CO Gale, RP Gertz, MA Gibson, J Goldschmidt, H Lazarus, HM McCarthy, PL Reece, DE Vesole, DH Giralt, SA AF Anagnostopoulos, Athanasios Hari, Parameswaran N. Perez, Waleska S. Ballen, Karen Bashey, Asad Bredeson, Christopher N. Freytes, Cesar O. Gale, Robert Peter Gertz, Morie A. Gibson, John Goldschmidt, Hartmut Lazarus, Hillard M. McCarthy, Philip L. Reece, Donna E. Vesole, David H. Giralt, Sergio A. TI Autologous or allogeneic stem cell transplantation in patients with Waldenstrom's macroglobulinemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE autologous; allogeneic; stem cell transplantation; Waldenstrom's macroglobulinemia ID CONSENSUS PANEL RECOMMENDATIONS; BONE-MARROW-TRANSPLANTATION; 2ND INTERNATIONAL WORKSHOP; PROGNOSTIC-FACTORS; MULTIPLE-MYELOMA; MOBILIZATION; FLUDARABINE; CHEMOTHERAPY; FEASIBILITY; LEUKEMIA AB The role of hematopoietic stem cell transplantation (SCT) in Waldenstrom's macroglobulinemia (WM) has not been extensively studied. To determine the potential for long-term disease control using SCT in W-M, we performed a retrospective review of 36 patients with WM who received autologous (n = 10) or allogeneic (n = 26) SCT and were reported to the Center for International Blood and Marrow Transplant Research between 1986 and 2002. The following outcomes were described: nonrelapse mortality (NRM), relapse, progression-free survival (PFS), and overall survival (OS). Median age at the time of SCT was 51 years (range, 30-76 years), and median time from initial treatment to SCT was 29 months (range, 2-198 months). A total of 78% of the patients had 2 or more previous chemotherapy regimens, and 52% had disease resistant to salvage chemotherapy. In the allogeneic SCT group, 58% of the patients received myeloablative conditioning regimens containing total body irradiation (TBI), and of the allograft recipients, 19% received nonmyeloablative/reduced-intensity conditioning. After a median follow-up of 65 months, 15 of the 36 patients (42%) are alive. Primary disease accounted for 29% of the deaths in the allogeneic SCT group and 25% of the deaths in the autologous SCT group. The relapse rate at 3 years was 29% (95% confidence interval [CI], 14%-48%) in the allogeneic group and 24% (95% Cl, 4%-54%) in the autologous group. PFS at 3 years was 31% (95% CI, 14%-50%) in the allogeneic group and 65% (95% CI, 32%-91%) in the autologous group; OS was 46% (95% CI, 27%-65%) in the allogeneic group and 70% (95% CI, 40%-93%) in the autologous group. NRM at 3 years was 40% (95% CI, 23%-59%) in the allogeneic group and 11% (95% CI, 0-36%) in the autologous group. Autologous SCT is a safe and feasible treatment option for patients with W-M, especially for those who present with adverse prognostic factors. Allogeneic SCT carries a much higher (40%) risk of NRM and should not be considered outside the context of a clinical trial. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Alexandra Hosp, Athens, Greece. Massachusetts Gen Hosp, Bone Marrow Transplant Program, Boston, MA 02114 USA. Univ Calif San Diego, Bone Marrow Transplant Program, La Jolla, CA 92093 USA. CancerCare Manitoba, Winnipeg, MB, Canada. Univ Texas, Hlth Sci Ctr, Adult Bone Marrow Transplant Program, San Antonio, TX USA. Ctr Adv Studies Leukemia, Los Angeles, CA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Royal Prince Alfred Hosp, Dept Hematol, Camperdown, NSW 2050, Australia. Univ Heidelberg, Dept Internal Med, D-6900 Heidelberg, Germany. Univ Hosp Cleveland, Dept Med, Cleveland, OH 44106 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. St Vincents Comprehens Canc Ctr, New York, NY USA. Univ Texas, MD Anderson Canc Ctr, Blood & Bone Marrow Transplant Unit, Houston, TX 77030 USA. RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Hari, Parameswaran/0000-0002-8800-297X FU NCI NIH HHS [U24-CA76518] NR 39 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2006 VL 12 IS 8 BP 845 EP 854 DI 10.1016/j.bbmt.2006.04.010 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 072XI UT WOS:000239706000007 PM 16864055 ER PT J AU Li, R Lai, L Wax, D Hao, Y Murphy, CN Rieke, A Samuel, M Linville, ML Korte, SW Evans, RW Turk, JR Kang, JX Witt, WT Dai, Y Prather, RS AF Li, Rongfeng Lai, Liangxue Wax, David Hao, Yanhong Murphy, Clifton N. Rieke, August Samuel, Melissa Linville, Mike L. Korte, Scott W. Evans, Rhobert W. Turk, James R. Kang, Jing X. Witt, William T. Dai, Yifan Prather, Randall S. TI Cloned transgenic swine via in vitro production and cryopreservation SO BIOLOGY OF REPRODUCTION LA English DT Article DE assisted reproductive technology; early development ID LOW-TEMPERATURE PRESERVATION; STRAW OPS VITRIFICATION; FATTY-ACID-COMPOSITION; NUCLEAR TRANSFER; PORCINE EMBRYOS; SHEEP OOCYTES; PIGS; PIGLETS; BLASTOCYSTS; LIPIDS AB It has been notoriously difficult to successfully cryopreserve swine embryos, a task that has been even more difficult for in vitro-produced embryos. The first reproducible method of cryopreserving in vivo-produced swine embryos was after centrifugation and removal of the lipids. Here we report the adaptation of a similar process that permits the cryopreservation of in vitro-produced somatic cell nuclear transfer (SCNT) swine embryos. These embryos develop to the blastocyst stage and survive cryopreservation. Transfer of 163 cryopreserved SCNT embryos to two surrogates produced 10 piglets. Application of this technique may permit national and international movement of cloned transgenic swine embryos, storage until a suitable surrogate is available, or the long-term frozen storage of valuable genetics. C1 Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA. Univ Missouri, Natl Swine Resource & Res Ctr, Columbia, MO 65211 USA. Univ Missouri, Off Anim Resources, Columbia, MO 65211 USA. Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. Univ Missouri, Dept Vet Biomed Sci, Columbia, MO 65211 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Pittsburgh, Thomas Starzl Transplantat Inst, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. RP Prather, RS (reprint author), Univ Missouri, Div Anim Sci, 920 E Campus Dr,E125E ASRC, Columbia, MO 65211 USA. EM pratherr@missouri.edu RI Lai, Liangxue/H-4545-2011; OI Prather, Randall/0000-0002-6012-4035 FU NCRR NIH HHS [RR18877]; NHLBI NIH HHS [HL51670]; NIDDK NIH HHS [DK64207] NR 32 TC 50 Z9 56 U1 0 U2 6 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD AUG PY 2006 VL 75 IS 2 BP 226 EP 230 DI 10.1095/biolreprod.106.052514 PG 5 WC Reproductive Biology SC Reproductive Biology GA 065ZR UT WOS:000239199500010 PM 16672718 ER PT J AU Burkatovskaya, M Tegos, GP Swietlik, E Demidova, TN Castano, AP Hamblin, MR AF Burkatovskaya, M Tegos, GP Swietlik, E Demidova, TN Castano, AP Hamblin, MR TI Use of chitosan bandage to prevent fatal infections developing from highly contaminated wounds in mice SO BIOMATERIALS LA English DT Article DE chitin/chitosan; alginate; infection; wound dressing; antimicrobial; haemostasis ID TARGETED PHOTODYNAMIC THERAPY; IN-VIVO; ANTIBACTERIAL ACTIVITY; PROTEUS-MIRABILIS; BACTERIA; HEMORRHAGE; DRESSINGS; MEMBRANE; SWINE; MODEL AB HemCon (R) bandage is an engineered chitosan acetate preparation used as a hemostatic control dressing, and its chemical structure suggests that it should also be antimicrobial. We tested its ability to rapidly kill bacteria in vitro and in mouse models of infected wounds. We used the Gram-negative species Pseudomonas aeruginosa and Proteus mirabilis and the Gram-positive Staphylococcus aureus that had all been stably transduced with the entire bacterial lux operon to allow in vivo bioluminescence imaging. An excisional wound in Balb/c mice was inoculated with 50-250 million cells followed after 30 min by application of HemCon bandage, alginate sponge bandage, silver sulfadiazine cream or no treatment. HemCon was more adhesive to the wound and conformed well to the injury compared to alginate. Animal survival was followed over 15 days with observations of bioluminescence emission and animal activity daily. Chitosan acetate treated mice infected with P. aeruginosa and P. mirabilis all survived while those receiving no treatment, alginate and silver sulfadiazine demonstrated 25-100% mortality. Chitosan acetate was Much more effective than other treatments in rapidly reducing bioluminescence in the wound consistent with its rapid bactericidal activity in vitro as well as its light-scattering properties. S. aureus formed only nonlethal localized infections after temporary immunosuppression of the mice but HemCon was again more effective in reducing bioluminescence. The data suggest that chitosan acetate rapidly kills bacteria in the Wound before systemic invasion can take place, and is superior to alginate bandage and silver sulfadiazine that may both encourage bacterial growth in the short term. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Med Univ Warsaw, Dept Immunol, Inst Biostruct Res, Warsaw, Poland. Tufts Univ, Sch Med, Grad Program Cell Mol & Dev Biol, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,BAR414, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-04] NR 29 TC 97 Z9 102 U1 8 U2 49 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 AUG PY 2006 VL 27 IS 22 BP 4157 EP 4164 DI 10.1016/j.biomaterials.2006.03.028 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 049DN UT WOS:000237996100011 PM 16616364 ER PT J AU Wang, H Eliaz, N Xiang, Z Hsu, HP Spector, M Hobbs, LW AF Wang, H Eliaz, N Xiang, Z Hsu, HP Spector, M Hobbs, LW TI Early bone apposition in vivo on plasma-sprayed and electrochemically deposited hydroxyapatite coatings on titanium alloy SO BIOMATERIALS LA English DT Article DE bone; hydroxyapatite coatings; plasma spraying; titanium alloy; TEM ID CALCIUM-PHOSPHATE COATINGS; MINERALIZED TISSUE; NAOH-TREATMENT; THIN-FILMS; COLLAGEN; ELECTROCRYSTALLIZATION; ELECTRODEPOSITION; ULTRASTRUCTURE; DISSOLUTION; IMPLANTS AB Three different implants, bare Ti-6Al-4V alloy, Ti-6Al-4V alloy coated with plasma-sprayed hydroxyapatite (PSHA), and Ti-6Al-4V alloy coated with electrochemically deposited hydroxyapatite (EDHA), were implanted into canine trabecular bone for 6 h, 7, and 14 days, respectively. Environmental scanning electron microscopy study showed that PSHA coatings had higher bone apposition ratios than those exhibited by bare Ti-6Al-4V and EDHA coatings after 7 days; however, at 14 days after implantation, EDHA and PSHA coatings exhibited similar bone apposition ratios, much higher than that for bare Ti-6Al-4V. The ultrastructure of the bone/implant interface observed by transmission electron microscope showed that the earliest mineralization (6 h-7 days) was in the form of nano-ribbon cluster mineral deposits with a Ca/P atomic ratio lower than that of hydroxyapatite. Later-stage mineralization (7-14 days) resulted in bone-like tissue with the characteristic templating of self-assembied collagen fibrils by HA platelets. Though adhesion of EDHA coatings to Ti-6Al-4V substrate proved problematical and clearly needs to be addressed through appropriate manipulation of electrodepositon parameters, the finely textured microstructure of EDHA coatings appears to provide significant advantage for the integration of mineralized bone tissue into the coatings. (c) 2006 Elsevier Ltd. All rights reserved. C1 MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. Tel Aviv Univ, Dept Solid Mech Mat & Syst, IL-69978 Tel Aviv, Israel. VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Wang, H (reprint author), MIT, Dept Mat Sci & Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM hao.wang@tch.harvard.edu RI Eliaz, Noam/A-3021-2010 OI Eliaz, Noam/0000-0002-1184-4706 NR 34 TC 96 Z9 103 U1 4 U2 20 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 AUG PY 2006 VL 27 IS 23 BP 4192 EP 4203 DI 10.1016/j.biomaterials.2006.03.034 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 050UL UT WOS:000238114100002 PM 16618502 ER PT J AU Gilbert, RJ Magnusson, LH Napadow, VJ Benner, T Wang, RP Wedeen, VJ AF Gilbert, Richard J. Magnusson, Lee H. Napadow, Vitaly J. Benner, Thomas Wang, Ruopeng Wedeen, Van J. TI Mapping complex myoarchitecture in the bovine tongue with diffusion-spectrum magnetic resonance imaging SO BIOPHYSICAL JOURNAL LA English DT Article ID FIBER ARCHITECTURE; HUMAN BRAIN; TENSOR MRI; WATER DIFFUSION; NMR; MOVEMENT; MUSCLE; TISSUE; DEFORMATION; VALIDATION AB The ability to resolve complex fiber populations in muscular tissues is important for relating tissue structure with mechanical function. To address this issue in the case of tongue, we employed diffusion spectrum imaging ( DSI), an MRI method for determining three-dimensional myoarchitecture where myofiber populations are variably aligned. By specifically varying gradient field strength, molecular displacement in a tissue can be determined by Fourier-transforming the echo intensity against gradient strength at fixed gradient pulse spacing. The displacement profiles are visualized by graphing three-dimensional isocontour icons for each voxel, with the isocontour shape and size representing the magnitude and direction of the constituting fiber populations. To validate this method, we simulated a DSI experiment within the constraints of arbitrary crossing fibers, and determined that DSI accurately depicts the angular relationships between these fibers. Considering the fiber relationships in the whole bovine tongue, we compared the images obtained by DSI with those obtained by diffusion tensor imaging in an anterior slice of the lingual core, a region known to possess extensive fiber crossing. In contrast to diffusion tensor imaging, which depicts the anterior core solely as a region with low anisotropy due to the presence of mixed-orientation fiber populations, DSI shows two distinct fiber populations, with an explicit orthogonal relationship to each other. In imaging the whole lingual tissue, we discerned arrays of crossing and noncrossing fibers involving the intrinsic and extrinsic muscles, which merged at regions of interface. We conclude that DSI has the capacity to determine three-dimensional fiber orientation in structurally complex muscular tissues. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Imaging Ctr, Boston, MA 02114 USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rgilbert@mit.edu FU NIDCD NIH HHS [R01 DC05604, R01 DC005604]; NIMH NIH HHS [R01 MH64044, R01 MH064044] NR 48 TC 26 Z9 28 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2006 VL 91 IS 3 BP 1014 EP 1022 DI 10.1529/biophysj.105.068015 PG 9 WC Biophysics SC Biophysics GA 064KA UT WOS:000239086800028 PM 16679361 ER PT J AU Glahn, DC Bearden, CE Barguil, M Barrett, J Soares, JC Velligan, DI AF Glahn, David C. Bearden, Carrie E. Barguil, Marcela Barrett, Jennifer Soares, Jair C. Velligan, Dawn I. TI Sensitivity and specificity of cognitive defects for bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 2nd Biennial Conference of the International-Society-for-Bipolar-Disorders CY AUG 02-04, 2006 CL Edinburgh, SCOTLAND C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2006 VL 8 SU 1 MA 5 BP 2 EP 3 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 065UV UT WOS:000239186300006 ER PT J AU Tohen, M Kryzhanovskaya, L Carlson, G DelBello, M Wozniak, J Kowatch, R Wagner, K Findling, R Lin, D Robertson-Plouch, C Xu, W Huang, X Dittmann, R Biederman, J AF Tohen, Mauricio Kryzhanovskaya, Ludmila Carlson, Gabrielle DelBello, Melissa Wozniak, Janet Kowatch, Robert Wagner, Karen Findling, Robert Lin, Daniel Robertson-Plouch, Carol Xu, Wen Huang, Xiaohong Dittmann, Ralf Biederman, Joe TI Olanzapine in the treatment of acute mania in adolescents with bipolar I disorder. A 3-week randomized double-blind placebo-controlled study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 2nd Biennial Conference of the International-Society-for-Bipolar-Disorders CY AUG 02-04, 2006 CL Edinburgh, SCOTLAND C1 Lilly Res Labs, Indianapolis, IN USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Lilly Deutschland Med Dept, Bad Homburg, Germany. Univ Hamburg, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2006 VL 8 SU 1 MA 60 BP 26 EP 26 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 065UV UT WOS:000239186300059 ER PT J AU Tohen, M Kryzhanovskaya, L Carlson, G DelBello, M Wozniak, J Kowatch, R Wagner, K Findling, R Lin, D Robertson-Plouch, C Xu, W Dittmann, R Biederman, J AF Tohen, Mauricio Kryzhanovskaya, Ludmila Carlson, Gabrielle DelBello, Melissa Wozniak, Janet Kowatch, Robert Wagner, Karen Findling, Robert Lin, Daniel Robertson-Plouch, Carol Xu, Wen Dittmann, Ralf Biederman, Joe TI Efficacy of olanzapine for the treatment of acute mania in subtypes of adolescent patients: A 3-week randomized double-blind placebo-controlled study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 2nd Biennial Conference of the International-Society-for-Bipolar-Disorders CY AUG 02-04, 2006 CL Edinburgh, SCOTLAND C1 Lilly Res Labs, Indianapolis, IN USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. Stony Brook Univ, Sch Med, Stony Brook, NY USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Lilly Deutschland Med Dept, Bad Homburg, Germany. Univ Hamburg, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2006 VL 8 SU 1 MA 59 BP 26 EP 26 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 065UV UT WOS:000239186300058 ER PT J AU Palomero, T T Odom, D O'Neil, J Ferrando, AA Margolin, A Neuberg, DS Winter, SS Larson, RS Li, W Liu, XS Young, RA Look, AT AF Palomero, Teresa T Odom, Duncan O'Neil, Jennifer Ferrando, Adolfo A. Margolin, Adam Neuberg, Donna S. Winter, Stuart S. Larson, Richard S. Li, Wei Liu, X. Shirley Young, Richard A. Look, A. Thomas TI Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia SO BLOOD LA English DT Article ID LOOP-HELIX PROTEINS; GENOME-WIDE ANALYSIS; GENE-EXPRESSION; IN-VIVO; ACTIVATION; SCL; DIFFERENTIATION; IDENTIFICATION; ONCOPROTEIN; E2A AB Aberrant expression of 1 or more transcription factor oncogenes is a critical component of the molecular pathogenesis of human T-cell acute lymphoblastic leukemia (T-ALL); however, oncogenic transcriptional programs downstream of T-ALL oncogenes are mostly unknown. TAL1/SCL is a basic helix-loop-helix (bHLH) transcription factor oncogene aberrantly expressed in 60% of human T-ALLs. We used chromatin immunoprecipitation (ChIP) on chip to identify 71 direct transcriptional targets of TAL1/SCL. Promoters occupied by TAL1 were also frequently bound by the class I bHLH proteins E2A and HEB, suggesting that TAL1/ E2A as well as TAL1/HEB heterodimers play a role in transformation of T-cell precursors. Using RNA interference, we demonstrated that TAL1 is required for the maintenance of the leukemic phenotype in Jurkat cells and showed that TAL1 binding can be associated with either repression or activation of genes whose promoters occupied by TAL1, E2A, and HEB. In addition, oligonucleotide microarray analysis of RNA from 47 primary T-ALL samples showed specific expression signatures involving TAL1 targets in TAL1-expressing compared with -nonexpressing human T-ALLs. Our results indicate that TAL1 may act as a bifunctional transcriptional regulator (activator and repressor) at the top of complex regulatory network that disrupts normal T-cell homeostasis and contributes to leukemogenesis. C1 Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Columbia Univ, Joint Ctr Syst Biol, New York, NY USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Ferrando, AA (reprint author), Columbia Univ, Inst Canc Genet, 1150 St Nicholas Ave,Rm 318A, New York, NY 10032 USA. EM af2196@columbia.edu RI Li, Wei/A-8544-2009; Young, Richard/F-6495-2012; Ferrando, Adolfo /Q-7026-2016 OI Young, Richard/0000-0001-8855-8647; FU NCI NIH HHS [CA114589-01, CA109901]; NHGRI NIH HHS [HG002668]; NIDDK NIH HHS [DK070813, DK68655] NR 42 TC 41 Z9 41 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 AUG 1 PY 2006 VL 108 IS 3 BP 986 EP 992 DI 10.1182/blood-2005-08-3482 PG 7 WC Hematology SC Hematology GA 068NK UT WOS:000239381000038 PM 16621969 ER PT J AU Verdier, V Guang-Chao-Chen Settleman, J AF Verdier, Valerie Guang-Chao-Chen Settleman, Jeffrey TI Rho-kinase regulates tissue morphogenesis via non-muscle myosin and LIM-kinase during Drosophila development SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID BINDING KINASE; ACTIN CYTOSKELETON; SIGNALING PATHWAY; FOCAL ADHESIONS; STRESS FIBERS; SMOOTH-MUSCLE; CELL-SHAPE; ROK-ALPHA; PHOSPHATASE; ROCK AB Background: The Rho-kinases (ROCKs) are major effector targets of the activated Rho GTPase that have been implicated in many of the Rho-mediated effects on cell shape and movement via their ability to affect acto-myosin contractility. The role of ROCKs in cell shape change and motility suggests a potentially important role for Rho-ROCK signaling in tissue morphogenesis during development. Indeed, in Drosophila, a single ROCK ortholog, DRok, has been identified and has been found to be required for establishing planar cell polarity. Results: We have examined a potential role for DRok in additional aspects of tissue morphogenesis using an activated form of the protein in transgenic flies. Our findings demonstrate that DRok activity can influence multiple morphogenetic processes, including eye and wing development. Furthermore, genetic studies reveal that Drok interacts with multiple downstream effectors of the Rho GTPase signaling pathway, including non-muscle myosin heavy chain, adducin, and Diaphanous in those developmental processes. Finally, in overexpression studies, we determined that Drok and Drosophila Lim-kinase interact in the developing nervous system. Conclusion: These findings indicate widespread diverse roles for DRok in tissue morphogenesis during Drosophila development, in which multiple DRok substrates appear to be required. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02139 USA. EM vlrverdier@yahoo.com; gcchen@gate.sinica.edu.tw; settleman@helix.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM060466, R01 GM60466] NR 37 TC 16 Z9 16 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD AUG 1 PY 2006 VL 6 AR 38 DI 10.1186/1471-213X/6/38 PG 11 WC Developmental Biology SC Developmental Biology GA 075SY UT WOS:000239906700001 PM 16882341 ER PT J AU Lee, SJ Kim, HT Ho, VT Cutler, C Alyea, EP Soiffer, RJ Antin, JH AF Lee, S. J. Kim, H. T. Ho, V. T. Cutler, C. Alyea, E. P. Soiffer, R. J. Antin, J. H. TI Quality of life associated with acute and chronic graft-versus-host disease SO BONE MARROW TRANSPLANTATION LA English DT Article DE quality of life; acute graft-versus-host disease; chronic graft-versus-host disease; stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVORS; HEMATOPOIETIC-CELL TRANSPLANTATION; UNRELATED-DONOR; FUNCTIONAL ASSESSMENT; RECIPIENTS; LEUKEMIA; HEALTH; METHOTREXATE; PROPHYLAXIS AB Acute and chronic graft-versus-host diseases (GVHD) are associated with increased morbidity and mortality after hematopoietic stem cell transplantation (HCT). We prospectively measured the quality of life (QOL) of patients undergoing allogeneic transplantation. Ninety-six subjects completed self-assessment surveys before HCT, and at 6 and/or 12 months post-HCT that included the Medical Outcomes Study Short Form 12 (SF12) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale. Eighty-three percent of survivors responded at 6 and 12 months. Physical and mental functioning assessed by the SF12 was not associated with either acute or chronic GVHD. In contrast, the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant was sensitive to occurrence of either acute or chronic GVHD. GVHD is a major determinant of the long-term QOL of survivors. The adverse effects of acute GVHD are detectable with the TOI at 6 months post transplantation after which development of chronic GVHD is the most strongly correlated with worse QOL. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA. EM sjlee@fhcrc.org FU NHLBI NIH HHS [P01 HL070149] NR 28 TC 84 Z9 91 U1 0 U2 0 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 AUG PY 2006 VL 38 IS 4 BP 305 EP 310 DI 10.1038/sj.bmt.1705434 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 071JV UT WOS:000239598900007 PM 16819438 ER PT J AU Goral, M Levy, ES Obler, LK Cohen, E AF Goral, Mira Levy, Erika S. Obler, Loraine K. Cohen, Eyal TI Cross-language lexical connections in the mental lexicon: Evidence from a case of trilingual aphasia SO BRAIN AND LANGUAGE LA English DT Article DE aphasia; bilinguals; inter-language activation; lexical similarities; mental lexicon; multilinguals; translation ID WORD TRANSLATION; BILINGUAL APHASIA; ENGLISH BILINGUALS; COGNATE; MEMORY; RECOGNITION; RECOVERY AB Despite anecdotal data on lexical interference among the languages of multilingual speakers, little research evidence about the lexical connections among multilinguals' languages exists to date. In the present paper, two experiments with a multilingual speaker who had suffered aphasia are reported. The first experiment provides data about inter-language activation during natural conversations; the second experiment examines performance on a word-translation task. Asymmetric patterns of inter-language interference and translation are evident. These patterns are influenced by age of language learning, degree of language recovery and use, and prevalence of shared lexical items. We conclude that whereas age of language learning plays a role in language recovery following aphasia, the degrees of language use prior to the aphasia onset and of shared vocabulary determine the ease with which words are accessed. The findings emphasize the importance of patterns of language use and the relations between the language pair under investigation in understanding lexical connections among languages in bilinguals and multilinguals. (c) 2006 Elsevier Inc. All rights reserved. C1 CUNY Herbert H Lehman Coll, New York, NY 10021 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA USA. CUNY, Grad Ctr, New York, NY 10021 USA. Columbia Univ, Teachers Coll, Dept Biobehav Sci, New York, NY 10027 USA. RP Goral, M (reprint author), CUNY Herbert H Lehman Coll, New York, NY 10021 USA. EM mgoral@bu.edu NR 49 TC 29 Z9 29 U1 4 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD AUG PY 2006 VL 98 IS 2 BP 235 EP 247 DI 10.1016/j.bandl.2006.05.004 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 079IH UT WOS:000240168700010 PM 16793130 ER PT J AU Golshan, M Kuten, A William, J Richardson, A Modarressi, A Matulonis, U AF Golshan, Mehra Kuten, Adam William, Jacquleine Richardson, Andrea Modarressi, Amir Matulonis, Ursula TI Metaplastic carcinoma of the breast with neuroglial differentiation SO BREAST LA English DT Article DE metaplastic carcinoma; neuroglial differentiation; neoadjuvant chemotherapy AB We present a case of a 34-year-old female who had a rapidly enlarging right breast mass. Biopsy results were consistent with a neuroblastic neoplasm of the breast. Neoadjuvant chemotherapy for a neuroblastoma was performed followed by a modified radical mastectomy was performed. Final pathology revealed small foci of poorly differentiated carcinoma randomly distributed within extensive areas of neuroglial differentiation. Such a lesion has not been described in the current literature to our knowledge, and we propose that this neoplasm is a metaplastic carcinoma with a novel heterogeneous differentiation. Subsequent therapy consisted of standard adjuvant breast cancer chemotherapy and radiation therapy. (c) 2005 Elsevier Ltd. All rights reserved. C1 [Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Kuten, Adam; William, Jacquleine; Richardson, Andrea] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Modarressi, Amir] St Marys Hosp, Dept Oncol, Lewiston, ME 04240 USA. [Matulonis, Ursula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 9 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD AUG PY 2006 VL 15 IS 4 BP 545 EP 549 DI 10.1016/j.breast.2005.09.003 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA V44PQ UT WOS:000203015000015 PM 16253505 ER PT J AU Rhee, DJ Peck, RE Belmont, J Martidis, A Liu, M Chang, J Fontanarosa, J Moster, MR AF Rhee, D. J. Peck, R. E. Belmont, J. Martidis, A. Liu, M. Chang, J. Fontanarosa, J. Moster, M. R. TI Intraocular pressure alterations following intravitreal triamcinolone acetonide SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RETINAL VEIN OCCLUSION; RANDOMIZED CLINICAL-TRIAL; DIABETIC MACULAR EDEMA; INJECTION; DEGENERATION; GLAUCOMA; SAFETY AB Aims: To determine the prevalence of intraocular pressure (IOP) alterations following intravitreal injection of triamcinolone acetonide (IVTA) and to assess possible risk factors of IOP elevation in eyes receiving single and/or repeat injections. Methods: Retrospective, consecutive case series. 570 consecutive eyes of 536 patients who received a single IVTA injection (4 mg/0.1 ml) and a second set of 43 eyes of 40 patients who received a second injection. Retrospective review of all IVTA cases performed by three vitreoretinal surgeons over a 42 month period beginning in 2000. The main outcome measure was change in IOP defined as absolute value of IOP elevation (5 mm Hg or higher, 10 mmHg or higher), and percentage of baseline (30% or higher increase from baseline IOP). Results: Of the 528 eyes receiving single injections, 281 (53.2%) had an IOP elevation; 267 eyes (50.6%) experienced an elevation of IOP of at least 30%, and 245 (45.8%) and 75 (14.2%) eyes had an increase of 5 mmHg or 10 mmHg or more, respectively. Baseline IOP greater than 16 mmHg is a risk factor for post-injection IOP elevation. Of the 43 eyes which received a second injection, 28 (65.1%) experienced an increase in IOP of at least 30% of baseline. Filtering surgery was required in five (0.094%) of the single and one (2.3%) of repeat injection eyes. Conclusions: Elevated IOP after IVTA is common and patients should be monitored beyond 6 months post-injection. Patients with a baseline IOP more than 16 mmHg or receiving a second injection should be carefully monitored for an elevated IOP. C1 Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. Wills Eye Hosp & Res Inst, Lab Mol Ophthalmol, Philadelphia, PA 19107 USA. Wills Eye Hosp & Res Inst, William & Anna Glaucoma Serv, Philadelphia, PA 19107 USA. Wills Eye Hosp & Res Inst, Retina Serv, Philadelphia, PA 19107 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com FU NEI NIH HHS [R03 EY013997, EY 13997-01] NR 28 TC 72 Z9 74 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD AUG PY 2006 VL 90 IS 8 BP 999 EP 1003 DI 10.1136/bjo.2006.090340 PG 5 WC Ophthalmology SC Ophthalmology GA 064TC UT WOS:000239111000023 PM 16597664 ER PT J AU Chan, ESL Montesinos, MC Fernandez, P Desai, A Delano, DL Yee, H Reiss, AB Pillinger, MH Chen, JF Schwarzschild, MA Friedman, SL Cronstein, BN AF Chan, Edwin S. L. Montesinos, Maria Carmen Fernandez, Patricia Desai, Avani Delano, David L. Yee, Herman Reiss, Allison B. Pillinger, Michael H. Chen, Jiang-Fan Schwarzschild, Michael A. Friedman, Scott L. Cronstein, Bruce N. TI Adenosine A(2A) receptors play a role in the pathogenesis of hepatic cirrhosis SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE purinergic receptor; methylxanthines; hepatic fibrosis; ethanol; methotrexate ID SUPEROXIDE ANION GENERATION; ADENOSINE A(2A) RECEPTOR; CARBON-TETRACHLORIDE; STELLATE CELLS; LEUKOCYTE ACCUMULATION; HUMAN-NEUTROPHILS; LIVER-CIRRHOSIS; TISSUE-INJURY; THP-1 CELLS; METHOTREXATE AB 1 Adenosine is a potent endogenous regulator of inflammation and tissue repair. Adenosine, which is released from injured and hypoxic tissue or in response to toxins and medications, may induce pulmonary fibrosis in mice, presumably via interaction with a specific adenosine receptor. We therefore determined whether adenosine and its receptors contribute to the pathogenesis of hepatic fibrosis. 2 As in other tissues and cell types, adenosine is released in vitro in response to the fibrogenic stimuli ethanol (40 mg dl(-1)) and methotrexate (100 nM). 3 Adenosine A(2A) receptors are expressed on rat and human hepatic stellate cell lines and adenosine A2A receptor occupancy promotes collagen production by these cells. Liver sections from mice treated with the hepatotoxins carbon tetrachloride (CCl4) (0.05 ml in oil, 50 : 50 v : v, subcutaneously) and thioacetamide (100 mg kg(-1) in PBS, intraperitoneally) released more adenosine than those from untreated mice when cultured ex vivo. 4 Adenosine A(2A) receptor-deficient, but not wild-type or A(3) receptor-deficient, mice are protected from development of hepatic fibrosis following CCl4 or thioacetamide exposure. 5 Similarly, caffeine (50 mg kg(-1) day(-1), po), a nonselective adenosine receptor antagonist, and ZM241385 (25 mg kg(-1) bid), a more selective antagonist of the adenosine A(2A) receptor, diminished hepatic fibrosis in wild-type mice exposed to either CCl4 or thioacetamide. 6 These results demonstrate that hepatic adenosine A(2A) receptors play an active role in the pathogenesis of hepatic fibrosis, and suggest a novel therapeutic target in the treatment and prevention of hepatic cirrhosis. C1 NYU, Sch Med, Div Clin Pharmacol, Dept Med, New York, NY 10016 USA. NYU, Sch Med, Div Rheumatol, Dept Med, New York, NY 10016 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. Winthrop Univ Hosp, Dept Med, Mineola, NY 11501 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. CUNY Mt Sinai Sch Med, Dept Med, Div Liver Dis, New York, NY 10029 USA. RP Cronstein, BN (reprint author), NYU, Sch Med, Div Clin Pharmacol, Dept Med, 550 1st Ave,NBV16N1, New York, NY 10016 USA. EM Bruce.Cronstein@nyumc.org RI Montesinos, M. Carmen/G-8852-2015; OI Montesinos, M. Carmen/0000-0003-1801-311X; Reiss, Allison B/0000-0002-4478-2441; Pillinger, Michael/0000-0003-3168-1542 FU NCRR NIH HHS [M01 RR000096, M01RR00096]; NIAAA NIH HHS [AA13336, R01 AA013336]; NIAMS NIH HHS [AR41911, R01 AR041911]; NIDDK NIH HHS [DK56621, R01 DK056621, R56 DK056621]; NIGMS NIH HHS [GM56268, R01 GM056268] NR 65 TC 101 Z9 104 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 2006 VL 148 IS 8 BP 1144 EP 1155 DI 10.1038/sj.bjp.0706812 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073QY UT WOS:000239758900014 PM 16783407 ER PT J AU Post, RM Altshuler, LL Leverich, GS Frye, MA Nolen, WA Kupka, RW Suppes, T McElroy, S Keck, PE Denicoff, KD Grunze, H Kitchen, CMR Mintz, J AF Post, R. M. Altshuler, L. L. Leverich, G. S. Frye, M. A. Nolen, W. A. Kupka, R. W. Suppes, T. McElroy, S. Keck, P. E. Denicoff, K. D. Grunze, H. Kitchen, C. M. R. Mintz, J. TI Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; ANTIDEPRESSANT DISCONTINUATION; SYMPTOMATOLOGY IDS; NUCLEUS-ACCUMBENS; NATURAL-HISTORY; DISORDER; NETWORK; 1-YEAR; IMIPRAMINE; TRIAL AB Background: Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression. Aims: To examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers. Method: In a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers. Results: A total of 174 adults with bipolar disorder 1, 11 or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49-53%) and remission (34-41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline. Conclusions: More caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling. Declaration of interest: None. C1 NIMH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. Univ Groningen Hosp, Groningen, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Univ Munich, Munich, Germany. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. RP Post, RM (reprint author), Bldg 10,Room 3S239,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. EM postr@mail.nih.gov RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 37 TC 195 Z9 201 U1 1 U2 6 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD AUG PY 2006 VL 189 BP 124 EP 131 PG 8 WC Psychiatry SC Psychiatry GA 074UH UT WOS:000239836800006 PM 16880481 ER PT J AU Brzezinski, M Schmidt, U Fitzsimons, MG AF Brzezinski, Marek Schmidt, Ulrich Fitzsimons, Michael G. TI Acute and massive hemorrhage due to caval perforation by an inferior vena cava filter - absolute indication for surgery? Case report and review of literature SO BURNS LA English DT Review ID SPONTANEOUS RETROPERITONEAL HEMATOMA; GREENFIELD FILTER; ARTERIAL HEMORRHAGE; CLINICAL-EXPERIENCE; COMPLICATIONS; INTERRUPTION; ENOXAPARIN; PENETRATION; DISLODGMENT; PREVENTION C1 Univ Calif San Francisco, Vet Adm Med Ctr, Dept Anesthesia & Perioperat Care, San Francisco, CA 94121 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Brzezinski, M (reprint author), Univ Calif San Francisco, Vet Adm Med Ctr, Dept Anesthesia & Perioperat Care, 4150 Clement St, San Francisco, CA 94121 USA. EM brzezinm@anesthesia.ucsf.edu NR 35 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD AUG PY 2006 VL 32 IS 5 BP 640 EP 643 DI 10.1016/j.burns.2006.02.002 PG 4 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 064PF UT WOS:000239100900019 PM 16777337 ER PT J AU Rodrigues, NA Chen, MH Catalona, WJ Roehl, KA Richie, JR D'Amico, AV AF Rodrigues, Neesha A. Chen, Ming-Hui Catalona, William J. Roehl, Kimberly A. Richie, Jerome R. D'Amico, Anthony V. TI Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer SO CANCER LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol DE prostate carcinoma; biochemical failure; androgen deprivation; prognostic factors; prostate-specific antigen nadir ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; TRIAL; NADIR; PROGRESSION; FAILURE; RISK; MITOXANTRONE; RADIOTHERAPY; SUPPRESSION AB BACKGROUND. The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer-specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate-specific antigen (PSA) levels after they received local treatment. METHODS. The study population consisted of 67 patients who had a PSA doubling time (DT) <= 6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS. A PSA nadir > 0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score >= 8 (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8% versus 50.9% for patients with a PSA nadir <= 0.2 ng/mL versus >= 0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score <= 7 versus >= 8, respectively. CONCLUSIONS. Among men with a PSA DT <= 6 months, both a PSA nadir > 0.2 ng/mL after ADT and a Gleason score >= 8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Radiat Oncol Program, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT USA. Northwestern Univ, Feinberg Sch Med, Dept Stat, Chicago, IL 60611 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. RP Rodrigues, NA (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM narodrigues@partners.org NR 32 TC 12 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2006 VL 107 IS 3 BP 514 EP 520 DI 10.1002/cncr.22018 PG 7 WC Oncology SC Oncology GA 065KC UT WOS:000239157800010 PM 16795068 ER PT J AU Michaelson, MD Kaufman, DS Kantoff, P Oh, WK Smith, MR AF Michaelson, M. Dror Kaufman, Donald S. Kantoff, Philip Oh, William K. Smith, Matthew R. TI Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer SO CANCER LA English DT Article DE bone metastases; osteoporosis; bisphosphonates; alkaline phosphatase; N-telopeptide ID ENDOTHELIN-RECEPTOR ANTAGONIST; PLACEBO-CONTROLLED TRIAL; SKELETAL COMPLICATIONS; PHARMACOKINETICS; PROGRESSION; MARKERS; DISEASE; SAFETY; PAIN AB BACKGROUND. Metastatic prostate cancer is characterized by the presence of osteoblastic bone metastases. Bone metastases account for most of the morbidity from this disease. Inhibition of osteoclast activity with the potent bisphosphonate zoledronic acid reduces skeletal complications and decreases serum levels of biochemical bone turnover markers compared with placebo. Atrasentan is an investigational agent that inhibits endothelin-1 receptor, resulting in decreased osteoblast activity. METHODS. The effects of atrasentan alone versus combination therapy with atrasentan and zoledronic acid were investigated on bone turnover markers in men with bone metastases from prostate cancer. Forty-four men were randomized to receive either atrasentan alone or combination therapy, and 33 completed at least 12 weeks of treatment and were included in the primary analysis. RESULTS. Treatment with the combination resulted in significantly lower serum levels of N-telopeptide, a marker of bone resorption, compared with treatment with atrasentan alone. There was no difference between groups in serum levels of bone-specific alkaline phosphatase, a marker of bone formation, at 12 weeks. Commonly observed adverse effects were edema, rhinitis, fatigue, and shortness of breath, most of which were NCI CTC (version 3.0) Grade 1. No Grade 4 or 5 treatment-related toxicities were observed. There was minimal clinical efficacy, with no objective responses and only 1 prostate-specific antigen (PSA) response. CONCLUSIONS. There is no evidence for additive or synergistic effects of combination therapy with atrasentan and zoledronic acid on bone turnover markers in men with metastatic prostate cancer. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM dmichaelson1@partners.org RI Oh, William/B-9163-2012; OI Oh, William/0000-0001-5113-8147; Michaelson, Dror/0000-0001-9249-6338 FU NCI NIH HHS [1K12CA87723] NR 20 TC 35 Z9 36 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2006 VL 107 IS 3 BP 530 EP 535 DI 10.1002/cncr.22043 PG 6 WC Oncology SC Oncology GA 065KC UT WOS:000239157800012 PM 16804927 ER PT J AU Krop, IE AF Krop, Ian E. TI Chemokine signaling in gliomas - Prognostic factor, therapeutic target or both? SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE chemokine; glioma; CXCL12; CXCR4; SDF-1; prognostic factor ID BREAST-CANCER METASTASIS; HUMAN GLIOBLASTOMA; RECEPTOR CXCR4; CELL INVASION; CXCL12 EXPRESSION; TUMOR-GROWTH; ANGIOGENESIS; METALLOPROTEINASE; IDENTIFICATION; ACTIVATION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Krop, IE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ikrop@partners.org NR 26 TC 3 Z9 3 U1 0 U2 1 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 AUG PY 2006 VL 5 IS 8 BP 1039 EP 1041 PG 3 WC Oncology SC Oncology GA 110SU UT WOS:000242400700033 PM 16931903 ER PT J AU Cohen, JH Schoenbach, VJ Kaufman, JS Talcott, JA Schenck, AP Peacock, S Symons, M Amamoo, MA Carpenter, WR Godley, PA AF Cohen, JH Schoenbach, VJ Kaufman, JS Talcott, JA Schenck, AP Peacock, S Symons, M Amamoo, MA Carpenter, WR Godley, PA TI Racial differences in clinical progression among Medicare recipients after treatment for localized prostate cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE prostate cancer; recurrence; race ID COMORBIDITY INDEX; POPULATION; SURVIVAL; STATISTICS; RACE AB Objective Prostate cancer recurrence impacts patient quality of life and risk of prostate-cancer specific death following definitive treatment. We investigate differences in disease-free survival among white, black, Hispanic, and Asian patients in a large, population-based database. Methods Merged Surveillance, Epidemiology, and End Results Program (SEER) and Medicare files provided data on 23,353 white patients, 2,814 black patients, 480 Hispanic patients, and 566 Asian patients diagnosed at age 65-84 years with clinically localized prostate cancer between 1986 and 1996 in five SEER sites. Patients were followed through 1998. Racial differences in disease-free survival were assessed using Kaplan-Meier survival curves and Cox regression models. Results The 75th percentile disease-free survival time for black patients was 13 months less than that for white patients (95% confidence interval [CI]: 6.2-19.8 months), 29.7 months less than that for Hispanic patients (95% CI: 4.4-55.0 months), and 39.1 months less than that for Asian patients (95% CI: 12.1-66.1 months). In multivariate analysis, black race predicted shorter disease-free survival among surgery patients, but not among radiation patients. Conclusions Black patients experienced shorter disease-free survival compared to white, Hispanic, and Asian patients, and the disease-free survival of white, Hispanic, and Asian patients were not statistically different. Earlier recurrence of prostate cancer may help explain black patients' increased risk of mortality from prostate cancer. C1 Suny Downstate Med Sch, Dept Urol, Brooklyn, NY 11203 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Med, Div Hematol Oncol, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Med Review N Carolina Inc, Cary, NC USA. Shaw Univ, Inst Hlth Social & Comuity Res, Raleigh, NC 27601 USA. RP Cohen, JH (reprint author), Suny Downstate Med Sch, Dept Urol, Brooklyn, NY 11203 USA. EM jhcohen4@gmail.com RI Carpenter, William/E-5125-2013 FU NCI NIH HHS [1 U01 CA114629-01]; NIMHD NIH HHS [1 P60 MD00244-01] NR 24 TC 25 Z9 25 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2006 VL 17 IS 6 BP 803 EP 811 DI 10.1007/s10552-006-0017-7 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053XR UT WOS:000238340000006 PM 16783608 ER PT J AU Carrasco, DR Fenton, T Sukhdeo, K Protopopova, M Enos, M You, MJ Di Vizio, D Nogueira, C Stommel, J Pinkus, GS Fletcher, C Hornick, JL Cavenee, WK Furnari, FB DePinho, RA AF Carrasco, Daniel R. Fenton, Tim Sukhdeo, Kumar Protopopova, Marina Enos, Miriam You, Mingjian J. Di Vizio, Dolores Nogueira, Cristina Stommel, Jayne Pinkus, Geraldine S. Fletcher, Christopher Hornick, Jason L. Cavenee, Webster K. Furnari, Frank B. DePinho, Ronald A. TI The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans (vol 9, pg 379, 2006) SO CANCER CELL LA English DT Correction C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci,Belfer Fdn,Inst Innovat Canc Sc, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu NR 1 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2006 VL 10 IS 2 BP 171 EP 171 DI 10.1016/j.ccr.2006.07.012 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 075NH UT WOS:000239891300011 ER PT J AU Fantin, VR St-Pierre, J Leder, P AF Fantin, Valeria R. St-Pierre, Julie Leder, Philip TI Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance (vol 9, pg 425, 2006) SO CANCER CELL LA English DT Correction C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Leder, P (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM leder@genetics.med.harvard.edu NR 1 TC 2 Z9 2 U1 4 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2006 VL 10 IS 2 BP 172 EP 172 DI 10.1016/j.ccr.2006.07.011 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 075NH UT WOS:000239891300012 ER PT J AU Foster, MC Kleinerman, RA Abramson, DH Seddon, JM Tarone, RE Tucker, MA AF Foster, Meredith C. Kleinerman, Ruth A. Abramson, David H. Seddon, Johanna M. Tarone, Robert E. Tucker, Margaret A. TI Tobacco use in adult long-term survivors of retinoblastoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHILDHOOD-CANCER SURVIVORS; FOLLOW-UP; CIGARETTE-SMOKING; LUNG-CANCER; RISK; BEHAVIORS; AGE AB A significant risk of lung cancer was identified among hereditary, but not nonhereditary, retinoblastoma (Rb) patients. Tobacco use was investigated to determine whether differences in smoking prevalence might explain the lung cancer excess and to characterize smoking patterns in adult survivors of Rb. Subjects were 441 hereditary and 395 nonhereditary 1-year survivors of Rb, age >= 18 years, who responded to a telephone survey about current health behavior, including tobacco use. Response rates were 76% for hereditary and 73% for nonhereditary survivors. We compared patterns and predictors of current tobacco use among hereditary and nonhereditary survivors with other childhood cancer survivor studies and the U.S. population. Hereditary Rb survivors currently smoke cigarettes significantly less frequently than nonhereditary survivors (16.8% versus 24.3%), although among current smokers, age at smoking initiation (17 years old) and average cigarettes (1.5 packs) smoked daily are similar. Predictors of current and ever cigarette smoking include nonhereditary Rb, older age, being female, less education, and use of other tobacco products. Rb survivors smoke cigarettes significantly less than the U.S. population (rate ratio, 0.63; 95% confidence interval, 0.5-0.8 for males; rate ratio, 0.75; 95% confidence interval, 0.6-0.9 for females), but Rb survivors have comparable smoking rates with other childhood cancer survivors. Smoking did not account for the increased risk of lung cancer among hereditary Rb patients, and this may point to an enhanced sensitivity to the carcinogenic effects of tobacco. Adult survivors of Rb should be encouraged to stop smoking. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Int Epidemiol Inst, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kleinerman, RA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS 7044,6120 Execut Blvd, Rockville, MD 20852 USA. EM kleinerr@mail.nih.gov RI Tucker, Margaret/B-4297-2015; OI Kleinerman, Ruth/0000-0001-7415-2478 FU Intramural NIH HHS NR 24 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1464 EP 1468 DI 10.1158/1055-9965.EPI-05-0783 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500007 PM 16896033 ER PT J AU Cabelof, DC Ikeno, Y Nyska, A Busuttil, RA Anyangwe, N Vijg, J Matherly, LH Tucker, JD Wilson, SH Richardson, A Heydari, AR AF Cabelof, Diane C. Ikeno, Yuji Nyska, Abraham Busuttil, Rita A. Anyangwe, Njwen Vijg, Jan Matherly, Larry H. Tucker, James D. Wilson, Samuel H. Richardson, Arlan Heydari, Ahmad R. TI Haploinsufficiency in DNA polymerase beta increases cancer risk with age and alters mortality rate SO CANCER RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; CALORIC RESTRICTION; GENOME MAINTENANCE; OXIDATIVE STRESS; MICE LACKING; IN-VIVO; MOUSE; MECHANISMS; SENESCENCE; PARAMETERS AB This study uses a base excision repair (BER)-deficient model, the DNA polymerase heterozygous mouse, to investigate the effect of BER deficiency on tumorigenicity and aging. Aged beta-pol(+/-) mice express 50% less beta-pol transcripts and protein (P < 0.05) than aged beta-pol(+/+) mice, showing maintenance of the heterozygous state over the life span of the mouse. This reduction in beta-pol expression was not associated with an increase in mutation rate but was associated with a 100% increase in the onset of hypoploidy. Aged beta-pol(+/-) mice exhibited a 6.7-fold increase in developing lymphoma (P < 0.01). Accordingly, 38% of beta-pol(+/-) mice exhibited lymphoid hyperplasia, whereas none of the beta-pol(+/-) exhibited this phenotype. beta-pol(+/-) mice were also more likely to develop adenocarcinoma (2.7-fold increase; P < 0.05) and more likely to develop multiple tumors, as 20% of the beta-pol(+/-) animals died bearing multiple tumors compared with only 5% of the beta-pol(+/-) animals (P < 0.05). In spite of accelerated tumor development, no gross effect of O-pol heterozygosity was seen with respect to life span. However, the survival curves for the beta-pol(+/-) and beta-pol(+/-) mice are not identical. A maximum likelihood estimation analysis showed a modest but significant (P < 0.05) acceleration of the age-dependent mortality rate in beta-pol(+/-) mice. Thus, the beta-pol(+/-) mouse represents a model in which mortality rate and tumor development are accelerated and provides evidence supporting the role of genomic maintenance in both aging and carcinogenesis. C1 Wayne State Univ, Karmanos Canc Inst, Sch Med, Dev Therapeut Program, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. Wayne State Univ, Dept Nutr & Food Sci, Detroit, MI 48201 USA. Wayne State Univ, Dept Biol Sci, Detroit, MI 48201 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. RP Cabelof, DC (reprint author), Wayne State Univ, Karmanos Canc Inst, Sch Med, Dev Therapeut Program, 110 E Warren, Detroit, MI 48201 USA. EM d.cabelof@wayne.edu FU NIA NIH HHS [1P01 AG 14674, P01 AG 19316, 1P30 AG 13319, R01 AG 20438, P01 AG 17242]; NIDDK NIH HHS [1R21 DK 62256]; NIEHS NIH HHS [ES 06639, ES 11044, 1F32 ES 013643] NR 35 TC 42 Z9 48 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2006 VL 66 IS 15 BP 7460 EP 7465 DI 10.1158/0008-5472.CAN-06-1177 PG 6 WC Oncology SC Oncology GA 069XU UT WOS:000239483500013 PM 16885342 ER PT J AU Gizatullin, F Yao, Y Kung, V Harding, MW Loda, M Shapiro, GI AF Gizatullin, Farid Yao, Yao Kung, Victor Harding, Matthew W. Loda, Massimo Shapiro, Geoffrey I. TI The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function SO CANCER RESEARCH LA English DT Article ID SPINDLE ASSEMBLY CHECKPOINT; TETRAPLOIDY CHECKPOINT; CYTOKINESIS FAILURE; DNA-DAMAGE; B KINASE; A KINASE; CANCER; P53; ARREST; DISRUPTION AB VX-680 is a potent inhibitor of Aurora kinases that induces the accumulation of cells with >= 4N DNA content, followed by cell death. Here, we define the role of p53 and p21(Waf1/Cip1) in cell cycle perturbations following exposure to VX-680. Endoreduplication and apoptosis in response to VX-680 are limited in A549 and MCF-7 cells expressing wild-type p53, and markedly enhanced in cells lacking p53, including those engineered to express the HPV16-E6 oncoprotein or short interfering RNA pools targeting p53. In contrast, endoreduplication and apoptosis occur in the p53 wild-type cell lines, RKO and U2OS. The difference in response to VX-680 among these cell lines correlates with the timing of induction of p21(Waf1/Cip1) and its ability to inhibit cyclin E-cdk2 activity. In A549 cells, VX-680 induces the expression of p53 and p21(Waf1/Cip1) within 24 hours, with consequent inhibition of cyclin E-cdk2, and reduction of retinoblastoma protein phosphorylation, limiting endoreduplication. In RKO and U2OS cells, the induction of p21(Waf1/Cip1) is delayed and associated with higher residual cyclin E-cdk2 kinase activity and retinoblastoma protein phosphorylation, followed by progressive endoreduplication and apoptosis. Abrogation of p21(Waf1/Cip1) expression by short interfering RNA targeting in A549 cells results in a substantial increase in the degree of endoreduplication, whereas inducible expression of p21(Waf1/Cip1) in p53-negative NCI-H1299 cells inhibits VX-680-induced endoreduplication and cell death. These data suggest that the integrity of the p53-p21(Waf1/Cip1)-dependent postmitotic checkpoint governs the response to Aurora kinase inhibition. Although cells with intact checkpoint function arrest with 4N DNA content, those with compromised checkpoint function are more likely to undergo endoreduplication followed by eventual apoptosis. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Vertex Pharmaceut Inc, Cambridge, MA USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 810A,44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu FU NCI NIH HHS [P20 CA 90573, R01 CA 90687] NR 34 TC 144 Z9 146 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2006 VL 66 IS 15 BP 7668 EP 7677 DI 10.1158/0008-5472.CAN-05-3353 PG 10 WC Oncology SC Oncology GA 069XU UT WOS:000239483500039 PM 16885368 ER PT J AU Goerge, T Barg, A Schnaeker, EM Poppelmann, B Shpacovitch, V Rattenholl, A Maaser, C Luger, TA Steinhoff, M Schneider, SW AF Goerge, Tobias Barg, Alexej Schnaeker, Eva-Maria Poppelmann, Birgit Shpacovitch, Victoria Rattenholl, Anke Maaser, Christian Luger, Thomas A. Steinhoff, Martin Schneider, Stefan W. TI Tumor-derived matrix metalloproteinase-1 targets endothelial proteinase-activated receptor 1 promoting endothelial cell activation SO CANCER RESEARCH LA English DT Article ID VONWILLEBRAND-FACTOR; MALIGNANT-MELANOMA; THROMBIN RECEPTOR; METASTASIS; CANCER; EXPRESSION; INVASION; INFLAMMATION; PLATELETS; ADHESION AB In the vascular system, circulating tumor cells interact with endothelial cells. Tumor-endothelial cross-talk transforms the intravascular milieu to a prothrombotic, proinflammatory, and cell-adhesive state called endothelial cell activation (ECA). In the present study, we analyze the potential of metastatic tumor-derived soluble factors to transform the vascular endothelium into a prothrombotic and proinflammatory activated state. Supernatant from cultured melanoma and colon cancer cells (A375, WM9, A7, and HT-29) induced an acute activation of macrovascular and microvascular endothelial cells (human umbilical vein endothelial cells and human dermal microvascular endothelial cells) as shown by intracellular calcium flux and secretion of von Willebrand factor and interleukin-8, all markers of acute ECA. This process was inhibited using specific proteinase-activated receptor 1 (PAR1) inhibitors (RWJ-58259 and SCH-79797), indicating a mediating role for endothelial thrombin receptors. Immunofluorescence, Western blot analysis, and collagenase activity assay of tumor cells and culture supernatant revealed the presence of matrix metalloproteinase-1 (MMP-1), a recently described activator of PARI. Inhibition of MMP-1 in supernatant from cultured tumor cells significantly attenuated ECA. Additional studies using isolated human MMP-1 (5 nmol/L) proved the presence of a functional MMP-1/PAR1 axis in tumor-endothelial communication. These findings show a new pathway of tumor-endothelial cross-talk via an intravascular MMP1/PAR1 axis in microvascular and macrovascular endothelium. Inhibition of this cross-talk may be a powerful means to prevent tumor-induced ECA and thus thrombotic and inflammatory cell adhesion. C1 Klin Forsch Munster, Dept Dermatol, Munster, Germany. Klin Forsch Munster, Inst Physiol 2, Munster, Germany. Klin Forsch Munster, Interdisziplinares Zentrum, Munster, Germany. Univ Munster, Ludwig Boltzmann Inst Immunol & Cell Biol Skin, D-4400 Munster, Germany. Univ Munster, Dept Med B, D-4400 Munster, Germany. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res,Inst Biomed Res, Boston, MA 02115 USA. RP Schneider, SW (reprint author), Univ Munster, Dept Dermatol, Von Esmarch Str 58, D-48149 Munster, Germany. EM sschnei@mednet.uni-muenster.de RI Steinhoff, Martin/F-6312-2013; Silva, Mariana/B-9530-2012; OI Steinhoff, Martin/0000-0002-7090-2187 NR 47 TC 82 Z9 84 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2006 VL 66 IS 15 BP 7766 EP 7774 DI 10.1158/0008-5472.CAN-05-3897 PG 9 WC Oncology SC Oncology GA 069XU UT WOS:000239483500051 PM 16885380 ER PT J AU Miller, KL Karagas, MR Kraft, P Hunter, DJ Catalano, PJ Byler, SH Nelson, HH AF Miller, Katie L. Karagas, Margaret R. Kraft, Peter Hunter, David J. Catalano, Paul J. Byler, Steven H. Nelson, Heather H. TI XPA, haplotypes, and risk of basal and squamous cell carcinoma SO CARCINOGENESIS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-A; MULTIVARIATE CONFOUNDER SCORE; ACID SUBSTITUTION VARIANTS; NONMELANOMA SKIN-CANCER; DNA-REPAIR; LUNG-CANCER; GENETIC-VARIATION; DAMAGE RECOGNITION; POLYMORPHISM AB Nucleotide excision repair (NER) is instrumental in removing DNA lesions caused by ultraviolet (UV) radiation, the dominant risk factor for keratinocyte carcinoma, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We evaluated whether BCC or SCC risk was influenced by the A23G single nucleotide polymorphism (SNP) in Xeroderma pigmentosum group A (XPA), which codes for an essential protein in NER. We also investigated whether haplotypes of XPA, determined by seven haplotype-tagging SNPs, better define susceptibility to keratinocyte carcinoma. Incident cases of BCC and SCC from New Hampshire were identified through dermatologists and pathology laboratories. Population-based controls were frequency-matched to cases by gender and age. Cases of BCC (886) and of SCC (682) were compared with controls (796). Models controlled for age, gender, pigmentation factors and severe sunburns and were restricted to Caucasians. Using GG as the reference, the A allele was less frequent among cases of BCC (ORAG = 0.82,95% CI (0.66, 1.01); ORAA= 0.74,95% CI (0.53,1.03); trend test P = 0.03) and SCC (ORAG = 0.85, 95% CI (0.67, 1.07); ORAA = 0.74, 95% CI (0.52, 1.05); trend test P = 0.05) than controls. Risk from > 3 severe sunburns was elevated for those with the GG genotype only, and this interaction was nearly significant for BCC (P = 0.07). XPA genotype also modified a relationship between SCC and the amount of pigmentation (P = 0.02). Using a haplotype analysis identifying seven common XPA haplotypes indicated that the A23G polymorphism alone captured the differences in susceptibility to keratinocyte carcinoma. The common G allele of the A23G polymorphism was associated with an increased risk of BCC and SCC and this polymorphism appeared to be the determining polymorphism in XPA that alters cancer susceptibility. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Epidemiol & Biostat Sect, Lebanon, NH USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH USA. RP Nelson, HH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM hnelson@hsph.harvard.edu FU NCI NIH HHS [R01CA57494, R01 CA082354, CA006515]; NIEHS NIH HHS [T32 ES007155] NR 36 TC 50 Z9 53 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2006 VL 27 IS 8 BP 1670 EP 1675 DI 10.1093/carcin/bgi376 PG 6 WC Oncology SC Oncology GA 074VY UT WOS:000239841100018 PM 16513681 ER PT J AU Kalva, SP Athanasoulis, CA Fan, CM Curvelo, M Geller, SC Greenfield, AJ Waltman, AC Wicky, S AF Kalva, SP Athanasoulis, CA Fan, CM Curvelo, M Geller, SC Greenfield, AJ Waltman, AC Wicky, S TI "Recovery (TM)" vena cava filter: Experience in 96 patients SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE thrombo-embolism; IVC filters; retreivable filters; pulmonary embolism; deep venous thrombosis ID DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM; CLINICAL-EXPERIENCE; COMPLICATIONS; PREVENTION; RETRIEVAL; TEMPORARY; INSERTION; REGISTRY; TRAUMA AB The purpose of the study was to assess the clinical safety and efficacy of the "Recovery(TM)" (Bard) inferior vena cava (IVC) filter. We retrospectively evaluated the clinical and imaging data of patients who had a "Recovery(TM)" IVC filter placed between January 2003 and December 2004 in our institution. The clinical presentation, indications, and procedure-related complications during placement and retrieval were evaluated. Follow-up computed tomography (CT) examinations of the abdomen and chest were evaluated for filter-related complications and pulmonary embolism (PE), respectively. "Recovery" filters were placed in 96 patients (72 males and 24 females; age range: 16-87 years; mean: 46 years). Twenty-four patients presented with PE, 13 with deep vein thrombosis (DVT) and 2 with both PE and DVT. The remaining 57 patients had no symptoms of thromboembolism. Indications for filter placement included contraindication to anticoagulation (n = 27), complication of anticoagulation (n = 3), failure of anticoagulation (n = 5), and prophylaxis (n = 61). The device was successfully deployed in the infrarenal (n = 95) or suprarenal (n = 1) IVC through a femoral vein approach. Retrieval was attempted in 11 patients after a mean period of 117 days (range: 24-426). The filter was successfully removed in nine patients (82%). Failure of retrieval was due to technical difficulty (n = 1) and the presence of thrombus in the filter (n = 1). One of the nine patients who had the filter removed developed IVC thrombus after retrieval and another had an intimal tear of the IVC. Follow-up abdominal CT (n = 40) at a mean of 80 days (range: 1-513) showed penetration of the IVC by the filter arms in 11, of which 3 had fracture of filter components. In one patient, a broken arm migrated into the pancreas. Asymmetric deployment of the filter legs was seen in 12 patients and thrombus within the filter in 2 patients. No filter migration or caval occlusion was encountered. Follow-up chest CT (n = 27) at a mean of 63 days (range: 1-386) showed PE in one patient (3%). During clinical follow-up, 12 of 96 patients developed symptoms of PE and only 1 of the 12 had PE on CT. There was no fatal pulmonary embolism in our group of patients following "Recovery" filter placement. However, the current version of the filter is associated with structure weakness, a high incidence of IVC wall penetration, and asymmetric deployment of the filter legs. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kalva, SP (reprint author), GRB 290 MGH,55 Fruit St, Boston, MA 02115 USA. EM skalva@partners.org NR 28 TC 44 Z9 45 U1 0 U2 2 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 AUG PY 2006 VL 29 IS 4 BP 559 EP 564 DI 10.1007/s00270-005-0271-1 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 047DV UT WOS:000237860900011 PM 16565794 ER PT J AU Scholz, D McDermott, P Garnovskaya, M Gallien, TN Huettelmaier, S DeRienzo, C Cooper, G AF Scholz, Dimitri McDermott, Paul Garnovskaya, Maria Gallien, Thomas N. Huettelmaier, Stefan DeRienzo, Christina Cooper, George TI Microtubule-associated protein-4 (MAP-4) inhibits microtubule-dependent distribution of mRNA in isolated neonatal cardiocytes SO CARDIOVASCULAR RESEARCH LA English DT Article DE mRNA; microtubule; cardiocyte; translocation ID CONTAINING RIBONUCLEOPROTEIN-PARTICLES; OVERLOAD CARDIAC-HYPERTROPHY; GREEN FLUORESCENT PROTEIN; HIPPOCAMPAL-NEURONS; PRESSURE-OVERLOAD; BINDING PROTEIN; CONTRACTILE DYSFUNCTION; STAUFEN PROTEIN; NUCLEAR-PORE; SOMATODENDRITIC DOMAIN AB Objectives: Active mRNA distribution in the form of ribonucleoprotein particles moving along microtubules has been shown in several cell types, but not yet in cardiocytes. This study addresses two hypotheses: 1) a similar mRNA distribution mechanism operates in cardiocytes; 2) decoration of microtubules with microtubule-associated proteins compromises this distribution. Methods: To visualize ribonucleoproteins in cultured neonatal rat cardiocytes, they were transfected with vectors encoding zipcode binding protein-1 and Staufen fused with GFP. The velocity of microtubular transport and elongation were calculated on time-lapse confocal pictures. Results: ZBP-1 and Staufen labeled particles co-localized with each other and with microtubules and moved along microtubules over a distance of 1-20 mu m with a mean speed of 80 nm/s. The average speed decreased about 50% after decoration of microtubules by adenoviral microtubule-associated protein-4 (MAP-4). The elongation speed measured using the GFP-tagged end-binding protein-1 exceeded 200 nm/s and was not influenced by MAP-4. Conclusions: We demonstrate for the first time ribonucleoprotein particles in cardiocytes, their microtubular-related movement, and its inhibition (but not of the microtubular elongation), by the MAP-4 decoration of microtubules. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Charleston, SC 29403 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Div Nephrol, Charleston, SC 29425 USA. Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. RP Scholz, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, 114 Doughty St,Rm 302, Charleston, SC 29403 USA. EM scholzd@musc.edu FU NHLBI NIH HHS [HL-48788] NR 91 TC 9 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD AUG 1 PY 2006 VL 71 IS 3 BP 506 EP 516 DI 10.1016/j.cardiores.2006.04.001 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 075KM UT WOS:000239883900015 PM 16750521 ER PT J AU Letal, A Scorrano, L AF Letal, A. Scorrano, L. TI Laying the foundations of programmed cell death - Stan Korsmeyer SO CELL DEATH AND DIFFERENTIATION LA English DT Editorial Material ID CYTOCHROME-C RELEASE; ENDOPLASMIC-RETICULUM; MITOCHONDRIAL APOPTOSIS; BCL-X; CHROMOSOMAL BREAKPOINT; CA2+ CONCENTRATION; BAX; GENE; SURVIVAL; COMPONENT C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dulbecco Telethon Inst, Venetian Inst Mol Med, I-35129 Padua, Italy. RP Letal, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu; luca.scorrano@unipd.it RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU Telethon [TCP02016] NR 37 TC 6 Z9 6 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD AUG PY 2006 VL 13 IS 8 BP 1245 EP 1247 DI 10.1038/sj.cdd.4401999 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 064JK UT WOS:000239084900001 PM 16838033 ER PT J AU Tilly, JL AF Tilly, J. L. TI Personal reflections on Stan Korsmeyer and his continuing impact on our work to delineate the role of Bax in female reproduction SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID PROGRAMMED CELL-DEATH; CHROMOSOMAL BREAKPOINT; FOLLICULAR LYMPHOMA; OVARIAN FAILURE; STEM-CELLS; APOPTOSIS; INVOLVEMENT; ATRESIA; GENE; MICE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, THR-901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org NR 21 TC 0 Z9 0 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 AUG PY 2006 VL 13 IS 8 BP 1296 EP 1298 DI 10.1038/sj.cdd.4401951 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 064JK UT WOS:000239084900013 PM 16676003 ER PT J AU Walensky, LD AF Walensky, L. D. TI BCL-2 in the crosshairs: tipping the balance of life and death SO CELL DEATH AND DIFFERENTIATION LA English DT Review DE apoptosis; programmed cell death; BCL-2; BH3 domain; alpha-helix; structure; small molecule; peptide; targeted therapy ID CYTOCHROME-C RELEASE; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; ANTIAPOPTOTIC PROTEIN BCL-2; SMALL-MOLECULE INHIBITORS; PROGRAMMED CELL-DEATH; DNA-DAMAGE RESPONSE; BH3-ONLY PROTEINS; PROAPOPTOTIC ACTIVITY; INDUCED APOPTOSIS; BH3 DOMAIN AB The discovery of B-cell lymphoma-2 (BCL-2) over 20 years ago revealed a new paradigm in cancer biology: the development and persistence of cancer can be driven by molecular roadblocks along the natural pathway to cell death. The subsequent identification of an expansive family of BCL-2 proteins provoked an intensive investigation of the interplay among these critical regulators of cell death. What emerged was a compelling tale of guardians and executioners, each participating in a molecular choreography that dictates cell fate. Ten years into the BCL-2 era, structural details defined how certain BCL-2 family proteins interact, and molecular targeting of the BCL-2 family has since become a pharmacological quest. Although many facets of BCL-2 family death signaling remain a mechanistic mystery, small molecules and peptides that effectively target BCL-2 are eliminating the roadblock to cell death, raising hopes for a medical breakthrough in cancer and other diseases of deregulated apoptosis. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Program Canc Chem Biol, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp, Boston, MA 02215 USA. RP Walensky, LD (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. EM Loren_Walensky@dfci.harvard.edu FU NHLBI NIH HHS [K08HL074049] NR 145 TC 139 Z9 170 U1 1 U2 11 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 AUG PY 2006 VL 13 IS 8 BP 1339 EP 1350 DI 10.1038/sj.cdd.4401992 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 064JK UT WOS:000239084900019 PM 16763614 ER PT J AU Kensinger, EA Schacter, DL AF Kensinger, Elizabeth A. Schacter, Daniel L. TI Neural processes underlying memory attribution on a reality-monitoring task SO CEREBRAL CORTEX LA English DT Article DE fMRI; memory distortion; self-referential processing; visual processing ID EVENT-RELATED FMRI; PREFRONTAL CORTEX; PARIETAL CORTEX; FALSE MEMORIES; RETRIEVAL; ACTIVATION; SELF; IMAGERY; DEACTIVATION; RECOGNITION AB A relatively common form of memory distortion arises when individuals must discriminate items they have seen from those they have imagined (reality monitoring). The present fMRI investigation (at 1.5 T) focused on the processes that relate to memory assignment regardless of accuracy (e.g. that correspond with the belief that an item was presented as a picture, regardless of whether that belief is correct). Prior to the scan, participants (n = 16) viewed concrete nouns and formed mental images of the object named. Half of the names were followed by the object's photo. During the scan, participants saw the object names and indicated whether the corresponding photo had been studied. Activity in visual-processing regions (including the precuneus and fusiform gyrus) corresponded with the attribution of an item to a pictorial presentation. In contrast, activity in regions thought to be important for self-referential processing (including the ventromedial prefrontal cortex and posterior cingulate gyrus) was associated with attribution to a nonpresented source. These neural findings converge with behavioral evidence indicating that individuals use the amount of different types of information retrieved (e.g. perceptual detail, information about cognitive operations) to determine whether an item was imagined or perceived. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kensinger, EA (reprint author), 33 Kirkland St, Cambridge, MA 02138 USA. EM ekensing@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [MH070199, MH60941] NR 49 TC 40 Z9 40 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2006 VL 16 IS 8 BP 1126 EP 1133 DI 10.1093/cercor/bhj054 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 061XE UT WOS:000238906300008 PM 16648457 ER PT J AU Akilov, OE Kosaka, S O'Riordan, K Song, XZ Sherwood, M Flotte, TJ Foley, JW Hasan, T AF Akilov, Oleg E. Kosaka, Sachiko O'Riordan, Katie Song, Xiangzhi Sherwood, Margaret Flotte, Thomas J. Foley, James W. Hasan, Tayyaba TI The role of photosensitizer molecular charge and structure on the efficacy of photodynamic therapy against Leishmania parasites SO CHEMISTRY & BIOLOGY LA English DT Article ID CUTANEOUS LEISHMANIASIS; ZINC PHTHALOCYANINES; INTRACELLULAR STAGES; SINGLET OXYGEN; AMAZONENSIS; LIPOPHOSPHOGLYCAN; PROMASTIGOTES; AMASTIGOTES; FLUORESCEIN; BEHAVIOR AB Photodynamic therapy (PDT) is emerging as a potential therapeutic modality in the clinical management of cutaneous leishmaniasis (CL). In order to establish a rationale for effective PDT of CL, we investigated the impact of the molecular charge and structure of photosensitizers on the parasitic phototoxic response. Two photosensitizers from the benzophenoxazine family that bear an overall cationic charge and two anionic porphyrinoid molecules were evaluated. The photodynamic activity of the photosensitizers decreases in the following order: EtNBSe > EtNBS > BpD > PpIX. The studies suggest that compared to hydrophobic anionic photosensitizers, the hydrophilic cationic benzophenoxazine analogs provide high effectiveness of PDT possibly due to (1) their strong attraction to the negatively charged parasitic membrane, (2) their hydrophilicity, (3) their high singlet oxygen quantum yield, and (4) their efficacy in targeting intracellular organelles. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Rowland Inst, Cambridge, MA 02142 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@partners.org NR 37 TC 33 Z9 36 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD AUG PY 2006 VL 13 IS 8 BP 839 EP 847 DI 10.1016/j.chembiol.2006.06.008 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 081PP UT WOS:000240329800008 PM 16931333 ER PT J AU Williams, DL Goldstein, G Minshew, NJ AF Williams, Diane L. Goldstein, Gerald Minshew, Nancy J. TI Neuropsychologic functioning in children with autism: Further evidence for disordered complex information-processing SO CHILD NEUROPSYCHOLOGY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; IMPAIRED MEMORY FUNCTIONS; NEOCORTICAL SYSTEMS; EXECUTIVE FUNCTIONS; SPECTRUM DISORDERS; INFANTILE-AUTISM; JOINT ATTENTION; INDIVIDUALS; PERFORMANCE AB A wide range of abilities was assessed in 56 high-functioning children with autism and 56 age- and IQ-matched controls. Stepwise discriminant analyses produced good group discrimination for sensory-perceptual, motor, complex language, and complex memory domains but lower agreement for the reasoning domain than previously obtained for adults. Group discrimination did not occur for attention, simple language, simple memory, and visuospatial domains. Findings provide additional support for a complex information-processing model for autism, previously based on adult data, demonstrating a pattern across domains of selective impairments on measures with high demands for integration of information and sparing when demands were low. Children as compared to adults with autism exhibited more prominent sensory-perceptual symptoms and less pronounced reasoning deficits reflecting brain maturation. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. VA PIttsburgh Healthcare Syst, Pittsburgh, PA USA. RP Minshew, NJ (reprint author), Webster Hall,Suite 300,3811 OHara St, Pittsburgh, PA 15213 USA. EM minshewnj@upmc.edu RI Williams, Diane/B-4128-2017 FU NICHD NIH HHS [U19HD35469, U19 HD035469, U19 HD035469-06, U19 HD035469-07, U19 HD035469-08, U19 HD035469-09, U19 HD035469-10]; NIDCD NIH HHS [K23 DC006691, K23DC00691] NR 97 TC 87 Z9 88 U1 6 U2 33 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PD AUG PY 2006 VL 12 IS 4-5 BP 279 EP 298 DI 10.1080/09297040600681190 PG 20 WC Clinical Neurology SC Neurosciences & Neurology GA 073UL UT WOS:000239768000004 PM 16911973 ER PT J AU Ahmed, A Rich, MW Fleg, JL Zile, MR Young, JB Kitzman, DW Love, TE Aronow, WS Adams, KF Gheorghiade, M AF Ahmed, Ali Rich, Michael W. Fleg, Jerome L. Zile, Michael R. Young, James B. Kitzman, Dalane W. Love, Thomas E. Aronow, Wilbert S. Adams, Kirkwood F., Jr. Gheorghiade, Mihai TI Effects of digoxin on morbidity and mortality in diastolic heart failure: The ancillary Digitalis Investigation Group trial SO CIRCULATION LA English DT Article DE digoxin; heart failure; morbidity; mortality ID VENTRICULAR SYSTOLIC FUNCTION; EJECTION FRACTION; DIG TRIAL; OLDER-ADULTS; DYSFUNCTION; ASSOCIATION; GLYCOSIDES; OUTCOMES AB Background - About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near-normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study have not previously been published. Methods and Results - Ambulatory chronic heart failure patients (n = 988) with normal sinus rhythm and ejection fraction > 45% (median, 53%) from the United States and Canada (1991 to 1993) were randomly assigned to digoxin (n = 492) or placebo (n = 496). During follow-up with a mean length of 37 months, 102 patients (21%) in the digoxin group and 119 patients (24%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63 to 1.07; P = 0.136) experienced the primary combined outcome of heart failure hospitalization or heart failure mortality. Digoxin had no effect on all-cause or cause-specific mortality or on all-cause or cardiovascular hospitalization. Use of digoxin was associated with a trend toward a reduction in hospitalizations resulting from worsening heart failure (HR, 0.79; 95% CI, 0.59 to 1.04; P = 0.094) but also a trend toward an increase in hospitalizations for unstable angina (HR, 1.37; 95% CI, 0.99 to 1.91; P = 0.061). Conclusions - In ambulatory patients with chronic mild to moderate diastolic heart failure and normal sinus rhythm receiving angiotensin-converting enzyme inhibitor and diuretics, digoxin had no effect on natural history end points such as mortality and all-cause or cardiovascular hospitalizations. C1 Univ Alabama, Birmingham, AL 35294 USA. Washington Univ, St Louis, MO USA. VA Med Ctr, Birmingham, AL USA. NHLBI, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. New York Med Coll, Valhalla, NY 10595 USA. Univ N Carolina, Chapel Hill, NC USA. Northwestern Univ, Chicago, IL 60611 USA. RP Ahmed, A (reprint author), Univ Alabama, 1530 3rd Ave S,CH-19,Suite 219, Birmingham, AL 35294 USA. EM aahmed@uab.edu RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 FU NIA NIH HHS [1-K23-AG19211-04, K23 AG019211, K23 AG019211-04, R01 AG018915, R37 AG018915] NR 29 TC 242 Z9 264 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 2006 VL 114 IS 5 BP 397 EP 403 DI 10.1161/CIRCULATIONAHA.106.628347 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 069CK UT WOS:000239422500011 PM 16864724 ER PT J AU Kobayashi, N Barnard, RJ Henning, SM Elashoff, D Reddy, ST Cohen, P Leung, P Hong-Gonzalez, J Freedland, SJ Said, J Gui, D Seeram, NP Popoviciu, LM Bagga, D Heber, D Glaspy, JA Aronson, WJ AF Kobayashi, Naoko Barnard, R. James Henning, Susanne M. Elashoff, David Reddy, Srinivasa T. Cohen, Pinchas Leung, Pak Hong-Gonzalez, Jenny Freedland, Stephen J. Said, Jonathan Gui, Dorina Seeram, Navindra P. Popoviciu, Laura M. Bagga, Dilprit Heber, David Glaspy, John A. Aronson, William J. TI Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E-2 SO CLINICAL CANCER RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MESSENGER-RNA; GROWTH-FACTOR; TUMOR-GROWTH; CELL-GROWTH; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID; CARCINOMA-CELLS; SCID MICE; IN-VITRO AB Purpose: To determine whether altering the dietary content of omega-6 (n-6) ando)-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E-2 (PGE(2)) levels. Experimental Design: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection. Results: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase-mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE(2) levels, and decreased vascular endothelial growth factor expression. Conclusion: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE(2) and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer. C1 Univ Calif Los Angeles, Dept Urol, Ctr Hlth Sci 66 124, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Div Clin Nutr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Div Pediat Endocrinol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Duke Univ, Sch Med, Vet Adm Med Ctr, Dept Surg, Durham, NC USA. Duke Univ, Sch Med, Urol Sect, Dept Surg, Durham, NC USA. Univ Calif Los Angeles, Sch Med, Dept Cardiol, Los Angeles, CA 90095 USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Dept Urol, Ctr Hlth Sci 66 124, Sch Med, Box 951738, Los Angeles, CA 90095 USA. EM waronson@ucla.edu FU NCCIH NIH HHS [AT00151, P50 AT000151]; NCI NIH HHS [P01 CA042710, 1R01CA100938, 5P01 CA42710, P50 CA092131, P50 CA92131-01A1, R01 CA100938] NR 50 TC 89 Z9 95 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2006 VL 12 IS 15 BP 4662 EP 4670 DI 10.1158/1078-0432.CCR-06-0459 PG 9 WC Oncology SC Oncology GA 073NR UT WOS:000239750400029 PM 16899616 ER PT J AU Chakravarti, A Erkkinen, MG Nestler, U Stupp, R Mehta, M Aldape, K Gilbert, MR Black, PM Loeffler, JS AF Chakravarti, Arnab Erkkinen, Michael G. Nestler, Ulf Stupp, Roger Mehta, Minesh Aldape, Ken Gilbert, Mark R. Black, Peter McL. Loeffler, Jay S. TI Temozolomide-mediated radiation enhancement in glioblastoma: A report on underlying mechanisms SO CLINICAL CANCER RESEARCH LA English DT Article ID MALIGNANT GLIOMA; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; MISMATCH REPAIR; ADJUVANT TEMOZOLOMIDE; ANAPLASTIC GLIOMAS; CELLS; RADIOTHERAPY; RESISTANCE; SENSITIVITY; CONCOMITANT AB Purpose: In this study, we investigated the mechanisms by which temozolomide enhances radiation response in glioblastoma cells, Experimental Design: Using a panel of four primary human glioblastoma cell lines with heterogeneous O-6-methylguanine-DNA methyltransferase (MGMT) protein expression, normal human astrocytes, and U87 xenografts, we investigated (a) the relationship of MGMT status with efficacy of temozolomide-based chemoradiation using a panel of in vitro and in vivo assays; (b) underlying mechanisms by which temozolomide enhances radiation effect in glioblastoma cells; and (c) strategies to overcome resistance to radiation + temozolomide. Results: Temozolomide enhances radiation response most effectively in glioblastomas without detectable MGMT expression. On concurrent radiation + temozolomide administration in MGMT-negative glioblastomas, there seems to be decreased double-strand DNA (dsDNA) repair capacity and enhanced dsDNA damage compared either with radiation alone or with sequentially administered temozolomide. Our data suggest that O-6-benzylguanine can enhance the antitumor effects of concurrent radiation + temozolomide in MGMT-positive cells by enhancing apoptosis and the degree of dsDNA damage. O-6-Benzylguanine was most effective when administered concurrently with radiation + temozolomide and had less of an effect when administered with temozolomide in the absence of radiation or when administered sequentially with radiation. Our in vivo data using U87 xenografts confirmed our in vitro findings. Conclusions: The present study shows that temozolomide enhances radiation response most effectively in MGMT-negative glioblastomas by increasing the degree of radiation-induced double-strand DNA damage. In MGMT-positive glioblastomas, depletion of MGMT by the addition of O-6-benzylguanine significantly enhances the antitumor effect of concurrent radiation + temozolomide. These are among the first data showing mechanisms of synergy between radiation and temozolomide and the effect of MGMT. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. Univ Lausanne Hosp, Dept Multidisciplinary Oncol, Lausanne, Switzerland. Univ Wisconsin, Dept Human Oncol, Madison, WI USA. Univ Texas, MD Anderson Canc Ctr, Dept Neuropathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM achakravarti@partners.org RI Nestler, Ulf/D-6503-2014; Gilbert, Mark/J-7494-2016; OI Nestler, Ulf/0000-0002-2963-4344; Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [R01CA108633] NR 25 TC 126 Z9 128 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2006 VL 12 IS 15 BP 4738 EP 4746 DI 10.1158/1078-0432.CCR-06-0596 PG 9 WC Oncology SC Oncology GA 073NR UT WOS:000239750400038 PM 16899625 ER PT J AU Spiegel, BMR Dulai, GS Lim, BS Mann, N Kanwal, F Gralnek, IM AF Spiegel, Brennan M. R. Dulai, Gareth S. Lim, Brian S. Mann, Neel Kanwal, Fasiha Gralnek, Ian M. TI The cost-effectiveness and budget impact of intravenous versus oral proton pump inhibitors in peptic ulcer hemorrhage SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID PROSPECTIVE RANDOMIZED-TRIAL; UPPER GASTROINTESTINAL HEMORRHAGE; HYPERTONIC SALINE-EPINEPHRINE; SUCCESSFUL ENDOSCOPIC THERAPY; BLEEDING ULCERS; DOUBLE-BLIND; BIPOLAR ELECTROCOAGULATION; ADRENALINE INJECTION; AGGRESSIVE CARE; HEATER PROBE AB Background & Aims: The most cost-effective route of administering proton pump inhibitor (PPI) therapy in peptic ulcer hemorrhage remains uncertain. Oral (PO) PPI therapy may be less effective than intravenous (IV) PPI therapy, but is less expensive and does not mandate a 72-hour posthemostasis hospital stay to complete a full therapeutic course. Because there are currently no published head-to-head clinical trials comparing IV vs PO PPIs, we used decision analysis with budget impact modeling to measure the clinical and economic outcomes of these competing modes of administration. Methods: We compared 3 postendoscopic strategies for high-risk peptic ulcer hemorrhage: (1) PO PPI therapy, (2) IV PPI therapy, and (3) IV histamine(2) receptor antagonist therapy. The primary outcomes were cost per quality-adjusted life-year gained, and per-member per-month cost in a hypothetical managed care organization with 1,000,000 covered lives. Results: Compared with the PPI strategies, the histamine2 receptor antagonist strategy was more expensive and less effective. Of the 2 PPI strategies, using IV instead of PO PPI cost an incremental $708,735 per year to gain 1 additional quality-adjusted life-year. Substituting IV in lieu of PO PPI cost each member $2.86 per month to subsidize. The IV PPI strategy became dominant when the rebleed rate with PO PPIs exceeded 24% (base case = 13%), and when the hospital stay on IV PPIs decreased to less than 72 hours. Conclusions: The higher effectiveness of IV PPI therapy may not offset its increased costs vs PO PPI therapy in ulcer hemorrhage. The managed care budget impact of IV PPIs exceeds most benchmarks. C1 Technion Israel Inst Technol, Rappaport Fac Med, Rambam Med Ctr, GI Outcomes Unit,Dept Gastroenterol, Haifa, Israel. Vet Adm Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Vet Adm Ctr Outcomes Res & Educ, Los Angeles, CA USA. CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Gralnek, IM (reprint author), Technion Israel Inst Technol, Rappaport Fac Med, Rambam Med Ctr, GI Outcomes Unit,Dept Gastroenterol, Haifa, Israel. EM i_gralnek@rambam.health.gov.il FU NCRR NIH HHS [K23 RR-16188] NR 64 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2006 VL 4 IS 8 BP 988 EP 997 DI 10.1016/j.cgh.2006.05.019 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 073BX UT WOS:000239718600009 PM 16844422 ER PT J AU Siegel, CA Hur, C Korzenik, JR Gazelle, GS Sands, BE AF Siegel, Corey A. Hur, Chin Korzenik, Joshua R. Gazelle, G. Scott Sands, Bruce E. TI Risks and benefits of infliximab for the treatment of Crohn's disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; POPULATION-BASED COHORT; LYMPHOMA; AZATHIOPRINE; THERAPY; SAFETY; 6-MERCAPTOPURINE; MAINTENANCE; EXPERIENCE; REMISSION AB Background & Aims: Infliximab is effective for the treatment of active Crohn's disease. However, rare but serious complications related to infliximab therapy including lymphoma, sepsis, and death have been reported. The purpose of this study was to analyze the risks and benefits of infliximab for the treatment of Crohn's disease with the goal of providing data to aid both physicians and patients in the process of making a decision about treatment. Methods: A decision analytic model was constructed to determine the risks and benefits of infliximab when compared with standard therapy. The analysis simulated 2 cohorts of 100,000 patients each, with one arm receiving infliximab while the other remained on standard therapy. Results: Model results showed that in 100,000 patients at :1 year, infliximab will lead to 12,216 more patients in remission, 4255 fewer surgeries, and 33 fewer deaths from flares of disease. This is at the cost of 201 more lymphomas and 249 more deaths related to complications from infliximab. Overall, the infliximab strategy resulted in more quality-adjusted life years (QALYs/patient) than the standard therapy strategy (.77 QALYs/ patient vs .75 QALYs/patient). Conclusions: Despite an increased risk of lymphoma and death associated with use of infliximab, the substantial clinical improvement and fewer surgeries as a result of infliximab result in an increase in QALYs. In properly selected patients, the benefits of infliximab could outweigh its risks. These data should help guide decision making and the informed consent process when considering the use of infliximab for the treatment of Crohn's disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study IBD,Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study IBD,Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dartmouth Hitchcock Med Ctr, Sect Gastroenterol & Hepatol, Inflammatory Bowel Dis Ctr, Lebanon, NH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Hur, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study IBD,Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 NR 35 TC 97 Z9 98 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2006 VL 4 IS 8 BP 1017 EP 1024 DI 10.1016/j.cgh.2006.05.020 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 073BX UT WOS:000239718600013 PM 16843733 ER PT J AU Gay, K Robicsek, A Strahilevitz, J Park, CH Jacoby, G Barrett, TJ Medalla, F Chiller, TM Hooper, DC AF Gay, K Robicsek, A Strahilevitz, J Park, CH Jacoby, G Barrett, TJ Medalla, F Chiller, TM Hooper, DC TI Plasmid-mediated quinolone resistance in non-Typhi serotypes of Salmonella enterica SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; ANTIBIOTIC-RESISTANCE; TRANSFERABLE PLASMID; GENE AB Background. Serious infections with Salmonella species are often treated with fluoroquinolones or extended-spectrum beta-lactams. Increasingly recognized in Enterobacteriaceae, plasmid-mediated quinolone resistance is encoded by qnr genes. Here, we report the presence of qnr variants in human isolates of non-Typhi serotypes of Salmonella enterica (hereafter referred to as non-Typhi Salmonella) from the United States National Antimicrobial Resistance Monitoring System for Enteric Bacteria. Methods. All non-Typhi Salmonella specimens from the United States National Antimicrobial Resistance Monitoring System for Enteric Bacteria collected from 1996 to 2003 with ciprofloxacin minimum inhibitory concentrations >= 0.06 mu g/mL (233 specimens) and a subset with minimum inhibitory concentrations <= 0.03 mg/mL (102 specimens) were screened for all known qnr genes (A, B, and S) by polymerase chain reaction. For isolates with positive results, qnr and quinolone resistance-determining region sequences were determined. Plasmids containing qnr genes were characterized by conjugation or transformation. Results. Conjugative plasmids harboring qnrB variants were detected in 7 Salmonella enterica serotype Berta isolates and 1 Salmonella enterica serotype Mbandaka isolate. The S. Mbandaka plasmid also had an extended-spectrum beta-lactamase. Variants of qnrS on nonconjugative plasmids were detected in isolates of Salmonella enterica serotype Anatum and Salmonella enterica serotype Bovismorbificans. Conclusions. Plasmid-mediated quinolone resistance appears to be widely distributed, though it is still uncommon in non-Typhi Salmonella isolates from the United States, including strains that are quinolone susceptible by the criteria of the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards). The presence of this gene in non-Typhi Salmonella that causes infection in humans suggests potential for spread through the food supply, which is a public health concern. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Atlanta Res & Educ Fdn, Atlanta, GA USA. Evanston NW Healthcare, Evanston, IL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lahey Clin Fdn, Burlington, MA USA. RP Gay, K (reprint author), Ctr Dis Control & Prevent, Mail Stop G-29,1600 Clifton Rd, Atlanta, GA 30333 USA. EM kgay@cdc.gov FU NIAID NIH HHS [R01 AI057576, AI43312, AI57576] NR 22 TC 145 Z9 159 U1 3 U2 10 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2006 VL 43 IS 3 BP 297 EP 304 DI 10.1086/505397 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 057XK UT WOS:000238628300006 PM 16804843 ER PT J AU McGovern, BH Ditelberg, JS Taylor, LE Gandhi, RT Christopoulos, KA Chapman, S Schwartzapfel, B Rindler, E Fiorino, AM Zaman, MT Sax, PE Graeme-Cook, F Hibberd, PL AF McGovern, BH Ditelberg, JS Taylor, LE Gandhi, RT Christopoulos, KA Chapman, S Schwartzapfel, B Rindler, E Fiorino, AM Zaman, MT Sax, PE Graeme-Cook, F Hibberd, PL TI Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; MITOCHONDRIAL-DNA CONTENT; ANTIRETROVIRAL-THERAPY; LIVER STEATOSIS; CORE PROTEIN; NONALCOHOLIC STEATOHEPATITIS; OXIDATIVE STRESS; LACTIC-ACIDOSIS; TRANSGENIC MICE AB Background. We conducted a study to determine the prevalence and factors associated with hepatic steatosis in human immunodeficiency virus (HIV)-seropositive patients with hepatitis C and to investigate whether steatosis is associated with liver fibrosis. Methods. Retrospective chart reviews were conducted in 4 hospitals that serve community-based and incarcerated HIV-infected patients who had undergone a liver biopsy for evaluation of hepatitis C virus (HCV) infection during the period of 2000-2003. Demographic characteristics and medication and laboratory data were collected from the time of the biopsy. A pathologist blinded to all clinical data evaluated the specimens. The primary outcome was presence or absence of steatosis. Results. Of 260 HIV-HCV-coinfected patients, 183 met inclusion criteria and had a biopsy specimen adequate for review. Steatosis was present in 69% of patients (graded as minimal in 31%, mild in 27%, moderate in 18%, and severe in 1%). Factors associated with steatosis included use of dideoxynucleoside analogues, such as didanosine and stavudine (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.55-13.82). There was a trend toward presence of steatosis and use of other nucleoside analogues or infection with HCV genotype 3 (OR, 2.65 [95% CI, 0.95 7.41] and 3.38 [95% CI, 0.86-13.28], respectively). The presence of steatosis was associated with fibrosis (OR, 1.37; 95% CI, 1.03-1.81). Conclusions. In this multiracial population of HIV-HCV-coinfected patients, steatosis was prevalent and was associated with severity of liver fibrosis. Use of nucleoside analogues (particularly didanosine and stavudine) and HCV genotype 3 infection were associated with hepatic steatosis. The development of steatosis is multifactorial in nature and may play a contributory role in the progression of liver disease in HIV-infected patients. C1 Lemuel Shattuck Hosp, HIV HCV Coinfect Clin, Jamaica Plain, MA 02494 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Harvard Univ, Sch Med, Boston, MA USA. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP McGovern, BH (reprint author), Lemuel Shattuck Hosp, HIV HCV Coinfect Clin, 170 Morton St, Jamaica Plain, MA 02494 USA. EM bmcgovern@tufts-nemc.org FU NCRR NIH HHS [M01RR000054]; NIDA NIH HHS [P30DA013868] NR 65 TC 89 Z9 91 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2006 VL 43 IS 3 BP 365 EP 372 DI 10.1086/505495 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 057XK UT WOS:000238628300017 PM 16804853 ER PT J AU Kudolo, GB Wang, W Javors, M Blodgett, J AF Kudolo, George B. Wang, Wen Javors, Martin Blodgett, Janet TI The effect of the ingestion of Ginkgo biloba extract (EGb 761) on the pharmacokinetics of metformin in non-diabetic and type 2 diabetic subjects - A double blind placebo-controled, crossover study SO CLINICAL NUTRITION LA English DT Article DE Ginkgo biloba extract; type 2 diabetes; metformin; pharmacokinetics; drug-herb interaction ID BETA-CELL FUNCTION; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE; MELLITUS; INDIVIDUALS; RESISTANCE; EFFICACY; HEALTHY; DISEASE; NIDDM AB Background & aims: Ginkgo biloba extract (EGb 761) has been shown to ameliorate some defects associated with the insulin resistance syndrome and so patients with Type 2 diabetes mellitus (T2DM) may be inclined to co-ingest the herb with their medications, such as metformin. This study was designed to determine if the coingestion of EGb 761 and metformin would alter the pharmacokinetic properties of metformin in T2DM patients and persons without diabetes, who may ingest it for other purposes. Method: Normal glucose tolerance (NGT) subjects (n = 10; age, 39.2+/-14.0 years; fasting plasma glucose (FPG), 90+/-7 mg/dl; body mass index (BMI), 24.1 +/- 3.7 kg/m(2)) and 10 T2DM patients (n = 10; age, 51.7 +/- 8.9 years; FPG, 150 +/- 7 mg/dl; BMI, 33.7 +/- 5.7 kg/m(2)) completed a randomized, double-blind, placebo - control led crossover study. They ingested either EGb 761 (120 mg/day as a single dose) or a vegetable-based placebo during each arm for 3 months. At the end of each arm, the NGT subject ingested a single 500 mg dose of metformin (non-diabetics) and the T2DM subject took his/her prescribed metformin dose (250-850 mg) with 120 mg EGb 761. Blood and urine samples were collected over an 8-h period, and in the case of T2DM subjects, additionally over the first 2 h of the subsequent 3 days. Results: Ingestion of EGb 761 produced no significant changes in diagnostic laboratory tests in either group, except reducing glycosylated hemoglobin A(1c) levels (from 7.7+/-1.2 to 7.2+/-0.9%, P<0.05) in T2DM the subjects. The pharmacokinetic parameters of metformin were all significantly different (P<0.05) between the NGT (500 mg) and 8 out of 10 of the T2DM subjects who were prescribed 500 mg of metformin during the placebo cycles. During the EGb 761 cycles, only the elimination half-life in the T2DM subjects was significantly increased (0.117 +/- 0.085 to 0. 141 +/- 0.100, P < 0.05). Conclusion: The co-ingestion of 120 mg of EGb 761 and 500 mg of metformin did not significantly affect the pharmacokinetic properties of metformin. Further studies are required to verify this observation for smaller and larger dose of metformin with other doses of EGb 761, since T2DM patients on medication constitute a very heterogeneous group. (C) 2006 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Clin Sci Lab, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Audie L Murphy Vet Affairs Hosp, San Antonio, TX 78284 USA. RP Kudolo, GB (reprint author), Univ Texas, Hlth Sci Ctr, Dept Clin Sci Lab, MSC 6246,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Kudolo@uthscsa.edu FU NCCIH NIH HHS [R01-AT-00832]; NCRR NIH HHS [M01-RR-01346] NR 27 TC 22 Z9 22 U1 1 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 J9 CLIN NUTR JI Clin. Nutr. PD AUG PY 2006 VL 25 IS 4 BP 606 EP 616 DI 10.1016/j.clnu.2005.12.012 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 082NA UT WOS:000240392300008 PM 16698134 ER PT J AU Barrack, RL Miller, LS Sotile, WM Sotile, MO Rubash, HE AF Barrack, Robert L. Miller, Linda S. Sotile, Wayne M. Sotile, Mary O. Rubash, Harry E. TI Effect of duty hour standards on burnout among orthopaedic surgery residents SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB We surveyed orthopaedic surgery residents and faculty from two university training programs to quantify quality of life measures including burnout, general health, and relationship issues. Residents exhibited high levels of burnout and emotional exhaustion but only average levels of personal achievement, while faculty showed lower levels of burnout and emotional exhaustion with above average scores for personal achievement. Resident burnout was positively correlated with number of hours worked while faculty hours worked was inversely related to burnout. The survey was readministered two years after implementing the Accreditation Council on Graduate Medical Education guidelines on residency duty hours. At this time resident scores for personal accomplishment had improved, while scores for emotional exhaustion showed a strong trend towards decreasing, and depersonalization scores also showed a possible trend towards decreasing. Resident duty hour limitation was associated with improvement in objective measures of burnout. C1 Washington Univ, Sch Med, Dept Orthopaed Surg, St Louis, MO 63110 USA. Tulane Univ, Sch Med, Dept Orthopaed Surg, New Orleans, LA 70112 USA. Sotile Psychol Associates PLLC, Winston Salem, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Barrack, RL (reprint author), Washington Univ, Sch Med, Dept Orthopaed Surg, 1 Barnes Jewish Hosp Plaza,Suite 11300, St Louis, MO 63110 USA. EM barrackr@wustl.edu NR 6 TC 25 Z9 25 U1 0 U2 2 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 AUG PY 2006 IS 449 BP 134 EP 137 DI 10.1097/01.blo.0000224030.78108.58 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119OF UT WOS:000243020900024 PM 16888530 ER PT J AU Bhattacharyya, T Seng, K Nassif, NA Freedman, I AF Bhattacharyya, Timothy Seng, Khemarin Nassif, Nader A. Freedman, Ilan TI Knee pain after tibial nailing - The role of nail prominence SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SHAFT FRACTURES; INTRAMEDULLARY; FIXATION AB We analyzed the relationship between knee pain after tibial nailing and nail prominence. We identified 70 patients in our trauma registry with healed fractures initially treated with intramedullary nails. Subjective pain and function were measured with visual analog pain scales and Lysholm knee scores at a mean of 20 months after fracture. These scores were compared with nail prominence measured on postoperative radiographs. More than 49% of patients had knee pain. Subjective knee pain was more common in women and patients with a smaller plateau width. Anterior nail prominence was associated with increased pain at rest. Patients with superior nail prominence had increased pain with kneeling and walking. Nail prominence correlated with increased knee pain. We think surgeons can decrease, but not eliminate, the severity of knee pain after tibial nailing by burying the tip of the nail as reflected on lateral radiographs. C1 Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02118 USA. Brigham & Womens Hosp, Boston, MA 02118 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, 55 Fruit St,Yawkey 3600, Boston, MA 02118 USA. NR 16 TC 24 Z9 25 U1 0 U2 0 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 AUG PY 2006 IS 449 BP 303 EP 307 DI 10.1097/01.blo.0000223976.91089.08 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119OF UT WOS:000243020900054 PM 16702914 ER PT J AU Seidman, LJ AF Seidman, Lany J. TI Neuropsychological functioning in people with ADHD across the lifespan SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE ADHD; executive dysfunction; neuropsychology; attention; cognition ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; CLINICALLY REFERRED SAMPLE; CONTINUOUS PERFORMANCE-TEST; RESPONSE-INHIBITION; EXECUTIVE FUNCTION; LEARNING-DISABILITIES; READING-DISABILITY; PRESCHOOL-CHILDREN; WORKING-MEMORY AB ADHD is defined by behavioral characteristics similar to neuropsychological disorders of executive dysfunction. This paper is a literature review of the neurocognitive characteristics of ADHD from early childhood through adulthood. The author addresses the development of the concept of attention and executive function (EF) deficits in ADHD, clinical neuropsychological studies of pre-teenage children, teenagers and adults with ADHD, gender and the role of psychiatric co-morbidity including the relationship of learning disabilities to ADHD, heterogeneity of neuropsychological dysfunctions, experimental neuropsychological studies, the relationship of brain structure to function, psychopharmacology of ADHD, and clinical neuropsychological assessment. The group data clearly supports the hypothesis that executive dysfunctions are correlates of ADHD regardless of gender and age, and these EF deficits are exacerbated by co-morbidity with learning disabilities such as dyslexia. However, there is limited data on children under the age of 5, teenagers from age 13-18, and adults with ADHD over the age of 40. Studies of individual classification of people with ADHD compared to healthy, non-psychiatric controls do not support the use of neuropsychological tests for the clinical diagnosis of ADHD, and indicate that not all persons with ADHD have EF deficits. Some persons with ADHD may have deficits in brain reward systems that are relatively independent of EF impairments. Future research should clarify the multiple sources of ADHD impairments, continue to refine neuropsychological tools optimized for assessment, and incorporate longitudinal, developmental designs to understand ADHD across the lifespan. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Pediat Psychopharmacol Clin & Res Program, Boston, MA USA. Pediat Neurosci Program, Boston, MA USA. Commonwealth Res Ctr, Boston, MA USA. Neuropsychol Lab, Boston, MA USA. Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Seidman, LJ (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 725, Boston, MA 02114 USA. EM lseidman@bidmc.harvard.edu FU NIMH NIH HHS [R01-MH62152, MH50657, R01-MH41314] NR 182 TC 181 Z9 188 U1 13 U2 79 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 EI 1873-7811 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD AUG PY 2006 VL 26 IS 4 BP 466 EP 485 DI 10.1016/j.cpr.2006.01.004 PG 20 WC Psychology, Clinical SC Psychology GA 069XA UT WOS:000239481300006 PM 16473440 ER PT J AU Doan, TL Fung, HB Mehta, D Riska, PF AF Doan, Thien-Ly Fung, Horatio B. Mehta, Dhara Riska, Paul F. TI Tigecycline: A glycylcycline antimicrobial agent SO CLINICAL THERAPEUTICS LA English DT Review DE tigecycline; glycylcycline; complicated skin and skin-structure infection; complicated intraabdominal infection ID RESISTANT STAPHYLOCOCCUS-AUREUS; IN-VITRO ACTIVITY; SKIN-STRUCTURE INFECTIONS; COMPLICATED INTRAABDOMINAL INFECTIONS; GRAM-NEGATIVE BACTERIA; ACQUIRED RESPIRATORY-TRACT; MULTIDRUG EFFLUX PUMP; HEALTHY-SUBJECTS; ANTIBACTERIAL ACTIVITIES; KLEBSIELLA-PNEUMONIAE AB Background: Tigecycline, the first glycylcycline to be approved by the US Food and Drug Administration, is a structural analogue of minocycline that was designed to avoid tetracycline resistance mediated by ribosomal protection and drug efflux. It is indicated for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections and is available for intravenous administration only. Objective: This article summarizes the in vitro and in vivo activities and pharmacologic and pharmacokinetic properties of tigecycline, and reviews its clinical efficacy and tolerability profile. Methods: Relevant information was identified through a search of MEDLINE (1966-April 2006), Iowa Drug Information Service (1966-April 2006), and International Pharmaceutical Abstracts (1970-April 2006) using the terms tigecycline, GAR-936, and glycylcycline. Also consulted were abstracts and posters from meetings of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (19992006) and documents provided for formulary consideration by the US manufacturer of tigecycline. Results: Like the tetracyclines, tigecycline binds to the 30S subunit of bacterial ribosomes and inhibits protein synthesis by preventing the incorporation of amino acid residues into elongating peptide chains. In vitro, tigecycline exhibits activity against a wide range of clinically significant gram-positive and gram-negative bacteria, including multi drug-resistant strains (eg, oxacillin-resistant Stapbylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacteriaceae), and anaerobes (eg, Bacteroides spp). In pharmacokinetic studies in human adults, tigecycline had a large Vd (7-9 L/kg), was moderately bound to plasma protein (71%-89%), had an elimination t(1/2) of 42.4 hours, and was eliminated primarily by biliary/fecal (59%) and renal (33%) excretion. Dose adjustment did not appear to be necessary based on age, sex, renal function, or mild to moderate hepatic impairment (Child-Pugh class A-B). In patients with severe hepatic impairment (Child-Pugh class Q, the maintenance dose should be reduced by 50%. In 4 Phase III clinical trials in patients with complicated skin and skin-structure infections and complicated intra-abdominal infections, tigecycline was reported to be noninferior to its comparators (vancomycin + aztreonam in 2 studies and imipenem/cilastatin in 2 studies), with clinical cure rates among clinically evaluable patients of > 80% (P < 0.001 for noninferiority). The most frequently reported ( >= 5%) adverse events with tigecycline were nausea (28.5%), vomiting (19.4%), diarrhea (11.6%), local IV-site reaction (8.2%), infection (6.7%), fever (6.3%), abdominal pain (6.0%), and headache (5.6%). The recommended dosage of tigecycline is 100 mg IV given as a loading dose, followed by 50 mg IV q12h for 5 to 14 days. Conclusions: In clinical trials, tigecycline was effective for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections. With the exception of gastrointestinal adverse events, tigecycline was generally well tolerated. With a broad spectrum of activity that includes multidrug-resistant gram-positive and gram-negative pathogens, tigecycline may be useful in the treatment of conditions caused by these pathogens. C1 James Peters VA Med Ctr, Med Surg Patient Care Ctr, Bronx, NY 10468 USA. Long Isl Jewish Med Ctr, Dept Pharm, New Hyde Pk, NY 11042 USA. James Peters VA Med Ctr, Serv Pharm, Bronx, NY 10468 USA. James Peters VA Med Ctr, Infect Dis Sect, Bronx, NY 10468 USA. RP Fung, HB (reprint author), James Peters VA Med Ctr, Med Surg Patient Care Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM horatio.fung@va.gov NR 101 TC 82 Z9 87 U1 0 U2 17 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD AUG PY 2006 VL 28 IS 8 BP 1079 EP 1106 DI 10.1016/j.clinthera.2006.08.011 PG 28 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 084GP UT WOS:000240521000002 PM 16982286 ER PT J AU Lindblad, CI Hanlon, JT Gross, CR Sloane, RJ Pieper, CF Hajjar, ER Ruby, CM Schmader, KE AF Lindblad, Catherine I. Hanlon, Joseph T. Gross, Cynthia R. Sloane, Richard J. Pieper, Carl F. Hajjar, Emily R. Ruby, Christine M. Schmader, Kenneth E. CA Multidisciplinary Consensus Panel TI Clinically important drug-disease interactions and their prevalence in older adults SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 23-26, 2005 CL San Francisco, CA SP Amer Coll Clin Pharm DE drug-disease interactions; epidemiology; aged ID INAPPROPRIATE MEDICATION USE; URINARY-INCONTINENCE; PSYCHOTROPIC-DRUGS; EXPLICIT CRITERIA; CONSENSUS PANEL; COMMUNITY; MANAGEMENT; PEOPLE; BENZODIAZEPINES; DEPRESSION AB Background: Older adults may have decreased homeostatic reserve, have multiple chronic diseases, and take multiple medications. Therefore, they are at risk for adverse outcomes after receiving a drug that exacerbates a chronic disease. Objectives: The aims of this study were to compile a list of clinically important drug-disease interactions in older adults, obtain the consensus of a multidisciplinary panel of geriatric health care professionals on these interactions, and determine the prevalence of these interactions in a sample of outpatients. Methods: This analysis included a 2-round modified Delphi survey and cross-sectional study. Possible drug-disease interactions in patients aged >= 65 years were identified through a search of the English-language literature indexed on MEDLINE and International Pharmaceutical Abstracts (1966-July 2004) using terms that included drug-disease interaction, medication errors, and inappropriate prescribing. Nine health care professionals with expertise in geriatrics (2 geriatricians, 7 geriatric clinical pharmacist specialists) were selected based on specialty training and continuing clinical work in geriatrics, academic appointments, and geographic location. The panel rated the importance of the potential drug-disease interactions using a 5-point Likert scale (from 1 = definitely not serious to 5 = definitely serious). Consensus on a drug-disease interaction was defined as a lower bound of the 95% CI >= 4.0. The prevalence of drug-disease interactions was determined by applying the consensus criteria to a convenience sample of frail older veterans at hospital discharge who were enrolled in a health services intervention trial. Results: The panel reached consensus on 28 individual drug-disease interactions involving 14 diseases or conditions. Overall, 205 (15.3%) of the 1340 veterans in the sample had >= 1 drug-disease interaction. The 2 most common drug-disease interactions were use of first-generation calcium channel blockers in patients with congestive heart failure and use of aspirin in patients with peptic ulcer disease (both, 3.7%) Conclusions: A survey of multidisciplinary geriatric health care professionals resulted in a concise consensus list of clinically important drug-disease interactions in older adults. Further research is needed to examine the impact of these drug-disease interactions on health outcomes and their applicability as national measures for the prevention of drug-related problems. C1 Univ Minnesota, Coll Pharm, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA. Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Minneapolis, MN USA. Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. Duke Univ, Med Ctr, Dept Med, Div Geriatr Med, Durham, NC 27710 USA. Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. RP Lindblad, CI (reprint author), Univ Minnesota, Coll Pharm, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA. EM lindb047@umn.edu FU NIA NIH HHS [P30 AG 024827, P30 AG024827, R01 AG 14158, R01 AG 15432]; NIAID NIH HHS [K24 AI 51324] NR 64 TC 51 Z9 52 U1 1 U2 8 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD AUG PY 2006 VL 28 IS 8 BP 1133 EP 1143 DI 10.1016/j.clinthera.2006.08.006 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 084GP UT WOS:000240521000006 PM 16982290 ER PT J AU Weisler, RH Biederman, J Spencer, TJ Wilens, TE Faraone, SV Chrisman, AK Read, SC Tulloch, SJ AF Weisler, Richard H. Biederman, Joseph Spencer, Thomas J. Wilens, Timothy E. Faraone, Stephen V. Chrisman, Allan K. Read, Stephanie C. Tulloch, Simon J. CA SLI381 303 Study Grp TI Mixed amphetamine salts extended-release in the treatment of adult ADHD: A randomized, controlled trial SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; SLI381 ADDERALL-XR; YOUNG-ADULTS; DOUBLE-BLIND; FOLLOW-UP; CHILDREN; PLACEBO; ADOLESCENTS; FORMULATION AB Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a serious neurobehavioral disorder of childhood onset that often persists into adolescence and adulthood. Functional impairments, underachievement, and difficult interpersonal relationships illustrate the need for effective treatment of ADHD through adulthood. Method:This prospective, multisite, randomized, double-blind, placebo-controlled, parallel-group, dose-escalation study was conducted to assess the efficacy, safety, and duration of action of mixed amphetamine salts extended-release (MAS XR) in adults with ADHD, combined type. Adults 18 years of age were given placebo or MAS XR 20, 40, or 60 mg/day for 4 weeks. The main outcome measures were the ADHD Rating Scale and Conners' Adult ADHD Rating Scale Short Version Self-Report (CAARS-S-S). Results: Two hundred fifty-five subjects were randomly assigned to treatment with MAS XR or placebo. MAS XR treatment was associated with statistically and clinically significant ADHD symptom reduction at endpoint; mean ADHD Rating Scale scores were 18.5 for the 20-mg group (P=.001), 18.4 for the 40-mg group (P<.001), and 18.5 for the 60-mg group (P<.001). Adults with severe symptoms (ADHD Rating Scale score >= 32 at baseline) had significantly greater symptom reduction with the highest MAS XR dose (60 mg/day), however, this dose-response relationship was determined by post-hoc analysis. The mean MAS XR effect size was 0.8. Statistically significant (P<.05) improvements in CAARS-S-S ADHD index scores occurred at 4- and 12-hours postdose for all MAS XR groups, indicating a 12-hour duration of effect. Symptoms improved within the first treatment week. Most adverse events reported were mild or moderate in intensity, and the most commonly reported adverse events were consistent with the known profile of stimulant medications. Vital signs and electrocardiograms showed no clinically significant cardiovascular changes. Conclusion: These results suggest that MAS XR is safe and effective in adults with ADHD and controlled ADHD symptoms for up to 12 hours. C1 Univ N Carolina, Chapel Hill, NC USA. Duke Univ, Durham, NC USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MGH, Subst Abuse Serv Pediat Psychopharmacol, Boston, MA USA. SUNY Upstate Med Univ, Syracuse, NY USA. Duke Univ, Med Ctr, Div Child Psychiat, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Shire Pharmaceut Inc, Globe Med Affairs, Wayne, PA USA. Shire Pharmaceut Inc, CNS Strateg Therapeut Area, Wayne, PA USA. RP Weisler, RH (reprint author), 700 Spring Forest Rd,Suite 125, Raleigh, NC 27609 USA. EM rweisler@aol.com OI Faraone, Stephen/0000-0002-9217-3982 NR 41 TC 95 Z9 95 U1 2 U2 12 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD AUG PY 2006 VL 11 IS 8 BP 625 EP 639 PG 17 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 076VM UT WOS:000239986200013 PM 16871129 ER PT J AU Hofmann, SG Miller, AL AF Hofmann, Stefan G. Miller, Alec L. TI Full steam ahead: An editorial update SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Editorial Material C1 Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hofmann, SG (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM shofmann@bu.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 1 TC 0 Z9 0 U1 1 U2 1 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2006 VL 13 IS 3 BP 177 EP 177 DI 10.1016/j.cbpra.2006.04.004 PG 1 WC Psychology, Clinical SC Psychology GA 174HW UT WOS:000246934000001 ER PT J AU Mouton-Odum, S Keuthen, NJ Wagener, PD Stanley, MA DeBakey, ME AF Mouton-Odum, Suzanne Keuthen, Nancy J. Wagener, Paula D. Stanley, Melinda A. DeBakey, Michael E. TI StopPulling.com: An interactive, self-help program for trichotillomania SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; MGH HAIRPULLING SCALE; HABIT-REVERSAL; COLLEGE-STUDENTS; DOUBLE-BLIND; PANIC DISORDER; NERVOUS HABITS; HAIR PULLERS; FOLLOW-UP; TRIAL AB Despite the widespread nature and significant impact of trichotillomania (TTM), relatively few controlled studies have evaluated treatment options for people with this disorder. Pharmacological treatment and behavior therapy are the two most widely accepted approaches to treating TTM, but few mental health professionals with appropriate expertise are available to provide care. The cost Of treatment also is prohibitive in some cases. A number of self-help books are available for people with TTM, but no empirical data have documented associated outcomes. This paper describes the development and two phases of program evaluation for an alternative, Internet-based self-help treatment strategy for repetitive hair putting. StopPulling. com is an on-line, interactive self-help approach derived from evidence-based cognitive behavioral models of treatment for TTM. Following program development, an initial test phase elicited feedback from individuals with repetitive hair pulling and professionals with expertise in the treatment of TTM or Web site development. StopPulling. com was modified in accordance with feedback From this initial test phase, and a revised version was made available to the public in January 2003. Prelimonary data from 265 users of the program during the first year of public availability suggested signficant improvement in symptoms, with some evidence that duration of program use accounted for reductions in symptom severity. Response rates were comparable to long-term follow-up after none intense cognitive behavioral treatment. StopPulling. com may provide a potentially useful self-help alternative or adjunctive strategy for repetitive hair pulling. C1 Baylor Coll Med, MEDVAMC 152, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Stanley, MA (reprint author), Baylor Coll Med, MEDVAMC 152, Menninger Dept Psychiat & Behav Sci, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mstanley@bcm.tmc.edu RI Citations, TLC SAB/C-4006-2011 NR 50 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2006 VL 13 IS 3 BP 215 EP 226 DI 10.1016/j.cbpra.2005.05.004 PG 12 WC Psychology, Clinical SC Psychology GA 174HW UT WOS:000246934000009 ER PT J AU Salters-Pedneault, K Roemer, L Tull, MT Rucker, L Mennin, DS AF Salters-Pedneault, Kristalyn Roemer, Lizabeth Tull, Matthew T. Rucker, Latanya Mennin, Douglas S. TI Evidence of broad deficits in emotion regulation associated with chronic worry and generalized anxiety disorder SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE generalized anxiety disorder; anxiety disorders; emotion regulation; emotions; anxiety ID OPERATING CHARACTERISTIC ANALYSIS; SELF-REPORT; QUESTIONNAIRE; DYSREGULATION; VALIDATION; AVOIDANCE; SUPPRESSION; EFFICACY; VALIDITY; THERAPY AB This study examined the relationship between emotion regulation deficits and GAD-related outcomes in an analogue sample. Consistent with hypotheses, general emotion dysregulation was associated with reports of chronic worry and with analogue GAD status. Also, specific regulation deficits, including deficits in emotional clarity, acceptance of emotions, ability to engage in goal directed behaviors when distressed, impulse control, and access to effective regulation strategies, were associated with worry and analogue GAD above and beyond variance contributed by negative affectivity. These findings provide additional preliminary evidence for an emotion regulation deficit model of GAD and are discussed in terms of clinical implications and directions for future research. C1 VA Boston Healthcare Syst 116B 5, Natl Ctr PTSD, Boston, MA 02130 USA. Univ Massachusetts, Dept Psychol, Boston, MA USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. RP Salters-Pedneault, K (reprint author), VA Boston Healthcare Syst 116B 5, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM kristalyn.salters@va.gov RI Mennin, Douglas/C-9421-2012; OI Roemer, Lizabeth/0000-0002-2453-5435 NR 45 TC 102 Z9 106 U1 6 U2 34 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD AUG PY 2006 VL 30 IS 4 BP 469 EP 480 DI 10.1007/s10608-006-9055-4 PG 12 WC Psychology, Clinical SC Psychology GA 113OB UT WOS:000242606100005 ER PT J AU Brown, SD Zurakowski, D Rodriguez, DP Dunning, PS Hurley, RJ Taylor, GA AF Brown, Stephen D. Zurakowski, David Rodriguez, Diana P. Dunning, Patricia S. Hurley, Richard J. Taylor, George A. TI Ultrasound diagnosis of mouse pregnancy and gestational staging SO COMPARATIVE MEDICINE LA English DT Article ID IN-UTERO; FETAL DEVELOPMENT; BLOOD-FLOW; MICE; BIOMICROSCOPY; HEART; DOPPLER; EMBRYO; ECHOCARDIOGRAPHY; REPRODUCTION AB Phenotypic analysis of mutant mice is limited by lack of accurate, simple, and nondestructive in utero imaging techniques. This study evaluated the usefulness of ultrasound imaging (US) to stage fetal mouse gestational age (GA) and depict morphologic development. We imaged 16 pregnant CD-1 mice and a total of 92 fetuses with a 15-MHz US transducer from 9.5 d postcoitus (DPC) until 20.5 DPC or delivery. Parameters recorded included gestational sac dimensions, crown-rump length (CRL), biparietal diameter (BPD), thoracoabdominal diameter (TAD), onset of cardiac activity, and morphologic development. At 9.5 d DPC, all gestations appeared as rounded sacs, with a diameter (mean standard error) of 4.41 mm. BPD, CRL, and GA were highly correlated. The following structures were first identifiable at the following GA: cardiac activity, 10.5 DPC; major cardiovascular structures, 11.5 DPC; limb buds, 10.5 DPC; spine, 12.5 DPC; face and skull ossification, 13.5 DPC; rib ossification, 15.5 DPC; hind- and forelimb digits, 15.5 DPC; stomach and urinary bladder, 17.5 DPC; visualization of the rhombencephalic vesicle, 13.5 DPC; and visualization of the lateral ventricles, 14.5 DPC. The echogenic lungs were distinct from the liver as early as 12.5 DPC. The circle of Willis was detectable with color Doppler as early as 13.5 DPC and was easily visualized at 15.5 DPC. We found that US provides accurate, simple staging criteria for fetal mouse gestational development after 9.5 DPC and may be a nondestructive means of documenting phenotypic alterations in mutant mice in utero. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. RP Brown, SD (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM stephen.brown@childrens.harvard.edu NR 21 TC 19 Z9 19 U1 0 U2 4 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2006 VL 56 IS 4 BP 262 EP 271 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 080WI UT WOS:000240278800005 PM 16941953 ER PT J AU Li, XC Xu, RH AF Li, XC Xu, RH TI Empirical and kernel estimation of covariate distribution conditional on survival time SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE survival; censoring; covariate; conditional distribution; smoothing ID TERM SURVIVORS; LONG-TERM AB In biomedical research there is often interest in describing covariate distributions given different survival groups. This is not immediately available due to censoring. In this paper we develop an empirical estimate of the conditional covariate distribution under the proportional hazards regression model. We show that it converges weakly to a Gaussian process and provide its variance estimate. We then apply kernel smoothing to obtain an estimate of the corresponding density function. The density estimate is consistent and has the same rate of convergence as the classical kernel density estimator. We have developed an R package to implement our methodology, which is demonstrated through the Mayo Clinic primary biliary cirrhosis data. (C) 2005 Elsevier B.V. All rights reserved. C1 Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif San Diego, Div Biostat, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Math, San Diego, CA 92103 USA. RP Li, XC (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM xiaochun@jimmy.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD AUG 1 PY 2006 VL 50 IS 12 BP 3629 EP 3643 DI 10.1016/j.csda.2005.08.002 PG 15 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 056EE UT WOS:000238503300015 ER PT J AU Sesso, HD Gaziano, JM Glynn, RJ Buring, JE AF Sesso, Howard D. Gaziano, J. Michael Glynn, Robert J. Buring, Julie E. TI Value of an Endpoints Committee versus the use of nosologists for validating cause of death SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE sensitivity; specificity; cause of death; nosologists; Endpoints Committee; epidemiological methods ID CORONARY-HEART-DISEASE; CERTIFICATE DIAGNOSIS; MALIGNANT NEOPLASMS; POPULATION; MINNESOTA; MORTALITY; ACCURACY; INDEX AB Purpose: Few studies have directly compared the use of nosologists versus other sources of mortality information deemed a gold standard, including the use of an Endpoints Committee (EC), which is commonly utilized in clinical studies. Methods: We conducted a study of 421 participants in the Physicians' Health Study (PHS), known to have died of confirmed causes during the period of April 1982 to January 1988. Classification of cause of death was compared when coded by certified nosologists directly from the death certificate without the availability of full hospital and medical records versus determinations made by the PHS Endpoints Committee (EC). Results: The sensitivity of the nosologists, using the PHS EC as the gold standard, was 90% for total cardiovascular death, 89% for cancer and 89% for other deaths. However, when considering more specific causes of death, sensitivity for acute MI, sudden cardiac deaths and deaths from other cardiovascular causes were lower. Specificity was generally excellent for all endpoints, ranging from 90% to 100%. In analyses stratified by age, nosologists tended to overestimate the frequency of cardiovascular deaths in the elderly. Conclusions: Mortality endpoints classified by trained nosologists versus the PHS EC indicate that nosologists can review death certificates to reasonably and quickly classify broad categories of causes of death in men, whereas an EC remains the preferable strategy when more specific causes of death must be ascertained by reviewing medical records and other accompanying information. (c) 2005 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. VA Boston Healthcare, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Sesso, HD (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM hsesso@hsph.harvard.edu FU NCI NIH HHS [CA-40360, R01 CA097193, CA-34944]; NHLBI NIH HHS [HL-34595, HL-42441, HL-26490] NR 21 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 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD AUG PY 2006 VL 27 IS 4 BP 333 EP 339 DI 10.1016/j.cct.2005.11.007 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 070UW UT WOS:000239551800003 PM 16387554 ER PT J AU Rieber, J Meissner, O Babaryka, G Reim, S Oswald, M Koenig, A Schiele, TM Shapiro, M Theisen, K Reiser, MF Klauss, V Hoffmann, U AF Rieber, Johannes Meissner, Oliver Babaryka, Gregor Reim, Susanne Oswald, Melanie Koenig, Andreas Schiele, Thomas M. Shapiro, Michael Theisen, Karl Reiser, Maximilian F. Klauss, Volker Hoffmann, Udo TI Diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of atherosclerotic plaque composition in ex-vivo coronary specimens: a comparison with histology SO CORONARY ARTERY DISEASE LA English DT Article DE atherosclerosis; histology; intravascular ultrasound; optical coherence tomography ID CLASSIFICATION; LESIONS; BACKSCATTER; ARTERIES; INVITRO AB Background Both intravascular ultrasound and optical coherence tomography have been purported to accurately detect and characterize coronary atherosclerotic plaque composition. The aim of our study was to directly compare the reproducibility and diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of coronary plaque composition ex vivo as compared with histology. Methods and results Intravascular ultrasound (20 MHz) and optical coherence tomography imaging was performed in eight heart specimens using motorized pullback. Standard histology using hematoxylin-eosin and van Gieson staining was performed on 4 mu m thick slices. Each slice was divided into quadrants and accurately matched cross-sections were analyzed for the presence of fibrous, lipid-rich, and calcified coronary plaque using standard definitions for both intravascular ultrasound and optical coherence tomography and correlated with histology. After exclusion of 145/468 quadrants, we analyzed the remaining 323 quadrants with excellent image quality in each procedure. Optical coherence tomography demonstrated a sensitivity and specificity of 91/88% for normal wall, 64/88% for fibrous plaque, 77/94% for lipid-rich plaque, and 67/97% for calcified plaque as compared with histology. Intravascular ultrasound demonstrated a sensitivity and specificity of 55/79% for normal wall, 63/59% for fibrous plaque, 10/96% for lipid-rich plaque, and 76/98% for calcified plaque. Both intravascular ultrasound and optical coherence tomography demonstrated excellent intraobserver and interobserver agreement (optical coherence tomography: kappa=0.90, kappa=0.82; intravascular ultrasound: kappa=0.87, kappa=0.86). Conclusion Optical coherence tomography is superior to intravascular ultrasound for the detection and characterization of coronary atherosclerotic plaque composition, specifically for the differentiation of noncalcified, lipid-rich, or fibrous plaque. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Univ Munich, Dept Cardiol, Div Internal Med, D-80539 Munich, Germany. Univ Munich, Inst Clin Radiol, D-80539 Munich, Germany. Univ Munich, Inst Pathol, D-80539 Munich, Germany. RP Rieber, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, CIMIT Suite 400,165 Cambridge St, Boston, MA 02114 USA. EM jrieber@med.uni-muenchen.de NR 22 TC 57 Z9 63 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD AUG PY 2006 VL 17 IS 5 BP 425 EP 430 DI 10.1097/00019501-200608000-00005 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 073AJ UT WOS:000239714300005 PM 16845250 ER PT J AU Caplan, D AF Caplan, David TI Aphasic deficits in syntactic processing SO CORTEX LA English DT Article DE aphasia; sentence comprehension; syntactic comprehension disorders ID SPOKEN-LANGUAGE COMPREHENSION; AGRAMMATIC BROCAS APHASIA; SENTENCE COMPREHENSION; GRAMMATICAL STRUCTURE; WERNICKE APHASIA; CAPACITY THEORY; WORKING-MEMORY; LEXICAL ACCESS; SINGLE PATTERN; PERFORMANCE AB Two main classes of theories of deficits in syntactic processing in aphasia have been suggested: impairments affecting specific syntactic operations and reductions in resources available for syntactic processing. This paper reviews the data upon which such theories are based and argues that they may support only the latter type of model. C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIDCD NIH HHS [DC00942, DC04608] NR 68 TC 13 Z9 13 U1 2 U2 3 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD AUG PY 2006 VL 42 IS 6 BP 797 EP 804 DI 10.1016/S0010-9452(08)70420-9 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 104QX UT WOS:000241974900003 PM 17131582 ER PT J AU Bice-Stephens, WM AF Bice-Stephens, Wynona M. TI Guest editorial - Ownership in the intensive care unit SO CRITICAL CARE NURSE LA English DT Editorial Material C1 VA PUget Sound Hlth Care Syst, Seattle, WA USA. RP Bice-Stephens, WM (reprint author), VA PUget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 J9 CRIT CARE NURSE JI Crit. Care Nurse PD AUG PY 2006 VL 26 IS 4 BP 10 EP + PG 2 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 069LG UT WOS:000239447400001 PM 16857996 ER PT J AU Zoghbi, GJ Iskandrian, AE AF Zoghbi, Gilbert J. Iskandrian, Ami E. TI Adenosine myocardial perfusion imaging SO CURRENT MEDICAL IMAGING REVIEWS LA English DT Review DE adenosine; SPECT; myocardial perfusion imaging ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; TRANSIENT ISCHEMIC DILATION; ST-SEGMENT DEPRESSION; BUNDLE-BRANCH BLOCK; SIGNIFICANT AORTIC-STENOSIS; TC-99M SESTAMIBI SPECT; DOPPLER GUIDE-WIRE; PHARMACOLOGICAL STRESS; BLOOD-FLOW AB Adenosine myocardial perfusion imaging is a commonly used modality for the evaluation of patients with known or suspected coronary artery disease (CAD). In this review we discuss the pharmacology of adenosine and its effects on myocardial blood flow and the generation of perfusion defects during myocardial perfusion imaging (MPI), the indications and contraindications of MPI, stress protocols, side effects, hemodynamic and electrocardiographic changes, comparison to other stress MPI modalities, the role of adenosine MPI in special patient populations and the recent advances in the field with the emergence of the new selective adenosine agonists. C1 Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Iskandrian, AE (reprint author), Univ Alabama, Dept Med, Div Cardiovasc Dis, 318 LHRB,1900 Univ Blvd, Birmingham, AL 35294 USA. EM aiskand@uab.edu NR 112 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4056 J9 CURR MED IMAGING REV JI Curr. Med. Imaging Rev. PD AUG PY 2006 VL 2 IS 3 BP 315 EP 327 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 063LV UT WOS:000239020600003 ER PT J AU Clark, S Camargo, CA AF Clark, Sunday Camargo, Carlos A., Jr. TI Emergency treatment and prevention of insect-sting anaphylaxis SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE anaphylaxis; emergency department; insect stings ID ALLERGIC DISEASE; UNITED-STATES; EPIDEMIOLOGY; MANAGEMENT; POPULATION; HYPERSENSITIVITY; HYMENOPTERA; SENSITIVITY; SEVERITY; UPDATE AB Purpose of review Hymenoptera stings are thought to cause systemic allergic reactions in 0.4-5% of individuals, and to account for 40-100 deaths annually in the USA. This review examines current research on insect-sting anaphylaxis in the emergency-department (ED), and provides suggestions on how to improve ED treatment and prevention. Recent findings Few published studies since January 2005 examine the emergency management of insect-sting allergic reactions. Earlier studies found that few ED patients with this problem received health education, a prescription for self-injectable epinephrine or referral to an allergy specialist at ED discharge. A recent multicenter study by our group demonstrated that ED patients with insect-sting allergic reactions continue to receive care discordant with national guidelines for the emergency management of anaphylaxis. Summary Concordance with national guidelines for the treatment of anaphylaxis remains poor among insect-sting allergy patients. The development of a simple, clinical definition of anaphylaxis is urgently needed to facilitate identification of cases. Such a definition would help tremendously with dissemination of emergency management guidelines and the creation of systems for their implementation. All of these steps are essential for the improved treatment and prevention of insect-sting anaphylaxis in the ED. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. RP Clark, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Emergency Med, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM sclark3@partners.org NR 38 TC 20 Z9 20 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD AUG PY 2006 VL 6 IS 4 BP 279 EP 283 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 070VA UT WOS:000239552200006 PM 16825869 ER PT J AU Mukhopadhyay, A Peterson, RT AF Mukhopadhyay, Arpita Peterson, Randall T. TI Fishing for new antimicrobials SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID ZEBRAFISH DANIO-RERIO; TOLL-LIKE RECEPTOR; CAENORHABDITIS-ELEGANS; MYCOBACTERIUM-MARINUM; DROSOPHILA-MELANOGASTER; BACTERIAL PATHOGENESIS; VIRULENCE FACTORS; TRIAZINE LIBRARY; ADULT ZEBRAFISH; MODEL AB The discovery of antibiotics and other antimicrobial agents in the 1930s is arguably the most significant therapeutic advance in medical history. Penicillin and the sulfa drugs touched off the search for and discovery of countless derivative compounds and several new antibiotic classes. However, the pace of discovery has slowed down, and there is growing appreciation that much of the low-lying fruit accessible to traditional methods of antimicrobial discovery has been harvested. Combating emerging drug-resistant strains of infectious agents may require the adoption of fresh approaches to drug target validation, small-molecule discovery and safety assessment. The recent development of several infectious disease models in zebrafish raises the possibility of a new paradigm in antimicrobial discovery. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA USA. RP Peterson, RT (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM peterson@cvrc.mgh.harvard.edu NR 58 TC 16 Z9 16 U1 2 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD AUG PY 2006 VL 10 IS 4 BP 327 EP 333 DI 10.1016/j.cbpa.2006.06.026 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 077UQ UT WOS:000240056600007 PM 16822704 ER PT J AU Kaufmann, SHE Walker, BD AF Kaufmann, Stefan H. E. Walker, Bruce D. TI Host-pathogen interactions SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany. Harvard Univ, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02192 USA. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Kaufmann, SHE (reprint author), Max Planck Inst Infect Biol, Dept Immunol, Schumannstr 21-22, D-10117 Berlin, Germany. EM kaufmann@mpjib-berlin.mpg.de; bwalker@partners.org RI Kaufmann, Stefan HE/I-5454-2014 OI Kaufmann, Stefan HE/0000-0001-9866-8268 NR 0 TC 6 Z9 7 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2006 VL 18 IS 4 BP 371 EP 373 DI 10.1016/j.coi.2006.05.OD9 PG 3 WC Immunology SC Immunology GA 067ZP UT WOS:000239341600001 PM 16777394 ER PT J AU Brander, C Frahm, N Walker, BD AF Brander, Christian Frahm, Nicole Walker, Bruce D. TI The challenges of host and viral diversity in HIV vaccine design SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; CLADE-B INFECTION; CROSS-CLADE; LYMPHOCYTE RESPONSES; IMMUNE-RESPONSES; TYPE-1 INFECTION; RHESUS-MONKEYS; IN-VIVO; IMMUNODOMINANT REGIONS AB Rational HIV vaccine design is crucially dependent on a number of factors, including a detailed understanding of the immune responses that control infection in individuals that have non-progressing disease, the impact of host genetics on these responses, and the degree of immunological cross-reactivity between the vaccine immunogen and the encountered virus antigens. Significant progress has been made in a number of these areas over the past five years, which might help in the generation of a more effective immunogen design and will provide opportunities for novel vaccine delivery options. However, the understanding of immune response(s) that can mediate protection from infection or, if infection ensues, that slow the rate of HIV disease progression is still incomplete and will require detailed studies in unprecedentedly large populations infected with different HIV clades, combining advances in virology, immunology, human host genetics and bioinformatics analyses for the optimal design of vaccine immunogens. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02192 USA. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Brander, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02192 USA. EM cbrander@partners.org OI Brander, Christian/0000-0002-0548-5778 NR 86 TC 36 Z9 38 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2006 VL 18 IS 4 BP 430 EP 437 DI 10.1016/j.coi.2006.05.012 PG 8 WC Immunology SC Immunology GA 067ZP UT WOS:000239341600009 PM 16777397 ER PT J AU Bonasio, R von Andrian, UH AF Bonasio, Roberto von Andrian, Ulrich H. TI Generation, migration and function of circulating dendritic cells SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID COLONY-STIMULATING FACTOR; CD8(+) T-CELLS; HUMAN PERIPHERAL-BLOOD; BONE-MARROW CULTURES; THORACIC-DUCT LYMPH; MHC CLASS-I; LANGERHANS CELLS; ANTIGEN PRESENTATION; B-CELLS; IMMUNE-RESPONSES AB Tissue-resident dendritic cells (DCs) that migrate from peripheral sites to lymphoid organs are essential in the initiation of adaptive immune responses and for the maintenance of peripheral tolerance, and have been extensively studied. By contrast, blood-borne DCs represent a heterogeneous population, the origin, destination and function of which are still unclear. Recent studies have shown that circulating DCs capture blood-borne antigen and transport it into the extravascular space of lymphoid tissues for processing and presentation. Other findings suggest that a fraction of tissue-resident DCs might enter the blood after having acquired antigen in the periphery. Together, these studies imply that circulating DCs might modulate immune responses by translocating antigenic material from its point of origin to remote target tissues. C1 CBR Inst Biomed Res Inc, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP von Andrian, UH (reprint author), CBR Inst Biomed Res Inc, Boston, MA 02215 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Bonasio, Roberto/P-1356-2014 OI Bonasio, Roberto/0000-0002-0767-0889 NR 74 TC 76 Z9 84 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2006 VL 18 IS 4 BP 503 EP 511 DI 10.1016/j.coi.2006.05.011 PG 9 WC Immunology SC Immunology GA 067ZP UT WOS:000239341600019 PM 16777395 ER PT J AU Fuchs, BB Mylonakis, E AF Fuchs, Beth Burgwyn Mylonakis, Eleftherios TI Using non-mammalian hosts to study fungal virulence and host defense SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID INNATE IMMUNE-RESPONSE; CRYPTOCOCCUS-NEOFORMANS; CAENORHABDITIS-ELEGANS; GALLERIA-MELLONELLA; DROSOPHILA-MELANOGASTER; DICTYOSTELIUM-DISCOIDEUM; MODEL; PATHOGENESIS; GENOME; PATHOGENICITY AB Non-mammalian hosts have been used to study host-fungal interactions. Hosts such as Drosophila melanogaster, Caenorhabditis elegans, Acathamoeba castellanii, Dictyostelium discoideum, and Galleria mellonella have provided means to examine the physical barriers, cellular mechanisms and molecular elements of the host response. The Drosophila host-response to fungi is mediated through the Toll pathway, whereas in C. elegans the host-response is TIR-1 dependent. Virulence traits that are involved in mammalian infection are important for the interaction of fungi with these hosts. Screening of fungal virulence traits using mutagenized fungi to determine changes in fungal infectivity of nonmammalian hosts has been used to identify novel virulence proteins used to infect C. elegans such as Kin1 (a serine/threonine protein kinase) and Rom2 (a Rho1 guanyl-nucleotide exchange factor) from Cryptococcus neoformans. These heterologous non-mammalian hosts highlight the similarities and differences between different hosts in fungal pathogenesis and they complement studies in mammalian systems and those using other genetic approaches. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIAID NIH HHS [AI63084-01] NR 49 TC 90 Z9 96 U1 0 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 EI 1879-0364 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD AUG PY 2006 VL 9 IS 4 BP 346 EP 351 DI 10.1016/j.mib.2006.06.004 PG 6 WC Microbiology SC Microbiology GA 077UO UT WOS:000240056400004 PM 16814595 ER PT J AU Zubair, AC Kao, G Daley, H Schott, D Freedman, A Ritz, J AF Zubair, A. C. Kao, G. Daley, H. Schott, D. Freedman, A. Ritz, J. TI CD34(+) CD38(-) and CD34(+) HLA-DR- cells in BM stem cell grafts correlate with short-term engraftment but have no influence on long-term hematopoietic reconstitution after autologous transplantation SO CYTOTHERAPY LA English DT Article DE ABMT; CD34(+); engraftment; leukemia; lymphoma ID BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CYCLOPHOSPHAMIDE; COLONY-STIMULATING FACTOR; BLOOD PROGENITOR CELLS; NON-HODGKINS-LYMPHOMA; PERIPHERAL-BLOOD; MONOCLONAL-ANTIBODIES; PREDICTIVE FACTORS; SUBSETS; MOBILIZATION AB Background Prior studies have demonstrated that relatively immature hematopoietic stem cells, including CD34(+) CD38(-) and CD34(+) HLA-DR- subsets, correlate with short-term hematopoietic reconstruction ( SHR) after transplantation. The aim of this study was to investigate whether these immature CD34(+) subsets also correlate with long-term hematopoietic reconstitution ( LHR) in recipients of ABMT. Methods We examined stem cell grafts from 58 patients with B-cell lymphoma or CLL who underwent ABMT after myeloablative conditioning. We determined whether total mononuclear cell dose ( MNC), colony-forming unit-granulocyte-monocyte ( CFU-GM), CD34(+) cell dose and CD34(+) cell subsets ( CD34(+) CD38(-) and CD34(+) HLA-DR-) were associated with SHR and/or LHR. Time to neutrophil engraftment ( TNE) and time to platelet engraftment ( TPE) were used to measure SHR, while platelet counts at day 100 and 1 year post-ABMT were used as indicators for LHR. Results and discussion C D34(+) cell dose and CD34(+) cell subsets were significantly associated with SHR. However, at day 100 and 1 year post-transplant only total CD34(+) cell dose was associated with LHR. The association of total CD34(+) cell dose with LHR persisted after adjusting for age, sex and disease. None of the CD34(+) cell subsets analyzed showed evidence of significant association with LHR. C1 Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. Dana Farber Canc Inst, Connell Oreilly Cell Manipulat Core Facil, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zubair, AC (reprint author), Mayo Clin, Dept Pathol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM zubair.abba@mayo.edu FU NCI NIH HHS [CA102824]; NHLBI NIH HHS [HL04095] NR 41 TC 9 Z9 9 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD AUG PY 2006 VL 8 IS 4 BP 399 EP 407 DI 10.1080/14653240600847241 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 076JK UT WOS:000239953200012 PM 16923616 ER PT J AU Ge, H Player, CM Zou, LH AF Ge, Hui Player, Christopher M. Zou, Lihua TI Toward a global picture of development: Lessons from genome-scale analysis in Caenorhabditis elegans embryonic development SO DEVELOPMENTAL DYNAMICS LA English DT Review DE genomics; high-throughput approaches; computational analysis ID JAK/STAT SIGNALING COMPONENTS; C-ELEGANS; GENE-EXPRESSION; RNA INTERFERENCE; EARLY EMBRYOGENESIS; DROSOPHILA; MAP; IDENTIFICATION; NETWORKS; PATHWAY AB Development is the result of complex events, including cascades of transcriptional programs and numerous molecular interactions. Traditionally, research focus has been given to the characterization of individual mutants, regulators, or interactions. With the availability of complete genome sequences and high-throughput (HT) experimental techniques, probing development on a system level has become feasible. Pioneering work initiated in invertebrate model systems such as Caenorhabditis elegans has provided first drafts of catalogs of essential components, transcriptional regulatory diagrams and molecular interaction networks underlying developmental processes. Integrating these drafts approximates a system-level picture of development and provides local models for protein/gene functions. Here we summarize the progress toward elucidating developmental processes on a system level, including the applications of genomic technologies and computational analyses. We discuss C. elegans embryonic development in case studies to illustrate how various HT approaches can be integrated and how biological insights can be gained from these approaches. C1 Whitehead Inst, Cambridge, MA 02142 USA. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ge, H (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM hge@wi.mit.edu NR 37 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 2006 VL 235 IS 8 BP 2009 EP 2017 DI 10.1002/dvdy.20865 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 071GZ UT WOS:000239588800001 PM 16779860 ER PT J AU Esser, AT Smith, KC Weaver, JC Levin, M AF Esser, Axel T. Smith, Kyle C. Weaver, James C. Levin, Michael TI Mathematical model of morphogen electrophoresis through gap junctions SO DEVELOPMENTAL DYNAMICS LA English DT Review DE gap junctional communication; embryonic patterning; asymmetry; model; electrophoresis; serotonin ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; MEMBRANE H+-ATPASE; MEDIATED CELL COMMUNICATION; EARLY AMPHIBIAN EMBRYO; AUXIN POLAR TRANSPORT; PLANT-TISSUE CULTURES; CHICK LIMB BUD; INTERCELLULAR COMMUNICATION; INTRACELLULAR PH AB Gap junctional communication is important for embryonic morphogenesis. However, the factors regulating the spatial properties of small molecule signal flows through gap junctions remain poorly understood. Recent data on gap junctions, ion transporters, and serotonin during left-right patterning suggest a specific model: the net unidirectional transfer of small molecules through long-range gap junctional paths driven by an electrophoretic mechanism. However, this concept has only been discussed qualitatively, and it is not known whether such a mechanism can actually establish a gradient within physiological constraints. We review the existing functional data and develop a mathematical model of the flow of serotonin through the early Xenopus embryo under an electrophoretic force generated by ion pumps. Through computer simulation of this process using realistic parameters, we explored quantitatively the dynamics of morphogen movement through gap junctions, confirming the plausibility of the proposed electrophoretic mechanism, which generates a considerable gradient in the available time frame. The model made several testable predictions and revealed properties of robustness, cellular gradients of serotonin, and the dependence of the gradient on several developmental constants. This work quantitatively supports the plausibility of electrophoretic control of morphogen movement through gap junctions during early left-right patterning. This conceptual framework for modeling gap junctional signaling-an epigenetic patterning mechanism of wide relevance in biological regulation-suggests numerous experimental approaches in other patterning systems. C1 Forsyth Inst, Ctr Regenerat & Dev Biol, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Sch Dent Med, Boston, MA USA. RP Levin, M (reprint author), Forsyth Inst, Ctr Regenerat & Dev Biol, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCRR NIH HHS [C06 RR-11244]; NIGMS NIH HHS [GM-06227, GM-63857] NR 228 TC 44 Z9 44 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 2006 VL 235 IS 8 BP 2144 EP 2159 DI 10.1002/dvdy.20870 PG 16 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 071GZ UT WOS:000239588800012 PM 16786594 ER PT J AU Kahn, SE Zinman, B Haffner, SM O'Neill, MC Kravitz, BG Yu, DH Freed, MI Herman, WH Holman, RR Jones, NP Lachin, JM Viberti, GC AF Kahn, Steven E. Zinman, Bernard Haffner, Steven M. O'Neill, M. Colleen Kravitz, Barbara G. Yu, Dahong Freed, Martin I. Herman, William H. Holman, Rury R. Jones, Nigel P. Lachin, John M. Viberti, Giancarlo C. CA ADOPT Study Grp TI Obesity is a major determinant of the association of C-reactive protein levels and the metabolic syndrome in type 2 diabetes SO DIABETES LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; INSULIN-RESISTANCE ATHEROSCLEROSIS; CHOLESTEROL EDUCATION-PROGRAM; CARDIOVASCULAR-DISEASE; WEIGHT-LOSS; HEART-DISEASE; RISK-FACTORS; ACUTE-PHASE; INFLAMMATION; MELLITUS AB The inflammatory factor C-reactive protein (CRP) and the fibrinolytic variables fibrinogen and plasminogen activator-1 (PAI-1) are associated with long-term cardiovascular morbidity. To determine the contribution of body adiposity (BMI), insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], and glycemia (HbA(1c) [A1C]) to the levels of these inflammatory and fibrinolytic variables in recently diagnosed (<= 3 years), drug-naive, type 2 diabetic subjects (fasting plasma glucose <= 10 mmol/l), we examined a representative subgroup (n = 921) of the U.S. cohort in ADOPT (A Diabetes Outcome Progression Trial). The relationship between levels of CRP, fibrinogen, PAI-1 antigen and PAI-1 activity, and baseline variables including National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome phenotype were explored. All four factors increased significantly with increasing numbers of metabolic syndrome components (P = 0.0136 to P < 0.0001). BMI (P < 0.0001) and HOMA-IR (P < 0.0001) but not A1C (P = 0.65) increased with increasing numbers of metabolic syndrome components. Adjustment of CRP levels for BMI eliminated the association between CRP and the number of metabolic syndrome components, while adjusting for HOMA-IR did not (P = 0.0028). The relationships of PAI-1 antigen and PAI-1 activity with the number of metabolic syndrome components were maintained after adjusting for BMI (P = 0.0002 and P = < 0.0001, respectively) or HOMA-IR (P = 0.0008 and P = < 0.0001, respectively), whereas that with fibrinogen was eliminated after adjusting for BMI but not after adjusting for HOMA-IR (P = 0.013). Adjustment for A1C had no effect on any of the relationships between the inflammatory and fibrinolytic factors and the metabolic syndrome. We conclude that in recently diagnosed, drugnaive type 2 diabetic subjects, markers of inflammation and fibrinolysis are strongly related to the number of metabolic syndrome components. Further, for CRP and fibrinogen this relationship is determined by body adiposity and not by insulin sensitivity or glucose control. C1 VA Puget Sound Hlth Care Syst, Dept Internal Med, Div Metab, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. Kings Coll London, Sch Med, London WC2R 2LS, England. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Internal Med, Div Metab, 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu RI Zinman, Bernard/E-7266-2013; OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 NR 37 TC 106 Z9 112 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2006 VL 55 IS 8 BP 2357 EP 2364 DI 10.2337/db06-0116 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 069SK UT WOS:000239468300024 PM 16873701 ER PT J AU Draznin, B AF Draznin, Boris TI Molecular mechanisms of insulin resistance: Serine phosphorylation of insulin receptor substrate-1 and increased expression of p85 alpha - The two sides of a coin SO DIABETES LA English DT Article ID NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE B; P70 S6 KINASE; PHOSPHOINOSITIDE 3-KINASE; SKELETAL-MUSCLE; MAMMALIAN TARGET; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNALING PATHWAYS; GLUCOSE-TRANSPORT; MICE LACKING AB Initial attempts to unravel the molecular mechanism of insulin resistance have strongly suggested that a defect responsible for insulin resistance in the majority of patients lies at the postreceptor level of insulin signaling. Subsequent studies in insulin-resistant animal models and humans have consistently demonstrated a reduced strength of insulin signaling via the insulin receptor substrate (IRS)-1/phosphatidylinositol (PI) 3-kinase pathway, resulting in diminished glucose uptake and utilization in insulin target tissues. However, the nature of the triggering event(s) remains largely enigmatic. Two separate, but likely, complementary mechanisms have recently emerged as a potential explanation. First, it became apparent that serine phosphorylation of IRS proteins can reduce their ability to attract PI 3-kinase, thereby minimizing its activation. A number of serine kinases that phosphorylate serine residues of IRS-1 and weaken insulin signal transduction have been identified. Additionally, mitochondrial dysfunction has been suggested to trigger activation of several serine kinases, leading to a serine phosphorylation of IRS-1. Second, a distinct mechanism involving increased expression of p85 alpha has also been found to play an important role in the pathogenesis of insulin resistance. Conceivably, a combination of both increased expression of p85a and increased serine phosphorylation of IRS-1 is needed to induce clinically apparent insulin resistance. C1 Denver VA Med Ctr, Res Serv 151, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Boulder, CO 80309 USA. RP Draznin, B (reprint author), Denver VA Med Ctr, Res Serv 151, 1055 Clermont St, Denver, CO 80220 USA. EM boris.draznin@med.va.gov NR 94 TC 151 Z9 168 U1 3 U2 25 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2006 VL 55 IS 8 BP 2392 EP 2397 DI 10.2337/db06-0391 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 069SK UT WOS:000239468300029 PM 16873706 ER PT J AU Munshi, M Grande, L Hayes, M Ayres, D Suhl, E Capelson, R Lin, S Milberg, W Weinger, K AF Munshi, Medha Grande, Laura Hayes, Mellody Ayres, Darlene Suhl, Emmy Capelson, Roberta Lin, Susan Milberg, William Weinger, Katie TI Cognitive dysfunction is associated with poor diabetes control in older adults SO DIABETES CARE LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Diabetes-Association CY JUN 10-14, 2005 CL San Diego, CA SP Amer Diabet Assoc ID CLOCK-DRAWING TEST; COMORBID DEPRESSION; ALZHEIMER-DISEASE; FUNCTIONAL STATUS; MAJOR DEPRESSION; US ADULTS; MELLITUS; IMPAIRMENT; PREVALENCE; DEMENTIA AB OBJECTIVE - To evaluate the association between cognitive dysfunction and other barriers and glycemic control in older adults with diabetes. RESEARCH DESIGN AND METHODS - Patients over the age of 70 years presenting to a geriatric diabetes clinic were evaluated for barriers to successful diabetes management. Patients were screened for cognitive dysfunction with the Mini Mental State Examination (MMSE) and a clock-drawing test (CDT) scored by 1) a method validated by Mendez et al. and 2) a modified CDT (clock in a box [CIB]). Depression was evaluated with the Geriatric Depression Scale. Interview questionnaires surveyed activities of daily living (ADLs) and instrumental ADLs (IADLs), as well as other functional disabilities. RESULTS - Sixty patients (age 79 - 5 years, diabetes duration 14 +/- 13 years) were evaluated. Thirty-four percent of patients had low CIB (>= 5), and 38% of patients had low CDT (<= 13). Both CIB as well as CDT were inversely correlated with HbA(1c) suggesting that cognitive dysfunction is associated with poor glycemic control (r = -0.37, P < 0.004 and r = -0.38, P < 0.004, respectively). Thirty-three percent of patients had depressive symptoms with greater difficulty completing the tasks of the IADL survey (5.7 +/- 1.7 vs. 4.6 +/- 2.0; P < 0.03). These older adults with diabetes had a high incidence of functional disabilities, including hearing impairment (48%), vision impairment (53%), history of recent falls (33%), fear of falls (44%), and difficulty performing IADLs (39%). CONCLUSIONS - Older adults with diabetes have a high risk of undiagnosed cognitive dysfunction, depression, and functional disabilities. Cognitive dysfunction in this population is associated with poor diabetes control. C1 Beth Israel Deaconess Med Ctr, Gerontol Div, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Adult Diabet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. New England Geriatr Res Educ & Clin Ctr, Geriatr Neuropsychol Lab, Vet Affairs Boston Hlth Care Syst, Boston, MA USA. RP Munshi, M (reprint author), Beth Israel Deaconess Med Ctr, Div Geriatr, 110 Francis St,LMOB 1B, Boston, MA 02215 USA. EM mmunshi@bidmc.harvard.edu FU NIA NIH HHS [P60 AG008812-10, P60 AG008812, P60 AG008812-11A10002, P60 AG008812-120002, T32 AG023480, T32 AG023480-01]; NIDDK NIH HHS [5P30 DK36836-19, DK60115, P30 DK036836, R01 DK060115] NR 43 TC 144 Z9 151 U1 3 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2006 VL 29 IS 8 BP 1794 EP 1799 DI 10.2337/dc06-0506 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071HA UT WOS:000239589000012 PM 16873782 ER PT J AU Nathan, DM Buse, JB Davidson, MB Heine, RJ Holman, RR Sherwin, R Zinman, B AF Nathan, David M. Buse, John B. Davidson, Mayer B. Heine, Robert J. Holman, Rury R. Sherwin, Robert Zinman, Bernard TI Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy - A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes SO DIABETES CARE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BLOOD-GLUCOSE CONTROL; GLYCEMIC CONTROL; MICROVASCULAR COMPLICATIONS; CARDIOVASCULAR-DISEASE; COMBINATION THERAPY; EXENATIDE EXENDIN-4; INSULIN THERAPY; LIFE-STYLE; TREATED PATIENTS C1 Massachusetts Gen Hosp, Diabet Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Charles R Drew Univ, Clin Trials Unit, Los Angeles, CA USA. VU Univ, Ctr Med, Diabet Ctr, Amsterdam, Netherlands. Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England. Yale Univ, Sch Med, Dept Internal Med & Endocrinol, New Haven, CT USA. Univ Toronto, Mt Sinai Hosp, Dept Endocrinol & Metab, Toronto, ON, Canada. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Diabet Ctr, Boston, MA 02114 USA. EM dnathan@partners.org RI Zinman, Bernard/E-7266-2013 NR 76 TC 695 Z9 757 U1 3 U2 18 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2006 VL 29 IS 8 BP 1963 EP 1972 DI 10.2337/dc06-9912 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071HA UT WOS:000239589000043 PM 16873813 ER PT J AU Nathan, DM Buse, JB Davidson, MB Heine, RJ Holman, RR Sherwin, R Zinman, B AF Nathan, D. M. Buse, J. B. Davidson, M. B. Heine, R. J. Holman, R. R. Sherwin, R. Zinman, B. TI Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy - A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes SO DIABETOLOGIA LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; BLOOD-GLUCOSE CONTROL; GLYCEMIC CONTROL; MICROVASCULAR COMPLICATIONS; CARDIOVASCULAR-DISEASE; COMBINATION THERAPY; EXENATIDE EXENDIN-4; INSULIN THERAPY; LIFE-STYLE; TREATED PATIENTS AB This document was reviewed and approved by the Professional Practice Committee of the American Diabetes Association and by an ad hoc committee of the European Association for the Study of Diabetes ( U. Smith, Gothenburg, Sweden; S. Del Prato, Pisa, Italy; C. Bailey, Birmingham, UK; and B. Charbonnel, Nantes, France). Simultaneous publication: This article is being simultaneously published in 2006 in Diabetes Care and Diabetologia by the American Diabetes Association and the European Association for the Study of Diabetes. Copyright 2006 by the American Diabetes Association, Inc. and Springer. Copying with attribution allowed for any noncommercial use of the work. C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. Charles R Drew Univ Med & Sci, Clin Trial Unit, Los Angeles, CA 90059 USA. VU Univ, Med Ctr, Ctr Diabet, Amsterdam, Netherlands. Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet, Oxford OX1 2JD, England. Yale Univ, Sch Med, Dept Internal Med & Endocrinol, New Haven, CT 06520 USA. Univ Toronto, Mt Sinai Hosp, Dept Endocrinol, Toronto, ON M5G 1X5, Canada. Univ Toronto, Mt Sinai Hosp, Dept Metab, Toronto, ON M5G 1X5, Canada. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. EM dnathan@partners.org RI Zinman, Bernard/E-7266-2013 NR 76 TC 222 Z9 240 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2006 VL 49 IS 8 BP 1711 EP 1721 DI 10.1007/s00125-006-0316-2 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061GR UT WOS:000238859900001 PM 16802130 ER PT J AU Jimenez-Chillaron, JC Hernandez-Valencia, M Lightner, A Faucette, RR Reamer, C Przybyla, R Ruest, S Barry, K Otis, JP Patti, ME AF Jimenez-Chillaron, J. C. Hernandez-Valencia, M. Lightner, A. Faucette, R. R. Reamer, C. Przybyla, R. Ruest, S. Barry, K. Otis, J. P. Patti, M. E. TI Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birthweight SO DIABETOLOGIA LA English DT Article DE caloric restriction; catch-up growth; diabetes; frowth rate; intrauterine growth retardation; low birthweight; obesity ID CATCH-UP GROWTH; FOR-GESTATIONAL-AGE; CORONARY-HEART-DISEASE; INSULIN-RESISTANCE; PROSPECTIVE COHORT; THRIFTY PHENOTYPE; YOUNG ADULTHOOD; SKELETAL-MUSCLE; ADIPOSE-TISSUE; BLOOD-PRESSURE AB Low birthweight (LBW) and rapid postnatal weight gain, or catch-up growth, are independent risk factors for the development of obesity and diabetes during adult life. Individuals who are both small at birth and have postnatal catch-up growth are at the highest risk. We hypothesised that dietary interventions designed to attenuate catch-up growth in LBW subjects may have long-term beneficial consequences. We used our previously described mouse model of LBW-associated diabetes, created by restricting maternal food intake to 50% during the last week of gestation. Control (C) dams and dams that had been subjected to undernutrition (U) were then provided either chow ad libitum after delivery or 50% food restriction on a per-day basis from delivery until weaning. We designated the resulting four groups control-control (CC), undernutrition-control (UC), control-undernutriton (CU) and undernutrition-undernutrition (UU), indicating the prenatal and postnatal experimental conditions, respectively. Carbohydrate metabolism and adiposity were assessed prospectively in offspring until age 6 months. Males that were small at birth and exhibited early postnatal catch-up growth developed glucose intolerance and obesity by age 6 months. In contrast, LBW mice without catch-up growth (UU) remained smaller than controls (CC), and glucose intolerance and obesity was prevented. Similarly, mice with normal birthweight that had blunted catch-up growth (CU) were leaner and had better tolerance test than CC mice. Catch-up growth during the first week of life correlated better than birthweight with glucose, fat mass and glucose tolerance up to 6 months of age. Prevention of early catch-up growth reversed the development of glucose intolerance and obesity in our mouse model of LBW-associated diabetes. C1 Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Dept Cellular & Mol Physiol, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU NIDDK NIH HHS [DK 062948, P30 DK 36836] NR 42 TC 79 Z9 83 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2006 VL 49 IS 8 BP 1974 EP 1984 DI 10.1007/s00125-006-0311-7 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061GR UT WOS:000238859900031 PM 16761107 ER PT J AU Malecki, MT Lebrun, P Pezzolesi, M Warram, JH Krolewski, AS Jhala, US AF Malecki, M. T. Lebrun, P. Pezzolesi, M. Warram, J. H. Krolewski, A. S. Jhala, U. S. TI A newly identified mutation in an IPF1 binding site of the insulin gene promoter may predispose to type 2 diabetes mellitus SO DIABETOLOGIA LA English DT Article AB Autosomal dominant diabetes is a heterogeneous subtype of the disease usually characterised by early onset and a primary defect in insulin secretion. To date, six genes have been found to be associated with early-onset autosomal dominant diabetes, also called MODY. Five of them are transcription factors directly or indirectly involved in the process of insulin gene expression [1]. Many regulatory enhancer elements, including the critical glucose response elements, have been identified in the insulin promoter, several within the proximal 300-400 bp region. Remarkably, most transcription factors known to be associated with MODY have been shown to regulate insulin gene expression directly through these sites [2]. A search for mutations in the most proximal part of the insulin promoter in a large set of pedigrees with autosomal dominant diabetes resulted in the identification of a -80A -> G point mutation within the insulin promoter factor 1, homeodomain transcription factor (IPF1, also known as MODY4 and PDX1) binding site of the glucose response region. The role of this mutation in susceptibility to diabetes is discussed below. C1 Univ Calif San Diego, Whittier Inst, Islet Res Labs, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. Fac Med Nice, INSERM, U145, IFR50, F-06034 Nice, France. Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-30059 Krakow, Poland. RP Jhala, US (reprint author), Univ Calif San Diego, Whittier Inst, Islet Res Labs, 9894 Genesee Ave 225, La Jolla, CA 92037 USA. EM ujhala@ucsd.edu RI LEBRUN, Patricia/O-5765-2016 FU FIC NIH HHS [1R03 TW 01351-01]; NIDDK NIH HHS [DK 47475] NR 8 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2006 VL 49 IS 8 BP 1985 EP 1987 DI 10.1007/s00125-006-0302-8 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061GR UT WOS:000238859900032 PM 16741735 ER PT J AU Gasic, GP Barco, A Avila, J Lerma, J AF Gasic, Gregory P. Barco, Angel Avila, Jesus Lerma, Juan TI A meeting to remember - Meeting on memory and related disorders SO EMBO REPORTS LA English DT Editorial Material DE associative learning; medial temporal lobe; neurodegeneration; neurodevelopment; synaptic plasticity ID REMOTE SPATIAL MEMORY; SYNAPTIC PLASTICITY; ALZHEIMERS-DISEASE; TRANSGENIC MICE; ORBITOFRONTAL CORTEX; BASOLATERAL AMYGDALA; HIPPOCAMPAL-LESIONS; ACTINOMYCIN-D; COCAINE; RATS C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. CSIC, MH, Inst Neurociencias Alicante, Alicante 03550, Spain. Univ Autonoma Madrid, CSIC, CBM, E-28049 Madrid, Spain. RP Gasic, GP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM ggasic@nmr.mgh.harvard.edu RI Barco, Angel/C-3062-2008; Lerma, Juan/G-7907-2015 OI Barco, Angel/0000-0002-0653-3751; Lerma, Juan/0000-0001-7838-5199 NR 45 TC 2 Z9 2 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD AUG PY 2006 VL 7 IS 8 BP 768 EP 773 DI 10.1038/sj.embor.7400746 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 099KL UT WOS:000241593200007 PM 16845373 ER PT J AU Metlay, JP Fishman, NO Joffe, MM Kallan, MJ Chittams, JL Edelstein, PH AF Metlay, Joshua P. Fishman, Neil O. Joffe, Marshall M. Kallan, Michael J. Chittams, Jesse L. Edelstein, Paul H. TI Macrolide resistance in adults with bacteremic pneumococcal pneumonia SO EMERGING INFECTIOUS DISEASES LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; STREPTOCOCCUS-PNEUMONIAE; PENICILLIN-RESISTANT; RISK-FACTORS; ANTIMICROBIAL RESISTANCE; UNITED-STATES; INFECTIONS; THERAPY; RECALL; ANTIBIOTICS AB We conducted a case-control study of adults with bacteremic pneumococcal pneumonia to identify factors associated with macrolide resistance. Study participants were identified through population-based surveillance in a 5-county region surrounding Philadelphia. Forty-three hospitals contributed 444 patients, who were interviewed by telephone regarding potential risk factors. In multivariable analyses, prior exposure to a macrolide antimicrobial agent (odds ratio [OR] 2.8), prior flu vaccination (OR 2.0), and Hispanic ethnicity (OR 4.1) were independently associated with an increased probability of macrolide resistance, and a history of stroke was independently associated with a decreased probability of macrolide resistance (OR 0.2). Fifty-five percent of patients with macrolide-resistant infections reported no antimicrobial drug exposure in the preceding 6 months. Among patients who reported taking antimicrobial agents in the 6 months preceding infection, failure to complete the course of prescribed drugs was associated with an increased probability of macrolide resistance (OR 3.4). C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Metlay, JP (reprint author), Ctr Clin Epidemiol & Biostat, 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jmetlay@cceb.med.upenn.edu FU NIAID NIH HHS [R01 AI 46645, R01 AI046645] NR 31 TC 12 Z9 13 U1 1 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD AUG PY 2006 VL 12 IS 8 BP 1223 EP 1230 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 068FQ UT WOS:000239358500007 PM 16965701 ER PT J AU Giraud, GD Louey, S Jonker, S Schultz, J Thornburg, KL AF Giraud, G. D. Louey, S. Jonker, S. Schultz, J. Thornburg, K. L. TI Cortisol stimulates cell cycle activity in the cardiomyocyte of the sheep fetus SO ENDOCRINOLOGY LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; GROWTH-HORMONE RECEPTOR; NEONATAL RAT-HEART; FETAL SHEEP; LATE-GESTATION; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; BLOOD-PRESSURE; CARDIAC MYOCYTES; OVINE FETUS; CORTICOSTEROID RECEPTORS AB The role of cortisol in regulating cardiac myocyte growth in the near-term fetal sheep is unknown. We hypothesized that cortisol would suppress cardiomyocyte proliferation and stimulate cardiomyocyte binucleation and enlargement, signs of terminal differentiation. Cardiomyocyte dimensions and percent binucleation were determined in isolated cardiac myocytes from seven cortisol-treated and seven control fetuses; percentage of myocytes positive for Ki-67 was determined in an additional four cortisol-treated and four control hearts. Cortisol was infused into the circumflex coronary artery at subpressor rates (0.5 mu g/kg center dot min, 7 d). Cortisol infusion had no hemodynamic effects, compared with controls or pretreatment conditions. Cortisol treatment increased heart weight (44.0 +/- 8.7 g vs. control, 34.9 +/- 9.1 g, P < 0.05). Heart to body weight ratio was greater in treated hearts, compared with controls (10.3 +/- 1.9 vs. 7.7 +/- 0.9 g/kg, P < 0.01). Ventricular myocyte length, width, and percent binucleation were not different between groups. The proportion of treated myocytes in the cell cycle staining for Ki-67 was higher in the left ventricle (5.5 +/- 0.1 vs. 2.7 +/- 0.4%, P < 0.005) and right ventricle (4.4 +/- 0.4 vs. 3.7 +/- 0.7%, P < 0.05), compared with controls. Wet weight to dry weight ratios from cortisol-treated and control hearts were not different. In conclusion, whereas cortisol infused into the fetal sheep heart has no effect on cardiomyocyte size or maturational state, it stimulates entry of cardiomyocytes in the cell cycle. Thus, increases in fetal heart mass associated with subpressor doses of cortisol are due to cardiomyocyte proliferation and not hypertrophic growth. C1 Oregon Hlth Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med Cardiovasc Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Surg Cardiothorac, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Thornburg, KL (reprint author), Oregon Hlth Sci Univ, Heart Res Ctr, L464,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM thornbur@ohsu.edu OI Jonker, Sonnet/0000-0002-1097-2562 FU NICHD NIH HHS [P01HD34430] NR 55 TC 55 Z9 55 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2006 VL 147 IS 8 BP 3643 EP 3649 DI 10.1210/en.2006-0061 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 064FH UT WOS:000239074100002 PM 16690807 ER PT J AU Swartz, BE Houser, CR Tomiyasu, U Walsh, GO DeSalles, A Rich, JR Delgado-Escueta, A AF Swartz, Barbara E. Houser, Carolyn R. Tomiyasu, Uwami Walsh, Gregory O. DeSalles, Antonio Rich, J. Ronald Delgado-Escueta, Antonio TI Hippocampal cell loss in posttraumatic human epilepsy SO EPILEPSIA LA English DT Article DE temporal lobe epilepsy; traumatic brain injury; hippocampal sclerosis; dentate gyrus ID TEMPORAL-LOBE EPILEPSY; TRAUMATIC BRAIN-INJURY; DENTATE GYRUS; HEAD TRAUMA; SURGICAL OUTCOMES; DUAL PATHOLOGY; NEURON LOSS; REORGANIZATION; RAT; PATHOGENESIS AB Purpose: We performed this study to determine whether significant head trauma in human adults can result in hippocampal cell loss, particularly in hilar (polymorph) and CA3 neurons, similar to that observed in animal models of traumatic brain injury. We examined the incidence of hippocampal pathology and its relation to temporal neocortical pathology, neuronal reorganization, and other variables. Methods: Twenty-one of 200 sequential temporal lobectomies had only trauma as a risk factor for epilepsy. Tissue specimens from temporal neocortex and hippocampus were stained with glial fibrillary acidic protein (GFAP) and hematoxylin and eosin (H&E). Eleven hippocampal specimens had additional analysis of neuronal distributions by using cresyl violet and immunolabeling of a neuron-specific nuclear protein. Results: The median age at onset of trauma was 19 years, the median time between trauma and onset of seizures was 2 years, and the median epilepsy duration was 16 years. The length of the latent period was inversely related to the age at the time of trauma (r = 0.75; Spearman). The neocortex showed gliosis in all specimens, with hemosiderosis (n = 8) or heterotopias (n = 6) in some, a distribution differing from chance (p = 0.02; Fisher). Hippocampal neuronal loss was found in 94% of specimens, and all of these had cell loss in the polymorph (hilar) region of the dentate gyrus. Hilar cell loss ranged from mild, when cell loss was confined to the hilus, to severe, when cell loss extended into CA3 and CA1. Some degree of mossy fiber sprouting was found in the dentate gyrus of all 10 specimens in which it was evaluated. Granule cell dispersion (n = 4) was seen only in specimens with moderate to severe neuronal loss. Conclusions: Neocortical pathology was universally present after trauma. Neuronal loss in the hilar region was the most consistent finding in the hippocampal formation, similar to that found in the fluid-percussion model of traumatic head injury. These findings support the idea that head trauma can induce hippocampal epilepsy in humans in the absence of other known risk factors. C1 Hoag Mem Hosp, Epilepsy Ctr, Newport Beach, CA 92658 USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Pathol Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Calif Comprehens Epilepsy Program, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA USA. RP Swartz, BE (reprint author), Hoag Mem Hosp, Epilepsy Ctr, 1 Hoag Dr,POB 6100, Newport Beach, CA 92658 USA. EM BSwartz@Hoaghospital.org OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU BLRD VA [I01 BX000404] NR 53 TC 59 Z9 68 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2006 VL 47 IS 8 BP 1373 EP 1382 DI 10.1111/j.1528-1167.2006.00602.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 071XB UT WOS:000239636100015 PM 16922884 ER PT J AU Leritz, EC Grande, LJ Bauer, RM AF Leritz, Elizabeth C. Grande, Laura J. Bauer, Russell M. TI Temporal lobe epilepsy as a model to understand human memory: The distinction between explicit and implicit memory SO EPILEPSY & BEHAVIOR LA English DT Review DE temporal lobe epilepsy; anterior temporal lobectomy; explicit memory; implicit memory; associative memory; relational memory; hippocampus; medial temporal lobe ID RELATIONAL MEMORY; ALZHEIMERS-DISEASE; HUMAN HIPPOCAMPUS; FUNCTIONAL MRI; PROCESSING ACCOUNT; ITEM RECOGNITION; AMNESIC SUBJECTS; VERBAL EXPLICIT; ASSOCIATIONS; LOBECTOMY AB Decades of research have provided substantial evidence of memory impairments in patients with temporal lobe epilepsy (TLE), including deficits in the encoding, storage, and retrieval of new information. These findings are not surprising, given the associated underlying neuroanatomy, including the hippocampus and surrounding medial temporal lobe structures. Because of its associated anatomic and cognitive characteristics, TLE has provided an excellent model by which to examine specific aspects of human memory functioning, including classic distinctions such as that between explicit and implicit memory. Various clinical and experimental research studies have supported the idea that both conscious and unconscious processes support memory functioning, but the role of relevant brain structures has been the subject of debate. This review is concerned with a discussion of the current status of this research and, importantly, how TLE can inform future studies of memory distinctions. (C) 2006 Elsevier Inc. All rights reserved. C1 Boston VA Healthcare Syst, GRECC, Boston, MA USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. RP Leritz, EC (reprint author), Boston VA Healthcare Syst, GRECC, Boston, MA USA. EM bleritz@heartbrain.com FU NIMH NIH HHS [F31 MH12997] NR 106 TC 29 Z9 31 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD AUG PY 2006 VL 9 IS 1 BP 1 EP 13 DI 10.1016/j.yebeh.2006.04.012 PG 13 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 068MR UT WOS:000239378900001 PM 16759913 ER PT J AU McDonald, CR Swartz, BE Halgren, E Patell, A Daimes, R Mandelkern, M AF McDonald, Carrie R. Swartz, Barbara E. Halgren, Eric Patell, Ashok Daimes, Richard Mandelkern, Mark TI The relationship of regional frontal hypometabolism to executive function: A resting fluorodeoxyglucose PET study of patients with epilepsy and healthy controls SO EPILEPSY & BEHAVIOR LA English DT Article DE frontal lobe epilepsy; executive functioning; fluorodeoxyglucose positron emission tomography; cognition; juvenile myoclonic epilepsy ID TEMPORAL-LOBE EPILEPSY; CARD SORTING TEST; POSITRON EMISSION TOMOGRAPHY; COMPARATIVE CYTOARCHITECTONIC ANALYSIS; CORTICOCORTICAL CONNECTION PATTERNS; INTERICTAL GLUCOSE HYPOMETABOLISM; PRIMARY GENERALIZED EPILEPSY; COMPLEX PARTIAL SEIZURES; FOCAL CORTICAL-LESIONS; PREFRONTAL CORTEX AB Executive dysfunction is common in patients with frontal lobe damage and may depend on the location of pathology within the frontal lobes. However, it is unclear how specific brain regions contribute to different aspects of executive functioning. Eighteen patients with frontal lobe epilepsy, 10 patients with juvenile myoclonic epilepsy, and 14 controls completed a series of tests that measure a broad range of executive functions. Resting fluorodeoxyglucose positron emission tomography scans were collected and regional cerebral rates of glucose uptake values were regressed on test scores. Results revealed that frontal lobe metabolic values were strong predictors of executive functioning in patients with epilepsy, but not in healthy controls. However, nonfrontal regions also contributed unique variance on several measures, suggesting that (1) a network of frontal and nonfrontal regions subserve many executive functions and (2) resting hypometabolism can be a useful predictor of executive dysfunction in patients with epilepsy. (C) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 USA. Hoag Mem Hosp, Epilepsy Ctr, Newport Beach, CA USA. W Los Angeles Vet Adm Res Serv & PET Lab, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP McDonald, CR (reprint author), Vet Adm San Diego Healthcare Syst, Psychol Serv 116B, Delis Lab, 3350 La Jolla Village Dr, La Jolla, CA 92611 USA. EM camcdonald@ucsd.edu FU NIMH NIH HHS [T32 MH018399, T32-MH18399] NR 83 TC 20 Z9 21 U1 3 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD AUG PY 2006 VL 9 IS 1 BP 58 EP 67 DI 10.1016/j.yebeh.2006.04.007 PG 10 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 068MR UT WOS:000239378900008 PM 16713363 ER PT J AU Ali, S Moriarty, J Mullatti, N David, A AF Ali, Sherese Moriarty, John Mullatti, Nandini David, Anthony TI Psychiatric comorbidity in adult patients with hypothalamic hamartoma SO EPILEPSY & BEHAVIOR LA English DT Article DE hypothalamus; hamartoma; epilepsy; psychiatric comorbidity ID GELASTIC SEIZURES; SENSATION SEEKING; RISK BEHAVIOR; EPILEPSY; CHILDREN; SURGERY AB The objective was to investigate the prevalence of psychiatric comorbidity in adults with hypothalamic hamartoma (HH). A standardized clinical interview and assessment scales were used to assess for depression, anxiety, personality, and sexual behavior, based on previous findings in the pediatric population. We found a high prevalence of mood and anxiety disorders, with Major Depressive Disorder and Social Anxiety Disorder being the most common. "Anxious" personality types were the most common. Symptoms of Asperger syndrome were high in males versus females. We concluded that depression and anxiety are common in adult patients with HH. Remission of cognitive, behavioral, and autistic symptoms has been reported with surgical tumor resection. Whether this can correct the psychiatric disturbances remains to be investigated. The need for adjunctive psychiatric treatment may nevertheless remain. (C) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Kings Coll Hosp London, London, England. Inst Psychiat, London, England. RP Ali, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM sali7@partners.org NR 28 TC 7 Z9 7 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD AUG PY 2006 VL 9 IS 1 BP 111 EP 118 DI 10.1016/j.yebeh.2006.03.016 PG 8 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 068MR UT WOS:000239378900016 PM 16697263 ER PT J AU Van Hirtum-Das, M Licht, EA Koh, S Wu, JY Shields, WD Sankar, R AF Van Hirtum-Das, Michele Licht, Eliot A. Koh, Susan Wu, Joyce Y. Shields, W. Donald Sankar, Raman TI Children with ESES: Variability in the syndrome SO EPILEPSY RESEARCH LA English DT Article; Proceedings Paper CT International Symposium on Epileptic Syndromes in Infancy and Early Childhood CY APR 29-MAY 01, 2005 CL Tokyo, JAPAN SP Infantile Seizure Soc DE electrical status epilepticus in sleep; continuous spikes and waves during slow wave sleep; Landau-Kleffner syndrome; EEG; developmental delay ID LANDAU-KLEFFNER-SYNDROME; ELECTRICAL STATUS EPILEPTICUS; SLOW-WAVE SLEEP; LANGUAGE REGRESSION; CONVULSIVE DISORDER; CONTINUOUS SPIKES; ACQUIRED APHASIA; LEVETIRACETAM; EPILEPSY; EEG AB Objective: We under-took a retrospective study of children who present with significant activation of paroxysmal discharges during sleep to examine the clinical spectrum of disorders that present with such an EEG abnormality. Background: Electrical status epilepticus in sleep (ESES) is an electrographic pattern characterized by nearly continuous spike-wave discharges in slow wave sleep, usually with a frequency of 1.5-3 Hz and usually diffuse and bilateral in distribution. A variety of neurocognitive and behavioral problems have been associated with this EEG pattern. Methods: We conducted a retrospective review of 1497 EEG records of patients admitted to University of California, Los Angeles (UCLA) for overnight video-EEG monitoring during a 5 year interval. Demographic, clinical and electroencephalographic variables were evaluated. Results: EEG records for 102 patients meeting criteria were identified. Clinical information was available for 90 of those patients. Eighteen of these patients could be diagnosed with Landau-Kleffner syndrome (LKS). Key findings include: (1) neuroimaging abnormalities were uncommon in our LKS patients; (2) among children who do not fit the specific diagnostic criteria for LKS, a spike-wave index (SWI) > 50% was more likely to be associated with global developmental disturbances than SWI <= 50% (p < 0.05); (3) Children with generalized discharges were more likely to experience severe or global developmental disturbance than those with focal abnon-nalities, without reaching statistical significance (P = 0.07). Conclusions: Severity of ESES can vary over time between and within patients and clinical status does not always directly correlate with SWI. However, the prognosis of LKS is substantially better than CSWS and these two disorders could be classified in a dichotomous manner rather than be seen as two points along a continuum. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat & Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Neurol, Neurobehavior Unit, Los Angeles, CA USA. RP Sankar, R (reprint author), Univ Calif Los Angeles, Med Ctr, Room 22-474 MDCC, Los Angeles, CA 90095 USA. EM RSankar@ucla.edu FU NINDS NIH HHS [NS046516, NS051637, NS45911] NR 37 TC 60 Z9 60 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD AUG PY 2006 VL 70 SU 1 BP S248 EP S258 DI 10.1016/j.eplepsyres.2006.01.020 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 083PE UT WOS:000240469900029 PM 16806829 ER PT J AU Rieber, J Sheth, T Mooyaart, EAQ Shapiro, M Klauss, V Hoffmann, U AF Rieber, J. Sheth, T. Mooyaart, E. A. Q. Shapiro, M. Klauss, V. Hoffmann, U. TI Computed tomographic angiography for the grading of coronary collaterals in total occlusions SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Munich, Dept Cardiol, D-80539 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 143 EP 144 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668401036 ER PT J AU Joner, M Finn, AV Farb, A Ladich, E Kolodgie, FD Skorija, K Gold, HK Virmani, R AF Joner, M. Finn, A. V. Farb, A. Ladich, E. Kolodgie, F. D. Skorija, K. Gold, H. K. Virmani, R. CA CVPATH TI Stent thrombosis in the drug-eluting stents era: Incidence, predictors, mechanisms SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 CVPATH, Gaithersburg, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. FDA, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 MA 1011 BP 154 EP 154 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668401079 ER PT J AU Januzzi, J AF Januzzi, J. CA PRIDE Study Grp TI The integrative value of natriuretic peptide and troponin T testing for prognosis estimation in acute heart failure SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 211 EP 211 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668401308 ER PT J AU Januzzi, J AF Januzzi, J. CA PRIDE Study Grp TI The importance of NT-proBNP versus echocardiography for evaluation of dyspneic patients in the emergency department SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 213 EP 213 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668401315 ER PT J AU Januzzi, J AF Januzzi, J. CA PRIDE Study Grp TI Race and dender do not influence the usefulness of amino-terminal proBrain natriuretic peptide (NT-proBNP) testing in dyspneic subjects SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 215 EP 216 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668401326 ER PT J AU Neuzil, P Reddy, VY Mraz, T Formanek, P Beldova, Z Taborsky, M Niederle, P AF Neuzil, P. Reddy, V. Y. Mraz, T. Formanek, P. Beldova, Z. Taborsky, M. Niederle, P. TI Left atrial appendage occlusion in patients with atrial fibrillation and high risk of thromboembolic complications SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Homolce Hosp, Prague, Czech Republic. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 237 EP 237 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668401415 ER PT J AU Tsai, TT Eagle, KA Fattori, R Trimarchi, S Cooper, JV Isselbacher, E Nienaber, C Bossone, E AF Tsai, T. T. Eagle, K. A. Fattori, R. Trimarchi, S. Cooper, J. V. Isselbacher, E. Nienaber, C. Bossone, E. CA International Registry of Acute A TI Characterization of medically managed patients with acute type A aortic dissection: insights from the international registry of acute aortic dissection (IRAD) SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Univ Bologna, Hosp S Orsola, Bologna, Italy. Inst Policlin San Donato, Milan, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rostock, D-2500 Rostock 1, Germany. CNR, Lecce, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 264 EP 264 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668401522 ER PT J AU Slucca, M Raffel, OC Bouma, BE Tearney, GJ Jang, IK AF Slucca, M. Raffel, O. C. Bouma, B. E. Tearney, G. J. Jang, I. K. TI Are there gender differences in coronary plaque characteristics? In-vivo evaluation using optical coherence tomography SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 366 EP 366 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668402297 ER PT J AU Neuzil, P Taborsky, M Kralovec, S Wallace, D Sediva, L Ruskin, JN Reddy, VY AF Neuzil, P. Taborsky, M. Kralovec, S. Wallace, D. Sediva, L. Ruskin, J. N. Reddy, V. Y. TI Transseptal puncture using a robotic navigation system: Initial clinical experience SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Nemocnice Na Homolce Hosp, Dept Cardiol, Prague 5, Czech Republic. Na Homolce Hosp, Prague, Czech Republic. Hansen Med Inc, Palo Alto, CA USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 471 EP 471 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668403212 ER PT J AU Samani, NJ Mahadeva, H Chong, N Shaw, SY AF Samani, N. J. Mahadeva, H. Chong, N. Shaw, S. Y. TI Knockdown in zebrafish supports important role myocyte stress (ms1) in cardiac development and function SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 473 EP 473 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668403220 ER PT J AU Anand, IS Rector, T Deswal, A Iverson, E Anderson, S Mann, D Cohn, JN Demets, D AF Anand, I. S. Rector, T. Deswal, A. Iverson, E. Anderson, S. Mann, D. Cohn, J. N. Demets, D. TI Relationship between proinflammatory cytokines and anemia in heart failure SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Univ Minnesota, Minneapolis, MN 55455 USA. VA Med Ctr, Minneapolis, MN USA. VA Med Ctr, Houston, TX USA. Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 9 Z9 9 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 485 EP 485 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668403267 ER PT J AU Thibault, H Gomez, L Roesch, O Couture-Lepetit, E Jouniaux, J Scherrer-Crosbie, M Ovize, M Derumeaux, G AF Thibault, H. Gomez, L. Roesch, O. Couture-Lepetit, E. Jouniaux, J. Scherrer-Crosbie, M. Ovize, M. Derumeaux, G. TI Effect of age on ischemia-reperfusion consequences in mice SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Lyon Univ, Lyon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 560 EP 560 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668403576 ER PT J AU Thibault, H Gomez, L Chalabreysse, L Pelloux, S Scherrer-Crosbie, M Ovize, M Derumeaux, G AF Thibault, H. Gomez, L. Chalabreysse, L. Pelloux, S. Scherrer-Crosbie, M. Ovize, M. Derumeaux, G. TI Consequences of different durations of ischemia assessed by Strain Rate Imaging in mice SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Lyon Univ, Hop Louis Pradel, Lyon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 560 EP 560 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668403574 ER PT J AU Giugliano, RP Stone, PH Simon, DI Schweiger, M Bouchard, A Goulder, M Deitcher, SR Braunwald, E AF Giugliano, R. P. Stone, P. H. Simon, D. I. Schweiger, M. Bouchard, A. Goulder, M. Deitcher, S. R. Braunwald, E. CA ANTHEM-TIMI 32 Investigators TI Tissue-factor/factor VIIa inhibition with higher-dose rNAPc2 reduces ischemia in patients with NSTE-ACS managed with an early invasive strategy in ANTHEM-TIMI 32 SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Brigham & Womens Hosp, Timi Study Off, Div Cardiovasc, Boston, MA 02115 USA. Baystate Med Ctr, Springfield, MA 01199 USA. Baptist Med Ctr, Birmingham, AL 35211 USA. Nottingham Clin Res Ltd, Nottingham, England. Nuvelo Inc, Stat, San Carlos, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 643 EP 643 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668404297 ER PT J AU Marijon, E Hausse-Mocumbi, AO Gamra, H Thanh, NV Kamblock, J Esteves, C Palacios, I Vahanian, A AF Marijon, E. Hausse-Mocumbi, A. O. Gamra, H. Thanh, N. Vo Kamblock, J. Esteves, C. Palacios, I. Vahanian, A. TI Differences in the presentation of candidates for percutaneous mitral commissurotomy across the world: do they influence the results of the procedure? SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Hop Xavier Bichat, Dept Cardiol, Paris, France. ICOR, Dept Cardiol, Maputo, Mozambique. Fattouma Bourguiba Hosp, Dept Cardiol, Monastir, Tunisia. Choray Hosp, Dept Cardiol, Ho Chi Minh City, Vietnam. Taaone Hosp, Dept Cardiol, Papeete, Fr Polynesia. Dante Pazzanese Inst, Dept Cardiol, Sao Paulo, Brazil. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 895 EP 895 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668406263 ER PT J AU Antman, EM Morrow, DA Mccabe, CH Braunwald, E AF Antman, E. M. Morrow, D. A. Mccabe, C. H. Braunwald, E. CA ExTRACT-TIMI Investigators TI Impact of patient characteristics on response to enoxaparin vs UFH in STEMI: an ExTRACT-TIMI 25 analysis SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 911 EP 911 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668406327 ER PT J AU Takano, M Jang, IK Mizuno, K AF Takano, Masamichi Jang, Ik-Kyung Mizuno, Kyoichi TI Neointimal proliferation around malapposed struts of a sirolimus-eluting stent: optical coherence tomography findings SO EUROPEAN HEART JOURNAL LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Mizuno, K (reprint author), Chiba Hokusoh Hosp, Nippon Med Sch, Dept Internal Med, 1715 Kamakari, Imba, Chiba 2701694, Japan. EM mizunok@nms.ac.jp NR 0 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 IS 15 BP 1763 EP 1763 DI 10.1093/eurheartj/ehi744 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 072EV UT WOS:000239656900002 PM 16476695 ER PT J AU Jassal, DS Neilan, TG Fifer, MA Palacios, IF Lowry, PA Vlahakes, GJ Picard, MH Yoerger, DM AF Jassal, Davinder S. Neilan, Tomas G. Fifer, Michael A. Palacios, Igor F. Lowry, Patrica A. Vlahakes, Gus J. Picard, Michael H. Yoerger, Danita M. TI Sustained improvement in left ventricular diastolic function after alcohol septal ablation for hypertrophic obstructive cardiomyopathy SO EUROPEAN HEART JOURNAL LA English DT Article DE echocardiography; hypertrophic obstructive cardiomyopathy; diastolic dysfunction; alcohol septal ablation ID REDUCTION THERAPY; TRANSCORONARY ABLATION; FILLING PRESSURES; MYOCARDIAL ABLATION; EXERCISE CAPACITY; FOLLOW-UP; ECHOCARDIOGRAPHY; RELAXATION; VELOCITY; MYECTOMY AB Aims Impaired diastolic function is responsible for many of the clinical features of hypertrophic cardiomyopathy. In patients with hypertrophic obstructive cardiomyopathy (HOCM) whose symptoms are refractory to medical therapy, alcohol septal. ablation (ASA) reduces left ventricular (W) outflow tract gradient, with short-term improvement in LV diastolic function. Little is known about the longer term impact of ASA on diastolic function. Methods and results We evaluated LV diastolic function at baseline and 1- and 2-year follow-up after successful ASA. In 30 patients (58 +/- 15 years, 22 men) who underwent successful ASA, New York Heart Association class was tower at 1-year follow-up compared with baseline (3.0 +/- 0.5 to 1.5 +/- 0.7; P < 0.0001). LV outflow tract gradient (76 +/- 37 to 19 +/- 12; P < 0.0001), interventricular septal. thickness (19 +/- 2 to 14 +/- 2; P < 0.0001), and left atrial. volume (26 +/- 5 to 20 +/- 4; P < 0.0001) were decreased. Significant improvement in E-wave deceleration time, isovolumic relaxation time, early diastolic mitral lateral annular velocity (E), mitral inflow propagation velocity (V-p), ratio of transmitral early LV fitting velocity (E) to early diastolic Doppler tissue imaging of the mitral annulus (E/E'), and E/V-p were observed at I year following successful ASA. These changes persisted in the subset cohort (n = 21) for whom 2-year data were available. Conclusion Successful ASA for HOCM leads to significant and sustained improvement in echocardiographic measures of diastolic function, which may contribute to improved functional status after successful ASA. C1 Massachusetts Gen Hosp, Cardiol Div, Cardiac Ultrasount Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Med Sch, Dept Surg,Cardiac Surg Div, Boston, MA USA. RP Yoerger, DM (reprint author), Massachusetts Gen Hosp, Cardiol Div, Cardiac Ultrasount Lab, YAW 5,55 Fruit St, Boston, MA 02114 USA. EM dyoerger@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 32 TC 36 Z9 39 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 IS 15 BP 1805 EP 1810 DI 10.1093/eurheartj/ehl106 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 072EV UT WOS:000239656900013 PM 16774986 ER PT J AU Neilan, TG Jassal, DS Perez-Sanz, TM Raher, MJ Pradhan, AD Buys, ES Ichinose, F Bayne, DB Halpern, EF Weyman, AE Derumeaux, G Bloch, KD Picard, MH Scherrer-Crosbie, M AF Neilan, Tomas G. Jassal, Davinder S. Perez-Sanz, Teresa M. Raher, Michael J. Pradhan, Aruna D. Buys, Emmanuel S. Ichinose, Fumito Bayne, David B. Halpern, Elkan F. Weyman, Arthur E. Derumeaux, Genevieve Bloch, Kenneth D. Picard, Michael H. Scherrer-Crosbie, Marielle TI Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury SO EUROPEAN HEART JOURNAL LA English DT Article DE echocardiography; tissue Doppler imaging; doxorubicin; apoptosis; heart failure ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HEART-FAILURE; HYPERTROPHIC CARDIOMYOPATHY; MYOCARDIAL ABNORMALITIES; ANTHRACYCLINE THERAPY; SYSTOLIC DYSFUNCTION; WALL-MOTION; DOXORUBICIN; CARDIOTOXICITY; CANCER AB Aims Currently available non-invasive imaging methods frequently fait to detect alterations in left ventricular (W) function despite histological evidence of injury Tissue Doppler imaging (TDI) can detect subtle LV dysfunction. The aim of this study was to investigate whether TDI indices can predict LV systolic dysfunction and mortality following exposure to doxorubicin (DOX) in mice. Methods and results TDI-derived peak endocardial systolic velocity (V-ENDO) and strain rate (SR), as welt as M-mode and two-dimensional indices of LV systolic function, were measured serially in mice after receiving DOX as a single dose (20 mg/kg). Haemodynamic measurements were obtained invasively before and at 1, 2, 4, and 5 days after the single DOX dose. Cardiac apoptosis was measured before and at 1 day after DOX. VENDO and SIR decreased after 1 and 2 days, respectively, whereas changes in fractional shortening (FS) and LV ejection fraction (LVEF) were not detected before 5 days. The reduction in both V-ENDO and SIR correlated with the decrease in dP/dt(MAX), and the change in V-ENDO correlated with the early increase in cardiac cell apoptosis. In a subsequent experiment, DOX was administered at 4 mg/kg/week for 5 weeks, and LV function was followed serially for 16 weeks. In this chronic experiment, TDI indices decreased before FS and LVEF, correlated with late LV dysfunction, and predicted DOX-induced mortality. Conclusion In a murine model of DOX-induced cardiac injury, TDI detects LV dysfunction prior to alterations in conventional echocardiographic indices and predicts mortality. This study suggests that TDI may be a reliable tool to detect early subtle changes in DOX-induced cardiac dysfunction. C1 Harvard Univ, Sch Med, Cardiac Ultrasound Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr,Cardiol Div, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Cambridge, MA 02138 USA. Hosp Louis Pradel, Dept Cardiol, Lyon, France. RP Scherrer-Crosbie, M (reprint author), Harvard Univ, Sch Med, Cardiac Ultrasound Lab, Cambridge, MA 02138 USA. EM mariette@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-70896, HL-42397, HL-71987] NR 33 TC 80 Z9 81 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 IS 15 BP 1868 EP 1875 DI 10.1093/eurheartj/ehl013 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 072EV UT WOS:000239656900023 PM 16717080 ER PT J AU Wong, M Staszewsky, L Carretta, E Barlera, S Latini, R Chiang, YT Glazer, RD Cohn, JN AF Wong, Maylene Staszewsky, Lidia Carretta, Elisa Barlera, Simona Latini, Roberto Chiang, Yann-Tong Glazer, Robert D. Cohn, Jay N. TI Signs and symptoms in chronic heart failure: Relevance of clinical trial results to point of care - data from Val-HeFT SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE orthopnoea; resting and paroxysmal nocturnal dyspnoea ID ANGIOTENSIN-RECEPTOR BLOCKER; RANDOMIZED-TRIAL; FUNCTIONAL CLASS; MORBIDITY; MORTALITY; VALSARTAN AB Background: Clinical trials emphasize mortality and morbidity endpoints. Aims: To bring relevance of trial results to point of care by examining the prognostic and therapeutic value of individual signs and symptoms (S&S). Methods: We analysed data from 5010 patients with stable chronic heart failure and left ventricular dysfunction who were participants in the Val-HeFT study Individual S&S were stratified by severity. Treatment differences between valsartan and placebo were analysed by S&S strata at baseline and endpoint by logistical regression, and an overall S&S score by ANCOVA. Hazard ratios of S&S strata were calculated for mortality and heart failure hospitalisation. Prognostic contributions of S&S to other variables were determined by multivariate analysis. Results: At endpoint, there were significantly fewer valsartan and more placebo patients with severe symptoms. Over time, improvement in the S&S overall score was significantly more favourable for valsartan than placebo. S&S strata were significantly predictive of risk for hospitalisation and death. S&S were each independent and incremental predictors of mortality compared to other variables. Symptom strata separated out moderately symptomatic patients with a mortality rate which was intermediate between that for N_YHA Class II and III. Conclusion: Risk stratification of individual S&S defined prognosis, identified patients with an intermediate mortality between Class II and III, and treatment benefits of valsartan over placebo. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Ist Ric Farmacol Mario Negri, Milan, Italy. Novartis Pharmaceut Corp, E Hanover, NJ USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Wong, M (reprint author), 1661 Pine St,819, San Francisco, CA 94109 USA. EM maylene617@yahoo.com NR 12 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD AUG PY 2006 VL 8 IS 5 BP 502 EP 508 DI 10.1016/j.ejheart.2005.11.001 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 083BI UT WOS:000240430500008 PM 16386464 ER PT J AU Junt, T Tumanov, AV Harris, N Heikenwalder, M Zeller, N Kuprash, DV Aguzzi, A Ludewig, B Nedospasov, SA Zinkernagel, RM AF Junt, Tobias Tumanov, Alexei V. Harris, Nicola Heikenwalder, Mathias Zeller, Nicolas Kuprash, Dmitry V. Aguzzi, Adriano Ludewig, Burkhard Nedospasov, Sergei A. Zinkernagel, Rolf M. TI Expression of lymphotoxin beta governs immunity at two distinct levels SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antibody; cytotoxic T lymphocyte; lymphoid structure; virus infections ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; SECONDARY LYMPHOID-TISSUES; MARGINAL ZONE MACROPHAGES; T-CELL; DEFICIENT MICE; DENDRITIC CELLS; B-CELL; MEMBRANE LYMPHOTOXIN; ABNORMAL-DEVELOPMENT; ORGAN DEVELOPMENT AB interaction of lymphotoxin alpha(1)beta(2) (LT alpha(1)beta(2)) with its receptor is key for the generation and maintenance of secondary lymphoid organ microstructure. We used mice, conditionally deficient for LT beta on different lymphocyte subsets to determine how the LT beta-dependent lymphoid structure influences immune reactivity. All conditionally LT beta-deficient mice mounted normal immune responses against vesicular stomatitis virus (VSV), and were protected against lymphocytic choriomeningitis virus (LCMV). In contrast, they exhibited reduced immune responses against non-replicating antigens. Completely LT beta-deficient mice failed to retain VSV in the marginal zone and died from VSV infections, and they became virus carriers following infection with the non-cytopathic LCMV, which was correlated with defective virus replication in dendritic cells. It was ruled out that LT beta expression on lymphocytes influenced their activation, homing capacity, or maturation. We therefore conclude that LT beta expression influences immune reactivity at two distinct levels: (i) Expression of LT beta on lymphocytes enhances the induction of immune responses against limiting amounts of antigen. (ii) Expression of LT beta on non-lymphocytes governs antiviral immunity by enhancing antigen presentation on antigen-presenting cells. This prevents cytotoxic T lymphocytes exhaustion or death of the host by uncontrolled virus spread. C1 Univ Zurich, Inst Expt Immunol, CH-8091 Zurich, Switzerland. Engelhardt Inst Mol Biol, Lab Mol Immunol, Moscow, Russia. Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland. Kantonsspital, Dept Res, CH-9007 St Gallen, Switzerland. RP Junt, T (reprint author), Harvard Univ, Sch Med, CBR, Biomed Res Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM junt@cbrinstitute.org RI Aguzzi, Adriano/A-3351-2008; Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016; OI Kuprash, Dmitry/0000-0002-1488-4148; Aguzzi, Adriano/0000-0002-0344-6708 NR 52 TC 28 Z9 28 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2006 VL 36 IS 8 BP 2061 EP 2075 DI 10.1002/eji.200626255 PG 15 WC Immunology SC Immunology GA 075BB UT WOS:000239855900007 PM 16841297 ER PT J AU Willert, RP Delaney, C Hobson, AR Thompson, DG Woolf, CJ Aziz, Q AF Willert, Robert P. Delaney, Claire Hobson, Anthony R. Thompson, David G. Woolf, Clifford J. Aziz, Qasim TI Constitutive cyclo-oxygenase-2 does not contribute to the development of human visceral pain hypersensitivity SO EUROPEAN JOURNAL OF PAIN LA English DT Article DE visceral hypersensitivity; oesophagus; COX-2; valdecoxib and central sensitisation ID SPINAL-CORD; CENTRAL SENSITIZATION; PROSTAGLANDIN E-2; FORMALIN TEST; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; PARECOXIB SODIUM; NMDA RECEPTOR; HYPERALGESIA; COX-2 AB Background and aims: Central sensitisation (CS), contributes to the development and maintenance of gastrointestinal pain hypersensitivity. Constitutive cyclo-oxygenase-2 (COX-2) contributes to central sensitisation in somatic pain hypersensitivity but its role in mediating visceral pain hypersensitivity is unknown. We therefore conducted a study to determine if COX-2 inhibition with Valdecoxib attenuates the development or early maintenance of CS in a validated human oesophageal pain hypersensitivity model. Methods: Healthy volunteers were studied in two randomised, double blind, crossover studies in which pain thresholds (PT) to electrical stimulation were assessed in the proximal oesophagus, chest wall and foot, prior to and following a distal oesophageal acid infusion. Protocol 1: Valdecoxib, (40 mg) or matching placebo was given orally for 4 days prior to oesophageal acid infusion. Protocol 2: IV Parecoxib (40 mg) or saline was given 120 min after oesophageal acid infusion. Results: Valdecoxib did not prevent the induction of secondary allodynia in the proximal oesophagus nor did it attenuate it following its establishment. Chest wall PT fell following oesophageal acid but foot PT remained unchanged; highlighting the development viscero-somatic convergence due to CS. Valdecoxib had no analgesic or anti-hyperalgesic effect on chest wall or foot PT. Conclusions: Neither the induction nor initial maintenance of acid induced oesophageal pain hypersensitivity is prevented by Valdecoxib, suggesting that constitutive spinal COX-2 does not contribute to the development or early maintenance of acute visceral central sensitisation. (C) 2005 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. C1 Hope Hosp, Gastrointestinal Sci Grp, Salford M6 8HD, Lancs, England. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. RP Aziz, Q (reprint author), Hope Hosp, Gastrointestinal Sci Grp, Salford M6 8HD, Lancs, England. EM rpwillert@yahoo.co.uk; qaziz@fsl.ho.man.ac.uk NR 51 TC 12 Z9 12 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1090-3801 J9 EUR J PAIN JI Eur. J. Pain PD AUG PY 2006 VL 10 IS 6 BP 487 EP 494 DI 10.1016/j.ejpain.2005.07.003 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 068QV UT WOS:000239390400002 PM 16122956 ER PT J AU Papakostas, GI AF Papakostas, George I. TI Dopaminergic-based pharmacotherapies for depression SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Review DE dopamine; treatment; depression ID PLACEBO-CONTROLLED TRIAL; BUPROPION SUSTAINED-RELEASE; CHRONIC-FATIGUE-SYNDROME; TREATMENT-RESISTANT DEPRESSION; MONOAMINE-OXIDASE INHIBITORS; TREATMENT-REFRACTORY DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; BLIND CONTROLLED TRIAL; BIPOLAR-II DEPRESSION; MAJOR DEPRESSION AB The serendipitous discovery of the precursors of two of the major contemporary antidepressant families during the late 1950s, iproniazid for the monoamine oxidase inhibitors (MAOIs) and imipramine for the tricyclic antidepressants (TCAs), has guided the subsequent development of antidepressant compounds with predominantly serotonergic, noradrenergic or combined serotonergic and noradrenergic activity. Unfortunately, however, many depressed patients continue to remain symptomatic despite adequate treatment with pharmacologic agents currently available. When one reviews the list of pharmacologic agents currently approved for the treatment of Major Depressive Disorder (MDD), it is apparent that relatively few treatments with dopaminergic activity have been developed to date. Therefore, developing effective antidepressant treatments with pro-dopaminergic properties which also possess a relatively wide safety margin may further improve the standard of care for depression. In the present article we will briefly review studies focusing on the role of dopamine in depression followed by a comprehensive review of pharmacotherapies for depression with pro-dopaminergic activity. (c) 2005 Elsevier B.V. and ECNP. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp,Sch Med, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp,Sch Med, Depress Clin & Res Program, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 184 TC 103 Z9 107 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2006 VL 16 IS 6 BP 391 EP 402 DI 10.1016/j.euroneuro.2005.12.002 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 068HI UT WOS:000239363600001 PM 16413172 ER PT J AU Restrepo, MI Mortensen, EM Pugh, JA Anzueto, A AF Restrepo, M. I. Mortensen, E. M. Pugh, J. A. Anzueto, A. TI COPD is associated with increased mortality in patients with community-acquired pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE chronic obstructive pulmonary disease; community-acquired pneumonia; mortality ID PROGNOSTIC FACTORS; RISK-FACTORS; SEVERITY; ADULTS; VALIDATION; MANAGEMENT; GUIDELINES; ADMISSION; ETIOLOGY; OUTCOMES AB Patients with chronic obstructive pulmonary disease (COPD) who develop community-acquired pneumonia (CAP) may experience worse clinical outcomes. However, COPD is not included as a distinct diagnosis in validated instruments that predict mortality in patients with CAP. The aim of the present study was to evaluate the impact of COPD as a comorbid condition on 30- and 90-day mortality in CAP patients. A retrospective observational study was conducted at two hospitals. Eligible patients had a discharge diagnosis and radiological confirmation of CAP. Among 744 patients with CAP, 215 had a comorbid diagnosis of COPD and 529 did not have COPD. The COPD group had a higher mean pneumonia severity index score (105 +/- 32 versus 87 +/- 34) and were admitted to the intensive care unit more frequently (25 versus 18%). After adjusting for severity of disease and processes of care, CAP patients with COPD showed significantly higher 30- and 90-day mortality than non-COPD patients. Chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia exhibited higher 30- and 90-day mortality than patients without chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease should be evaluated for inclusion in community-acquired pneumonia prediction instruments. C1 Univ Texas, Hlth Sci Ctr, Div Pulm & Crit Care Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Gen Med, San Antonio, TX USA. Audie L Murphy Vet Hosp, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. RP Restrepo, MI (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, VERDICT 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Pugh, Jacqueline/0000-0003-4933-141X; Mortensen, Eric/0000-0002-3880-5563 NR 26 TC 113 Z9 116 U1 0 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD AUG PY 2006 VL 28 IS 2 BP 346 EP 351 DI 10.1183/0903936.06.00131905 PG 6 WC Respiratory System SC Respiratory System GA 070LW UT WOS:000239525000016 PM 16611653 ER PT J AU Doran, N VanderVeen, J McChargue, D Spring, B Cook, JW AF Doran, Neal VanderVeen, Joe McChargue, Dennis Spring, Bonnie Cook, Jessica Werth TI Effect of nicotine on negative affect among more impulsive smokers SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE impulsivity; nicotine; negative affect ID FAGERSTROM TOLERANCE QUESTIONNAIRE; STRUCTURED CLINICAL INTERVIEW; MAJOR DEPRESSED-PATIENTS; CIGARETTE-SMOKING; TRYPTOPHAN DEPLETION; PROLACTIN RESPONSE; WEIGHT CONCERNS; PERSONALITY; MOOD; CESSATION AB In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N = 70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity X Condition (nicotinized vs. de-nicotinized) X Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation. C1 Univ Illinois, Dept Psychol, Chicago, IL 60607 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Psychol Serv, Hines, IL 60141 USA. Puget Sound Vet Affairs Hosp, Seattle, WA USA. RP Doran, N (reprint author), Univ Illinois, Dept Psychol, MC 285,1007 W Harrison St, Chicago, IL 60607 USA. EM ndoran1@uic.edu RI Doran, Neal/E-5653-2013 FU NIDA NIH HHS [DA14144] NR 73 TC 21 Z9 23 U1 3 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD AUG PY 2006 VL 14 IS 3 BP 287 EP 295 DI 10.1037/1064-1297.14.3.287 PG 9 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 076IP UT WOS:000239950700002 PM 16893271 ER PT J AU Shah, HA Montezuma, SR Rizzo, JF AF Shah, Hassan A. Montezuma, Sandra R. Rizzo, Joseph F., III TI In vivo electrical stimulation of rabbit retina: Effect of stimulus duration and electrical field orientation SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retinal prosthesis; ERG (electroretinogram); EECP (electrically evoked cortical potential); VECP (visual evoked cortical potential); electrode array; synaptic blocking drugs ID VISUAL-PERCEPTION; PROSTHESIS; BLIND; IMPLANTS; DEGENERATION; THRESHOLDS; PIGMENTOSA; EFFICACY; VISION; ARRAY AB Information that defines the depth of activation of retinal neurons is useful in considering strategies for stimulation with a retinal prosthesis, or interpreting the results from human studies that have previously been performed. The purpose of this study was to test the assertion that electrical pulse durations > 0.5 msec preferentially stimulate retinal neurons deep to the ganglion cell layer. Thirteen Dutch-belted rabbits (1.2-2.0 kg) were used in this study. A Goldmann-like dome was used to deliver photic stimuli to the retina to measure the electroretinogram (ERG) and the light-induced cortical potential (VECP). Then, a micromanipulator was used to position a 500 mu m inner diameter bipolar electrode near the visual streak on the epi-retinal surface. Symmetric biphasic pulses (7-1600 mu A; 0.25 msec and 2.0 msec pulses per phase; biphasic pulses delivered at 2 Hz) were delivered to the retina with a current source. Extra-dural electrodes were used to record electrical evoked cortical potentials (EECPs) over the occipital cortex by performing 50 consecutive computer-averaged stimulations. The effect on the EECP of sequential epi-retinal (i.e. return electrode on epi-retinal surface) vs. trans-retinal (i.e. return electrode behind sclera) stimulation was compared. The effect upon the ERG, VECP and EECP was then assessed after 2,3,dihydroxy-6-nitro-7-sulfamoyl-benzo-f-quinoxaline (NBQX) at 112 mu M concentration, D-2-amino-7-phosphonoheptanoic acid (D-AP7) at 1200 mu M concentration, and L-amino-4-phosphonobutyrate (APB) at 300 mu m concentration were delivered into the vitreous cavity to selectively block neuronal input to the retinal ganglion cells. Median values were reported. The amplitudes of the light-induced ERG and VECP were markedly reduced by instillation of the intra-vitreal synaptic blocking drugs. By comparison, pharmacological blockade of input to the retinal ganglion cells did not significantly alter the threshold charge or amplitude of the electrically-induced cortical responses (P > 0.05). For the electrical stimuli, there was no significant difference in threshold charge for the EECP for epi-retinal vs. trans-retinal stimulation (P > 0.05). The amplitude of the EECP increased linearly with increasing charge using both 0.25 msec and 2.0 msec pulses, even after synaptic blockade of input to the ganglion cells. The lack of obvious degradation of cortical amplitudes after drug instillation indicates that neurons of the middle retina are not being preferentially driven with epi-retinal stimulation, at least not with stimulus pulses up to 2.0 msec in duration. This conclusion is in contrast to prior evidence that 2.0 msec pulses would preferentially stimulate deeper retinal neurons, specifically the bipolar cells. Based upon our own observations in other studies, we believe that preferential stimulation of the middle retina in fact can be achieved by epi-retinal stimulation, by using pulse durations at least 5 times longer than those used in this study. (c) 2006 Published by Elsevier Ltd. C1 VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. Univ Louisville, Kentucky Lions Eye Ctr, Dept Ophthalmol & Visual Sci, Louisville, KY 40202 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Rizzo, JF (reprint author), VA Med Ctr, Ctr Innovat Visual Rehabil, 150 S Huntington Ave, Boston, MA 02130 USA. EM joseph_rizzo@meei.harvard.edu NR 28 TC 24 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 2006 VL 83 IS 2 BP 247 EP 254 DI 10.1016/j.exer.2005.11.023 PG 8 WC Ophthalmology SC Ophthalmology GA 061ND UT WOS:000238878400003 PM 16750527 ER PT J AU Jensen, RJ Rizzo, JF AF Jensen, Ralph J. Rizzo, Joseph F., III TI Thresholds for activation of rabbit retinal ganglion cells with a subretinal electrode SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retinal ganglion cell; electrophysiology; electrical stimulation; retinal prosthesis ID ELECTRICAL-STIMULATION; MICROSTIMULATION; MICROELECTRODE; VISION AB The ultimate success of a retinal prosthesis to create vision will likely depend upon developing a base of knowledge of how best to electrically stimulate the retina. Previously, we studied the responses of rabbit retinal ganglion cells (RGCs) to current pulses applied with an electrode placed on the epiretinal surface. In the present study, we examined the responses of rabbit RGCs to current pulses applied with a subretinal electrode. Single-unit extracellular recordings were made from OFF RGCs and ON RGCs in isolated retinas, which were stimulated with monophasic current pulses (0.1-50 ms in duration), delivered through a 500-mu m diameter electrode. All RGCs elicited one or more bursts of action potentials upon electrical stimulation of the retina. The timing of the bursts depended upon both the polarity of the electrical stimulus and the RGC type. With near-threshold current pulses, the response latencies of OFF RGCs to anodal stimulation were comparable to those of ON RGCs to cathodal stimulation, whereas the response latencies of OFF RGCs to cathodal stimulation were comparable to those of ON RGCs to anodal stimulation. Threshold currents for activation of RGCs decreased with increased pulse duration. For OFF RGCs, threshold currents for cathodal current pulses were, on average, 2-7.5 times higher (depending upon pulse duration) than the threshold currents for anodal current pulses. For ON RGCs, threshold currents for cathodal and anodal current pulses were, on average, nearly identical for all pulse durations and were equivalent to threshold currents of OFF RGCs to anodal stimulation. With respect to a subretinal prosthesis, our findings suggest the possibility that cathodal current pulses may bias activation of ON RGCs in blind patients. Published by Elsevier Ltd. C1 VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Jensen, RJ (reprint author), VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, 150 S Huntington Ave,Mail Stop 151E, Boston, MA 02130 USA. EM ralph.jensen@med.va.gov NR 16 TC 67 Z9 67 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 2006 VL 83 IS 2 BP 367 EP 373 DI 10.1016/j.exer.2006.01.012 PG 7 WC Ophthalmology SC Ophthalmology GA 061ND UT WOS:000238878400016 PM 16616739 ER PT J AU Honczarenko, M Glodek, AM Swierkowski, M Na, IK Silberstein, LE AF Honczarenko, Marek Glodek, Aleksandra M. Swierkowski, Marcin Na, Il-Kang Silberstein, Leslie E. TI Developmental stage-specific shift in responsiveness to chemokines during human B-cell development SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID PROTEIN-3-BETA EBI1-LIGAND CHEMOKINE; BONE-MARROW; RECEPTOR CXCR4; CC-CHEMOKINE; EXPRESSION; DIFFERENTIATION; PRECURSORS; CHEMOATTRACTANT; LYMPHOPOIESIS; ACTIVATION AB Objectives. To better understand the role of chemokines during human B-cell development in bone marrow. Methods. Differentiation stage-specific B cells (pro-B, pre-B, immature, and mature) were analyzed for chemokine receptor expression and for migration to corresponding ligands. We also hypothesized that inflammatory conditions may cause the upregulation of certain chemokine receptors on early B cells, rendering them sensitive to extramedullary chemotactic cues. To test this hypothesis, we used human pre-B 697 cells to investigate whether various inflammatory agents could modify chemokine receptor expression and function. Results. Chemotaxis to CXCL12 was observed for all B cell subsets. However, chemotactic responses to CCL19, CCL21, CXCL13, and CCL20 were limited to late-stage, IgM(+) bone marrow B cells (immature B and mature B). Chemotactic responses to corresponding ligands correlated with the pattern of chemokine receptor expression. The expression of CCR7, however, was low on early (pro-B and pre-B) B cells and did not induce chemotaxis. Interestingly, both CCL19 and CCL21 could trigger ERK1/2 phosphorylation in early B cells. Exposure of pre-B 697 cells to TNF-alpha upregulated CCR7 and CXCR5 expression, whereas it had no effect on CCR6 surface expression. Correspondingly, TNF-alpha-stimulated pre-B cells chemotaxed towards CCL19 and CXCL13, in contrast to non-TNF-alpha-stimulated controls. Conclusion. We postulate that CXCR5, CCR7, and CCR6 participate in bone marrow trafficking and/or bone marrow egress of late-stage B cells under steady-state conditions, whereas inflammation-induced expression of CCR7 and CXCR5 may facilitate early B-cell emigration out of the bone marrow and their positioning in secondary lymphoid organs. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Joint Program Transfus Med, Childrens Hosp Boston,Dana Farber Canc Inst, Boston, MA 02115 USA. Mil Med Inst, Dept Oncol, Warsaw, Poland. RP Silberstein, LE (reprint author), Harvard Univ, Sch Med, Joint Program Transfus Med, Childrens Hosp Boston,Dana Farber Canc Inst, Boston, MA 02115 USA. EM leslie.silberstein@childrens.harvard.edu NR 23 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2006 VL 34 IS 8 BP 1093 EP 1100 DI 10.1016/j.exphem.2006.05.013 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 073OG UT WOS:000239751900015 PM 16863916 ER PT J AU Richardson, PG Mitsiades, C Hideshima, T Anderson, KC AF Richardson, Paul G. Mitsiades, Constantine Hideshima, Teru Anderson, Kenneth C. TI Lenalidomide in multiple myeloma SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE dexamethasone; lenalidomide; multiple myeloma; pharmacodynamics; refractory; relapsed; safety ID THALIDOMIDE ANALOGS; REFRACTORY MYELOMA; ALPHA PRODUCTION; DRUG-RESISTANCE; IN-VIVO; DEXAMETHASONE; CELLS; CC-5013; COMBINATION; BORTEZOMIB AB Current therapies for multiple myeloma include steroids, alkylating agents and high-dose chemotherapy with autologous stem cell transplant. These approaches are typically associated with initially good response rates, but they ultimately fail as a result of disease progression. New therapies that overcome resistance, lower toxicity and maintain remission are needed. Recent advances in the treatment of multiple myeloma include bortezomib and thalidomide. Lenalidomide (Revlimid (R)) is an immunomodulatory drug that has undergone rapid clinical development in multiple myeloma and was recently approved by the US FDA for use in patients with relapsed disease. Clinical trials demonstrate that lenalidomide, particularly in combination with dexamethasone, produces durable clinical responses in patients with relapsed and refractory disease and is generally well tolerated, with manageable toxicities. This review summarizes the profile of lenalidomide and the current evidence for its efficacy in multiple myeloma. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Oncol, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu; constantine_mitsiades@dfci.harvard.edu; teru_hideshima@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu NR 51 TC 33 Z9 34 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD AUG PY 2006 VL 6 IS 8 BP 1165 EP 1173 DI 10.1586/14737140.6.8.1165 PG 9 WC Oncology SC Oncology GA 090AQ UT WOS:000240923400008 PM 16925483 ER PT J AU Ryan, ET Calderwood, SB Qadri, F AF Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi TI Live attenuated oral cholera vaccines SO EXPERT REVIEW OF VACCINES LA English DT Review DE 103-HgR; attenuated; cholera; cardiovascular disease; killed whole-cell oral cholera vaccine; oral; Peru-15; vaccine; Vibrio cholerae ID TOXIN-COREGULATED PILI; SHIGELLA-SONNEI LIPOPOLYSACCHARIDE; MANNOSE-SENSITIVE HEMAGGLUTININ; RURAL EAST PAKISTAN; SUBUNIT-WHOLE CELL; FREE MOUSE MODEL; VIBRIO-CHOLERAE; CVD 103-HGR; B-SUBUNIT; IMMUNE-RESPONSES AB Live, orally administered, attenuated vaccine strains of Vibrio cholerae have many theoretical advantages over killed vaccines. A single oral inoculation could result in intestinal colonization and rapid immune responses, obviating the need for repetitive dosing. Live V. cholerae organisms can also respond to the intestinal environment and immunological exposure to in vivo expressed bacterial products, which could result in improved immunological protection against wild-type V. cholerae infection. The concern remains that live oral cholera vaccines may be less effective among partially immune individials in cholera endemic areas as pre-existing antibodies can inhibit live organisms and decrease colonization of the gut. A number of live oral cholera vaccines have been developed to protect against cholera caused by the classical and EI Tor serotypes of V. cholerae O1, including CVD 103-HgR, Peru-15 and V. cholerae 638. A number of live oral cholera vaccines have also been similarly developed to protect against cholera caused by V. choleroe O139, including CVD 112 and Bengal-15. Live, orally administered, attenuated cholera vaccines are in various stages of development and evaluation. C1 Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Dhaka 1000, Bangladesh. Massachusetts Gen Hosp, Trop & Geog Med Ctr, Div Infect Dis, Boston, MA 02114 USA. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Div Sci Lab, GPO Box 128, Dhaka 1000, Bangladesh. EM etryan@partners.org; scalderwood@partners.org; fqadri@icddrb.org NR 130 TC 39 Z9 42 U1 1 U2 8 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD AUG PY 2006 VL 5 IS 4 BP 483 EP 494 DI 10.1586/14760584.5.4.483 PG 12 WC Immunology SC Immunology GA 125ZU UT WOS:000243482800017 PM 16989629 ER PT J AU Coon, JT Castelnuovo, E Pitt, M Cramp, M Siebert, U Stein, K AF Coon, Joanna Thompson Castelnuovo, Emanuela Pitt, Martin Cramp, Matthew Siebert, Uwe Stein, Ken TI Case finding for hepatitis C in primary care: a cost utility analysis SO FAMILY PRACTICE LA English DT Article DE case finding; cost-benefit analysis; hepatitis C; intravenous substance abuse; primary health care ID FOLLOW-UP; CIRRHOSIS; BIOPSY AB Background. Hepatitis C is an important public health problem. The need for more intensified action to identify those infected with the virus has been recognized. Primary care is an important setting for case finding. Objectives. To estimate the cost utility of case finding for hepatitis C in primary care, specifically amongst former injecting drug users (IDUs). Methods. A Markov model was developed to investigate the impact of case finding and treatment on progression of hepatitis C (HCV) in a hypothetical cohort of 1000 former IDUs. Comparison was made with a similar cohort in which no systematic case finding was implemented but spontaneous presentation for testing was allowed. Two scenarios were explored. The testing protocol utilized ELISA and PCR tests. Those eligible for treatment received combination therapy with pegylated interferon and ribavirin. Parameter estimates were obtained from literature searches and experts in the field. Results. Few estimates of the uptake of HCV testing in primary care are available. Cost utility was estimated at around 16000 pound/QALY for both scenarios. At a willingness to pay of 30 pound 000/ QALY, there is approximately a 75% probability that the initiatives would be cost-effective. Choices regarding the utility data, discounting and the rates of spontaneous/re-presentation outside of a case-finding programme appear to be important areas of uncertainty in this model. Conclusion. Case finding for HCV in primary care is likely to be considered cost-effective but uncertainties remain. Further research is needed on different approaches to case primary care. C1 Univ Plymouth, Peninsula Med Sch, Peninsula Technol Assessment Grp, Exeter EX2 5DW, Devon, England. Univ Exeter, Exeter EX2 5DW, Devon, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & HTA, Hall IT, Austria. Derriford Hosp, Hepatol Dept, Plymouth PL6 8DH, Devon, England. Peninsula Med Sch, Plymouth, Devon, England. RP Coon, JT (reprint author), Univ Plymouth, Peninsula Med Sch, Peninsula Technol Assessment Grp, Noy Scott House,Barrack Rd, Exeter EX2 5DW, Devon, England. EM Joanna.Thompson-Coon@pentag.nhs.uk NR 25 TC 14 Z9 14 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-2136 J9 FAM PRACT JI Fam. Pr. PD AUG PY 2006 VL 23 IS 4 BP 393 EP 406 DI 10.1093/fampra/cml032 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 072EZ UT WOS:000239657300002 ER PT J AU Semkova, I Fauser, S Lappas, A Smyth, N Kociok, N Kirchhof, B Paulsson, M Poulaki, V Joussen, AM AF Semkova, Irina Fauser, Sascha Lappas, Alexandra Smyth, Neil Kociok, Norbert Kirchhof, Bernd Paulsson, Mats Poulaki, Vassiliki Joussen, Antonia M. TI Overexpression of FasL in retinal pigment epithelial cells reduces choroidal neovascularization SO FASEB JOURNAL LA English DT Article DE choroidal neovascularization; apoptosis; inflammation ID ENDOTHELIAL GROWTH-FACTOR; DISCIFORM MACULAR DEGENERATION; SUBRETINAL NEOVASCULARIZATION; TARGETED DISRUPTION; IMMUNE PRIVILEGE; APOPTOSIS; LIGAND; MEMBRANES; EXPRESSION; RETINOPATHY AB Choroidal neovascularization (CNV) is responsible for the severe visual loss in age-related macular degeneration. CNV formation is considered to be due to an imbalance between pro-and antiangiogenic factors that lead to neovascular growth from the choriocapillaris into the subretinal space. To define whether FasL overexpression in retinal pigment epithelial cells (RPE) can inhibit choroidal neovascularization through Fas-FasL-mediated apoptosis, we examined the role of this pathway in a mouse model of laser-induced choroidal neovascularization. FasL was expressed in the retinal pigment epithelium of transgenic mice. Polymerase chain reaction (PCR), immunoblot, and immunohistochemistry confirmed that the transgene FasL was specifically expressed in RPE. The established laser model was used to induce choroidal neovascularization (CNV) in wild-type (WT) and transgenic mice. CNV formation was compared with respect to fluorescein angiographic leakage (at days 0 and 14 after laser injury) and histological appearance. The lesions were assessed on RPE-choroidal flatmounts after CD31-labeling and with confocal microscopy after perfusion with rhodamine-labeled concanavalin A (Con A). Apoptosis was quantified by TUNEL positivity and caspase activation. FasL mRNA and protein were highly expressed in the RPE of the transgenic mice before and after laser photocoagulation. In contrast, FasL was only weakly expressed in the RPE layer of WT C57BL/ 6J mice. While ruptures of Bruch's membrane and CNV formation were observed histologically two weeks after laser photocoagulation in transgenic as well as control eyes, the shape and size of CNV lesions were reduced in the transgenic mice. The area of leakage was decreased by 70% in FasL transgenic mice compared with WT mice (P < 0.005). The number of TUNEL-positive cells was greater in FasL-overexpressing mice and correlated with the expression of activated caspases. Th expression of other antiangiogenic factors such as PEDF remained unchanged. The specific overexpression of FasL in RPE layer reduced CNV formation in our laser model. Our results strongly point to the FasL-Fas pathway as a potential therapeutic target in controlling pathological choroidal neovascularization. C1 Univ Cologne, Dept Vitreoretinal Surg, Ctr Ophthalmol, D-50931 Cologne, Germany. Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany. Univ Southampton, Ctr Biochem, Southampton, Hants, England. Univ Southampton, Sch Biol Sci, Southampton, Hants, England. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Joussen, AM (reprint author), Univ Cologne, Dept Vitreoretinal Surg, Ctr Ophthalmol, Joseph Stelzmannstr 9, D-50931 Cologne, Germany. EM joussena@googlemail.com NR 63 TC 23 Z9 27 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2006 VL 20 IS 10 BP 1689 EP + DI 10.1096/fj.05-5653fje PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 080RV UT WOS:000240266600016 PM 16807368 ER PT J AU Engelbrektson, AL Korzenik, JR Sanders, ME Clement, BG Leyer, G Klaenhammer, TR Kitts, CL AF Engelbrektson, Anna L. Korzenik, Joshua R. Sanders, Mary Ellen Clement, Brian G. Leyer, Gregory Klaenhammer, Todd R. Kitts, Christopher L. TI Analysis of treatment effects on the microbial ecology of the human intestine SO FEMS MICROBIOLOGY ECOLOGY LA English DT Article DE terminal restriction fragment length polymorphism; probiotics; antibiotics; prebiotics; gastrointestinal microbiota ID GRADIENT GEL-ELECTROPHORESIS; 16S RIBOSOMAL-RNA; FRAGMENT-LENGTH-POLYMORPHISM; CULTURE-INDEPENDENT ANALYSIS; HUMAN FECES; LACTOBACILLUS-ACIDOPHILUS; BACTERIAL COMMUNITIES; GASTROINTESTINAL-TRACT; EFFECTIVE STRATEGY; FECAL MICROBIOTA AB A large number of studies have investigated gastrointestinal microbiota and changes in the gastrointestinal community. However, a concern in these studies is how best to assess changes in gastrointestinal community structure. This paper presents two different human trials where the fecal terminal restriction fragment length polymorphism data sets were analyzed to search for treatment effects. Principle components analysis and cluster analysis based on grouped data are compared with analysis of data by subject using distance coefficients. Comparison with baseline within an individual before grouping by treatment provided a clearer indication of treatment effects than did an evaluation of data grouped before analysis. In addition, a large within-subject sample size and multiple baseline samples are necessary to accurately analyze treatment effects. C1 Calif Polytech State Univ San Luis Obispo, Dept Biol Sci, Environm Biotechnol Inst, San Luis Obispo, CA 93407 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Dairy & Food Culture Technol, Centennial, CO USA. Univ Calif San Diego, Scripps Inst Oceanog, San Diego, CA 92103 USA. Danisco USA, Madison, WI USA. N Carolina State Univ, Raleigh, NC 27695 USA. RP Kitts, CL (reprint author), Calif Polytech State Univ San Luis Obispo, Dept Biol Sci, Environm Biotechnol Inst, San Luis Obispo, CA 93407 USA. EM ckitts@calpoly.edu RI Engelbrektson, Anna/K-5563-2012; Engelbrektson, Anna/F-1687-2013 NR 48 TC 28 Z9 28 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0168-6496 J9 FEMS MICROBIOL ECOL JI FEMS Microbiol. Ecol. PD AUG PY 2006 VL 57 IS 2 BP 239 EP 250 DI 10.1111/j.1574-6941.2006.00112.x PG 12 WC Microbiology SC Microbiology GA 061QD UT WOS:000238886400007 PM 16867142 ER PT J AU Vu, F Maillard, M Pascual, M Michetti, P Felley, C AF Vu, Francis Maillard, Michel Pascual, Manuel Michetti, Pierre Felley, Christian TI De novo inflammatory bowel diseases after liver transplantation: description of four new cases and a review of the literature SO GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE LA French DT Article ID PRIMARY SCLEROSING CHOLANGITIS; ULCERATIVE-COLITIS; CYCLOSPORINE; IMMUNOSUPPRESSION; RECIPIENTS; ARGUMENT; THERAPY; GRAFT; STILL AB Inflammatory bowel diseases are a result of an aberrant mucosal immune response to gut microflora. Several groups have reported newly diagnosed inflammatory bowel diseases following solid organ transplantation and subsequent immunosuppressive therapy. We describe four cases of newly diagnosed inflammatory bowel diseases following liver transplantation in a pool of 120 transplanted patients. These patients had no prior history of inflammatory bowel diseases or primary sclerosing cholangitis and were immunosuppressed. Two patients were transplanted for a hepatitis C related cirrhosis, one for alcoholic cirrhosis and one patient for autoimmune cirrhosis. Three patients were diagnosed with ulcerative colitis and one with Crohn's disease. These four patients were on a cyclosporin monotherapy when their inflammatory bowel diseases were diagnosed. These data suggest that cyclosporin monotherapy following solid organ transplantation does not prevent development of inflammatory bowel diseases. C1 CHU Vaudois, Div Gastroenterol & Hepatol, CH-1011 Lausanne, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. CHU Vaudois, Ctr Transplantat Organes, CH-1011 Lausanne, Switzerland. RP Vu, F (reprint author), CHU Vaudois, Div Gastroenterol & Hepatol, BH10, CH-1011 Lausanne, Switzerland. EM christian.felley@chuv.ch NR 27 TC 4 Z9 4 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0399-8320 J9 GASTROEN CLIN BIOL JI Gastroenterol. Clin. Biol. PD AUG-SEP PY 2006 VL 30 IS 8-9 BP 1096 EP 1101 DI 10.1016/S0399-8320(06)73484-4 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 104BC UT WOS:000241929900019 PM 17075459 ER PT J AU Naliboff, BD Berman, S Suyenobu, B Labus, JS Chang, L Stains, J Mandelkern, MA Mayer, EA AF Naliboff, Bruce D. Berman, Steve Suyenobu, Brandall Labus, Jennifer S. Chang, Lin Stains, Jean Mandelkern, Mark A. Mayer, Emeran A. TI Longitudinal change in perceptual and brain activation response to visceral stimuli in irritable bowel syndrome patients SO GASTROENTEROLOGY LA English DT Article ID ANTERIOR CINGULATE CORTEX; IBS PATIENTS; CEREBRAL ACTIVATION; RECTAL DISTENSION; AMYGDALA RESPONSE; PAIN PERCEPTION; MECHANISMS; SENSITIVITY; MODULATION; HYPERSENSITIVITY AB Background & Aims: Symptom-related fears and associated hypervigilance toward visceral stimuli may play a role in central pain amplification and irritable bowel syndrome (IBS) pathophysiology. Repeated stimulus exposure leads to decreased salience of threat and reduction of hypervigilance. We sought to evaluate hypervigilance in IBS visceral hypersensitivity and associated brain activity. Methods: Twenty IBS patients (14 female; moderate to severe symptoms) and 14 healthy controls participated in symptom and rectal distention assessments 6 times over 12 months. In a subset of 12 IBS patients, H(2)(15)O-positron emission tomography images were obtained during baseline, rectal distentions, and anticipation of an aversive distention during the first and last session. Statistical parametric mapping (SPM99) was used to identify areas and networks activated during each session as well as those with differential activation across the 2 sessions. Results: Perceptual ratings of the rectal inflations normalized over 12 months, whereas IBS symptom severity did not. There were no sex-related differences in these response patterns. Stable activation of the central pain matrix was observed over 12 months, and activity in limbic, paralimbic, and pontine regions decreased. During the anticipation condition, there were significant decreases in amygdala, dorsal anterior cingulate cortex, and dorsal brainstem activation at 12 months. Covariance analysis supported the hypothesis of changes in an arousal network including limbic, pontine, and cortical areas underlying the decreased perception seen over the multiple stimulations. Conclusions: In IBS patients, repeated exposure to experimental aversive visceral stimuli results in the habituation of visceral perception and central arousal, despite stable activation of networks processing visceral pain and its anticipation. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Irvine, Dept Nucl Med, Irvine, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA USA. RP Naliboff, BD (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu FU NCCIH NIH HHS [R24 AT002681]; NIDDK NIH HHS [DK 48351, P50 DK64539]; NINR NIH HHS [NR04881] NR 60 TC 119 Z9 121 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2006 VL 131 IS 2 BP 352 EP 365 DI 10.1053/j.gastro.2006.05.014 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 072WX UT WOS:000239704800008 PM 16890589 ER PT J AU Giallourakis, C Cao, ZF Green, T Wachtel, H Xie, XH Lopez-Illasaca, M Daly, M Rioux, J Xavier, R AF Giallourakis, Cosmas Cao, Zhifang Green, Todd Wachtel, Heather Xie, Xiaohui Lopez-Illasaca, Marco Daly, Mark Rioux, John Xavier, Ramnik TI A molecular-properties-based approach to understanding PDZ domain proteins and PDZ ligands SO GENOME RESEARCH LA English DT Article ID LARGE TUMOR-SUPPRESSOR; ASYMMETRIC CELL-DIVISION; KAPPA-B ACTIVATION; IMMUNE SYNAPSE; C-ELEGANS; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; SOMATIC MUTATIONS; BINDING-PROTEIN; ROLLING-PEBBLES AB PDZ domain-containing proteins and their interaction partners are mutated in numerous human diseases and function in complexes regulating epithelial polarity, ion channels, cochlear hair cell development, vesicular sorting, and neuronal synaptic communication. Among several properties of a collection of documented PDZ domain-ligand interactions, we discovered embedded in a large- scale expression data set the existence of a significant level of co-regulation between PDZ domain-encoding genes and these ligands. From this observation, we show how integration of expression data, a comparative genomics catalog of 899 mammalian genes with conserved PDZ-binding motifs, phylogenetic analysis, and literature mining can be utilized to infer PDZ complexes. Using molecular studies we map novel interaction partners for the PDZ proteins DLG1 and CARD11. These results provide insight into the diverse roles of PDZ-ligand complexes in cellular signaling and provide a computational framework for the genome-wide evaluation of PDZ complexes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. RP Xavier, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM Xavier@molbio.mgh.harvard.edu RI Rioux, John/A-9599-2015 OI Rioux, John/0000-0001-7560-8326 FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 82 TC 32 Z9 33 U1 0 U2 3 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 AUG PY 2006 VL 16 IS 8 BP 1056 EP + DI 10.1101/gr.5285206 PG 19 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 069JE UT WOS:000239441400012 PM 16825666 ER PT J AU Christoforidis, JB Warden, SM DeMattia, M D'Amico, DJ AF Christoforidis, John B. Warden, Scott M. DeMattia, Massimo D'Amico, Donald J. TI In vivo redirection of retinal blood flow into borosilicate micro-cannulas in rabbits SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol DE retina; cannulation; blood flow; vessel ID TISSUE-PLASMINOGEN ACTIVATOR; VEIN OCCLUSION; VESSELS; SURGERY AB Background: Microvascular manipulation is one application in the emerging field of retinal vascular surgery that could lead to new therapeutic approaches for retinal disease. Research in this field has largely focused on vessel cannulation and injection of vasoactive substances. This study expands on applications for retinal vessel manipulation by demonstrating that redirection of retinal blood flow in vivo can be achieved through retinal vessel cannulation in a rabbit model. Methods: Dutch-belted rabbits were anesthetized, and a sectoral peritomy and sclerotomy 1 mm from the superotemporal limbus were performed. Borosilicate glass microtips with external diameters of 10-20 mu m were introduced into the vitreous through the sclerotomy site. Using an operating microscope and a direct contact lens for visualization, we cannulated the rabbits' retinal vessels, and blood flow was redirected through the microtips. Results: Retinal vessels approximately 30-60 mu m in size were cannulated, and controlled blood flow through the microcannula was demonstrated with minimal or no vitreous hemorrhage. Though still achievable, flow after arterial cannulation was more difficult to demonstrate. Conclusions: This study demonstrates that partial diversion of blood flow from a native vessel lumen could be successfully accomplished by retinal vessel cannulation. This early work indicates that more advanced retinal vascular procedures, such as vessel bypass around a thrombus or shunting blood towards an area of ischemic retina, may be feasible in the future. C1 Harvard Univ, Sch Med, Retina Serv, Dept Ophthalmol,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP D'Amico, DJ (reprint author), Harvard Univ, Sch Med, Retina Serv, Dept Ophthalmol,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM djdamico@meei.harvard.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD AUG PY 2006 VL 244 IS 8 BP 1022 EP 1025 DI 10.1007/s00417-005-0214-1 PG 4 WC Ophthalmology SC Ophthalmology GA 070XE UT WOS:000239559000018 PM 16418840 ER PT J AU Cole, LA Khanlian, SA Muller, CY Giddings, A Kohorn, E Berkowitz, R AF Cole, Laurence A. Khanlian, Sarah A. Muller, Carolyn Y. Giddings, Almareena Kohorn, Ernest Berkowitz, Ross TI Gestational trophoblastic diseases: 3. Human chorionic gonadotropin-free beta-subunit, a reliable marker of placental site trophoblastic tumors SO GYNECOLOGIC ONCOLOGY LA English DT Article DE hCG-free beta-subunit; placenta site trophoblastic tumor; nontrophoblastic neoplasm; hyperglycosylated hCG; germ cell tumor; dysgerminoma PSTT ID CORE FRAGMENT; HCG; CHORIOCARCINOMA; EXPERIENCE AB Objectives. Placental site trophoblastic tumor (PSTT) commonly presents with low and variable concentration of hCG immunoreactivity in serum which can be difficult to differentiate from early stage choriocarcinoma/gestational trophoblastic neoplasm (GTN) or quiescent gestational trophoblastic disease (quiescent GTD). Nontrophoblastic malignancies such as germ cell tumors or other tumors secreting low hCG must also be considered in the differential diagnosis. Because treatments for these conditions are different, a means of differentiating PSTT from other diagnoses is important. We investigate the usefulness of hCG-free beta-subunit to make this discrimination. Methods. Data collected on cases referred to the USA hCG Reference Service for consultation served as a basis for this retrospective analysis. There were 13 cases with histology proven PSTT and 12 with nontrophoblastic malignancy. hCG-free beta-subunit was measured by immunoassay and reported as a proportion of total hCG (hCG-free beta-subunit(%)). hCG-free beta-subunit(%) results were determined for all histologically proven cases of PSTT and for the nontrophoblastic malignancies. Comparisons of hCG-free beta-subumt(%) were made and compared with those of the 82 choriocarcinoma/GTN cases and 69 quiescent GTD cases. The accuracy of hCG-free beta-subunit(%) to discriminate these malignancies was analyzed by investigating the areas under receiver-operating characteristics curve standard error. Results. hCG-firee beta-subunit(%) was the predominant hCG form in cases of PSTT (mean standard deviation, 60 +/- 19%) and nontrophoblastic malignancies (91 +/- 11%), thus discriminating these diagnoses from choriocarcinoma/GTN (9.3 +/- 9.2%) and from quiescent GTD (5.4 +/- 7.8%). The cutoff of > 35% free beta-subunit is proposed. At this cutoff, 100% detection at 0% false-positive is achieved. The accuracy of hCG-free beta-subunit(%) for this discrimination is 100 0%. At a proposed cutoff of > 80%, the free beta-subunit test will also distinguish PSTT from nontropboblastic malignancy, with 77% detection at 23% false-positive or an accuracy of 92 +/- 3.2%. Conclusion. Measurement of the proportion hCG-free beta-subunit(%) was found to be useful in the diagnosis of PSTT using proposed cutoff values of > 35% and > 80%. While this finding needs to be confirmed by larger studies, it would be reasonable to measure hCG-free beta-subunit(%) whenever the diagnosis of PSTT is considered. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ New Mexico, Dept Obstet & Gynecol, USA hCG Reference Serv, Albuquerque, NM 87131 USA. Univ New Mexico, Div Gynecol Oncol, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. Yale Univ, Yale Trophoblast Ctr, Dept Obstet & Gynecol, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Obstet & Gynecol,New E, Boston, MA 02115 USA. RP Cole, LA (reprint author), Univ New Mexico, Dept Obstet & Gynecol, USA hCG Reference Serv, MSC10 5580 1, Albuquerque, NM 87131 USA. EM larry@hcglab.com NR 18 TC 40 Z9 42 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2006 VL 102 IS 2 BP 160 EP 164 DI 10.1016/j.ygyno.2005.12.046 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 068BV UT WOS:000239347600006 PM 16631918 ER PT J AU Litzow, MR Lee, S Bennett, JM Dewald, GW Gallagher, RE Jain, V Paietta, EM Racevskis, J Rousey, SR Mazza, JJ Tallman, MS AF Litzow, Mark R. Lee, Sandra Bennett, John M. Dewald, Gordon W. Gallagher, Robert E. Jain, Vibha Paietta, Elisabeth M. Racevskis, Janis Rousey, Steven R. Mazza, Joseph J. Tallman, Martin S. TI A phase II trial of arsenic trioxide for relapsed and refractory acute lymphoblastic leukemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE acute lymphoblastic leukemia; relapse; arsenic trioxide ID ACUTE PROMYELOCYTIC LEUKEMIA; PHILADELPHIA-CHROMOSOME; CELL LINES; APOPTOSIS; INDUCTION; REMISSION; RITUXIMAB; IMATINIB AB We designed a phase 11 trial of arsenic trioxide (AT) for the treatment of relapsed and refractory acute lymphoblastic leukemia (ALL). The dose administered was 0.25 mg/kg/day intravenously for 5-7 days per week for up to 60 days. Of 11 patients eligible, eight had B-cell and three T-cell ALL and two were Philadelphia chromosome-positive. The median duration of therapy was 21 days (range 7-28). One patient died of an infection. There were no responses. Ten patients have died. The median survival was 3.2 months (range 1.2-4.1). We conclude that AT is not active in the treatment of ALL. C1 Mayo Clin, Coll Med, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA USA. Univ Rochester, Ctr Canc, Rochester, NY USA. Mayo Clin, Coll Med, Dept Lab Med, Rochester, NY USA. Montefiore Med Ctr, Dept Oncol, Bronx, NY 10467 USA. Our Lady Mercy Med Ctr, Ctr Comprehens Canc, Bronx, NY USA. Metro Minnesota CCOP, St Louis Pk, MN USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. Eastern Cooperat Oncol Grp, Boston, MA USA. RP Litzow, MR (reprint author), Mayo Clin, Coll Med, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM litzow.mark@mayo.edu FU NCI NIH HHS [CA17145, CA11083, CA13650, CA14958, CA21115, CA23318, CA66636] NR 20 TC 13 Z9 14 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD AUG PY 2006 VL 91 IS 8 BP 1105 EP 1108 PG 4 WC Hematology SC Hematology GA 070LI UT WOS:000239523500015 PM 16870552 ER PT J AU Wei, II Virnig, BA John, DA Morgan, RO AF Wei, Iris I. Virnig, Beth A. John, Dolly A. Morgan, Robert O. TI Using a Spanish surname match to improve identification of Hispanic women in medicare administrative data SO HEALTH SERVICES RESEARCH LA English DT Article DE women; minorities; Medicare race code; Spanish surname; sensitivity and specificity ID BENEFICIARIES; ACCURACY; TRENDS; CODES AB Objective. To assess the effectiveness of a Spanish surname match for improving the identification of Hispanic women in Medicare administrative data in which Hispanics are historically underrepresented. Data Sources. We collected self-identified race/ethnicity data (N=2,997) from a mailed survey sent to elderly Medicare beneficiaries who resided in 11 geographic areas consisting of eight metropolitan counties and three nonmetropolitan areas ( 171 counties) in the fall of 2004. The 1990 Census Spanish Surname list was used to identify Hispanics in the Medicare data. In addition, we used data published on the U. S. Census Bureau website to obtain estimates of elderly Hispanics. Study Design. We used self-identified race/ethnicity as the gold standard to examine the agreement with Medicare race code alone, and with Medicare race code+Spanish surname match. Additionally, we estimated the proportions of Hispanic women and men, in each of the 11 geographic areas in our survey, using the Medicare race code alone and the Medicare race code+Spanish surname match, and compared those estimates with estimates derived from U. S. Census 2000 data. Principal Findings. The Spanish surname match dramatically increased the accuracy of the Medicare race code for identifying both Hispanic and white women, producing improvements comparable with those seen for men. Conclusions. We recommend the addition of a proxy race code in the Medicare data using the Spanish surname match to improve the accuracy of racial/ethnic representation. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Univ Minnesota, Sch Publ Hlth, Div Hlth Serv Res & Policy, Minneapolis, MN 55455 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. Baylor Coll Med, Dept Med, Hlth Serv Res Sect, Houston, TX 77030 USA. RP Wei, II (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. RI Morgan, Robert/A-8577-2009 FU NIA NIH HHS [R01 AG019284, R01/AG019284-01A2] NR 16 TC 34 Z9 34 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2006 VL 41 IS 4 BP 1469 EP 1481 DI 10.1111/j.1475-6773.2006.00550.x PN 1 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 065VQ UT WOS:000239188400019 PM 16899019 ER PT J AU Ho, ICK Milan, DJ Mansour, MC Mela, T Guy, ML Ruskin, JN Ellinor, PT AF Ho, Ivan C. K. Milan, David J. Mansour, Moussa C. Mela, Theofanie Guy, Mary L. Ruskin, Jeremy N. Ellinor, Patrick T. TI Fungal infection of implantable cardioverter-defibrillators: Case series of five patients managed over 22 years SO HEART RHYTHM LA English DT Article DE implantable cardioverter-defibrillator; fungal infection; device explantation ID CHRONIC HEART-FAILURE; CARDIAC-RESYNCHRONIZATION; ASPERGILLUS; ENDOCARDITIS; DIAGNOSIS; THERAPY AB BACKGROUND With the increasing use of implantable cardioverter-defibrillators (ICDs), device complications are becoming more common. Fungal-related ICD infections have rarely been reported, and little is known about the presentation, prevalence, and treatment options for these morbid infections. OBJECTIVES The purpose of this study was to characterize the clinical features, treatment, and outcomes of patients with fungal ICD infections. METHODS We performed a retrospective review of ICD procedures performed at a single academic center and identified all ICD-related infections managed between 1983 and 2005. RESULTS Among a total of 3,648 ICD-related procedures performed between 1983 and 2005, we identified 47 (1.3%) cases of ICD infections, of which 5 (0.1%) were due to a fungal pathogen. Fungal infections were more likely to be associated with abdominal devices, to have a local rather than systemic infection, and to have a longer duration from the original implant to presentation. All patients were treated with ICD system explantation and antifungal therapy. CONCLUSION Fungal infection of ICDs is a rare but serious complication of device implantation that must be treated aggressively with complete hardware explantation and prolonged antifungal therapy. Because most infections are late complications and have indolent onsets, a high level of clinical suspicion is required for early diagnosis. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM pellinor@partners.org FU NHLBI NIH HHS [HL71632] NR 20 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2006 VL 3 IS 8 BP 919 EP 923 DI 10.1016/j.hrthm.2006.04.012 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 073ME UT WOS:000239746400010 PM 16876740 ER PT J AU Aqel, RA Lloyd, SG Gupta, H Zoghbi, GJ AF Aqel, Raed A. Lloyd, Steven G. Gupta, Himanshu Zoghbi, Gilbert J. TI Three-vessel coronary artery disease, aortic stenosis, and constrictive pericarditis 27 years after chest radiation therapy: A case report SO HEART SURGERY FORUM LA English DT Article ID HODGKINS-DISEASE; CARDIAC-DISEASE; HEART-DISEASE; FOLLOW-UP; IRRADIATION AB A patient with a history of Hodgkin's lymphoma presented with recurrent left pleural effusions and dyspnea on exertion 27 years after radiation therapy. Further evaluation disclosed suspected radiation-induced constrictive pericarditis, aortic stenosis and regurgitation, and severe coronary artery disease. He underwent successful 3-vessel coronary artery bypass grafting, aortic valve replacement, and pericardiectomy. C1 Univ Alabama, Div Cardiovasc Dis, Dept Internal Med, Birmingham, AL 35233 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Zoghbi, GJ (reprint author), Univ Alabama, Div Cardiovasc Dis, Dept Internal Med, BVAMC Heart Stn 6th Floor,700 19th St S, Birmingham, AL 35233 USA. EM gzoghbi@uab.edu NR 10 TC 3 Z9 3 U1 0 U2 0 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PD AUG PY 2006 VL 9 IS 4 BP E728 EP E730 DI 10.1532/HSF98.20061031 PG 3 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 077ZH UT WOS:000240069900014 PM 16844629 ER PT J AU Malaty, HM Abudayyeh, S Graham, DY Gilger, MA Rabeneck, L O'Malley, K AF Malaty, Hoda M. Abudayyeh, Suhaib Graham, David Y. Gilger, Mark A. Rabeneck, Linda O'Malley, Kimberly TI A prospective study for the association of Helicobacter pylori infection to a multidimensional measure for recurrent abdominal pain in children SO HELICOBACTER LA English DT Article DE recurrent abdominal pain; children; Helicobacter pylori; epidemiology ID UNITED-STATES; SOCIOECONOMIC-STATUS; CHILDHOOD; POPULATION; COMMUNITY; SYMPTOMS; AGE; EPIDEMIOLOGY; SOMATIZATION; ADOLESCENTS AB Background: There is a controversial association between Helicobacter pylori infection and recurrent abdominal pain (RAP) in childhood and inconsistent information on specific symptomatology of the infection. Aim: To examine the prevalence of H. pylori infection among children with RAP compared to asymptomatic children. Methods: Two prospective studies were conducted. The first study enrolled 223 children diagnosed with RAP from two pediatric gastroenterology clinics in Houston, Texas. Children were qualified if they were identified by their physician as having RAP. A new multidimensional measure for RAP (MM-RAP) consisting of four scales (pain intensity scale, symptoms scale, disability scale, and satisfaction scale) was administered to each child/parent. The second study enrolled 330 asymptomatic children from the same community who did not have any upper gastrointestinal symptoms. Symptomatic and asymptomatic children underwent C-13-urea breath testing. Results: In the first study, the prevalence of H. pylori in children with RAP was 11% and fell with age from 20% at age <= 5 years to 7% for children > 10 years (OR = 2.7, 95% CI = 0.7-11.2). There was no association between the mother's educational level and H. pylori prevalence; (12% among children whose mothers completed college versus 11% among those who had elementary school, p = .8). No relationship was found between H. pylori and mean scores of the RAP scales. In the second study, the prevalence of H. pylori in asymptomatic children was 17% and increased with age from 11% for children <= 5 years to 40% for children > 10 years (OR = 5.4, 95% CI = 2.0-13.8). The mother's educational level was inversely correlated with H. pylori (OR = 3.0, 95% CI = 2.2-6.1, p < .01). Conclusions: The epidemiologic patterns of H. pylori infection differed significantly between symptomatic and asymptomatic children. Younger children suffering from RAP are more likely to be infected with H. pylori than older children with the same complaint, suggesting that early acquisition may manifest in symptoms that lead to clinic visits. C1 Baylor Coll Med, Vet Affairs Med Ctr 111D, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. Univ Toronto, Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto, ON, Canada. RP Malaty, HM (reprint author), Baylor Coll Med, Vet Affairs Med Ctr 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Hmalaty@bcm.tmc.edu NR 39 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2006 VL 11 IS 4 BP 250 EP 257 DI 10.1111/j.1523-5378.2006.00412.x PG 8 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 063GC UT WOS:000239005100006 PM 16882328 ER PT J AU Oleastro, M Cordeiro, R Menard, A Queiroz, D Yamaoka, Y Megraud, F Monteiro, L AF Oleastro, M. Cordeiro, R. Menard, A. Queiroz, D. Yamaoka, Y. Megraud, F. Monteiro, L. TI Distribution and allelic diversity of a novel peptic ulcer marker candidate in different geographical regions SO HELICOBACTER LA English DT Meeting Abstract CT 19th International Workshop on Helicobacter and Related Bacteric in Chronic Digestive Inflammation CY SEP 07-09, 2006 CL Wroclaw, POLAND C1 Inst Nacl Saude Dr Ricardo Jorge, Ctr Bacteriol, Lisbon, Portugal. Univ Victor Segalen, Lab Bacteriol, Bordeaux, France. Univ Fed Minas Gerais, Fac Med, Lab Pesquisa Bacteriol, Belo Horizonte, MG, Brazil. Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2006 VL 11 IS 4 BP 336 EP 336 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 063GC UT WOS:000239005100058 ER PT J AU Kudo, T Lu, H Ohno, T Graham, DY Genta, RM Yamaoka, Y AF Kudo, T. Lu, H. Ohno, T. Graham, D. Y. Genta, R. M. Yamaoka, Y. TI Pattern of transcription factor activation in Helicobacter pylori-infected Mongolian gerbils SO HELICOBACTER LA English DT Meeting Abstract CT 19th International Workshop on Helicobacter and Related Bacteric in Chronic Digestive Inflammation CY SEP 07-09, 2006 CL Wroclaw, POLAND C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX USA. Univ Geneva, Dept Pathol, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2006 VL 11 IS 4 BP 347 EP 347 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 063GC UT WOS:000239005100090 ER PT J AU Vilaichone, R Mahachai, V Yamaoka, Y Graham, D AF Vilaichone, R. Mahachai, V. Yamaoka, Y. Graham, D. TI Evaluation of rapid antibody tests for the diagnosis of Helicobacter pylori infection in Thailand, Japan, and United States SO HELICOBACTER LA English DT Meeting Abstract CT 19th International Workshop on Helicobacter and Related Bacteric in Chronic Digestive Inflammation CY SEP 07-09, 2006 CL Wroclaw, POLAND C1 Thammasat Univ Hosp, Bangkok, Thailand. Chulalongkorn Univ Hosp, Bangkok, Thailand. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2006 VL 11 IS 4 BP 383 EP 383 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 063GC UT WOS:000239005100192 ER PT J AU Oh, WK AF Oh, William K. TI Hematology/oncology clinics of North America - Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM William_oh@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2006 VL 20 IS 4 BP XIII EP XIV DI 10.1016/j.hoc.2006.07.011 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 072TQ UT WOS:000239696300001 ER PT J AU Ross, R Harisinghani, M AF Ross, Robert Harisinghani, Mukesh TI New clinical imaging modalities in prostate cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; SUPERPARAMAGNETIC IRON-OXIDE; LYMPH-NODE METASTASES; CONTRAST-ENHANCED MRI; PHASED-ARRAY COIL; COLOR DOPPLER US; WHOLE-BODY MRI; RADICAL PROSTATECTOMY; ENDORECTAL COIL; BONE-SCINTIGRAPHY AB This article reviews novel imaging modalities for prostate cancer, including novel ultrasound, magnetic resonance imaging, and nuclear medicine techniques. These modalities are considered within the different prostate cancer disease states in which they are most promising. While this field is rapidly changing, many important questions need to be answered before these techniques find a place in the imaging algorithm for prostate cancer patients. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Ross, R (reprint author), Dana Farber Canc Inst, Dana 1230,44 Binney St, Boston, MA 02115 USA. EM rwross@partners.org NR 107 TC 6 Z9 6 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2006 VL 20 IS 4 BP 811 EP + DI 10.1016/j.hoc.2006.03.009 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA 072TQ UT WOS:000239696300004 PM 16861116 ER PT J AU Morishima, C Morgan, TR Everhart, JE Wright, EC Shiffman, ML Everson, GT Lindsay, KL Lok, ASF Bonkovsky, HL Di Bisceglie, AM Lee, WM Dienstag, JL Ghany, MG Gretch, DR AF Morishima, Chihiro Morgan, Timothy R. Everhart, James E. Wright, Elizabeth C. Shiffman, Mitchell L. Everson, Gregory T. Lindsay, Karen L. Lok, Anna S. F. Bonkovsky, Herbert L. Di Bisceglie, Adrian M. Lee, William M. Dienstag, Jules L. Ghany, Marc G. Gretch, David R. CA HALT-C Trial Grp TI HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial SO HEPATOLOGY LA English DT Article ID TRANSCRIPTION-MEDIATED AMPLIFICATION; INTERFERON-ALPHA THERAPY; ANALYTE-SPECIFIC REAGENT; VIRUS-RNA; VIROLOGICAL RESPONSE; PERFORMANCE-CHARACTERISTICS; PEGINTERFERON ALPHA-2A; QUALITATIVE ASSAY; FOLLOW-UP; QUANTIFICATION AB For making treatment decisions related to chronic hepatitis C, the utility of HCV RNA tests with increased sensitivity has not been defined. Prior interferon nonresponders with advanced fibrosis (n = 1,145) were retreated with peginterferon alpha-2a and ribavirin. Patients who were HCV RNA-negative by a polymerase chain reaction (PCR)-based assay (Roche COBAS Amplicor (TM) HCV Test, v. 2.0; lower limit of detection [LOD] 100 IU/mL) at week 20 (W20) received treatment for 48 weeks. Stored specimens were tested using the Bayer VERSANT (R) HCV RNA Qualitative (TMA) Assay (LOD 9.6 IU/mL) and compared to PCR results for the ability to predict sustained virological response (SVR, defined as undetectable HCV RNA by PCR at W72). Nearly all PCR-positive samples (1006/1007, 99.9%) were positive as assessed by TMA. Among 1,294 PCR-negative samples, 22% were TMA-positive. Negative TMA results were more predictive of SVR than were negative PCR results at W12 (82% vs. 64%, P <.001) and at W20 (66% vs. 52%, P = 0.001). SVR was more likely the earlier TMA had become negative during treatment (82% at W12, 44% at W20, 20% at W24). Among 45 patients who were TMA-positive but were PCR-negative at W20 and W24, none achieved SVR (95% CI: 0%-8%). Approximately 10% of patients with a single positive TMA result at the end of treatment still achieved SVR. In conclusion, negative TMA results at or after W12 were superior to negative PCR results for predicting SVR. In patients with negative PCR results during treatment, a single positive TMA test did not exclude SVR, although persistently positive tests did. C1 Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. New England Res Inst, Watertown, MA 02172 USA. Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Univ Texas, SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75230 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NIDDKD, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Morishima, C (reprint author), Univ Washington, Dept Lab Med, Box 359690, Seattle, WA 98104 USA. EM chihiro@u.washington.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00051, M01RR-00042, M01RR-00043, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328] NR 22 TC 37 Z9 39 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2006 VL 44 IS 2 BP 360 EP 367 DI 10.1002/hep.21265 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 070LF UT WOS:000239523200010 PM 16871570 ER PT J AU Weiss, LA Ober, C Cook, EH AF Weiss, Lauren A. Ober, Carole Cook, Edwin H., Jr. TI ITGB3 shows genetic and expression interaction with SLC6A4 SO HUMAN GENETICS LA English DT Article ID WHOLE-BLOOD SEROTONIN; 1ST-DEGREE RELATIVES; AUTISTIC DISORDER; TRANSPORTER; FAMILIES; PROMOTER; PROBANDS AB Autism affects more males than females and is associated with disturbances of the serotonin system. The integrin beta 3 (ITGB3) and serotonin transporter (SLC6A4) genes were both recently identified as male quantitative trait loci (QTLs) for serotonin levels and alleles of each have been associated with autism. Here, we use publicly available genomic resources to determine whether regulation of expression level could be the mechanism behind association between serotonin level and noncoding variation in ITGB3. We also examine whether ITGB3 might interact with SLC6A4 to contribute to autism susceptibility. Using murine and human expression data, we observe that ITGB3 and SLC6A4 expression levels are correlated (0.38 < r < 0.78). Moreover, genetic variation in ITGB3 is associated with expression of both ITGB3 (P=0.012) and SLC6A4 (P=0.008) in unrelated CEPH individuals. We also show preliminary evidence that genotypes at the ITGB3 and SLC6A4 loci may interact to affect autism susceptibility (P=0.033). C1 Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. RP Weiss, LA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA 02114 USA. EM laweiss@chgr.mgh.harvard.edu OI Cook, Edwin/0000-0002-5848-5114 FU NCRR NIH HHS [M01 RR00055]; NHLBI NIH HHS [R01 HL72414]; NICHD NIH HHS [U19 HD35482] NR 27 TC 30 Z9 30 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 2006 VL 120 IS 1 BP 93 EP 100 DI 10.1007/s00439-006-0196-z PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 061HD UT WOS:000238861300010 PM 16721604 ER PT J AU Fisher, SA Hampe, J Onnie, CM Daly, MJ Curley, C Purcell, S Sanderson, J Mansfield, J Annese, V Forbes, A Lewis, CM Schreiber, S Rioux, JD Mathew, CG AF Fisher, Sheila A. Hampe, Jochen Onnie, Clive M. Daly, Mark J. Curley, Christine Purcell, Shaun Sanderson, Jeremy Mansfield, John Annese, Vito Forbes, Alastair Lewis, Cathryn M. Schreiber, Stefan Rioux, John D. Mathew, Christopher G. TI Direct or indirect association in a complex disease: The role of SLC22A4 and SLC22A5 functional variants in Crohn disease SO HUMAN MUTATION LA English DT Article DE Crohn disease; SLC22A4; SLC22A5; complex disease ID INFLAMMATORY-BOWEL-DISEASE; CATION TRANSPORTER GENES; SUSCEPTIBILITY; MUTATION; LOCUS; IBD5 AB A common haplotype spanning 250kb on chromosome 5q31 is strongly associated with Crohn disease (CD). Recently, two functional variants within the SLC22A4 and SLC22A5 genes at this locus (IBD5), L503F (c. 1507C > T) and G-207C (c.-207G > C), have been proposed to contribute directly to susceptibility to CD. However, extensive linkage disequilibrium at the IBD5 locus has complicated efforts to distinguish causal variants from association of the general risk haplotype. We genotyped the SLC22A4 and SLC22A5 variants and other polymorphisms across the risk haplotype in four populations of European origin, and applied regression, based haplotype analysis to over 1,200 fully genotyped case-control pairs, modeling case/control status on the presence of one or more SNPs to test for conditional association and to identify risk haplotypes. We found highly significant association of SNPs at the IBD5 locus with Crohn disease in all populations tested. However, the frequencies of L503F and G-207C in individuals who did not carry the general IBD5 risk haplotype were not significantly different in cases and controls, with associated disease odds ratios (ORs) of 0.90 (95% CI, 0.57-1.40) and 0.90 (95% CI, 0.65-1.23), respectively. Haplotype analysis showed that addition of the SLC22A4 and SLC22A5 variants to a null model that included the background risk haplotype did not significantly improve the model fit. In addition to the common risk haplotype, several rare haplotypes had an increased frequency in cases compared to controls. This study suggests that the molecular basis for Crohn disease susceptibility at the IBD5 locus remains to be defined, and highlights the challenge of the identification of causal variants in a complex disease in regions of extensive linkage disequilibrium. C1 Kings Coll London, Guys Hosp, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England. Univ Kiel, Inst Klin Mol Biol, Kiel, Germany. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard, Cambridge, MA USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Guys & St Thomas NHS Fdn Trust, St Thomas Hosp, Dept Gastroenterol, London, England. Univ Newcastle Upon Tyne, Royal Victoria Infirm, Dept Gastroenterol & Hepatol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. IRCCS Hosp, Casa Sollievo Sofferenza, Dept Gastroenterol, San Giovanni Rotondo, Italy. UCL Hosp Trust, Inst Digest Dis, London, England. Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. RP Mathew, CG (reprint author), Kings Coll London, Guys Hosp, Sch Med, Dept Med & Mol Genet, 8th Floor Guys Tower, London SE1 9RT, England. EM Christopher.mathew@genetics.kcl.ac.uk RI Schreiber, Stefan/B-6748-2008; Lewis, Cathryn/A-5225-2010; Hampe, Jochen/A-2555-2010; Rioux, John/A-9599-2015; Mathew, Christopher/G-3434-2015 OI Schreiber, Stefan/0000-0003-2254-7771; Lewis, Cathryn/0000-0002-8249-8476; Hampe, Jochen/0000-0002-2421-6127; Rioux, John/0000-0001-7560-8326; Mathew, Christopher/0000-0003-4178-1838 FU Wellcome Trust NR 22 TC 38 Z9 38 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD AUG PY 2006 VL 27 IS 8 BP 778 EP 785 DI 10.1002/humu.20358 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 068BZ UT WOS:000239348000008 PM 16835882 ER PT J AU Horowitz, RE AF Horowitz, Richard E. TI Expectations and essentials for the community practice of pathology SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-of-Pathology-Chairs CY JUL 28, 2005 CL Mt Tremblant, CANADA SP Assoc Pathol Chairs DE pathology residency training; pathology private practice; community hospital pathology AB In 3 surveys during the past 10 years, community hospital pathologists were asked what they want, need, or look for when employing a pathologist and, more specifically, what skills and knowledge a newly minted pathologist should have to be successful in the community practice of pathology. The most recent survey, done in spring of 2005, cited surgical pathology diagnosis, frozen section diagnosis, dissection, and fine-needle aspiration as essentials in anatomic pathology. For clinical gross, cytology, pathology, knowledge of clinical medicine and test strategies that use the laboratory for clinical problem solving was paramount. New expectations in the latest survey were knowledge of molecular pathology and experience in quality assurance procedures. New pathologists generally meet the expectations of the community hospital workplace; however, there were some deficiencies: they were not proficient in gross pathology or autopsy pathology, they were slow, and many lack the clinical knowledge and experience to be effective consultants. The principal attribute that determines success in the practice of pathology, however, is skill in communication and interpersonal relations, and this remains the major deficiency of the fledgling pathologist. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. Univ So Calif, Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Horowitz, RE (reprint author), Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. EM r.e.horowitz@ucla.edu NR 3 TC 21 Z9 21 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 2006 VL 37 IS 8 BP 969 EP 973 DI 10.1016/j.humpath.2006.01.035 PG 5 WC Pathology SC Pathology GA 072SW UT WOS:000239694300007 PM 16867856 ER PT J AU Welt, CK Jimenez, Y Sluss, PM Smith, PC Hall, JE AF Welt, C. K. Jimenez, Y. Sluss, P. M. Smith, P. C. Hall, J. E. TI Control of estradiol secretion in reproductive ageing SO HUMAN REPRODUCTION LA English DT Article DE androstenedione; aromatase; FSH; ovary ID FOLLICLE-STIMULATING-HORMONE; INHIBIN-B; MENSTRUAL CYCLES; DIMERIC INHIBIN; OVULATORY WOMEN; ACTIVIN-A; FSH RISE; AGE; SERUM; OLDER AB BACKGROUND: Estradiol (E-2) concentration is preserved in older reproductive-aged women despite a decrease in follicle number and androstenedione (AD) levels. We hypothesized that increased aromatase activity accounts for E-2 preservation in older women. METHODS: Older (36-46 years; n = 11) and younger (21-35 years; n = 10) women with 25- to 35-day menstrual cycles participated in a parallel design study. Daily blood samples were drawn starting at menses, and recombinant human FSH (rhFSH), 150 IU, was administered when the dominant follicle's diameter was >= 16 mm. FSH, LH, E-2, estrone (E-1), AD and the AD/E-1 ratio were compared. RESULTS: E-2 and E-1 concentrations and the E-1/E-2 ratio were similar across the follicular phase in older compared with younger women, whereas AD and the AD/E-1 ratio were lower. Older women had higher FSH concentrations in the early follicular phase and fewer small follicles. RhFSH-stimulated changes in E-1 were similar between older and younger subjects despite the smaller number of follicles. CONCLUSIONS: These findings suggest that E-2 secretion is maintained by increased aromatase function in older compared with younger reproductive-aged women, whereas there is no apparent difference in 17 beta-hydroxysteroid dehydrogenase activity. The increased aromatase is probably driven by increased FSH in the early follicular phase and compensates for the decreased follicle number in older reproductive-aged women. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [R01HD042708] NR 33 TC 24 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD AUG PY 2006 VL 21 IS 8 BP 2189 EP 2193 DI 10.1093/humrep/del136 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 075RC UT WOS:000239901900042 PM 16684841 ER PT J AU Smith, NJ Luttrell, LM AF Smith, Nicola J. Luttrell, Louis M. TI Signal switching, crosstalk, and arrestin scaffolds - Novel G protein-coupled receptor signaling in cardiovascular disease SO HYPERTENSION LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; CHRONIC HEART-FAILURE; II TYPE-1 RECEPTOR; PROMOTES CARDIOMYOCYTE HYPERTROPHY; PRESSURE-OVERLOAD HYPERTROPHY; A-MEDIATED PHOSPHORYLATION; Q-OVEREXPRESSING MICE; ANGIOTENSIN-II; BETA-ARRESTIN; EGF RECEPTOR 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. Baker Heart Res Inst, Mol Endocrinol Lab, Melbourne, Vic, Australia. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 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 RI Smith, Nicola/D-2541-2010 OI Smith, Nicola/0000-0002-7247-9562 FU NIDDK NIH HHS [DK55524, DK58283, DK64353] NR 75 TC 34 Z9 35 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 AUG PY 2006 VL 48 IS 2 BP 173 EP 179 DI 10.1161/01.HYP.0000232641.84521.92 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 069DZ UT WOS:000239427900001 PM 16818801 ER PT J AU Palmas, W Moran, A Pickering, T Eimicke, JP Teresi, J Schwartz, JE Field, L Weinstock, RS Shea, S AF Palmas, Walter Moran, Andrew Pickering, Thomas Eimicke, Joseph P. Teresi, Jeanne Schwartz, Joseph E. Field, Lesley Weinstock, Ruth S. Shea, Steven TI Ambulatory pulse pressure and progression of urinary albumin excretion in older patients with type 2 diabetes mellitus SO HYPERTENSION LA English DT Article DE albuminuria; blood pressure monitoring, ambulatory; diabetes mellitus ID COLUMBIA-UNIVERSITY INFORMATICS; TELEMEDICINE IDEATEL PROJECT; BLOOD-PRESSURE; SYSTOLIC HYPERTENSION; CARDIOVASCULAR RISK; RENAL-DISEASE; FOLLOW-UP; MICROALBUMINURIA; MORTALITY; POPULATION AB We studied whether ambulatory blood pressure monitoring added to office blood pressure in predicting progression of urine albumin excretion over 2 years of follow-up in a multiethnic cohort of older people with type-2 diabetes mellitus. Participants in the Informatics for Diabetes Education and Telemedicine study underwent a baseline evaluation that included office and 24-hour ambulatory blood pressure measurement and a spot urine measurement of albumin-to-creatinine ratio (ACR). Measurements of albumin-to-creatinine ratio were repeated 1 and 2 years later. In bivariate analyses, ambulatory 24-hour pulse pressure was the blood pressure variable most strongly associated with follow-up ACR. Repeated-measures mixed linear models (n=1040) were built adjusting for baseline ACR ratio, clustered randomization, time to follow-up, and multiple covariates. When both were entered into the model, ambulatory 24-hour pulse pressure and office pulse pressure were independently associated with follow-up ACR (beta [SE]=0.010 [0.002], P < 0.001, and 0.004 [0.001], P=0.002, respectively). Cox proportional hazards models examined associations with progression of albuminuria in 954 participants without macroalbuminuria at baseline, adjusting for all of the covariates independently associated with follow-up ACR in mixed linear models. Ambulatory 24-hour pulse pressure, but not office pulse pressure, was independently associated with progression of albuminuria (P=0.015 and 0.052, respectively). The adjusted hazards ratio (95% CI) per each 10-mm Hg increment in ambulatory pulse pressure was 1.23 (1.04 to 1.42). In conclusion, ambulatory pulse pressure may provide additional information to predict progression of albuminuria in elderly diabetic subjects above and beyond office blood pressure. C1 Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Med, New York, NY 10027 USA. Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. Columbia Univ, Dept Biomed Informat, New York, NY 10027 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Columbia Univ, Behav Cardiovasc Hlth & Hypertens Program, New York, NY 10027 USA. Hebrew Home Aged, Bronx, NY USA. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. SUNY Syracuse, Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. SUNY Syracuse, Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY USA. VA Med Ctr, Dept Vet Affairs, Syracuse, NY USA. RP Palmas, W (reprint author), Div Gen Med, 622 W 168th St,PH 9-East, New York, NY 10032 USA. EM wp56@columbia.edu NR 50 TC 34 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD AUG PY 2006 VL 48 IS 2 BP 301 EP 308 DI 10.1161/01.HYP.0000232644.98208.65 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 069DZ UT WOS:000239427900025 PM 16818800 ER PT J AU Fang, QQ Meaney, PA Paulsen, KD AF Fang, Qianqian Meaney, Paul A. Paulsen, Keith D. TI Singular value analysis of the Jacobian matrix in microwave image reconstruction SO IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION LA English DT Article DE Jacobian matrix; microwave imaging; singular value analysis; Zernike polynomial ID VALUE DECOMPOSITION; INVERSE SCATTERING; SYSTEM; INFORMATION; FIELDS; BREAST; PHASE AB For non-linear inverse scattering problems utilizing Gauss-Newton methods, the Jacobian matrix encodes rich information concerning the system performance and algorithm efficiency. In this paper, we perform an analytical evaluation. of a single-iteration Jacobian matrix based on a previously derived nodal adjoint representation. Concepts for studying linear ill-posed problems, such as the degree-of-ill-posedness, are used to assess the impact of important system parameters on the expected image quality. Analytical singular value decomposition (SVD) of the Jacobian matrix for a circular imaging domain is derived along with the numerical SVD for optimizing imaging system configurations. The results show significant reductions in the degree-of-ill-posedness when signal frequency, antenna array density and property parameter sampling are increased. Specifically, the decay rate in the singular spectrum of the Jacobian decreases monotonically with signal frequency being approximately 1/3 of its 0.1 GHz value at 3 GHz, is improved with antenna array density up to about 35 equally-spaced circumferentially positioned elements and drops significantly with increased property parameter sampling to more than twice the amount of measurement data. These results should serve as useful guidelines in the development of design specifications for an optimized hardware installation. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM fangq@mnr.mgh.harvard.edu; paul.m.meaney@dartmouth.edu; keith.d.paulsen@dartmouth.edu NR 33 TC 28 Z9 28 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-926X J9 IEEE T ANTENN PROPAG JI IEEE Trans. Antennas Propag. PD AUG PY 2006 VL 54 IS 8 BP 2371 EP 2380 DI 10.1109/TAP.2006.879192 PG 10 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 078PX UT WOS:000240116800022 ER PT J AU Moore, WH Holschneider, DP Givrad, TK Maarek, JMI AF Moore, William H. Holschneider, Daniel P. Givrad, Tina K. Maarek, Jean-Michel I. TI Transcutaneous RF-powered implantable minipump driven by a class-E transmitter SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE infusion pump; implantable device; radio-frequency field; transcutaneous coupling; wireless energy transfer ID NONTETHERED RATS; COUPLED COILS AB We describe the design and testing of an inductive coupling system used to power an implantable minipump for applications in ambulating rats. A 2 MHz class-E oscillator driver powered a coil transmitter wound around a 33-cm-diameter rat cage. A receiver coil, a filtered rectifier, and a voltage-sensitive switch powered the implant. The implant DC current at the center of the primary coil (5.1 V) exceeded the level required to activate the solenoid valve in the pump. The variations of the implant current in the volume of the primary coil reflected the variations of the estimated coupling coefficient between the two coils. The pump could be activated in-vivo, while accommodating the vertical and horizontal movements of the animal. Advantages of this design include a weight reduction for the implant, an operation independent from a finite power source, and a remote activation/deactivation. C1 Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. Univ So Calif, Alfred E Mann Inst, Los Angeles, CA 90089 USA. Univ So Calif, Dept Psychiat, Los Angeles, CA 90089 USA. Univ So Calif, Dept Neurol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Maarek, JMI (reprint author), Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. EM Holschne@usc.edu; maarek@usc.edu FU NINDS NIH HHS [1 R01 NS050171, R01 NS050171, R01 NS050171-01A1] NR 11 TC 18 Z9 18 U1 2 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD AUG PY 2006 VL 53 IS 8 BP 1705 EP 1708 DI 10.1109/TBME.2006.873698 PG 4 WC Engineering, Biomedical SC Engineering GA 066XH UT WOS:000239263400028 PM 16916107 ER PT J AU Hirahashi, J Mekala, D Van Ziffle, J Xiao, L Saffaripour, S Wagner, DD Shapiro, SD Lowell, C Mayadas, TN AF Hirahashi, Junichi Mekala, Divya Van Ziffle, Jessica Xiao, Ling Saffaripour, Simin Wagner, Denisa D. Shapiro, Steven D. Lowell, Clifford Mayadas, Tanya N. TI Mac-1 signaling via Src-farnily and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy SO IMMUNITY LA English DT Article ID FC-GAMMA RECEPTOR; FAMILY KINASES; LEUKOCYTE ADHESION; HUMAN NEUTROPHILS; POLYMORPHONUCLEAR LEUKOCYTES; COMPLEMENT ACTIVATION; EXTRACELLULAR-MATRIX; ENDOTHELIAL ADHESION; SHWARTZMAN REACTION; CELL ACTIVATION AB CD18 integrins promote neutrophil recruitment, and their engagement activates tyrosine kinases, leading to neutrophil activation. However, the significance of integrin-dependent leukocyte activation in vivo has been difficult to prove. Here, in a model of thrombo-hemorrhagic vasculitis, the CD18 integrin Mac-1 on neutrophils recognized complement C3 deposited within vessel walls and triggered a signaling pathway involving the Src-famlly kinase Hck and the Syk tyrosine kinase. This led to neutrophil elastase release, causing hemorrhage, fibrin deposition, and thrombosis. Mice genetically deficient in any of these components (C3, Mac-1, Hck, Syk, or elastase) were resistant to disease despite normal tissue neutrophil accumulation. Disease was restored in Mac-1-deficient mice infused with wild-type, but not kinase- or elastase-deficient, neutrophils. Elastase release in the inflamed tissue was reduced in Mac-1-deficient mice, and a deficiency of Mac-1 or the kinases blocked neutrophil elastase release in vitro. These data suggest that Mac-1 engagement of complement activates tyrosine kinases to promote elastase-dependent blood vessel injury in vivo. C1 Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Biomed Res Inst, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Mayadas, TN (reprint author), Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, 75 Francis St, Boston, MA 02115 USA. EM tmayadas@rics.bwh.harvard.edu FU NHLBI NIH HHS [R37 HL41002, T32HL07627, R01 HL54853, R01 HL041002]; NIAID NIH HHS [AI065495, R01 AI068150]; NIAMS NIH HHS [R01 AR050800]; NIDDK NIH HHS [DK51643] NR 67 TC 71 Z9 73 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 2006 VL 25 IS 2 BP 271 EP 283 DI 10.1016/j.immuni.2006.05.014 PG 13 WC Immunology SC Immunology GA 077RM UT WOS:000240047500013 PM 16872848 ER PT J AU Lu, LR Werneck, MBF Cantor, H AF Lu, Linrong Werneck, Miriam B. F. Cantor, Harvey TI The immunoregulatory effects of Qa-1 SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-CELL-RECEPTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; PLASMACYTOID DENDRITIC CELLS; DIFFERENT LY COMPONENTS; MYELIN BASIC-PROTEIN; CLASS IB MOLECULES; B7 FAMILY-MEMBER; IN-VIVO; HLA-E AB The immune system is not only well equipped to control infections but also tightly controlled to prevent autoimmune disease. Despite the negative selection of T-cell clones in the thymus, mature T cells capable of recognizing self-antigens are present in every individual. Several types of specialized regulatory cells maintain homeostasis and prevent expansion of autoreactive T cells. In this issue of Immunological Reviews, the role of CD4(+) regulatory T cells is extensively discussed. Suppression of T-cell responses by CD8(+) T cells has received less attention. Here, we review research on Qa-1-restricted CD8(+) regulatory T cells. We focus on the role of this class Ib major histocompatibility complex (MHC) molecule in both CD8(+) regulatory T-cell activity and protection of activated T cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), 44 Binney St, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu RI Werneck, Miriam/H-5802-2012; Lu, Linrong/A-1429-2013 FU NIAID NIH HHS [AI012184, AI 037562, AI048125] NR 81 TC 47 Z9 51 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2006 VL 212 BP 51 EP 59 DI 10.1111/j.0105-2896.2006.00418.x PG 9 WC Immunology SC Immunology GA 065WB UT WOS:000239189600004 PM 16903905 ER PT J AU Kretschmer, K Apostolou, I Jaeckel, E Khazaie, K von Boehmer, H AF Kretschmer, Karsten Apostolou, Irina Jaeckel, Elmar Khazaie, Khashayarsha von Boehmer, Harald TI Making regulatory T cells with defined antigen specificity: role in autoimmunity and cancer SO IMMUNOLOGICAL REVIEWS LA English DT Review DE autoimmune suppression; Foxp3; regulatory T cells; transforming growth factor-beta ID TRANSCRIPTION FACTOR FOXP3; IN-VIVO EXPANSION; DENDRITIC CELLS; CUTTING EDGE; STEADY-STATE; THYMIC EPITHELIUM; CD4(+)CD25(+); TOLERANCE; VITRO; INDUCTION AB There is increasing evidence that agonist ligand presentation either intrathymically or extrathymically plays a crucial if not essential role in the generation of regulatory T cells (Tregs). Thus, it is possible to induce Tregs of any desired specificity in vivo. The same goal can be achieved in vitro by expanding antigen-specific CD4(+) T cells and retrovirally transducing them. In contrast, in vitro expansion of Tregs is limited to antigens that have resulted in Treg generation in vivo. Antigen-specific Tregs can be used in cellular therapy with the goal to prevent autoimmune disease or even to interfere with established autoimmunity. The latter requires that the Tregs can suppress effector cells that have already caused harm, which is possible because of the antigen-dependent homing properties of Tregs, i.e. these cells can accumulate in antigen-draining lymph nodes and exit into inflamed tissue. Generally, the in vivo interference is dependent on cytokines such as transforming growth factor-beta and interleukin-10 that were dispensable in in vivo analysis of immunosuppression. The precise mechanisms of suppression remain enigmatic, however, but may be further elucidated by the molecular analysis of suppressed versus non-suppressed T cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Hannover Med Sch, Res Ctr, Krankenhaus Oststadt, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Kretschmer, Karsten/E-8174-2010 NR 59 TC 62 Z9 67 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2006 VL 212 BP 163 EP 169 DI 10.1111/j.0105-2896.2006.00411.x PG 7 WC Immunology SC Immunology GA 065WB UT WOS:000239189600012 PM 16903913 ER PT J AU Lichtenstein, GR Sands, BE Pazianas, M AF Lichtenstein, Gary R. Sands, Bruce E. Pazianas, Michael TI Prevention and treatment of osteoporosis in inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE CCFA guidelines ID BONE-MINERAL DENSITY; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; X-RAY ABSORPTIOMETRY; CORTICOSTEROID-INDUCED OSTEOPOROSIS; POPULATION-BASED COHORT; HORMONE REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; VERTEBRAL FRACTURE RISK; ONCE-WEEKLY ALENDRONATE; URINARY N-TELOPEPTIDE AB The following are guidelines for evaluation and consideration for treatment of patients with inflammatory bone disease (IBD) after bone mineral density (BMD) measurements. The Crohn's & Colitis Foundation of America (CCFA) has indicated that its recommendations are intended to serve as reference points for clinical decision-making, not as rigid standards, limits, or rules. They should not be interpreted as quality standards. C1 Univ Penn, Hosp Univ Penn, Sch Med, Dept Med,Div Gastroenterol, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. MGH IBD Ctr, Dept Med, Boston, MA USA. Univ Penn, Hosp Univ Penn, Sch Med, Ralston Penn Ctr,Dept Med, Philadelphia, PA 19104 USA. RP Lichtenstein, GR (reprint author), Univ Penn, Sch Med, Dept Med, Div Gastroenterol, 3400 Spruce St,3rd Floor,Ravdin Bldg, Philadelphia, PA 19104 USA. EM grl@uphs.upenn.edu NR 176 TC 41 Z9 45 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD AUG PY 2006 VL 12 IS 8 BP 797 EP 813 DI 10.1097/00054725-200608000-00016 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 072ZN UT WOS:000239712000019 PM 16917235 ER PT J AU Kyriacou, DN Monkkonen, EH Peek-Asa, C Lucke, RE Labbett, S Pearlman, KS Hutson, HR AF Kyriacou, D. N. Monkkonen, E. H. Peek-Asa, C. Lucke, R. E. Labbett, S. Pearlman, K. S. Hutson, H. R. TI Police deaths in New York and London during the twentieth century SO INJURY PREVENTION LA English DT Article ID PREDICTING MURDER RATES; INJURY-PREVENTION; FIREARM DEATHS; OFFICERS; SUICIDE; MORTALITY; HOMICIDE; COHORT; RISK; AVAILABILITY AB Objectives: To describe the incidences and causes of occupational police deaths in New York City in the United States and Greater London in the United Kingdom during the twentieth century. To assess the relation between overall societal violence and violence directed toward police officers in these metropolitan areas. Design and setting: Ecological study of New York and London from 1900 through 1999. Main outcome measures: Intentional and unintentional occupational police mortality rates for New York and London were estimated for each decade. The general population homicide rates of both New York and London were assessed for their correlation with their respective intentional occupational police mortality rates. Results: During the 20th century, 585 police officers in New York and 160 police officers in London died while participating in law enforcement activities. New York had markedly greater intentional police mortality rates compared to London throughout most of the 20th century, but these differences decreased significantly by the end of the century. Intentional gunshot wounds comprised 290 police deaths in New York, but only 14 police deaths in London. In New York, gun shot wounds ( both intentional and unintentional) accounted for more occupational police deaths (51.6%) than did all other injury mechanisms combined. In London, motor vehicle collision was the most common cause (47.5%) of occupational police death. There were no apparent correlations between the general population homicide rates and intentional police mortality rates in either New York (r(2) = 0.05, 95% CI -0.77 to 0.81) or London (r(2) = 0.34, 95% CI 20.61 to 0.89). Conclusions: During the 20th century, both intentional and unintentional occupational police mortality rates were significantly greater in New York compared to London. These differences are likely from several socioeconomic, cultural, and occupational factors. The declines in police deaths in New York during the latter part of the 20th century indicate that at least some measures taken by the New York Police Department have been successful at significantly reducing the incidence of both intentional and unintentional police deaths. C1 Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Publ Policy, Los Angeles, CA 90024 USA. Univ Iowa, Coll Publ Hlth, Dept Occupat & Environm Hlth, Iowa City, IA 52242 USA. Northwestern Univ, Dept Emergency Med, Evanston, IL 60208 USA. Sussex Police Headquaters, Lewes, E Sussex, England. Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kyriacou, DN (reprint author), 259 Erie St,Suite 100, Chicago, IL 60611 USA. EM dkyriacou@aol.com NR 46 TC 4 Z9 4 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 J9 INJURY PREV JI Inj. Prev. PD AUG PY 2006 VL 12 IS 4 BP 219 EP 224 DI 10.1136/ip.2005.010827 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 070CI UT WOS:000239497500006 PM 16887942 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Causes underlying the birth-cohort phenomenon of peptic ulcer: analysis of mortality data 1911-2000, England and Wales SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE duodenal ulcer; gastric ulcer; Helicobacter pylori; mortality rates; time trends of peptic ulcer ID HELICOBACTER-PYLORI INFECTION; GASTRIC-ACID SECRETION; DUODENAL-ULCER; TIME TRENDS; NEW-YORK; DISEASE; AGE; EPIDEMIOLOGY; STOMACH; EUROPE AB Background Since humans have been infected with Helicobacter pylori for millennia, it has remained an enigma why the occurrence of gastric and duodenal ulcer rose suddenly during 19th century. The study aim is to present a mathematical model of H. pylori epidemiology that explains the peculiar long-term trends of ulcer disease. Methods Gastric and duodenal ulcer mortality data from England and Wales between 1911 and 2000 were used to validate a model based on two simple and straightforward assumptions about H. pylori infection. First, the infection rate fell in the general population between 1800 and 2000. Second, gastric ulcer was caused by H. pylori infection contracted between the ages 5 and 15 and duodenal ulcer was caused by H. pylori infection contracted after the age of 15. As the infection receded in the general population, the two fractions of subjects who became infected between the ages 5 and 15 or after the age of 15 increased among. consecutive birth cohorts. Results The analysis of the actual long-term mortality from gastric and duodenal ulcer indicates an underlying birth-cohort pattern. These birth-cohort patterns of gastric and duodenal ulcer could be simulated by the interaction of two opposing time trends, namely a declining infection rate and a rising fraction of individuals acquiring their infection at increasingly older ages. The superimposition of a declining and a rising trend resulted in a bell-shaped curve of ulcer occurrence affecting consecutive birth-cohorts born between 1830 and 1970. Similar to the real data, the modelled cohort pattern of gastric ulcer preceded that of duodenal ulcer by 20 years. Conclusion The birth-cohort phenomenon of ulcer disease can be explained by a receding H. pylori infection accompanied by a simultaneous shift in its age of acquisition. C1 Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 60 TC 27 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2006 VL 35 IS 4 BP 1090 EP 1097 DI 10.1093/ije/dyl093 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 090GR UT WOS:000240939300044 PM 16709617 ER PT J AU Casas, A Perotti, C Ortel, B Di Venosa, G Saccoliti, M Batlle, A Hasan, T AF Casas, Adriana Perotti, Christian Ortel, Bernhard Di Venosa, Gabriela Saccoliti, Maria Batlle, Alcira Hasan, Tayyaba TI Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE photodynamic therapy; resistance; cross-resistance; aminolevulinic acid; hypoxia ID DELTA-AMINOLEVULINIC-ACID; IN-VITRO; METASTASIS; PHOTOSENSITIZERS; PORPHYRINS; INDUCTION; CARCINOMA; RATS; VIVO AB We isolated and characterized cell lines resistant to aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) derived from a murine adenocarcinoma and studied cross resistance with other injuries. The most resistant clones were numbers 4 and 8, which exhibited 6.7- and 4.2-fold increase in resistance respectively. Several characteristics were altered in these clones. A 2-fold increase in cell volume, higher cell spreading, and a more fibroblastic. dendritic pattern., were the morphology features that led us to think they could have different adhesive, invasive or metastatic phenotypes. The amount of porphyrins synthesized per cell in the resistant clones was similar to the parental line but, when it was expressed per mg protein, there was a 2-fold decrease, with a higher proportion of hydrophilic porphyrins. These cells were not cross-resistant to photosensitization with Benzoporphyrin derivative and Merocyanine 540, but exhibited a slight resistance to exogenous protoporphyrin IX treatment. Both clones displayed higher protein content and increased number of mitochondria, together with a higher oxygen consumption. The distinctive features found in the resistant lines led as to think how to exploit the changes induced by PDT treatment to target surviving cells. Those hypoxic cells can be also a preferential target of bioreductive drugs and hypoxia-directed gene therapy. and would be sensitive to treatment with other photosensitizers. C1 Univ Buenos Aires, Hosp Clin Gral Jose De San Martin, CIPYP, RA-1056 Buenos Aires, DF, Argentina. Consejo Nacl Invest Cient & Tecn, RA-1056 Buenos Aires, DF, Argentina. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed WEL 224, Boston, MA 02114 USA. Hosp Durand, Serv Patol, Buenos Aires, DF, Argentina. RP Casas, A (reprint author), CIPYP, Viamonte 1881,10mo Piso A, RA-1056 Buenos Aires, DF, Argentina. EM adriana@qb.fcen.uba.ar FU NCI NIH HHS [P01 CA84203]; NIAMS NIH HHS [R01 AR040352] NR 33 TC 25 Z9 25 U1 0 U2 5 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 2006 VL 29 IS 2 BP 397 EP 405 PG 9 WC Oncology SC Oncology GA 065AU UT WOS:000239132600012 PM 16820882 ER PT J AU Schwartz, GF Veronesi, U Clough, KB Dixon, JM Fentiman, IS Heywang-Kobrunner, SH Holland, R Hughes, KS Mansel, RE Margolese, R Mendelson, EB Olivotto, IA Palazzo, JP Solin, LJ AF Schwartz, Gordon F. Veronesi, Umberto Clough, Krishna B. Dixon, J. M. Fentiman, Ian S. Heywang-Kobrunner, Sylvia H. Holland, Roland Hughes, Kevin S. Mansel, Robert E. Margolese, Richard Mendelson, Ellen B. Olivotto, Ivo A. Palazzo, Juan P. Solin, Lawrence J. CA Consensus Conference Comm TI Proceedings of the consensus conference on breast conservation, Milan, Italy, April 28 May 1, 2005 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA. European Sch Oncol, Milan, Italy. Paris Breast Ctr, Paris, France. Western Gen Hosp, Edinbugh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Guys Hosp, Dept Surg Oncol, London SE1 9RT, England. Tech Univ Munich, Klinikum Rechts Isar, Dept Breast Imaging & Intervent, D-8000 Munich, Germany. Univ Nijmegen, Med Ctr, Natl Expert & Training Ctr Breast Canc Screening, Nijmegen, Netherlands. Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. Univ Cardiff Wales, Wales Coll Med, Div Hosp Specialties, Cardiff, S Glam, Wales. McGill Univ, Jewish Gen Hosp, Dept Surg, Montreal, PQ H3T 1E2, Canada. Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. Univ British Columbia, Div Radiat Oncol, Victoria, BC, Canada. British Columbia Canc Agcy, Victoria, BC, Canada. Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Schwartz, GF (reprint author), Breast Hlth Inst, 1616 Walnut St,Suite 1520, Philadelphia, PA 19103 USA. EM gordon.schwartz@yahoo.com NR 2 TC 6 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2006 VL 65 IS 5 BP 1281 EP 1288 DI 10.1016/j.ijrobp.2006.04.001 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 069JL UT WOS:000239442100001 PM 16924719 ER PT J AU Taghian, AG Kozak, KR Katz, A Adams, J Lu, HM Powell, SN DeLaney, TF AF Taghian, Alphonse G. Kozak, Kevin R. Katz, Angela Adams, Judith Lu, Hsiao-Ming Powell, Simon N. DeLaney, Thomas F. TI Accelerated partial breast irradiation using proton beams: Initial dosimetric experience SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol DE breast cancer; Partial breast irradiation; 3D-conformal; proton beams; cost analysis ID CLINICAL-EXPERIENCE; RADIATION-THERAPY; CONSERVING THERAPY; BRACHYTHERAPY; CANCER; RADIOTHERAPY; REPRODUCIBILITY; IMPLANT; SURGERY; TRIAL AB Purpose: The unique dosimetric features of proton radiotherapy make it an attractive modality for normal tissue sparing. We present our initial experience with protons for three-dimensional, conformal, external-beam accelerated partial breast irradiation (3D-CPBI). Methods and Materials: From March 2004 to June 2005, 25 patients with tumors <= 2 cm and negative axillary nodes were treated with proton 3D-CPBI. The prescribed dose was 32 Cobalt Gray Equivalents (CGE) in 4 CGE fractions given twice daily. One to three fields were used to provide adequate planning target volume (PTV) coverage and dose homogeneity. Results: Excellent PTV coverage and dose homogeneity were obtained in all patients with one to three proton beams. The median PTV receiving 95% of the prescribed dose was 100%. Dose inhomogeneity exceeded 10% in only 1 patient (4%). The median volume of nontarget breast tissue receiving 50% of the prescribed dose was 23%. Median volumes of ipsilateral lung receiving 20 CGE, 10 CGE, and 5 CGE were 0%, 1%, and 2%, respectively. The contralateral lung and heart received essentially no radiation dose. Cost analysis suggests that proton 3D-CPBI is only modestly more expensive (25%) than traditional whole-breast irradiation (WBI). Conclusion: Proton 3D-CPBI is technically feasible, providing both excellent PTV coverage and normal tissue sparing. It markedly reduces the volume of nontarget breast tissue irradiated compared with photon-based 3D-CPBI, addressing a principle disadvantage of external-beam approaches to PBI. As proton therapy becomes more widely available, it may prove an attractive tool for 3D-CPBI. (c) 2006 Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX-3, Boston, MA 02114 USA. EM ataghian@partners.org FU NCI NIH HHS [P50 CA89393, P01 CA21239] NR 25 TC 38 Z9 39 U1 0 U2 3 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 AUG 1 PY 2006 VL 65 IS 5 BP 1404 EP 1410 DI 10.1016/j.ijrobp.2006.03.017 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 069JL UT WOS:000239442100017 PM 16730137 ER PT J AU Cardinale, R Won, M Choucair, A Gillin, M Chakravarti, A Schultz, C Souhami, L Chen, A Pham, H Mehta, M AF Cardinale, Robert Won, Minhee Choucair, Ali Gillin, Michael Chakravarti, Arnab Schultz, Christopher Souhami, Luis Chen, Allan Pham, Huong Mehta, Minesh TI A phase II trial of accelerated radiotherapy using weekly stereotactic conformal boost for supratentorial glioblastoma multiforme: RTOG 0023 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE glioblastoma multiforme; stereotactic radiotherapy; accelerated radiotherapy; radiosurgery; dose escalation ID HYPERFRACTIONATED RADIATION-THERAPY; MALIGNANT GLIOMAS; FINAL REPORT; RADIOSURGERY; REPOPULATION; NITROSOUREA; IRRADIATION; ASTROCYTOMA; CARMUSTINE AB Purpose: This phase II trial was performed to assess the feasibility, toxicity, and efficacy of dose-intense accelerated radiation therapy using weekly fractionated stereotactic radiotherapy (FSRT) boost for patients with glioblastoma multiforme (GBM). Methods and Materials: Patients with histologicatly confirmed GBM with postoperative enhancing tumor plus tumor cavity diameter < 60 turn were enrolled. A 50-Gy dose of standard radiation therapy (RT) was given in daily 2-Gy fractions. In addition, patients received four FSRT treatments, once weekly, during Weeks 3 to 6. FSRT dosing of either 5 Gy or 7 Gy per fraction was given for a cumulative dose of 70 or 78 Gy in 29 (25 standard RT + 4 FSRT) treatments over 6 weeks. After the RT course, carmustine (BCNU) at 80 mg/m(2) was given for 3 days, every 8 weeks, for 6 cycles. Results: A total of 76 patients were analyzed. Toxicity included: 3 Grade 4 chemotherapy, 3 acute Grade 4 radiotherapy, and 1 Grade 3 late. The median survival time was 12.5 months. No survival difference is seen when compared with the RTOG historical database. Patients with gross total resection (41%) had a median survival time of 16.6 months vs. 12.0 months for historic controls with gross total resection (P = 0.14). Conclusion: This first, multi-institutional FSRT boost trial for GBM was feasible and well tolerated. There is no significant survival benefit using this dose-intense RT regimen. Subset analysis revealed a trend toward improved outcome for GTR patients suggesting that patients with minimal disease burden may benefit from this form of accelerated RT. (c) 2006 Elsevier Inc. C1 Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23284 USA. Radiat Therapy Oncol Grp Headquarters, Philadelphia, PA USA. LDS Hosp, Salt Lake City, UT USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. Univ Calif Davis, Davis, CA 95616 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. RP Cardinale, R (reprint author), Med Ctr Princeton, Dept Radiat Oncol, 253 Witherspoon St, Princeton, NJ 08540 USA. EM bobcardinale@aol.com OI mehta, minesh/0000-0002-4812-5713 NR 26 TC 45 Z9 48 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2006 VL 65 IS 5 BP 1422 EP 1428 DI 10.1016/j.ijrobp.2006.02.042 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 069JL UT WOS:000239442100020 PM 16750317 ER PT J AU Kuban, DA Levy, LB Potters, L Beyer, DC Blasko, JC Moran, BJ Ciezki, JP Zietman, AL Zelefsky, MJ Pisansky, TM Elshaikh, M Horwitz, EM AF Kuban, Deborah A. Levy, Larry B. Potters, Louis Beyer, David C. Blasko, John C. Moran, Brian J. Ciezki, Jay P. Zietman, Anthony L. Zelefsky, Michael J. Pisansky, Thomas M. Elshaikh, Mohamed Horwitz, Eric M. TI Comparison of biochemical failure definitions for permanent prostate brachytherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE brachytherapy; prostate; implant; PSA; failure ID ONCOLOGY CONSENSUS DEFINITION; RADIATION-THERAPY; AMERICAN-SOCIETY; FOLLOW-UP; RADICAL PROSTATECTOMY; CANCER; RADIOLOGY; RECOMMENDATIONS; RADIOTHERAPY; DOSIMETRY AB Purpose: To assess prostate-specific antigen (PSA) failure definitions for patients with Stage T1-T2 prostate cancer treated by permanent prostate brachytherapy. Methods and Materials: A total of 2,693 patients treated with radioisotopic implant as solitary treatment for T1-T2 prostatic adenocarcinoma were studied. All patients had a pretreatment PSA, were treated at least 5 years before analysis, 1988 to 1998, and did not receive hormonal therapy before recurrence. Multiple PSA failure definitions were tested for their ability to predict clinical failure. Results: Definitions which determined failure by a certain increment of PSA rise above the lowest PSA level to date (nadir + x ng/mL) were more sensitive and specific than failure definitions based on PSA doubling time or a certain number of PSA rises. The sensitivity and specificity for the nadir + 2 definition were 72% and 83%, vs. 51% and 81% for 3 PSA rises. The surgical type definitions (PSA exceeding an absolute value) could match this sensitivity and specificity but only when failure was defined as exceeding a PSA level in the 1-3 ng/mL range and only when patients were allowed adequate time to nadir. When failure definitions were compared by time varying covariate regression analysis, nadir + 2 ng/mL retained the best fit. Conclusions: For patients treated by permanent radioisotopic implant for prostate cancer, the definition nadir + 2 ng/mL provides the best surrogate for failure throughout the entire follow-up period, similar to patients treated by external beam radiotherapy. Therefore, the same PSA failure definition could be used for both modalities. For brachytherapy patients with long-term follow-up, at least 6 years, defining failure as exceeding an absolute PSA level in the 0.5 ng/mL range may be reasonable. (c) 2006 Elsevier Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. New York Prostate Inst, Oceanside, NY USA. Arizona Oncol Serv, Scottsdale, AZ USA. Seattle Prostate Inst, Seattle, WA USA. Chicago Prostate Inst, Chicago, IL USA. Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. RP Kuban, DA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Box 97, Houston, TX 77030 USA. EM dakuban@mdanderson.org OI Potters, Louis/0000-0003-4922-2061 NR 16 TC 74 Z9 78 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 AUG 1 PY 2006 VL 65 IS 5 BP 1487 EP 1493 DI 10.1016/j.ijrobp.2006.03.027 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 069JL UT WOS:000239442100028 PM 16750326 ER PT J AU Viswanathan, AN Lee, H Hanson, E Berkowitz, RS Crum, CP AF Viswanathan, Akila N. Lee, Hang Hanson, Emily Berkowitz, Ross S. Crum, Christopher P. TI Influence of margin status and radiation on recurrence after radical hysterectomy in Stage IB cervical cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE cervical cancer; margins; surgery; radiotherapy ID GYNECOLOGIC-ONCOLOGY-GROUP; SQUAMOUS-CELL CARCINOMA; PELVIC RADIATION; UTERINE CERVIX; POSTOPERATIVE RADIATION; OVARIAN TRANSPOSITION; PROGNOSTIC-FACTOR; ADJUVANT THERAPY; HIGH-RISK; RADIOTHERAPY AB Purpose: To examine the relationship between margin status and local recurrence (LR) or any recurrence after radical hysterectomy (RH) in women treated with or without radiotherapy (RT) for Stage IB cervical carcinoma. Methods and Materials: This study included 284 patients after RH with assessable margins between 1980 and 2000. Each margin was scored as negative (>= 1 cm), close (> 0 and < 1 cm), or positive. The outcomes measured were any recurrence, LR, and relapse-free survival. Results: The crude rate for any recurrence was 11%, 20%, and 38% for patients with negative, close, and positive margins, respectively. The crude rate for LR was 10%, 11%, and 38%, respectively. Postoperative RT decreased the rate of LR from 10% to 0% for negative, 17% to 0% for close, and 50% to 25% for positive margins. The significant predictors of decreased relapse-free survival on univariate analysis were the depth of tumor invasion (hazard ratio [HR] 2.14/cm increase, p = 0.007), positive margins (HR 3.92, p = 0.02), tumor size (HR 1.3/cm increase, p = 0.02), lymphovascular invasion (HR 2.19, p = 0.03), and margin status (HR 0.002/increasing millimeter from cancer for those with close margins, p = 0.03). Long-term side effects occurred in 8% after RH and 19% after RH and RT. Conclusion: The use of postoperative RT may decrease the risk of LR in patients with close paracervical margins. Patients with other adverse prognostic factors and close margins may also benefit from the use of postoperative RT. However, RT after RH may increase the risk of long-term side effects. (c) 2006 Elsevier Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM aviswanathan@partners.org OI Viswanathan, Akila/0000-0002-2003-0392 NR 43 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2006 VL 65 IS 5 BP 1501 EP 1507 DI 10.1016/j.ijrobp.2006.03.010 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 069JL UT WOS:000239442100030 PM 16750323 ER PT J AU Park, L DeLaney, TF Liebsch, NJ Hornicek, FJ Goldberg, S Mankin, H Rosenberg, AE Rosenthal, DI Suit, HD AF Park, Lily DeLaney, Thomas F. Liebsch, Norbert J. Hornicek, Francis J. Goldberg, Saveli Mankin, Henry Rosenberg, Andrew E. Rosenthal, Daniel I. Suit, Herman D. TI Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE chordoma; sacrum; radiation therapy; proton therapy ID CARBON ION RADIOTHERAPY; SACROCOCCYGEAL CHORDOMA; SURGICAL-TREATMENT; PROGNOSTIC-FACTORS; SPINAL CHORDOMAS; IRRADIATION; MANAGEMENT; EXPRESSION AB Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received >= 73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by >= 73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option. (c) 2006 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Park, L (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM lilypark@hotmail.com FU NCI NIH HHS [P01 CA21239] NR 30 TC 101 Z9 103 U1 0 U2 5 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 AUG 1 PY 2006 VL 65 IS 5 BP 1514 EP 1521 DI 10.1016/j.ijrobp.2006.02.059 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 069JL UT WOS:000239442100032 PM 16757128 ER PT J AU Kozak, KR Katz, A Adams, J Crowley, EM Nyamwanda, JA Feng, JK Doppke, KP DeLaney, TF Taghian, AG AF Kozak, Kevin R. Katz, Angela Adams, Judith Crowley, Elizabeth M. Nyamwanda, Jacqueline A. Feng, Jennifer K. Doppke, Karen P. DeLaney, Thomas F. Taghian, Alphonse G. TI Dosimetric comparison of proton and photon three-dimensional, conformal, external beam accelerated partial breast irradiation techniques SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE 3D-conformal; breast cancer; comparison; partial breast irradiation; protons ID VOLUME HISTOGRAM ANALYSIS; ENDOMYOCARDIAL BIOPSY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; PERFUSION CHANGES; RANDOMIZED-TRIAL; HEART-DISEASE; LUNG-CANCER; RADIOTHERAPY; TRASTUZUMAB AB Purpose: To compare the dosimetry of proton and photon-electron three-dimensional, conformal, external beam accelerated partial breast irradiation (3D-CPBI). Methods and Materials: Twenty-four patients with fully excised, Stage I breast cancer treated with adjuvant proton 3D-CPBI had treatment plans generated using the mixed-modality, photon-electron 3D-CPBI technique. To facilitate dosimetric comparisons, planning target volumes (PTVs; lumpectomy site plus 1.5-2.0 cm margin) and prescribed dose (32 Gy) were held constant. Plans were optimized for PTV coverage and normal tissue sparing. Results: Proton and mixed-modality plans both provided acceptable PTV coverage with 95% of the PTV receiving 90% of the prescribed dose in all cases. Both techniques also provided excellent dose homogeneity with a dose maximum exceeding 110% of the prescribed dose in only one case. Proton 3D-CPBI reduced the volume of nontarget breast tissue receiving 50% of the prescribed dose by an average of 36%. Statistically significant reductions in the volume of total ipsilateral breast receiving 100%, 75%, 50%, and 25% of the prescribed dose were also observed. The use of protons resulted in small, but statistically significant, reductions in the radiation dose delivered to 5%, 10%, and 20% of ipsilateral and contralateral lung and heart. The nontarget breast tissue dosimetric advantages of proton 3D-CPBI were not dependent on tumor location, breast size, PTV size, or the ratio of PTV to breast volume. Conclusions: Compared to photon-electron 3D-CPBI, proton 3D-CPBI significantly reduces the volume of irradiated nontarget breast tissue. Both approaches to accelerated partial breast irradiation offer exceptional lung and heart sparing. (c) 2006 Elsevier Inc. C1 Harvard Univ, Dept Radiat Oncol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Dept Radiat Oncol, Sch Med, Massachusetts Gen Hosp, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM ataghian@partners.org FU NCI NIH HHS [P50 CA89393] NR 34 TC 38 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2006 VL 65 IS 5 BP 1572 EP 1578 DI 10.1016/j.ijrobp.2006.04.025 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 069JL UT WOS:000239442100039 PM 16863934 ER PT J AU Montezuma, SR Loewenstein, J Scholz, C Rizzo, JF AF Montezuma, Sandra R. Loewenstein, John Scholz, Carmen Rizzo, Joseph F., III TI Biocompatibility of materials implanted into the subretinal space of Yucatan pigs SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LONG-TERM IMPLANTATION; RETINAL PROSTHESIS; ELECTRICAL-STIMULATION; MICROELECTRODE ARRAYS; ELECTRODE ARRAY; DETACHMENT; VITRECTOMY; RECOVERY; DIAMOND; DOGS AB PURPOSE. To assess the biocompatibility of materials for possible use in subretinal prostheses. METHODS. Strips ( 0.5 x 5 mm; 10-mu m thick) of either plain poly( imide) or poly( imide) coated with amorphous aluminum oxide ( AAO), amorphous carbon ( AC), parylene, poly( vinyl pyrrolidone) ( PVP), or poly( ethylene glycol) ( PEG) were each implanted into the subretinal space of four Yucatan miniature pigs. Two types of control surgery without implantation were performed in four other animals. Electroretinograms ( ERGs) were performed before and after surgery. All animals were euthanatized 3 months after surgery, and histologic slides of the retina were assessed for 15 criteria. Paired, two-tailed Student's t-tests were used for statistical analyses. RESULTS. Across all animals, the mean amplitude of the ERG b-wave did not differ from baseline after 3 months. In implanted animals, the histologic analyses revealed that ( 1) all the implanted materials produced abnormalities that were significantly greater than in the control subjects; ( 2) overall, PEG, parylene, and PVP produced less histologic disruption than the other three materials; ( 3) parylene and PEG did not differ significantly from the control in disturbing retinal anatomy; ( 4) only PI and AAO produced RPE alterations that were significantly greater than in control subjects; and ( 5) AAO and PI produced a significantly greater degree of peri-implant cellular responses than did the other materials. CONCLUSIONS. All implants produced some alteration of the retina, but there were clear differences among the materials in the degree to which their presence disturbed the normal anatomy of the retina or RPE or incited tissue reactions around the implant. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Univ Alabama, Dept Chem Engn, Huntsville, AL 35899 USA. VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM joseph_rizzo@meei.harvard.edu NR 24 TC 47 Z9 50 U1 0 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2006 VL 47 IS 8 BP 3514 EP 3522 DI 10.1167/iovs.06-0106 PG 9 WC Ophthalmology SC Ophthalmology GA 069JC UT WOS:000239441200040 PM 16877423 ER EF