FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gandhi, RT Spritzler, J Chan, E Asmuth, DM Rodriguez, B Merigan, TC Hirsch, MS Shafer, RW Robbins, GK Pollard, RB AF Gandhi, Rajesh T. Spritzler, John Chan, Ellen Asmuth, David M. Rodriguez, Benigno Merigan, Thomas C. Hirsch, Martin S. Shafer, Robert W. Robbins, Gregory K. Pollard, Richard B. CA ACTG 384 Team TI Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: Results from ACTG 384 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; antiretroviral therapy; immunologic outcomes; CD4 cell recovery; T-cell activation; memory and naive CD4 cell subsets ID SEQUENTIAL 3-DRUG REGIMENS; VIRUS-INFECTED PATIENTS; T-CELL DEPLETION; HIV-1 INFECTION; IMMUNE RECONSTITUTION; VIRAL SUPPRESSION; INDIVIDUALS; DISEASE; AGE; REDISTRIBUTION AB Objective: To assess the effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy (ART). Methods: Nine hundred eighty antiretroviral-naive HIV-1+ subjects were randomized to start stavudine/didanosine or zidovudine/lamivudine with nelfinavir, efavirenz, or both nelfinavir and efavirenz. Results: Greater CD4 cell recovery was associated with age of 40 years or younger, female sex, higher baseline naive/memory CD4 cell ratio, higher baseline virus load (VL), and virologic suppression (VS). Most subjects who maintained an undetectable VL had a substantial increase in CD4 cell count, but 13% of the subjects did not, even after 3 years of VS. Persistent T-cell activation was associated with lower CD4 cell recovery, even in subjects who achieved VS. Initial treatment assignment did not affect total CD4 cell recovery, naive/memory CD4 cell reconstitution, or decline in T-cell activation. In addition to CD4 cell recovery, B-cell counts rose substantially after ART initiation. Conclusions: In this large randomized trial, younger age, female sex, higher naive/memory CD4 cell ratio, higher baseline VL, and VS were associated with greater CD4 cell increase, whereas per sistent T-cell activation was associated with impaired CD4 cell recovery after ART initiation. Initial treatment assignment did not affect CD4 cell reconstitution. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Calif Davis, Med Ctr, Davis, CA 95616 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM rgandhi@partners.org RI Robbins, Gregory/F-7988-2011; Rodriguez, Benigno/C-3365-2009 OI Rodriguez, Benigno/0000-0001-9736-7957 FU NIAID NIH HHS [AI27659, AI25879, AI27666, AI38855, AI38858] NR 23 TC 99 Z9 102 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2006 VL 42 IS 4 BP 426 EP 434 DI 10.1097/01.qai.0000226789.51992.3f PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 064ZL UT WOS:000239129100006 PM 16810109 ER PT J AU Hulgan, T Hughes, M Xin, S Smeaton, LM Terry, E Robbins, GK Shafer, RW Clifford, DB McComsey, GA Canter, JA Morrow, JD Haas, DW AF Hulgan, Todd Hughes, Michael Xin Sun Smeaton, Laura M. Terry, Erin Robbins, Gregory K. Shafer, Robert W. Clifford, David B. McComsey, Grace A. Canter, Jeffery A. Morrow, Jason D. Haas, David W. TI Oxidant stress and peripheral neuropathy during antiretroviral therapy: An AIDS Clinical Trials Group Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 12th Conference on Retroviruses and Opportunistic Infections CY FEB 22-25, 2005 CL Boston, MA DE HIV; peripheral neuropathies; oxidative stress; reverse transcriptase inhibitors; drug toxicity ID REVERSE-TRANSCRIPTASE INHIBITORS; IMMUNODEFICIENCY-VIRUS-INFECTION; MITOCHONDRIAL-DNA DEPLETION; SEQUENTIAL 3-DRUG REGIMENS; LIPID-PEROXIDATION; NUCLEOSIDE ANALOGS; OXIDATIVE STRESS; HIV-1 INFECTION; INITIAL THERAPY; IN-VIVO AB Background: Peripheral neuropathy that complicates HIV nucleoside reverse transcriptase inhibitor (NRTI) therapy is likely caused by mitochondrial injury. Mitochondria play a central role in regulating oxidant stress. We explored the relationships between oxidant stress and NRTI-induced peripheral neuropathy. Methods: The AIDS Clinical Trials Group (ACTG) study 384 randomized antiretroviral -naive individuals to receive didanosine/stavudine or zidovudine/lamivudine, plus efavirenz, nelfinavir, or both. The participants were followed for up to 3 years. Peripheral neuropathy was ascertained by signs and symptoms. We performed a case-control study of ACTG 384 participants. Peripheral neuropathy cases and nonneuropathy control subjects were selected from didanosine/stavudine recipients. Alternate control subjects were selected from zidovudine/lamivudine recipients who developed peripheral neuropathy. Oxidant stress was assessed by quantifying F-2-isoprostanes (F-2-ISOPS) in cryopreserved plasma. Results: Seventy-five cases, 71 control subjects, and 18 alternate control subjects were identified. The median baseline F-2-ISOP values were 53 (interquartile range [IQR], 40-85), 57 (IQR, 41 - 77), and 53 (IQR, 47 - 101) pg/mL, respectively, and did not differ between cases and control subjects (P = 0.78) or alternate control subjects (P = 0.60). Changes in F2-ISOPS from baseline to time of peripheral neuropathy did not differ significantly between cases (median, 10 [IQR, - 17 to 26] pg/mL) and control subjects (median, 4 [IQR, -11 to 17] pg/mL; P = 0.48) or alternate control subjects (median, 1 [IQR, -48 to 10] pg/mL; P = 0.21). Conclusions: Peripheral neuropathy that complicates antiretroviral therapy with NRTIs was not associated with increased systemic oxidant stress assessed by plasma F-2-ISOPS. Conclusions: Peripheral neuropathy that complicates antiretroviral therapy with NRTIs was not associated with increased systemic oxidant stress assessed by plasma F-2-ISOPS. C1 Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37203 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Stanford Univ, Stanford, CA 94305 USA. Washington Univ, Sch Med, St Louis, MO USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Hulgan, T (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, 345 24th Ave N,Suite 105, Nashville, TN 37203 USA. EM todd.hulgan@vanderbilt.edu RI Robbins, Gregory/F-7988-2011; Hulgan, Todd/B-3947-2014 OI Hulgan, Todd/0000-0002-3339-067X NR 33 TC 8 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2006 VL 42 IS 4 BP 450 EP 454 DI 10.1097/01.qai.0000226792.16216.1c PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 064ZL UT WOS:000239129100009 PM 16791116 ER PT J AU Holmes, CB Wood, R Badri, M Zilber, S Wang, BX Maartens, G Zheng, H Lu, ZG Freedberg, KA Losina, E AF Holmes, Charles B. Wood, Robin Badri, Motasim Zilber, Sophia Wang, Bingxia Maartens, Gary Zheng, Hui Lu, Zhigang Freedberg, Kenneth A. Losina, Elena TI CD4 decline and incidence of opportunistic infections in Cape Town, South Africa: Implications for prophylaxis and treatment SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; opportunistic infections; CD4 cell count; South Africa; prophylaxis ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; TOTAL LYMPHOCYTE COUNT; AIDS-DEFINING ILLNESS; HIV-1-INFECTED ADULTS; COTE-DIVOIRE; TRIMETHOPRIM-SULFAMETHOXAZOLE; PREVENTIVE THERAPY; NATURAL-HISTORY AB Objectives: To determine the rate of CD4 decline and the incidence of opportunistic infections (OIs) among antiretroviral therapy-naive South African HIV-infected patients and inform timing of OI prophylaxis. Methods: We used mixed-effect models to estimate CD4 cell decline by CD4 cell count strata in HIV-infected patients in the Cape Town AIDS Cohort between 1984 and 2000. Stratum-specific OI incidence per 100 person-years of observation was determined using incidence density analysis. Results: Nine hundred seventy-four patients with 2 or more CD4 cell counts were included. CD4 counts declined by 47.1 cells/mu L per year in the stratum with more than 500 cells/mu L, 30.6 cells/mu L per year in the stratum with 351 to 500 cells/mu L, and 20.5 cells/mu L per year in the stratum with 201 to 350 cells/mu L. Tuberculosis and oral candidiasis were the only OIs that occurred frequently in the stratum with more than 200 CD4 cells/RL. Rates of chronic diarrhea, wasting syndrome, tuberculosis, and oral and esophageal candidiasis increased in the stratum with less than 200 cells/mu L, and rates of all OIs were highest in the stratum with 50 cells/mu L or less. Conclusions: CD4 cell count declines were dependent on CD4 strata and can inform timing of clinic visits and treatment initiation in South Africa. Incidence rates of OIs suggest that targeted OI prophylaxis could prevent substantial HIV-related morbidity in South Africa. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr AIDS Res, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Cape Town, Desmond Tutu Res Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. Univ Cape Town, Dept Clin Pharmacol, ZA-7925 Cape Town, South Africa. Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Holmes, CB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 9th Floor,50 Staniford St, Boston, MA 02114 USA. EM cbholmes@partners.org RI Wood, Robin/G-8509-2011; Maartens, Gary/F-3836-2014 OI Maartens, Gary/0000-0003-3080-6606 FU NIAID NIH HHS [K01 AI062440, K24 AI062476, K25 AI050436, K25 AI50436, P30 AI042851, P30 AI42851, T32 AI07433]; PHS HHS [CCU/U64 119525] NR 38 TC 102 Z9 103 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2006 VL 42 IS 4 BP 464 EP 469 DI 10.1097/01.qai.0000225729.79610.b7 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 064ZL UT WOS:000239129100012 PM 16810113 ER PT J AU McCasland, LD Budiman-Mak, E Weaver, FM Adams, E Miskevics, S AF McCasland, Leslie D. Budiman-Mak, Elly Weaver, Frances M. Adams, Elaine Miskevics, Scott TI Shoulder pain in the traumatically injured spinal cord patient - Evaluation of risk factors and function SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE spinal cord injury; shoulder pain; disability; tetraplegia; paraplegia ID UPPER EXTREMITY PAIN; WHEELCHAIR USERS; IMPINGEMENT SYNDROME; DISABILITY INDEX; INDIVIDUALS; RELIABILITY; PARAPLEGIA; VALIDITY; WUSPI AB Background: Shoulder pain in individuals with traumatic spinal cord injury (TSCI) is common and frequently results in chronic debilitating pain recalcitrant to treatment. Objective: Our objectives were to identify the risk factors associated with shoulder pain in the TSCI population. Methods: A telephone survey and medical record review were conducted on a convenience sample of patients with TSCI. Data variables included: Shoulder Pain and Disability Index (SPADI), demographics, injury type, treatment histories for shoulder pain/ dysfunction, assistive device use, and radiographic imaging. Results: Respondents (n = 63) were male (96%) and tetraplegia (51%) with a mean age of 58.1 years. The majority of patients (70%) currently had shoulder pain, one third had previous injury to the shoulder, and 52% reported bilateral pain. Tetraplegics had higher prevalence (80%) of shoulder pain and higher total SPADI scores than paraplegics (P = 0.001). Previous shoulder trauma increased the likelihood of shoulder pain. Self-care posed their most difficult task. Use of a manual wheelchair (71%) and/or trapeze bar (51%) was common. However, no differences were found in wheelchair or trapeze bar use or average body mass index between groups with and without pain. Respondents with pain tended to use trapeze bars less. Of the respondents reporting shoulder pain, an estimated 57% received physical therapy and massage with most reporting some benefit; 53% had pharmaceutical treatment with variable effect. Conclusion: Shoulder pain is common in patients with TSCI. Tetraplegics fared worse than paraplegics. Pain may limit transfer because respondents with pain used trapeze bars less. Understanding and addressing the factors contributing to shoulder pain in this vulnerable population is sorely needed. C1 Loyola Univ, Med Ctr, Dept Rheumatol, Maywood, IL 60153 USA. Dept Vet Affairs, Hines VA Hosp, Hines, IL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Midwest Ctr Hlth Serv & Policy Res, SCI QUERI, Hines, IL USA. RP Budiman-Mak, E (reprint author), Dept Vet Affairs, POB 5000 151-H, Hines, IL 60141 USA. EM elly.mak@va.gov NR 32 TC 23 Z9 24 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD AUG PY 2006 VL 12 IS 4 BP 179 EP 186 DI 10.1097/01.rhu.0000230532.54403.25 PG 8 WC Rheumatology SC Rheumatology GA 071OK UT WOS:000239611300005 PM 16891921 ER PT J AU Dagi, LR Walton, DS AF Dagi, Linda R. Walton, David S. TI Anterior axial lens subluxation, progressive myopia, and angle-closure glaucoma: Recognition and treatment of atypical presentation of ectopia lentis SO JOURNAL OF AAPOS LA English DT Article ID SPONTANEOUS FILTERING BLEBS; MARFAN-SYNDROME; MANIFESTATIONS; FAMILY AB Purpose: To describe the clinical features of an atypical presentation of ectopia lentis consisting of primary anterior axial lens subluxation in childhood, associated progressive myopia, and complicating angle-closure glaucoma; to facilitate early diagnosis of this triad; and to report the results of lensectomy for treatment. Methods., A retrospective case review of eight patients. Clinical course, visual acuity, gonioscopy, axial length, refraction, fundus examination, associated systemic features, and results of treatment are provided. Results. This subgroup of patients with ectopia lentis is at risk for progressive, synechial, angle-closure glaucoma. Identification of a clinical triad consisting of rapidly increasing myopia, normal axial length, and progressive axial subluxation leads to earlier diagnosis. Prophylactic lensectomy provides a safe and sight-saving treatment that arrests and, at times, reverses the progression of angle-closure glaucoma. Conclusions. Ectopia lentis with anterior axial subluxation and progressive myopia can be a sight-threatening condition when significant forward mobilization of the lens results in synechial angle-closure glaucoma. Recognition of this clinical entity can expedite diagnosis and prevent irreversible loss of vision secondary to glaucoma. Because the primary mechanism of angle closure is angle crowding, peripheral iridotomy does little to control the rise in intraocular pressure. Prophylactic lensectomy has proven to be the most reliable treatment in our experience. C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Dagi, LR (reprint author), Harvard Univ, Childrens Hosp, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. EM linda.dagi@childrens.harvard.edu NR 23 TC 10 Z9 11 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD AUG PY 2006 VL 10 IS 4 BP 345 EP 350 DI 10.1016/j.jaapos.2006.01.218 PG 6 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 083MF UT WOS:000240459300013 PM 16935236 ER PT J AU Gilbertson, MW Paulus, LA Williston, SK Gurvits, TV Lasko, NB Pitman, RK Orr, SP AF Gilbertson, Mark W. Paulus, Lynn A. Williston, Stephanie K. Gurvits, Tamara V. Lasko, Natasha B. Pitman, Roger K. Orr, Scott P. TI Neurocognitive function in monozygotic twins discordant for combat exposure: Relationship to posttraumatic stress disorder SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE PTSD; neuropsychology; twins ID SHORT-TERM-MEMORY; HIPPOCAMPAL VOLUME; VIETNAM VETERANS; PREFRONTAL CORTEX; SEXUAL ABUSE; SHORT FORMS; WAIS-R; PTSD; PERFORMANCE; SURVIVORS AB Neuropsychological deficits have been reported among trauma survivors with posttraumatic stress disorder (PTSD). It is often assumed that these cognitive difficulties are toxic consequences of trauma exposure. Alternatively, they may reflect preexisting characteristics that contribute to the likelihood of developing PTSD. To address this possibility, the authors evaluated cognitive performance in monozygotic twin pairs who were discordant for combat exposure. Pairs were grouped according to whether the combat-exposed brother developed PTSD. The combat-unexposed cotwins of combat veterans with PTSD largely displayed the same performance as their brothers, which was significantly lower than that of non-PTSD combat veterans and their brothers. The results support the notion that specific domains of cognitive function may serve as premorbid risk or protective factors in PTSD. C1 Manchester VA Med Ctr, Res Serv 151, Manchester, NH 03104 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gilbertson, MW (reprint author), Manchester VA Med Ctr, Res Serv 151, 718 Smyth Rd, Manchester, NH 03104 USA. EM mark.gilbertson@med.va.gov FU NIMH NIH HHS [K02-MH01110, R01-MH54636] NR 76 TC 91 Z9 94 U1 1 U2 16 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2006 VL 115 IS 3 BP 484 EP 495 DI 10.1037/0021-843X.115-3.484 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 068JH UT WOS:000239369300010 PM 16866589 ER PT J AU Biederman, J Petty, C Faraone, SV Henin, A Hirshfeld-Becker, D Pollack, MH de Figueiredo, S Feeley, R Rosenbaum, JF AF Biederman, Joseph Petty, Carter Faraone, Stephen V. Henin, Aude Hirshfeld-Becker, Dina Pollack, Mark H. de Figueiredo, Sophie Feeley, Robert Rosenbaum, Jerrold F. TI Effects of parental anxiety disorders in children at high risk for panic disorder: A controlled study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE children; anxiety; family; panic disorder ID MAJOR DEPRESSION; SOCIAL PHOBIA; PSYCHIATRIC-DISORDERS; COMORBIDITY; FAMILY; AGORAPHOBIA; HISTORY; PSYCHOPATHOLOGY; ASSOCIATION; ADOLESCENTS AB Background: To examine the association between anxiety disorders in parents and offspring in a sample of children at risk for panic disorder. We hypothesized that individual anxiety disorders will breed true in offspring. Methods: Comparisons were made between offspring of parents with PD + MD (N = 136), PD (N = 27), MD (N = 27), and Controls (N = 103). All subjects were assessed with structured diagnostic interviews. Individual anxiety disorders in the offspring were used as dependent variables in logistic regression models where parental PD status, parental MD, and the same parental anxiety diagnosis were used as independent binary variables. Results: Social phobia and separation anxiety disorder in the offspring were accounted for by the same disorders in the parent, whereas agoraphobia and OCD in the offspring were accounted for by parental panic disorder. Conclusions: These findings suggest that differing risk factors underlie the expression of individual anxiety disorders in children at risk for panic disorder. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care Yaw 6A, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care Yaw 6A, 32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH47077] NR 30 TC 21 Z9 22 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG PY 2006 VL 94 IS 1-3 BP 191 EP 197 DI 10.1016/j.jad.2006.04.012 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 075JI UT WOS:000239880600018 PM 16753222 ER PT J AU Feeney, ME Tang, YH Rathod, A Kneut, C McIntosh, K AF Feeney, Margaret E. Tang, Yanhua Rathod, Almas Kneut, Catherine McIntosh, Kenneth TI Absence of detectable viremia in a perinatally HIV-1-infected teenager after discontinuation of antiretroviral therapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE perinatal HIV; long-term nonprogressor; CCR5; cytotoxic T lymphocytes; CD4 T-H cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; PEDIATRIC HIV-1 INFECTION; MACROPHAGE-TROPIC HIV-1; T-LYMPHOCYTE RESPONSE; DISEASE PROGRESSION; GENETIC RESTRICTION; CELL PROLIFERATION; CCR5; RECEPTOR; CHILDREN AB A 15-year-old girl with perinatal HIV-1 infection has remained asymptomatic with undetectable plasma HIV-1 viremia for more than 5 years after discontinuing all antiretroviral therapy. Viral sequence analysis of proviral HIV-1 DNA revealed no evident fitness-attenuating deletions or mutations. This subject exhibited an unusually robust HIV-specific T-cell response, with an intact CD4(+) T cell-proliferative response to HIV-1 antigens. In addition, the subject was found to be heterozygous for the 32-bp deletion in the CCR5 gene, which encodes the primary coreceptor for HIV-1 entry into cells. This mutation mediates profound resistance to HIV infection in homozygotes and has been associated with delayed disease progression in heterozygotes after both horizontal and vertical HIV-1 infection. Although adults with long-term nonprogressive HIV disease have been studied at length, there is no prior description in the literature of a perinatally HIV-infected child whose plasma HIV-1 viremia is controlled to undetectable levels in the absence of antiretroviral therapy. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Feeney, ME (reprint author), 149 13th St,5th Floor, Charlestown, MA 02129 USA. EM mfeeney@partners.org NR 48 TC 5 Z9 5 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2006 VL 118 IS 2 BP 324 EP 330 DI 10.1016/j.jaci.2006.05.016 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 075IH UT WOS:000239877700004 PM 16890753 ER PT J AU Liu, SM Xavier, R Good, KL Chtanova, T Newton, R Sisavanh, M Zimmer, S Deng, CY Silva, DG Frost, MJ Tangye, SG Rolph, MS Mackay, CR AF Liu, Sue M. Xavier, Ramnik Good, Kim L. Chtanova, Tatyana Newton, Rebecca Sisavanh, Mary Zimmer, Sabine Deng, Chaoyang Silva, Diego G. Frost, Melinda J. Tangye, Stuart G. Rolph, Michael S. Mackay, Charles R. TI Immune cell transcriptome datasets reveal novel leukocyte subset-specific genes and genes associated with allergic processes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergy; gene profiling; leukocyte-specific; toll-like receptors ID HUMAN MAST-CELLS; B-CELLS; DENDRITIC CELL; T-CELLS; MICROARRAY EXPRESSION; ASTHMA PATHOGENESIS; BONE-MARROW; RECEPTOR; RESPONSES; MOUSE AB Background: The precise function of various resting and activated leukocyte subsets remains unclear. For instance, mast cells, basophils, and eosinophils play important roles in allergic inflammation but also participate in other immunologic responses. One strategy to understand leukocyte subset function is to define the expression and function of subset-restricted molecules. Objective: To use a microarray dataset and bioinformatics strategies to identify novel leukocyte markers as well as genes associated with allergic or innate responses. Methods: By using Affymetrix microarrays, we generated an immune transcriptome dataset composed of gene profiles from all of the major leukocyte subsets, including rare enigmatic subsets such as mast cells, basophils, and plasma cells. We also assessed whether analysis of genes expressed commonly by certain groups of leukocytes, such as allergic leukocytes, might identify genes associated with particular responses. Results: Transcripts highly restricted to a single leukocyte subset were readily identified (> 2000 subset-specific transcripts), many of which have not been associated previously with leukocyte functions. Transcripts expressed exclusively by allergy-related leukocytes revealed well known as well as novel molecules, many of which presumably contribute to allergic responses. Likewise, Nearest Neighbor Analysis of genes coexpressed with Toll-like receptors identified genes of potential relevance for innate immunity. Conclusion: Gene profiles from all of the major human leukocyte subsets provide a powerful means to identify genes associated with single leukocyte subsets, or different types of immune response. Clinical implications: A comprehensive dataset of gene expression profiles of human leukocytes should provide new targets or biomarkers for human inflammatory diseases. C1 Garvan Inst Med Res, Immunol & Inflammat Res Program, Sydney, NSW 2010, Australia. Univ Sydney, Cooperat Res Ctr Asthma, Sydney, NSW 2006, Australia. Univ New S Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW, Australia. Massachusetts Gen Hosp, Dept Med & Mol Biol, Boston, MA 02114 USA. Centenary Inst Canc Med & Cell Biol, Camperdown, NSW, Australia. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia. RP Mackay, CR (reprint author), Garvan Inst Med Res, Immunol & Inflammat Res Program, 384 Victoria St, Sydney, NSW 2010, Australia. EM c.mackay@garvan.org.au RI Mackay, Charles/A-9673-2008; Tangye, Stuart/H-4023-2014; OI Mackay, Charles/0000-0002-6338-7340; Good-Jacobson, Kim/0000-0003-1891-7274 FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 48 TC 33 Z9 34 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2006 VL 118 IS 2 BP 496 EP 503 DI 10.1016/j.jaci.2006.04.040 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 075IH UT WOS:000239877700028 PM 16890777 ER PT J AU Tsuang, DW Riekse, RG Purganan, KM David, AC Montine, TJ Schellenberg, GD Steinbart, EJ Petrie, EC Bird, TD Leverenz, JB AF Tsuang, Debby W. Riekse, Robert G. Purganan, Kristina M. David, Andrew C. Montine, Thomas J. Schellenberg, Gerard D. Steinbart, Ellen J. Petrie, Eric C. Bird, Thomas D. Leverenz, James B. TI Lewy body pathology in late-onset familial Alzheimer's disease: A clinicopathological case series SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Lewy body; alpha-synuclein; Alzheimer's disease; amygdala ID ALPHA-SYNUCLEIN; APOLIPOPROTEIN-E; PARKINSONS-DISEASE; BODIES; DEMENTIA; BRAINS; PROGRESSION; CONSORTIUM; ANTIBODIES; DIAGNOSIS AB Background: Lewy body pathology (LBP) is a common finding in Alzheimer's disease (AD), but the pathophysiology for this coexistent pathology remains unclear. Methods: We ascertained late-onset dementia (mean age > 60 years old) families with at least 3 autopsies. We then conducted systematic alpha-synuclein (SNCA) immunostaining to determine the frequency and distribution of LBP in families with late-onset AD. Results: All 32 subjects met NIA-Reagan neuropathological criteria for "high likelihood" of having AD. Hematoxylin and eosin staining detected LBP in the substantia nigra (SN) in 8 (25%) individuals. SNCA immunostaining detected LBP in 21 individuals (66%). While all subjects with SN LBP had co-existent amygdala LBP, many (9/21, 43%) of the cases with amygdala LBP did not have coexistent SN LBP (McNemar's chi-square test, p = 0.008). Each family had at least two cases with LBP, but no family had LBP in all autopsied cases. Conclusions: Presence of significant AD pathology in one family member was highly predictive of similar pathology in other family members. However, despite the use of more sensitive SNCA immunohistochemistry, the presence of LBP was variable within all 7 families. Consistent with previous studies in sporadic and familial AD, the amygdala appeared to be the most vulnerable region for LBP in AD. Additional clinical, neuropathologic, and genetic studies are necessary to determine the clinical and pathological significance of LBP in AD. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Educ Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med Gerontol Geroiatr Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol Neuropathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Tsuang, DW (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM dwt1@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [U01 AG016976, U01-AG16976]; NINDS NIH HHS [R01 NS48595] NR 26 TC 14 Z9 14 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD AUG PY 2006 VL 9 IS 3 BP 235 EP 242 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 091HC UT WOS:000241016700002 PM 16914833 ER PT J AU Liu, Z Lin, YE Stout, JE Hwang, CC Vidic, RD Yu, VL AF Liu, Z. Lin, Y. E. Stout, J. E. Hwang, C. C. Vidic, R. D. Yu, V. L. TI Effect of flow regimes on the presence of Legionella within the biofilm of a model plumbing system SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE biofilm; Legionella; stagnation ID WATER DISTRIBUTION-SYSTEMS; SHEAR-STRESS; PNEUMOPHILA; CONTAMINATION AB Aims: Stagnation is widely believed to predispose water systems to colonization by Legionella. A model plumbing system was constructed to determine the effect of flow regimes on the presence of Legionella within microbial biofilms. Methods and Results: The plumbing model contained three parallel pipes where turbulent, laminar and stagnant flow regimes were established. Four sets of experiments were carried out with Reynolds number from 10 000 to 40 000 and from 355 to 2000 in turbulent and laminar pipes, respectively. Legionella counts recovered from biofilm and planktonic water samples of the three sampling pipes were compared with to determine the effect of flow regime on the presence of Legionella. Significantly higher colony counts of Legionella were recovered from the biofilm of the pipe with turbulent flow compared with the pipe with laminar flow. The lowest counts were in the pipe with stagnant flow. Conclusions: We were unable to demonstrate that stagnant conditions promoted Legionella colonization. Significance and Impact of the Study: Plumbing modifications to remove areas of stagnation including deadlegs are widely recommended, but these modifications are tedious and expensive to perform. Controlled studies in large buildings are needed to validate this unproved hypothesis. C1 Univ Pittsburgh, Dept Mech Engn, Pittsburgh, PA 15261 USA. Natl Kaohsiung Normal Univ, Grad Inst Environm Educ, Kaohsiung, Taiwan. VA Pittsburgh Healthcare Syst, Infect Dis Sect, Special Pathogens Lab, Pittsburgh, PA USA. Univ Pittsburgh, Dept Civil & Environm Engn, Pittsburgh, PA 15260 USA. RP Lin, YE (reprint author), 62 Shen Chong Rd, Kaohsiung, Taiwan. EM easonlin@nknucc.nknu.edu.tw OI Vidic, Radisav/0000-0001-7969-6845 NR 16 TC 22 Z9 25 U1 1 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD AUG PY 2006 VL 101 IS 2 BP 437 EP 442 DI 10.1111/j.1365-2672.2006.02970.x PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 063GL UT WOS:000239006200020 PM 16882152 ER PT J AU Bengs, BC Scott, RD AF Bengs, Benjamin C. Scott, Richard D. TI The effect of patellar thickness on intraoperative knee flexion and patellar tracking in total knee arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE patella; range of motion; tracking; thickness; knee; arthroplasty ID GONIOMETRIC MEASUREMENTS; MOTION; RANGE; RELIABILITY; JOINT; OSTEOARTHRITIS; MOVEMENT; GAIT AB We designed a simple IRB-approved study to evaluate the intraoperative effect of patellar thickness on knee flexion and patellar tracking during total knee arthroplasty. Routine PCL-retaining total knee arthroplasty was performed in 31 consecutive knees. With clinical balance and congruent patella tracking established, custom trial patellar components that were thicker than the standard trial by 2-mm increments (2-8 mm) were sequentially placed and trialed. Passive flexion was recorded to the nearest 5 degrees with an intraoperative goniometer and gross mechanics of patellofemoral tracking were visually assessed. On average, passive knee flexion decreased 3 degrees for every 2-mm increment of patellar thickness. Furthermore, for the knee system used in this study, increased patellar thickness had no gross effect on patellar subluxation or tilt. C1 Massachusetts Gen Hosp, Harvard Combined Orthopaed Surg Residency, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, New England Baptist Hosp,Dept Orthopaed Surg, Boston, MA USA. RP Bengs, BC (reprint author), Massachusetts Gen Hosp, Harvard Combined Orthopaed Surg Residency, Dept Orthopaed Surg, GRB 6, Boston, MA 02114 USA. NR 52 TC 38 Z9 47 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 2006 VL 21 IS 5 BP 650 EP 655 DI 10.1016/j.arth.2005.07.020 PG 6 WC Orthopedics SC Orthopedics GA 074TX UT WOS:000239835800005 PM 16877149 ER PT J AU Davey, ME Duncan, MJ AF Davey, Mary E. Duncan, Margaret J. TI Enhanced biofilm formation and loss of capsule synthesis: Deletion of a putative glycosyltransferase in Porphyromonas gingivalis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI BIOFILMS; PSEUDOMONAS-AERUGINOSA; EPITHELIAL-CELLS; GENE-EXPRESSION; ORAL BACTERIA; ARG-GINGIPAIN; STAPHYLOCOCCUS-EPIDERMIDIS; IRREVERSIBLE ATTACHMENT; NEISSERIA-MENINGITIDIS; MULTISPECIES BIOFILMS AB Periodontitis is a biofilm-mediated disease. Porphyromonas gingivalis is an obligate anaerobe consistently associated with severe manifestations of this disease. As an opportunistic pathogen, the ability to proliferate within and disseminate from subgingival biofilm (plaque) is central to its virulence. Here, we report the isolation of a P. gingivalis transposon insertion mutant altered in biofilm development and the reconstruction and characterization of this mutation in three different wild-type strains. The mutation responsible for the altered biofilm phenotype was in a gene with high sequence similarity (similar to 61%) to a glycosyltransferase gene. The gene is located in a region of the chromosome that includes up to 16 genes predicted to be involved in the synthesis and transport of capsular polysaccharide. The phenotype of the reconstructed mutation in all three wild-type backgrounds is that of enhanced biofilm formation. In addition, in strain W83, a strain that is encapsulated, the glycosyltransferase mutation resulted in a loss of capsule. Further experiments showed that the W83 mutant strain was more hydrophobic and exhibited increased autoaggregation. Our results indicate that we have identified a gene involved in capsular-polysaccharide synthesis in P. gingivalis and that the production of capsule prevented attachment and the initiation of in vitro biofilm formation on polystyrene microtiter plates. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Davey, ME (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM mdavey@forsyth.org FU NIDCR NIH HHS [R01 DE010510, R01 DE10510] NR 90 TC 61 Z9 65 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2006 VL 188 IS 15 BP 5510 EP 5523 DI 10.1128/JB.01685-05 PG 14 WC Microbiology SC Microbiology GA 068IH UT WOS:000239366400020 PM 16855241 ER PT J AU Bingham, J Li, G AF Bingham, Jeffrey Li, Guoan TI An optimized image matching method for determining in-vivo TKA kinematics with a dual-orthogonal fluoroscopic imaging system SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID KNEE REPLACEMENT KINEMATICS; SINGLE-PLANE FLUOROSCOPY; IMPLANT MODELS; REGISTRATION; POSITION; ARTHROPLASTY AB This study presents an optimized matching algorithm for a dual-orthogonal fluoroscopic image system used to determine six degrees-of-freedom total knee arthroplasty (TYA) kinematics in-vivo. The algorithm was evaluated using controlled conditions and standard geometries. Results of the validation demonstrate the algorithm's robustness and capability of realizing-a pose from a variety of initial poses. Under idealized conditions, poses of a TKA system were recreated to within 0.02 +/- 0.01 mm and 0.02 +/- 0.03 deg for the femoral component and 0.07 +/- 0.09 mm and 0.16 +/- 0.18 deg for the tibial component. By employing a standardized geometry with spheres, the translational accuracy and repeatability under actual conditions was found to be 0.01 +/- 0.06 mm. Application of the optimized matching algorithm to a TKA patient showed that the pose of in-vivo TKA components can be repeatedly located, with standard deviations less than +/- 0.12 mm and +/- 0.12 deg for the femoral component and +/- 0.29 mm and +/- 0.25 deg for the tibial component. This methodology presents a useful tool that can be readily applied to the investigation of in-vivo motion of TKA kinematics. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. MIT, Dept Mech Engn, Boston, MA USA. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org RI Bingham, Jeffrey/I-6901-2012 OI Bingham, Jeffrey/0000-0002-9590-8526 FU NIAMS NIH HHS [R01 AR052408] NR 29 TC 51 Z9 53 U1 2 U2 8 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 EI 1528-8951 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD AUG PY 2006 VL 128 IS 4 BP 588 EP 595 DI 10.1115/1.2205865 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 066MK UT WOS:000239233600013 PM 16813450 ER PT J AU Bandyopadhyay, S Ni, J Ruggiero, A Walshe, K Rogers, MS Chattopadhyay, N Glicksman, MA Rogers, JT AF Bandyopadhyay, Sanghamitra Ni, Jake Ruggiero, Amy Walshe, Karen Rogers, Mark S. Chattopadhyay, Naibedya Glicksman, Marcie A. Rogers, Jack T. TI High-throughput drug screen targeted to the 5 ' untranslated region of Alzheimer amyloid precursor protein mRNA SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE Alzheimer disease; APP mRNA 5 ' UTR; HTS; luciferase; drugs; inhibitors ID HUMAN PRION PROTEIN; IRON-RESPONSIVE ELEMENT; MOLECULAR-CLONING; DISEASE; INHIBITORS; DISCOVERY; ASSAY; GENE; AMYLOIDOGENESIS; INTERLEUKIN-1 AB The authors employed a novel approach to identify therapeutics effective in Alzheimer disease (AD). The 5' untranslated region (5'UTR) of the mRNA of AD amyloid precursor protein (APP) is a significant regulator of the levels of the APP holo-protein and amyloid beta (A beta) peptide in the central nervous system. The authors generated stable neuroblastoma SH-SY5Y transfectants that express luciferase under the translational control of the 146-nucleotide APP mRNA 5'UTR. and green fluorescent protein (GFP) driven by a viral internal ribosomal entry site. Using a high-throughput screen (HTS), they screened for the effect of I 10,000 compounds obtained from the library of the Laboratory for Drug Discovery on Neurodegeneration (LDDN) on the APP mRNA 5'UTR-controlled translation of the luciferase reporter. This screening yielded several nontoxic specific inhibitors of APP mRNA 5'UTR-driven luciferase that had no effect on the GFP expression in the stable SH-SY5Y transfectants. Moreover, these compounds either did not inhibit or inhibited to a much lower extent the expression of the luciferase reporter regulated by a prion protein (PrP) mRNA 5'UTR, used as an alternative mRNA structure to counterscreen APP mRNA 5'UTR in stably transfected SH-SY5Y cell lines. The hits obtained from this robust, specific, and highly quantitative HTS will be characterized to identify agents that may be developed into useful future therapeutic agents to limit APP translation and A beta production for AD. C1 Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Genet & Aging Res Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Lab Drug Discovery Neurodegenerat, Boston, MA 02115 USA. Univ Coll Dublin, Sch Biol & Environm Sci, Dublin 2, Ireland. Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Rogers, JT (reprint author), MGH, Genet & Aging Res Unit, Charlestown, MA 02129 USA. EM jtrogers@rics.bwh.harvard.edu RI Rogers, Mark/M-4524-2013 OI Rogers, Mark/0000-0002-5288-0295 FU NIA NIH HHS [R0-1 AG20181] NR 41 TC 29 Z9 29 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD AUG PY 2006 VL 11 IS 5 BP 469 EP 480 DI 10.1177/1087057106287271 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 077AD UT WOS:000239999200002 PM 16928984 ER PT J AU Doornberg, J Lindenhovius, A Kloen, P Van Dijk, CN Zurakowski, D Ring, D AF Doornberg, Job Lindenhovius, Anneluuk Kloen, Peter Van Dijk, C. Niek Zurakowski, David Ring, David TI Two and three-dimensional computed tomography for the classification and management of distal humeral fractures - Evaluation of reliability and diagnostic accuracy SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID INTEROBSERVER RELIABILITY; PLAIN RADIOGRAPHS; INTRAOBSERVER REPRODUCIBILITY; ORTHOPEDIC SURGEONS; NEER-CLASSIFICATION; OBSERVER VARIATION; COMPLEX FRACTURES; RADIUS FRACTURES; PROXIMAL HUMERUS; AGREEMENT AB Background: Complex fractures of the distal part of the humerus can be difficult to characterize on plain radiographs and two-dimensional computed tomography scans. We tested the hypothesis that three-dimensional reconstructions of computed tomography scans improve the reliability and accuracy of fracture characterization, classification, and treatment decisions. Methods: Five independent observers evaluated thirty consecutive intra-articular fractures of the distal part of the humerus for the presence of five fracture characteristics: a fracture line in the coronal plane; articular comminution; metaphyseal comminution; the presence of separate, entirely articular fragments; and impaction of the articular surface. Fractures were also classified according to the AO/ASIF Comprehensive Classification of Fractures and the classification system of Mehne and Matta. Two rounds of evaluation were performed and then compared. Initially, a combination of plain radiographs and two-dimensional computed tomography scans (2D) were evaluated, and then, two weeks later, a combination of radiographs, two-dimensional computed tomography scans, and three-dimensional reconstructions of computed tomography scans (31)) were assessed. Results: Three-dimensional computed tomography improved both the intraobserver and the interobserver reliability of the AO classification system and the Mehne and Matta classification system. Three-dimensional computed tomography reconstructions also improved the intraobserver agreement for all fracture characteristics, from moderate (average kappa [K-2D] = 0.554) to substantial agreement (K-3D = 0.793). The addition of three-dimensional images had limited influence on the interobserver reliability and diagnostic characteristics (sensitivity, specificity, and accuracy) for the recognition of specific fracture characteristics. Three-dimensional computed tomography images improved intraobserver agreement (K-2D = 0.62 compared with K-3D = 0.75) but not interobserver agreement (K-2D = 0.24 compared with K-3D = 0.28) for treatment decisions. Conclusions: Three-dimensional reconstructions improve the reliability, but not the accuracy, of fracture classification and characterization. The influence of three-dimensional computed tomography was much more notable for intraobserver comparisons than for interobserver comparisons, suggesting that different observers see different things in the scans-most likely a reflection of the training, knowledge, and experience of the observer with regard to these relatively uncommon and complex injuries. C1 Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02116 USA. Acad Med Ctr, NL-1100 DD Amsterdam, Netherlands. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. RP Doornberg, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02116 USA. EM p.kloen@amc.uva.nl; dring@partners.org NR 39 TC 65 Z9 67 U1 1 U2 6 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 2006 VL 88A IS 8 BP 1795 EP 1801 DI 10.2106/JBJS.E.00944 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 071XV UT WOS:000239638100016 PM 16882904 ER PT J AU Li, GA Moses, JM Papannagari, R Pathare, NP DeFrate, LE Gill, TJ AF Li, Guoan Moses, Jeremy M. Papannagari, Ramprasad Pathare, Neil P. DeFrate, Louis E. Gill, Thomas J. TI Anterior cruciate ligament deficiency alters the in vivo motion of the tibiofemoral cartilage contact points in both the anteroposterior and mediolateral directions SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTICULAR-CARTILAGE; KNEE FLEXION; INJURED KNEE; FOLLOW-UP; JOINT KINEMATICS; RECONSTRUCTION; ACL; RUPTURE; OSTEOARTHRITIS; LESIONS AB Background: Quantifying the effects of anterior cruciate ligament deficiency on joint biomechanics is critical in order to better understand the mechanisms of joint degeneration in anterior cruciate ligament-deficient knees and to improve the surgical treatment of anterior cruciate ligament injuries. We investigated the changes in position of the in vivo tibiofemoral articular cartilage contact points in anterior cruciate ligament-deficient and intact contralateral knees with use of a newly developed dual orthogonal fluoroscopic and magnetic resonance imaging technique. Methods: Nine patients with an anterior cruciate ligament rupture in one knee and a normal contralateral knee were recruited. Magnetic resonance images were acquired for both the intact and anterior cruciate ligament-deficient knees to construct computer knee models of the surfaces of the bone and cartilage. Each patient performed a single-leg weight-bearing lunge as images were recorded with use of a dual fluoroscopic system at full extension and at 150, 300, 600, and 900 of flexion. The in vivo knee position at each flexion angle was then reproduced with use of the knee models and fluoroscopic images. The contact points were defined as the centroids of the areas of intersection of the tibial and femoral articular cartilage surfaces. Results: The contact points moved not only in the anteroposterior direction but also in the mediolateral direction in both the anterior cruciate ligament-deficient and intact knees. In the anteroposterior direction, the contact points in the medial compartment of the tibia were more posterior in the anterior cruciate ligament-deficient knees than in the intact knees at full extension and 150 of flexion (p < 0.05). No significant differences were observed with regard to the anteroposterior motion of the contact points in the lateral compartment of the tibia. In the mediolateral direction, there was a significant lateral shift of the contact points in the medial compartment of the tibia toward the medial tibial spine between full extension and 600 of flexion (p < 0.05). The contact points in the lateral compartment of the tibia shifted laterally, away from the lateral tibial spine, at 150 and 300 of flexion (p < 0.05). Conclusions: In the presence of anterior cruciate ligament injury, the contact points shift both posteriorly and laterally on the surface of the tibial plateau. In the medial compartment, the contact points shift toward the medial tibial spine, a region where degeneration is observed in patients with chronic anterior cruciate ligament injuries. Clinical Relevance: This in vivo measurement technique may be useful for assessing the ability of an anterior cruciate ligament reconstruction to restore normal tibiofemoral cartilage contact biomechanics. The observed altered motions of the tibiofemoral contact points might change contact stress distributions in the cartilage and predispose the joint to degenerative changes. C1 Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Li, G (reprint author), Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NIAMS NIH HHS [AR05248] NR 42 TC 118 Z9 120 U1 2 U2 9 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 2006 VL 88A IS 8 BP 1826 EP 1834 DI 10.2106/JBJS.E.00539 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 071XV UT WOS:000239638100020 PM 16882908 ER PT J AU Burnett, SAM Gunawardene, SC Bringhurst, FR Juppner, H Lee, H Finkelstein, JS AF Burnett, Sherri-Ann M. Gunawardene, Samantha C. Bringhurst, F. Richard Juppner, Harald Lee, Hang Finkelstein, Joel S. TI Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fibroblast growth factor 23; phosphate; homeostasis; nutrition ID TUMOR-INDUCED OSTEOMALACIA; GROWTH-FACTOR (FGF)-23; VITAMIN-D METABOLISM; PARATHYROID-HORMONE; PRIMARY HYPERPARATHYROIDISM; IN-VIVO; HYPOPHOSPHATEMIC RICKETS/OSTEOMALACIA; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ONCOGENIC OSTEOMALACIA; PHOSPHORUS HOMEOSTASIS AB FGF-23 is a novel regulator of phosphate metabolism. We studied the regulation of FGF-23 by dietary phosphate in 66 men and women using two assays. Dietary phosphate restriction decreased FGF-23 and loading increased FGF-23 significantly. An assay that measured intact FGF-23 showed the effects of dietary phosphate much more clearly than an assay that also measures presumed biologically inactive fragments. Dietary phosphate is a key regulator of circulating FGF-23; choice of assay is critical when studying FGF-23 physiology. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Burnett, SAM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. EM sburnett@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [F32 DK063761, K24 DK 02759] NR 52 TC 231 Z9 238 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 2006 VL 21 IS 8 BP 1187 EP 1196 DI 10.1359/JBMR.060507 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 067JZ UT WOS:000239299400002 PM 16869716 ER PT J AU Frankel, DS Piette, JD Jessup, M Craig, K Pickering, F Goldberg, LR AF Frankel, David S. Piette, John D. Jessup, Mariell Craig, Kimberly Pickering, Faith Goldberg, Lee R. TI Validation of prognostic models among patients with advanced heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure; prognosis; survival; risk factors; predictive models ID LEFT-VENTRICULAR DYSFUNCTION; RANDOMIZED-TRIAL; HOSPITAL READMISSION; PREDICTING MORTALITY; SURVIVAL; CARVEDILOL; MORBIDITY; DISEASE; RISK; ECHOCARDIOGRAPHY AB Background: The ability to accurately predict heart failure outcomes is essential to guiding treatment decisions but several competing risk stratification models exist. Methods and Results: We prospectively collected data on 280 patients with advanced heart failure recruited from 16 sites across the United States. Deaths and cardiac transplantations within the following 4 years were identified. Medline was searched to systematically identify widely cited heart failure severity classification models predicting long-term survival among patients with heart failure, and 4 were selected for validation. We used Kaplan-Meier survival curves, receiver-operating characteristic curves, and Cox proportional hazards modeling to identify the prognostic significance of each model's risk score and the individual contribution of the clinical components within each model. Average follow-up was 31.2 months; 148 deaths or transplantations occurred. Each model that we evaluated identified patients with significantly different prognoses. However, each was limited in overall predictive power, and many component patient characteristics did not have independent prognostic significance. Prognostic factors found to be most powerful within their models included: increasing age, ischemic cardiomyopathy, history of cardiomyopathy, ankle edema, decreased peak oxygen consumption, and absence of P-blocker use, Conclusion: Although each of the models succeeded in risk-stratifying patients to some extent, all 4 models had shortcomings. There is a need for a contemporary model, derived from a patient population managed in accordance with current heart failure guidelines, applicable to all heart failure etiologies, relying on readily available clinical data. C1 Univ Penn, Heart Failure & Cardiac Transplant Program, Philadelphia, PA 19104 USA. Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldberg, LR (reprint author), Univ Penn, Heart Failure & Cardiac Transplant Program, 6 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. OI Goldberg, Lee/0000-0002-7906-9638 NR 34 TC 11 Z9 13 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 BP 430 EP 438 DI 10.1016/j.cardfail.2006.03.010 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 078NZ UT WOS:000240111800005 PM 16911909 ER PT J AU Krauser, DG Chen, AA Tung, R Anwaruddin, S Baggish, AL Januzzi, JL AF Krauser, Daniel G. Chen, Annabel A. Tung, Roderick Anwaruddin, Saif Baggish, Aaron L. Januzzi, James L., Jr. TI Neither race nor gender influences the usefulness of amino-terminal pro-brain natriuretic peptide testing in dyspneic subjects: A ProBNP investigation of dyspnea in the emergency department (PRIDE) substudy SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE natriuretic peptides; acute heart failure; gender ID CONGESTIVE-HEART-FAILURE; NT-PROBNP; GENERAL-POPULATION; AFRICAN-AMERICANS; POOLED ANALYSIS; AGE; BNP; DIAGNOSIS; BLACKS; IMPACT AB Background: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for the diagnosis and exclusion of congestive heart failure (14F). Little is known about the effect of race on NT-proBNP concentrations. Also, NT-proBNP levels may be higher in apparently well women, but the effect of gender on NT-proBNP concentrations in dyspneic patients is not known. Methods and Results: NT-proBNP (Elecsys proBNP, Roche, Indianapolis, IN) was measured in 599 dyspneic patients in a prospective study. Of these, 44 were African American; 295 were female. NT-proBNP levels were examined according to race and gender in patients with and without acute HF using analysis of covariance. Receiver operating characteristic (ROC) curves assessed NT-proBNP by race and gender. Cut-points for diagnosis (450, 900, and 1800 pg/mL for ages < 50, 50 to 75, and > 75 years) and exclusion (300 pg/mL) were examined in African-American and female subjects. There was no difference in the rates of acute HF between African-American and non-African-American (30% versus 35%, P =.44) or male and female (35% versus 35%, P = .86) subjects. In subjects with HF, there was no difference in median NTLproBNP concentrations between African American and non-African American (6196 versus 3597 pg/mL, P = .37). In subjects without HF, unadjusted NT-proBNP levels were lower in African-American subjects than in non-African-American subjects (68 versus 148 pg/mL, P < .03); however, when adjusted for factors known to influence NT-proBNP concentrations (age, prior HF, creatinine clearance, atrial fibrillation, and body mass index), race no longer significantly affected NT-proBNP concentrations. There was no statistical difference in median NT-proBNP concentrations between male and female subjects with (4686 versus 3622 pg/mL, P = .53) or without HF (116 pg/mL versus 150 pg/ mL, P = .62). Among African Americans, NT-proBNP had an area under the ROC for acute HF of 0.96 (P < .0001), and at optimal cutpoints, had a sensitivity of 100% and a specificity of 90%. Among females, NT-proBNP had an area under the ROC for acute HF of 0.95 (P < .0001), and had a sensitivity of 89% and a specificity of 88%; 300 pg/mL had negative predictive value of 100% in African Americans and females. Conclusion: NT-proBNP is useful for the diagnosis and exclusion of acute HF in dyspneic subjects, irrespective of race or gender. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 20 Z9 21 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 BP 452 EP 457 DI 10.1016/j.cardfail.2006.04.005 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 078NZ UT WOS:000240111800008 PM 16911912 ER PT J AU Aguilar, D Bozkurt, B Pritchett, AM Petersen, NJ Deswal, A AF Aguilar, David Bozkurt, Biykem Pritchett, Allison M. Petersen, Nancy J. Deswal, Anita TI Thiazolidinediones are not associated with increased risk of heart failure hospitalizations in ambulatory patients with diabetes mellitus and heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 299 BP S93 EP S93 DI 10.1016/j.cardfail.2006.06.316 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000299 ER PT J AU Bart, BA Teerlink, JR Costanzo, MR Saltzberg, MT Sobotka, PA AF Bart, Bradley A. Teerlink, John R. Costanzo, Maria Rosa Saltzberg, Mitchell T. Sobotka, Paul A. TI Changes in serum creatinine during treatment of heart failure and volume overload with ultrafiltration or intravenous diuretics SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA. San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA USA. Midwest Heart Fdn, Naperville, IL USA. CHF Solut, Brooklyn Pk, MN USA. RI Teerlink, John/D-2986-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 375 BP S114 EP S114 DI 10.1016/j.cardfail.2006.06.394 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000375 ER PT J AU Brooks, WW Conrad, CH Marsilio, E Robinson, KG Bing, OHL AF Brooks, Wesley W. Conrad, Chester H. Marsilio, Erika Robinson, Kathleen G. Bing, Oscar H. L. TI Treatment reverses intrinsic myocardial dysfunction and genotypic changes associated with heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 VA Boston Healthcare Syst, Res Serv, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 039 BP S12 EP S13 DI 10.1016/j.cardfail.2006.06.049 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000039 ER PT J AU Butler, J Shapiro, M Jassal, D Neilan, T Nichols, J Hoffmann, U Brady, T Cury, R AF Butler, Javed Shapiro, Michael Jassal, Davinder Neilan, Thomas Nichols, John Hoffmann, Udo Brady, Thomas Cury, Ricardo TI Global and regional left ventricular function assessment with 64-slice MDCT in heart failure patients: A comparative study with echocardiography SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 426 BP S129 EP S129 DI 10.1016/j.cardfail.2006.06.445 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000426 ER PT J AU Butler, J Shapiro, M Neiman, K Nomura, C Hoffman, U Brady, T Cury, R AF Butler, Javed Shapiro, Michael Neiman, Koen Nomura, Cesar Hoffman, Udo Brady, Thomas Cury, Ricardo TI Cardiac 64-slice multi-detector computed tomography detection of infarct size in patients with post-infarct left ventricular dysfunction: A comparative study with SPECT imaging and cardiac biomarkers SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 076 BP S24 EP S24 DI 10.1016/j.cardfail.2006.06.085 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000076 ER PT J AU Chen, AA Tournoux, FB Fendelander, L Hames, M Haelewyn, K Moore, SA Semigran, MJ Heist, EK Ruskin, JN Picard, MH Singh, JP AF Chen, Annabel A. Tournoux, Francois B. Fendelander, Lahn Hames, Maureen Haelewyn, Kyle Moore, Stephanie A. Semigran, Marc J. Heist, E. Kevin Ruskin, Jeremy N. Picard, Michael H. Singh, Jagmeet P. TI The effect of dobutamine on echocardiographic indices of interventricular and intraventricular mechanical dyssynchrony SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Guidant Corp, St Paul, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 218 BP S68 EP S68 DI 10.1016/j.cardfail.2006.06.231 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000218 ER PT J AU Fitzgibbons, T Birjiniuk, V Biolo, A Maddukuri, P Crittenden, M Haime, M Lum, G Rocco, T Khuri, S Joseph, J AF Fitzgibbons, Timothy Birjiniuk, Vladimir Biolo, Andreia Maddukuri, Prasad Crittenden, Michael Haime, Miguel Lum, Gifford Rocco, Thomas Khuri, Shukri Joseph, Jacob TI B-type natriuretic peptide levels measured 12 hours after cardiac surgery correlate best with mortality SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. RI Biolo, Andreia/E-9860-2013; OI Fitzgibbons, Timothy/0000-0003-0229-034X NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 304 BP S94 EP S94 DI 10.1016/j.cardfail.2006.06.321 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000304 ER PT J AU Lewis, GD Shahzad, K Camuso, J Martinovic, ME Shaw, RV Systrom, DM Bloch, KD Gerszten, RE Semigran, MJ AF Lewis, Gregory D. Shahzad, Khurrham Camuso, Janice Martinovic, Maryann E. Shaw, Ravi V. Systrom, David M. Bloch, Kenneth D. Gerszten, Robert E. Semigran, Marc J. TI Sildenafil therapy for systolic heart failure with secondary pulmonary hypertension: A randomized double-blind, placebo-controlled study SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 223 BP S70 EP S70 DI 10.1016/j.cardfail.2006.06.237 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000223 ER PT J AU Maddukuri, P Woods, P Fitzgibbons, T Joseph, J Larsen, E Connolly, L O'Connel, C McIntyre, K Sharma, GVRK AF Maddukuri, Prasad Woods, Patricia Fitzgibbons, Timothy Joseph, Jacob Larsen, Elizabeth Connolly, Louise O'Connel, Carol McIntyre, Kevin Sharma, G. V. R. K. TI Noninvasive measurement of left ventricular end-diastolic pressures reveals management of heart failure by clinical assessment is sub-optimal in ambulatory patients SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Boston Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA USA. CVP Diagnost Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 405 BP S123 EP S123 DI 10.1016/j.cardfail.2006.06.424 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000405 ER PT J AU Maddukuri, P Woods, P Joseph, J Lindsey, N Larsen, E Aragam, J McIntyre, K Sharma, GVRK AF Maddukuri, Prasad Woods, Patricia Joseph, Jacob Lindsey, Nancy Larsen, Elizabeth Aragam, Jayashri McIntyre, Kevin Sharma, G. V. R. K. TI Inadequate hemodynamic management by clinical assessment alone leads to increased heart failure hospitalizations - A study using noninvasive assessment of left ventricular end-diastolic pressure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Boston Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, VA Boston HealthCare Syst, Boston, MA USA. CVP Diagnost Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 384 BP S117 EP S117 DI 10.1016/j.cardfail.2006.06.403 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000384 ER PT J AU Shalaby, A ElSaeed, A Saba, S AF Shalaby, Alaa ElSaeed, Aiman Saba, Samir TI Intracardiac ultrasound utilization to facilitate coronary sinus cannulation in cardiac resynchronization device implantation SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 VA Pittsburgh Hlth Care Syst, Div Cardiol, Pittsburgh, PA USA. Univ Pittsburgh, Div Cardiol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 205 BP S64 EP S64 DI 10.1016/j.cardfail.2006.06.218 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000205 ER PT J AU Stewart, GC Weintraub, J Semigran, MJ Brooks, K Camuso, J Tsang, S Anello, S Eramo, C Nguyen, V Lewis, EF Nohria, A Desai, AS Givertz, MM Stevenson, LW AF Stewart, Garrick C. Weintraub, Joanne Semigran, Marc J. Brooks, Kimberly Camuso, Janice Tsang, Sui Anello, Susan Eramo, Catherine Nguyen, Viviane Lewis, Eldrin F. Nohria, Anju Desai, Akshay S. Givertz, Michael M. Stevenson, Lynne Warner TI What do heart failure patients expect from implantable defibrillators? SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 441 BP S132 EP S132 DI 10.1016/j.cardfail.2006.06.460 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000440 ER PT J AU Stewart, GC Brooks, K Tsang, SW Semigran, MJ Smith, C James, L Page, D Saniuk, C Fang, JC Mudge, GH Couper, G Baughman, KL Stevenson, LW AF Stewart, Garrick C. Brooks, Kimberly Tsang, Sui W. Semigran, Marc J. Smith, Colleen, Jr. James, Linda Page, Deborah Saniuk, Catherine Fang, James C. Mudge, Gilbert H., Jr. Couper, Gregory Baughman, Kenneth L. Stevenson, Lynne Warner TI Who is the target patient for a ventricular assist device? SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 162 BP S49 EP S49 DI 10.1016/j.cardfail.2006.06.174 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000162 ER PT J AU Teuteberg, J Janosko, KM Starling, R Torre-Amione, G Dec, GW McTiernan, C McNamara, DM AF Teuteberg, Jeffrey Janosko, Karen M. Starling, Randall Torre-Amione, Guillermo Dec, G. William McTiernan, Charles McNamara, Dennis M. TI Gender differences in myocardial histology and gene expression in recent onset cardiomyopathy: Implications for recovery SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Methodist Hosp, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 018 BP S7 EP S7 DI 10.1016/j.cardfail.2006.06.028 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000019 ER PT J AU Weintraub, JR Tsang, S Brooks, K Anello, S Camuso, J Givertz, M Fang, J Eramo, K Stevenson, LW AF Weintraub, Joanne R. Tsang, Sui Brooks, Kimberly Anello, Susan Camuso, Janice Givertz, Michael Fang, James Eramo, Katherine Stevenson, Lynne W. TI What do heart failure patients think about research studies? SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 408 BP S124 EP S124 DI 10.1016/j.cardfail.2006.06.427 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000408 ER PT J AU Zardkoohi, O Singh, J Mela, T Ruskin, J Heist, K Chung, J Haelewyn, K AF Zardkoohi, Omeed Singh, Jagmeet Mela, Theofanie Ruskin, Jeremy Heist, Kevin Chung, Jeffrey Haelewyn, Kyle TI The impact of age, gender, and heart failure etiology on the outcome of cardiac resynchronization therapy SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 217 BP S67 EP S67 DI 10.1016/j.cardfail.2006.06.230 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000217 ER PT J AU Shin, HK Dunn, AK Jones, PB Boas, DA Moskowitz, MA Ayata, C AF Shin, Hwa Kyoung Dunn, Andrew K. Jones, Phillip B. Boas, David A. Moskowitz, Michael A. Ayata, Cenk TI Vasoconstrictive neurovascular coupling during focal ischemic depolarizations SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE anoxic depolarization; cerebral blood flow; laser speckle flowmetry; middle cerebral artery occlusion; neuroprotection; periinfarct depolarization ID MIDDLE CEREBRAL-ARTERY; CORTICAL SPREADING DEPRESSION; GLUTAMATE-RECEPTOR BLOCKADE; NEGATIVE DC DEFLECTIONS; NITRIC-OXIDE PRODUCTION; BLOOD-FLOW; PERIINFARCT DEPOLARIZATIONS; NMDA-RECEPTOR; SUBARACHNOID SPACE; THERAPEUTIC WINDOW AB Ischemic depolarizing events, such as repetitive spontaneous periinfarct spreading depolarizations (PIDs), expand the infarct size after experimental middle cerebral artery (MCA) occlusion. This worsening may result from increased metabolic demand, exacerbating the mismatch between cerebral blood flow (CBF) and metabolism. Here, we present data showing that anoxic depolarization (AD) and PIDs caused vasoconstriction and abruptly reduced CBF in the ischemic cortex in a distal MCA occlusion model in mice. This reduction in CBF during AD increased the area of cortex with 20% or less residual CBF by 140%. With each subsequent PID, this area expanded by an additional 19%. Drugs that are known to inhibit cortical spreading depression (CSD), such as N-methyl-D-aspartate receptor antagonists MK-801 and 7-chlorokynurenic acid, and sigma-1 receptor agonists dextromethorphan and carbetapentane, did not reduce the frequency of PIDs, but did diminish the severity of episodic hypoperfusions, and prevented the expansion of severely hypoperfused cortex, thus improving CBF during 90 mins of acute focal ischemia. In contrast, AMPA receptor antagonist NBQX, which does not inhibit CSD, did not impact the deterioration in CBF. When measured 24h after distal MCA occlusion, infarct size was reduced by MK-801, but not by NBQX. Our results suggest that AD and PIDs expand the CBF deficit, and by so doing negatively impact lesion development in ischemic mouse brain. Mitigating the vasoconstrictive neurovascular coupling during intense ischemic depolarizations may provide a novel hemodynamic mechanism of neuroprotection by inhibitors of CSD. C1 Harvard Univ, Stroke & Neurovasc Regulat Lab, Dept Neurol, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit,Dept Neur, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Stroke & Neurovasc Regulat Lab, Dept Neurol, Massachusetts Gen Hosp,Sch Med, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Moskowitz, Michael/D-9916-2011; Dunn, Andrew/I-9527-2014; OI Jones, Phillip/0000-0003-0525-6323 FU NIBIB NIH HHS [R01EB00790-01A2]; NINDS NIH HHS [K25NS041291, P01 NS35611, P50 NS10828] NR 89 TC 162 Z9 164 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2006 VL 26 IS 8 BP 1018 EP 1030 DI 10.1038/sj.jcbfm.9600252 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 067ZG UT WOS:000239340700003 PM 16340958 ER PT J AU Finkelstein, JS Leder, BZ Burnett, SAM Wyland, JJ Lee, H de la Paz, AV Gibson, K Neer, RM AF Finkelstein, Joel S. Leder, Benjamin Z. Burnett, Sherri-Ann M. Wyland, Jason J. Lee, Hang de la Paz, Amanda Victoria Gibson, Kate Neer, Robert M. TI Effects of teriparatide, alendronate, or both on bone turnover in osteoporotic men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARATHYROID-HORMONE 1-34; GROWTH-FACTOR-I; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; BIOCHEMICAL MARKERS; VERTEBRAL FRACTURES; ESTROGEN DEFICIENCY; RANDOMIZED-TRIAL; SPINAL BONE; PREVENTION AB Context: We have previously demonstrated that alendronate reduces the ability of teriparatide to increase bone mineral density (BMD) in osteoporotic men. The underlying basis for this observation is poorly understood. Objective: The primary aim of this study was to determine whether teriparatide increases osteoblast activity when the ability of teriparatide to increase osteoclast activity is suppressed by alendronate. Design: This was a nonblinded, randomized, controlled trial. Setting: The study was conducted at the General Clinical Research Center of a teaching hospital. Patients: We studied 63 men, age 46-85, with low spine and/or hip BMD. Interventions: Subjects received alendronate 10 mg daily (group 1), teriparatide 37 mu g sc daily (group 2), or both (group 3) for 30 months. Teriparatide was begun at month 6. Main Outcome Measures: The primary endpoint was the change in serum N-telopeptide, osteocalcin, and amino-terminal propeptide of type 1 procollagen. Results: In men receiving teriparatide monotherapy (group 2), levels of all bone turnover markers increased markedly during the first 6 months of teriparatide administration and then declined toward baseline during the next 18 months. In men who received combination therapy (group 3), bone turnover marker levels declined in the first 6 months (while receiving alendronate alone) and then returned to baseline levels (N-telopeptide) or above (osteocalcin and aminoterminal propeptide of type 1 procollagen) after teriparatide was added. Changes in each marker were significantly different between groups 1 and 2 (all P values < 0.001), groups 1 and 3 (all P values < 0.001), and groups 2 and 3 ( all P values < 0.03). Conclusions: As with BMD, alendronate impairs the action of teriparatide to increase bone turnover in men. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Ctr Biostat, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. EM jfinkelstein@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU NCRR NIH HHS [M01 RR 1066, K23 RR 016310]; NIAMS NIH HHS [5P50 AR 44855]; NIDDK NIH HHS [K24 DK 02759] NR 35 TC 77 Z9 80 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 2882 EP 2887 DI 10.1210/jc.2006-0190 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700014 PM 16684825 ER PT J AU Meigs, JB Wilson, PWF Fox, CS Vasan, RS Nathan, DM Sullivan, LM D'Agostino, RB AF Meigs, James B. Wilson, Peter W. F. Fox, Caroline S. Vasan, Ramachandran S. Nathan, David M. Sullivan, Lisa M. D'Agostino, Ralph B. TI Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-HEART-DISEASE; INSULIN-RESISTANCE; FAT DISTRIBUTION; NORMAL-WEIGHT; POSTMENOPAUSAL WOMEN; ABDOMINAL ADIPOSITY; OBESE INDIVIDUALS; MEN; MELLITUS; HEALTHY AB Context: Metabolic risk conferred by adiposity may be due to associated risk factor clustering. Objective: The objective of this study was to assess risk for diabetes or cardiovascular disease (CVD) stratified by body mass index (BMI) and the presence or absence of metabolic syndrome (MetS) or insulin resistance (IR). Design, Setting, and Participants: This was a community-based, longitudinal study of 2902 people (55% women, mean age 53 yr) without diabetes or CVD in 1989-1992 followed for up to 11 yr. We categorized subjects by normal weight (BMI < 25 kg/m(2)), overweight (25-29.9 kg/m(2)), or obese (> 30 kg/m(2)) and by the National Cholesterol Education Program's Adult Treatment Panel MetS or the top quartile of homeostasis model IR. We used proportional hazard models to estimate risk relative to normal weight and no MetS or IR. Main Outcome Measure: Incident type 2 diabetes (treatment or fasting glucose >= 7 mmol/liter, 141 events) or CVD (myocardial infarction, stroke, or claudication, 252 events) were measured. Results: Among 1056 normal-weight subjects, 7% had MetS and a risk factor-adjusted relative risk for diabetes of 3.97 (95% confidence interval, 1.35-11.6) and for CVD of 3.01 (1.68-5.41). Among 638 obese subjects, 37% did not have MetS or significantly increased risk. Obese subjects with MetS had an adjusted relative risk for diabetes of 10.3 (5.44-19.5) and for CVD of 2.13 (1.43-3.18). Results were similar in analyses of BMI-IR categories. Conclusions: People with normal weight and MetS or IR or with obesity but no MetS or IR were not uncommon in our sample. Risk factor clustering or IR appear to confer much of the risk for diabetes or CVD commonly associated with elevated BMI. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, NHLBI,Framingham Heart Study, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol & Hypertens, Boston, MA 02115 USA. Boston Univ, Sch Med, NHLBI, Framingham Heart Study, Boston, MA 02215 USA. Boston Univ, Sch Med, NHLBI, Evans Dept Med,Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Boston Univ, Sch Med, NHLBI, Prevent Med Sect, Boston, MA 02215 USA. Boston Univ, Dept Math Stat & Consulting, Boston, MA 02118 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Stanford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01 HC 25195, 2K24 HL 04334] NR 49 TC 392 Z9 406 U1 4 U2 25 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 2906 EP 2912 DI 10.1210/jc.2006-0594 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700018 PM 16735483 ER PT J AU Miller, KK Lee, EE Lawson, EA Misra, M Minihan, J Grinspoon, SK Gleysteen, S Mickley, D Herzog, D Klibanski, A AF Miller, Karen K. Lee, Ellen E. Lawson, Elizabeth A. Misra, Madhusmita Minihan, Jennifer Grinspoon, Steven K. Gleysteen, Suzanne Mickley, Diane Herzog, David Klibanski, Anne TI Determinants of skeletal loss and recovery in anorexia nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; YOUNG-WOMEN; HYPOTHALAMIC AMENORRHEA; ADOLESCENT GIRLS; OSTEOPENIA; MASS; OSTEOPOROSIS; BODY AB Context: Anorexia nervosa (AN) is complicated by severe bone loss. The effects of persistent undernutrition and consequent neuroendocrine dysfunction on bone mass and the factors influencing skeletal recovery have not been well characterized. Objective: The objective of the study was to determine the rate of bone loss at the spine and hip in women with AN and whether resumption of menstrual function and/or improvement in weight are determinants of skeletal recovery in AN. Design: The study had a longitudinal design. Setting: The study was conducted at a clinical research center. Study Participants: Participants included 75 ambulatory women with AN. Main Outcome Measures: Bone mineral density (BMD) and body composition were measured with dual x-ray absorptiometry. Results: In women not receiving oral contraceptives, those who did not improve weight or resume menses had a mean annual rate of decline of 2.6% at the spine and 2.4% at the hip. Those who resumed menses and improved weight had a mean annual increase of 3.1% at the posteroanterior spine and 1.8% at the hip. Women who recovered menses demonstrated a mean increase of posteroanterior spine but not hip BMD, independent of weight gain. Women who improved weight, regardless of whether they recovered menstrual function, demonstrated a mean increase of hip, but not spine, BMD. Increase in fat-free mass was a more significant determinant of increased BMD than weight or fat mass gain. In women receiving oral contraceptives, there was no increase in BMD at any site despite a mean 11.7% weight increase. Conclusions: These data suggest that rapid bone loss, at an average annual rate of about 2.5%, occurs in young women with active AN. Resumption of menstrual function is important for spine BMD recovery, whereas weight gain is critical for hip BMD recovery. We did not observe an increase in BMD with weight gain in women receiving oral contraceptives. Therefore, improvements in reproduction function and weight, with increases in lean body mass a critical component, are both necessary for skeletal recovery in women with AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Med Sch, Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02114 USA. Wilkins Ctr Eating Disorders, Greenwich, CT 06831 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU NCRR NIH HHS [M01 RR 01066, M01 RR001066]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11, R01 DK 52625, R01 DK052625] NR 29 TC 100 Z9 102 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 2931 EP 2937 DI 10.1210/jc.2005-2818 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700022 PM 16735492 ER PT J AU Dolan, SE Kanter, JR Grinspoon, S AF Dolan, Sara E. Kanter, Jenna R. Grinspoon, Steven TI Longitudinal analysis of bone density in human immunodeficiency virus-infected women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; X-RAY ABSORPTIOMETRY; MINERAL DENSITY; VITAMIN-D; PROTEASE INHIBITORS; OSTEOPENIA; METABOLISM; MARKERS; MASS; OSTEOPOROSIS AB Objectives: The objective of the study was to investigate change in bone mineral density (BMD) over time in HIV-infected women in comparison with healthy control subjects similar in age, race, and body mass index (BMI). Design: This was a prospective cohort study. Methods: BMD was measured by dual-energy x-ray absorptiometry in 100 HIV-infected females and 100 healthy controls similar in age (41 +/- 1 vs. 41 +/- 1 yr, P = 0.57), BMI (26.1 +/- 0.5 vs. 27.2 +/- 0.4 kg/m(2), P = 0.12), and race (60 vs. 65% non-Caucasian, P = 0.47, HIV-infected vs. controls). Changes in BMD were determined every 6 months over 24 months. Results: At baseline, HIV-infected subjects had lower BMD at the lumbar spine (1.01 +/- 0.01 vs. 1.07 +/- 0.01 g/cm(2), P = 0.001), hip (0.94 +/- 0.01 vs. 0.98 +/- 0.01 g/cm(2), P = 0.02), and femoral neck (0.83 +/- 0.01 vs. 0.87 +/- 0.01 g/cm(2), P = 0.02). Historical low weight, duration of nucleoside reverse transcriptase inhibitor use, and FSH were significantly associated with lumbar BMD, whereas duration of HIV, BMI, historical low weight, smoking pack-years, N-telopeptide of type 1 collagen, viral load, 25 hydroxyvitamin D, and osteocalcin were associated with hip BMD at baseline. In mixed model longitudinal analyses, BMD remained lower in HIV-infected subjects than in controls over 24 months of follow-up (P = 0.001 for the spine, P = 0.04 for the hip, and P = 0.02 for the femoral neck). These differences remained significant controlling for age, race, BMI, and menstrual function. In contrast, rates of change for the spine (P = 0.79), hip (P = 0.44), and femoral neck (P = 0.34) were not different between the HIV and control groups over 2 yr. In the HIV group, longitudinal changes in BMD were not associated with current protease inhibitor, nucleoside reverse transcriptase inhibitor, or non-nucleoside reverse transcriptase inhibitor use but were associated with CD4 count, weight, FSH, N-telopeptide of type 1 collagen, and baseline BMD. Conclusions: BMD is reduced at the spine, hip, and femoral neck among women with HIV in relationship to low weight, duration of HIV, smoking, and increased bone turnover. Over 2 yr of follow-up, BMD remained stable but lower in HIV-infected women, compared with control subjects. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [3M01 RR 01066, M01 RR001066]; NIDDK NIH HHS [P30 DK040561, DK 59535, P30 DK040561-11, R01 DK059535] NR 27 TC 97 Z9 100 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 2938 EP 2945 DI 10.1210/jc.2006-0127 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700023 PM 16735489 ER PT J AU Glenton, C Underland, V Kho, M Pennick, V Oxman, AD AF Glenton, Claire Underland, Vigdis Kho, Michelle Pennick, Victoria Oxman, Andrew D. TI Summaries of findings, descriptions of interventions, and information about adverse effects would make reviews more informative SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Review DE knowledge translation; patient-centred research; patient information; research quality; risk communication; systematic reviews ID SYSTEMATIC REVIEWS; DECISION-MAKING; TRIALS; SAFETY; ISSUES AB Background and Objective: To describe challenges when extracting and presenting relevant, consistent, and accessible information from systematic reviews. Materials and Methods: We systematically selected comparisons and outcomes from 18 Cochrane reviews, evaluated the quality of evidence for each outcome using the GRADE system, and developed standardized patient information. We evaluated the information using patient, review author, researcher, and clinician feedback. Results: Challenges included large numbers of comparisons and outcomes; missing information about treatments and adverse effects; and variations in how effect was measured and presented. By selecting comparisons and outcomes based on patient-relevance, quality, and nonredundancy, we halved the number of outcomes. We prepared information about treatments and adverse effects using other sources. We framed outcomes consistently and standardized the presentation of magnitude of effect. Conclusions: The incorporation of summary of findings tables in reviews could address these challenges. Problems could also be reduced if review groups agreed upon standard outcomes; excluded less relevant outcomes; incorporated more information about interventions and adverse effects; and implemented clearer guidelines for the presentation of results. (C) 2006 Elsevier Inc. All rights reserved. C1 Norwegian Hlth Serv Res Ctr, N-0130 Oslo, Norway. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Work & Hlth, Toronto, ON M5G 2E9, Canada. RP Glenton, C (reprint author), Norwegian Hlth Serv Res Ctr, Pb 7004 St Olavs Plass, N-0130 Oslo, Norway. EM claire.glenton@kunnskapssenteret.no NR 24 TC 27 Z9 29 U1 4 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 2006 VL 59 IS 8 BP 770 EP 778 DI 10.1016/j.jclinepi.2005.12.011 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 065KR UT WOS:000239159300003 PM 16828668 ER PT J AU Sands, BE Kilgore, KM Bloomfeld, RS Sandborn, WJ AF Sands, Bruce E. Kilgore, Karl M. Bloomfeld, Richard S. Sandborn, William J. TI Variation in severity assessment and initial mesalamine dose selection for ulcerative colitis in community practice SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE colitis; ulcerative (UC); inflammatory bowel diseases (IBD); mesalamine; practice guidelines and dosing of mesalamine in UC AB Background and Aims: Ulcerative colitis treatment is based largely on anatomic extent of inflammation and severity. Clinical severity is designated by the terms mild, moderate, or severe. The aims of this study are to assess consistency between: (1) community physicians and established treatment guidelines in their respective operational definitions of severity and (2) clinical severity ratings and resulting treatment. Methods: Medical records of 411 patients who were successfully treated with mesalamine delayed release tablets without requiring steroids were reviewed. Data recorded included the prescribed dose of mesalamine, clinical symptoms, and physician's global assessment (PGA). Results: Physicians were moderately consistent with the American College of Gastroenterology Guidelines in their assignments of PGA (kappa = 0.57, P < 0.001). An alternative decision rule, which deviated from the guidelines by placing a higher proportion of patients in the mild category, yielded a significantly higher kappa of 0.69 (P < 0.001). The associations between severity measures and mesalamine dose yielded tau statistics of 0.13, 0.16, and 0.14 (all P < 0.001), respectively for PGA, number of stools per day and percentage of stools with blood. Conclusions: Ulcerative colitis treatment quality may be enhanced by promoting a more consistent terminology for disease severity and reducing the unexplained variation in treatment dosing. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. Cetus Grp LLC, Lutherville Timonium, MD USA. Wake Forest Univ, Dept Gastroenterol, Winston Salem, NC 27109 USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org NR 6 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD AUG PY 2006 VL 40 IS 7 BP 587 EP 591 DI 10.1097/00004836-200608000-00005 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 073YG UT WOS:000239778000004 PM 16917398 ER PT J AU Van Kleek, EJ Schwartz, JM Rayhill, SC Rosen, HR Cotler, SJ AF Van Kleek, Erik J. Schwartz, Jonathan M. Rayhill, Stephen C. Rosen, Hugo R. Cotler, Scott J. TI Liver transplantation for hepatocellular carcinoma - A survey of practices SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE hepatocellular carcinoma; liver transplantation; survey of practices ID UNITED-STATES; CHEMOEMBOLIZATION; CIRRHOSIS; CANCER; RESECTION; BIOPSY AB Goal: To survey physician practices regarding liver transplantation for patients with hepatocellular carcinoma (HCC). Background: Many issues surrounding liver transplantation for HCC are controversial and physician practices have not been well characterized. Methods: Transplant physicians and surgeons were electronically surveyed regarding surveillance, diagnosis, selection criteria for deceased and living donor transplantation, and use of adjunctive therapy for HCC. Results: Eighty-nine of 174 (51%) physicians completed the survey (39 hepatologists, 41 transplant surgeons, and 9 others). Most respondents were from large US transplant centers. All reported screening for HCC during transplant evaluation, and 98% surveyed patients awaiting transplant. Sixty percent of respondents would biopsy lesions under selective conditions, whereas 32% never biopsy lesions, and 8% biopsy all lesions. Eighty two percent of respondents claimed to adhere to the Milan criteria (single lesion <= 5 cm or no more than 3 lesions each <= 3 cm without vascular invasion) for patient selection, however, 36% would transplant patients with tumors that invade a small portal branch. Forty one percent of respondents would consider living donor transplantation for patients with tumors exceeding the Milan criteria. Ninety-six percent of respondents treat HCC before transplantation, and 87% would transplant patients down-staged to meet the Milan criteria. Conclusions: There is consistency related to HCC surveillance and treatment in liver transplant candidates. Variations of responses regarding biopsy of lesions, patient selection for deceased donor and living donor transplantation highlight a need for evidence-based guidelines. C1 Oregon Hlth & Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Surg, Div Liver & Pancreas Transplantat, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Univ Illinois, Dept Med, Sect Hepatol MC 787, Chicago, IL 60612 USA. RP Schwartz, JM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Gastroenterol & Hepatol, PV 310,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM schwajon@ohsu.edu NR 17 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD AUG PY 2006 VL 40 IS 7 BP 643 EP 647 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 073YG UT WOS:000239778000017 PM 16917411 ER PT J AU Korzenik, JR AF Korzenik, Joshua R. TI Case closed? Diverticulitis: Epidemiology and fiber SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 1st Meeting of the National-Diverticulitis-Study-Group CY DEC 02, 2005 CL New York, NY SP Natl Diverticulitis Study Grp DE diverticular disease; diverticulitis; fiber; etiology ID DIETARY FIBER; LARGE-BOWEL; NATURAL-HISTORY; DISEASE; COLON; JAPAN; TRENDS; RISK; POLYPS; MEN AB A major advance in understanding diverticular disease occurred decades ago with the epidemiologic association between fiber intake and the development of diverticular disease. This association has been well documented with investigations into the emergence of diverticular disease in underdeveloped countries where the disease had been virtually unknown before the adoption of a westernized diet, low in fiber. The high frequency of right-sided diverticular disease in Asian countries diverges from what is seen in the West. The physiologic effects of insoluble fiber has been well examined as well, increasing bulk and decreasing transit time, with a deficiency contributing to the high pressures implicated in the physiology which leads to diverticular disease. However, at most, 10% to 25% of individuals with diverticular disease will develop diverticulitis. Risk factors for symptomatic diverticular have been increasingly described in recent years with obesity and red meat intake being of particular importance, in addition to age. However, the known factors poorly identify those at increased risk and the predisposing pathophysiology is incompletely understood as well. Insoluble fiber, but not soluble fiber, has been viewed as the principal component which has been deficient in western diets and is the culprit which leads to the establishment of diverticular disease and in turn, diverticulitis. Soluble fiber and its effect on the intestinal flora is proposed as having significant influence on the development of diverticulitis. This understanding, if demonstrated, would have important implications for the primary and secondary prevention of diverticulitis. C1 Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Dept Internal Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Korzenik, JR (reprint author), Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Dept Internal Med, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM jkorzenik@partners.org NR 36 TC 37 Z9 37 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD AUG PY 2006 VL 40 IS 7 SU 3 BP S112 EP S116 DI 10.1097/01.mcg.0000225503.59923.6c PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 074OR UT WOS:000239822200003 PM 16885692 ER PT J AU Yoshida, M Kobayashi, K Kuo, TT Bry, L Glickman, JN Claypool, SM Kaser, A Nagaishi, T Higgins, DE Mizoguchi, E Wakatsuki, Y Roopenian, DC Mizoguchi, A Lencer, WI Blumberg, RS AF Yoshida, Masaru Kobayashi, Kanna Kuo, Timothy T. Bry, Lynn Glickman, Jonathan N. Claypool, Steven M. Kaser, Arthur Nagaishi, Takashi Higgins, Darren E. Mizoguchi, Emiko Wakatsuki, Yoshio Roopenian, Derry C. Mizoguchi, Atsushi Lencer, Wayne I. Blumberg, Richard S. TI Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PATHOGEN CITROBACTER-RODENTIUM; INTESTINAL EPITHELIAL-CELLS; ALPHA-MUTANT MICE; DENDRITIC CELLS; CHRONIC COLITIS; B-CELLS; EFFACING PATHOGEN; TRANSGENIC MICE; GUT EPITHELIUM; EXPRESSION AB The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. Selective expression of FcRn in the epithelium is shown here to be associated with secretion of IgG into the lumen that allows for defense against an epithelium-associated pathogen (Citrobacter rodentium). This pathway of host resistance to a bacterial pathogen as mediated by FcRn involves retrieval of bacterial antigens from the lumen and initiation of adaptive immune responses in regional lymphoid structures. Epithelial-associated FcRn, through its ability to secrete and absorb IgG, may thus integrate luminal antigen encounters with systemic immune compartments and as such provide essential host defense and immunoregulatory functions at the mucosal surfaces. C1 Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Kyoto Univ, Div Clin Bioregulatory Sci, Kyoto, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Ctr Digest Dis, Boston, MA 02115 USA. RP Blumberg, RS (reprint author), Brigham & Womens Hosp, Dept Med, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM rblumberg@partners.org FU NIDDK NIH HHS [DK44319, DK51362, DK53056, DK64289, DK64351, K08 DK064289, R01 DK044319, R01 DK051362, R01 DK053056, R01 DK064351, R37 DK044319] NR 43 TC 123 Z9 127 U1 2 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2006 VL 116 IS 8 BP 2142 EP 2151 DI 10.1172/JCI27821 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 070DA UT WOS:000239499300015 PM 16841095 ER PT J AU Cauwels, A Janssen, B Buys, E Sips, P Brouckaert, P AF Cauwels, Anje Janssen, Ben Buys, Emmanuel Sips, Patrick Brouckaert, Peter TI Anaphylactic shock depends on PI3K and eNOS-derived NO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; PLATELET-ACTIVATING-FACTOR; MICE LACKING; IN-VIVO; ENDOTHELIAL-CELLS; VASCULAR ACTIONS; ENDOTOXIC-SHOCK; L-ARGININE; INHIBITION; LIPOPOLYSACCHARIDE AB Anaphylactic shock is a sudden, fife-threatening allergic reaction associated with severe hypotension. Platelet-activating factor (PAF) is implicated in the cardiovascular dysfunctions occurring in various shock syndromes, including anaphylaxis. Excessive production of the vasodilator NO causes inflammatory hypotension and shock, and it is generally accepted that transcriptionally regulated inducible iNOS is responsible for this. Nevertheless, the contribution of NO to PAF-induced shock or anaphylactic shock is still ambiguous. We studied PAF and anaphylactic shock in conscious mice. Surprisingly, hyperacute PAF shock depended entirely on NO, produced not by inducible iNOS, but by constitutive eNOS, rapidly activated via the PI3K pathway. Soluble guanylate cyclase (sGC) is generally regarded as the principal vasorelaxing mediator of NO. Nevertheless, although methylene blue partially prevented PAF shock, neither 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) nor sGC alpha 1 deficiency did. Also, in 2 different models of active systemic anaphylaxis, inhibition of NOS, PI3K, or Akt or eNOS deficiency provided complete protection. In contrast to the unsubstantiated paradigm that only excessive iNOS-derived NO underlies cardiovascular collapse in shock, our data strongly support the unexpected concept that eNOS-derived NO is the principal vasodilator in anaphylactic shock and define eNOS and/or PI3K or Akt as new potential targets for treating anaphylaxis. C1 Univ Ghent, Dept Mol & Biomed Res, Mol Pathophysiol & Expt Therapy Unit, B-9052 Ghent, Zwijnaarde, Belgium. Univ Ghent VIB, Ghent, Belgium. Univ Maastricht, Cardiovasc Res Inst, Dept Pharmacol & Toxicol, Maastricht, Netherlands. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Cauwels, A (reprint author), Univ Ghent, Dept Mol & Biomed Res, Mol Pathophysiol & Expt Therapy Unit, Technol Pl 927, B-9052 Ghent, Zwijnaarde, Belgium. EM Anje.Cauwels@dmbr.UGent.be OI Sips, Patrick/0000-0001-9241-5980 NR 60 TC 66 Z9 68 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2006 VL 116 IS 8 BP 2244 EP 2251 DI 10.1172/JCI25426 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 070DA UT WOS:000239499300026 PM 16886062 ER PT J AU Klein, MI Bang, S Florio, FM Hofling, JF Goncalves, RB Smith, DJ Mattos-Graner, RO AF Klein, Marlise I. Bang, Sungyon Florio, Flavia M. Hoefling, Jose Francisco Goncalves, Reginaldo B. Smith, Daniel J. Mattos-Graner, Renata O. TI Genetic diversity of competence gene loci in clinical genotypes of Streptococcus mutans SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BRAZILIAN NURSERY CHILDREN; BIOFILM FORMATION; STRESS TOLERANCE; GENOME SEQUENCE; PNEUMONIAE; TRANSFORMATION; IDENTIFICATION; PHEROMONE; TRANSMISSION; REGULATOR AB The frequencies of 21 competence genes were analyzed in 94 genotypes of Streptococcus mutans. These include those of a main regulatory system (comCDE), structural, and other regulatory orthologues identified in the genome of strain UA159. PCR and Southern blot analysis revealed that all genes are widespread within the species. C1 Univ Estadual Campinas, Fac Odontol Piracicaba, Piracicaba Sch Dent, Dept Microbiol & Immunol, BR-13414903 Sao Paulo, Brazil. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Forsyth Inst, Dept Immunol, Boston, MA USA. RP Mattos-Graner, RO (reprint author), Univ Estadual Campinas, Fac Odontol Piracicaba, Piracicaba Sch Dent, Dept Microbiol & Immunol, Av Limeira 901, BR-13414903 Sao Paulo, Brazil. EM rmgraner@fop.unicamp.br RI Mattos-Graner, Renata/C-9410-2012; Klein, Marlise/A-2550-2014 OI Mattos-Graner, Renata/0000-0001-8309-8135; Klein, Marlise/0000-0002-7916-1557 FU NIDCR NIH HHS [DE-06153, R37 DE006153] NR 28 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2006 VL 44 IS 8 BP 3015 EP 3020 DI 10.1128/JCM.02024-05 PG 6 WC Microbiology SC Microbiology GA 076UG UT WOS:000239982800055 PM 16891531 ER PT J AU Meyerhardt, JA Giovannucci, EL Holmes, MD Chan, AT Chan, JA Colditz, GA Fuchs, CS AF Meyerhardt, Jeffrey A. Giovannucci, Edward L. Holmes, Michelle D. Chan, Andrew T. Chan, Jennifer A. Colditz, Graham A. Fuchs, Charles S. TI Physical activity and survival after colorectal cancer diagnosis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR (IGF)-I; IGF-BINDING-PROTEINS; NATIONAL DEATH INDEX; COLON-CANCER; BODY-SIZE; ACTIVITY QUESTIONNAIRE; NORTHERN SWEDEN; BREAST-CANCER; NURSES HEALTH; RISK-FACTORS AB Purpose Physically active individuals have a lower risk of developing colorectal cancer but the influence of exercise on cancer survival is unknown. Patients and Methods By a prospective, observational study of 573 women with stage I to III colorectal cancer, we studied colorectal cancer-specific and overall mortality according to predefined physical activity categories before and after diagnosis and by change in activity after diagnosis. To minimize bias by occult recurrences, we excluded women who died within 6 months of their postdiagnosis physical activity assessment. Results Increasing levels of exercise after diagnosis of nonmetastatic colorectal cancer reduced cancer-specific mortality (P for trend = .008) and overall mortality (P for trend = .003). Compared with women who engaged in less than 3 metabolic equivalent task [MET] -hours per week of physical activity, those engaging in at least 18 MET-hours per week had an adjusted hazard ratio for colorectal cancer-specific mortality of 0.39 (95% Cl, 0.18 to 0.82) and an adjusted hazard ratio for overall mortality of 0.43 (95% CI, 0.25 to 0.74). These results remained unchanged even after excluding women who died within 12 and 24 months of activity assessment. Prediagnosis physical activity was not predictive of mortality. Women who increased their activity (when comparing prediagnosis to postdiagnosis values) had a hazard ratio of 0.48 (95% CI, 0.24 to 0.97) for colorectal cancer deaths and a hazard ratio of 0.51 (95% CI, 0.30 to 0.85) for any-cause death, compared with those with no change in activity. Conclusion Recreational physical activity after the diagnosis of stages I to III colorectal cancer may reduce the risk of colorectal cancer-specific and overall mortality. C1 Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Div Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [K07CA097992-01A1, P01CA087969] NR 50 TC 376 Z9 381 U1 3 U2 20 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 1 PY 2006 VL 24 IS 22 BP 3527 EP 3534 DI 10.1200/JCO.2006.06.0855 PG 8 WC Oncology SC Oncology GA 069JY UT WOS:000239443400005 PM 16822844 ER PT J AU Meyerhardt, JA Heseltine, D Niedzwiecki, D Hollis, D Saltz, LB Mayer, RJ Thomas, J Nelson, H Whittom, R Hantel, A Schilsky, RL Fuchs, CS AF Meyerhardt, Jeffrey A. Heseltine, Denise Niedzwiecki, Donna Hollis, Donna Saltz, Leonard B. Mayer, Robert J. Thomas, James Nelson, Heidi Whittom, Renaud Hantel, Alexander Schilsky, Richard L. Fuchs, Charles S. TI Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR-I; IGF-BINDING PROTEIN-3; QUALITY-OF-LIFE; COLORECTAL-CANCER; BREAST-CANCER; BODY-SIZE; FACTOR BINDING-PROTEIN-3; ACTIVITY QUESTIONNAIRE; NORTHERN SWEDEN; PLASMA-INSULIN AB Purpose Regular physical activity reduces the risk of developing colon cancer, however, its influence on patients with established disease is unknown. Patients and Methods We conducted a prospective observational study of 832 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on various recreational physical activities approximately 6 months after completion of therapy and were observed for recurrence or death. To minimize bias by occult recurrence, we excluded patients who experienced recurrence or died within 90 days of their physical activity assessment. Results Compared with patients engaged in less than three metabolic equivalent task (MET) -hours per week of physical activity, the adjusted hazard ratio for disease-free survival was 0.51 (95% CI, 0.26 to 0.97) for 18 to 26.9 MET-hours per week and 0.55 (95% CI, 0.33 to 0.91) for 27 or more MET-hours per week. The adjusted P for trend was .01. Postdiagnosis activity was associated with similar improvements in recurrence-free survival (P for trend = .03) and overall survival (P for trend = .01). The benefit associated with physical activity was not significantly modified by sex, body mass index, number of positive lymph nodes, age, baseline performance status, or chemotherapy received. Moreover, the benefit remained unchanged even after excluding participants who developed cancer recurrence or died within 6 months of activity assessment. Conclusion Beyond surgical resection and postoperative adjuvant chemotherapy for stage III colon cancer, for patients who survive and are recurrence free approximately 6 months after adjuvant chemotherapy, physical activity appears to reduce the risk of cancer recurrence and mortality. C1 Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Duke Univ, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Ohio State Univ, Div Med Oncol, Columbus, OH USA. Mayo Clin Fdn, Div Colon & Rectal Surg, Rochester, MN USA. Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. Loyola Univ, Dept Med, Maywood, IL 60153 USA. Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Div Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org OI Saltz, Leonard/0000-0001-8353-4670 FU NCI NIH HHS [1K07CA097992-01A1, CA31946] NR 50 TC 325 Z9 332 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2006 VL 24 IS 22 BP 3535 EP 3541 DI 10.1200/JCO.2006.06.0863 PG 7 WC Oncology SC Oncology GA 069JY UT WOS:000239443400006 PM 16822843 ER PT J AU Smalley, SR Benedetti, JK Williamson, SK Robertson, JM Estes, NC Maher, T Fisher, B Rich, TA Martenson, JA Kugler, JW Benson, AB Haller, DG Mayer, RJ Atkins, JN Cripps, C Pedersen, J Periman, PO Tanaka, MS Leichman, CG Macdonald, JS AF Smalley, Stephen R. Benedetti, Jacqueline K. Williamson, Stephen K. Robertson, John M. Estes, Norman C. Maher, Tracy Fisher, Barbara Rich, Tyvin A. Martenson, James A. Kugler, John W. Benson, Al B., III Haller, Daniel G. Mayer, Robert J. Atkins, James N. Cripps, Christine Pedersen, John Periman, Phillip O. Tanaka, Michael S., Jr. Leichman, Cynthia G. Macdonald, John S. TI Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED COLORECTAL-CANCER; TOTAL MESORECTAL EXCISION; CONTINUOUS-INFUSION FLUOROURACIL; TOTAL MESENTERIC EXCISION; LOW-DOSE LEUCOVORIN; RANDOMIZED-TRIAL; COLON-CANCER; SPHINCTER PRESERVATION; SURGICAL-TREATMENT; RADIATION-THERAPY AB Purpose Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens. Patients and Methods After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m(2)/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT). Patients were stratified by operation type, T and N stage, and time from surgery. Results Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 49% to 55% of the bolus arms versus 4% in the PVI arm. No disease-free survival (DFS) or OS difference was detected (3-year DFS, 67% to 69% and 3-year OS, 81% to 83% in all arms). Locoregional failure (LRF) at first relapse was 8% in arm 1, 4.6% in arm 2, and 7% in arm 3. LRF in T1-2, N1-2, and T3, N0-2 primaries who received low anterior resection (those most suitable for primary resection) was 5% in arm 1, 3% in arm 2, and 5% in arm 3. Conclusion All arms provide similar relapse-free survival and OS, with different toxicity profiles and central catheter requirements. LRF with postoperative therapy is low, justifying initial resection for T1-2, N0-2 and T3, and N0-2 anterior resection candidates. C1 Kansas City Commmunity Clin Oncol Program, Kansas City, KS USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Univ Kansas, Med Ctr, Kansas City, MO USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Univ Illinois, Coll Med, Peoria, IL 61656 USA. Illiois Oncol Res Assoc CCOP, Peoria, IL USA. Northwestern Univ, Chicago, IL USA. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Ottawa Hlth Res Inst, Ottawa, ON, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Mayo Clin, Rochester, MN USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wake Forest SW Canc Control Consortium, Winston Salem, NC USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. St Vincents Comprehens Canc Ctr, New York, NY USA. RP Smalley, SR (reprint author), SW Oncol Grp SWOG 9304, 14980 Omicron Dr, San Antonio, TX 78245 USA. EM pubs@swog.org FU NCI NIH HHS [CA35262, CA03096, CA03927, CA04919, CA04920, CA12213, CA12644, CA13612, CA14028, CA16385, CA17145, CA20319, CA21661, CA22433, CA25224, CA27057, CA28862, CA32102, CA32291, CA35090, CA35113, CA35119, CA35128, CA35176, CA35178, CA35192, CA35261, CA35281, CA35996, CA37981, CA38926, CA42777, CA45377, CA45450, CA45461, CA45560, CA45807, CA46113, CA46136, CA46282, CA46368, CA46441, CA52654, CA52757, CA52772, CA58348, CA58415, CA58416, CA58658, CA58686, CA58861, CA58882, CA63844, CA63845, CA63850, CA67575, CA67663, CA68183, CA74647, CA76429, CA76447, CA76462] NR 68 TC 93 Z9 100 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2006 VL 24 IS 22 BP 3542 EP 3547 DI 10.1200/JCO.2005.04.9544 PG 6 WC Oncology SC Oncology GA 069JY UT WOS:000239443400007 PM 16877719 ER PT J AU Kulke, MH Bergsland, EK Ryan, DP Enzinger, PC Lynch, TJ Zhu, AX Meyerhardt, JA Heymach, JV Fogler, WE Sidor, C Michelini, A Kinsella, K Venook, AP Fuchs, CS AF Kulke, Matthew H. Bergsland, Emily K. Ryan, David P. Enzinger, Peter C. Lynch, Thomas J. Zhu, Andrew X. Meyerhardt, Jcffrey A. Heymach, John V. Fogler, William E. Sidor, Carolyn Michelini, Ann Kinsella, Kate Venook, Alan P. Fuchs, Charles S. TI Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID ENDOTHELIAL GROWTH-FACTOR; ADVANCED SOLID TUMORS; ANTIANGIOGENIC THERAPY; INTRAVENOUS-INFUSION; STREPTOZOCIN; ANGIOGENESIS; FLUOROURACIL; DOXORUBICIN; EFFICACY; CANCER AB Purpose Endostatin is a 20-kd proteolytic fragment of Collagen XVIII that, in preclinical studies, has been shown to have antiangiogenic and antitumor activity. Both preclinical and human phase I studies of recombinant human endostatin (rhEndostatin) suggested activity in neuroendocrine tumors, which are known to be hypervascular. We therefore performed a multicenter phase 11 study of rhEndostatin in patients with carcinoid or pancreatic neuroendocrine tumors. Patients and Methods Forty-two patients with advanced pancreatic endocrine tumors or carcinoid tumors were treated with rhEndostatin administered as a bid subcutaneous injection at a starting dose of 60 mg/m(2)/d. Steady-state trough levels were obtained after 6 weeks of therapy; patients who did not achieve a target therapeutic level of 300 ng/mL underwent dose escalation to 90 mg/m(2)/d. Patients were observed for evidence of toxicity, response, and survival. Results rhEndostatin was associated with minimal toxicity. However, among 40 patients assessable for radiologic response, none experienced partial response to therapy, as defined by WHO criteria. The median steady-state trough level achieved after dose escalation was 331 ng/mL, within the postulated therapeutic range. Conclusion Treatment with rhEndostatin did not result in significant tumor regression in patients with advanced neuroendocrine tumors. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Entrmed Inc, Rockville, MD USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu FU NCI NIH HHS [K23 CA 093401]; NHLBI NIH HHS [K30 HL04095] NR 25 TC 129 Z9 141 U1 0 U2 5 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 1 PY 2006 VL 24 IS 22 BP 3555 EP 3561 DI 10.1200/JCO.2006.05.6762 PG 7 WC Oncology SC Oncology GA 069JY UT WOS:000239443400009 PM 16877721 ER PT J AU Perez, EA Jesse, RG Pritchard, KI Ingle, JN Martino, S Findlay, BP Shenkier, TN Tozer, RG Palmer, MJ Shepherd, LE Liu, SF Tu, DS Goss, PE AF Perez, Edith A. Jesse, Robert G. Pritchard, Kathleen I. Ingle, James N. Martino, Silvana Findlay, Brian P. Shenkier, Tamara N. Tozer, Richard G. Palmer, Michael J. Shepherd, Lois E. Liu, Shifang Tu, Dongsheng Goss, Paul E. TI Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: A companion study to NCICCTG MA.17 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; EXEMESTANE; THERAPY; ARIMIDEX AB Purpose Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen. Patients and Methods Eligible women had a baseline BMD T score of at least 2.0 in either the hip or L2-4 spine; all received calcium 500 mg and vitamin D 400 U daily. Percentage change in BMD (L2-L4 spine and hip) at 12 and 24 months, rate of osteoporosis, and change in markers of bone formation (serum bone alkaline phosphatase) and resorption (serum C-telopeptide and urine N-telopeptide) at 6, 12, and 24 months were compared. Results Two hundred twenty-six patients (122 letrozole, 104 placebo) were enrolled. Baseline characteristics were similar in the two groups, including BMD, median age of 60.7 years (81% < 70 years), and median follow-up of 1.6 years. At 24 months, patients receiving letrozole had a significant decrease in total hip BMD (-3.6% v -0.71%; P = .044) and lumbar spine BMD (-5.35% v -0.70%; P = .008). Letrozole increased urine N-telopeptide at 6, 12, and 24 months (P = .054, < .001, and .016, respectively). No patient went below the threshold for osteoporosis in total hip BMD, whereas at the L2-L4 (posteroanterior view), more women became osteoporotic by BMD while receiving letrozole (4.1% v 0%; P = .064). Conclusion After 5 years of adjuvant tamoxifen, subsequent letrozole causes a modest increase in bone resorption and reduction in bone mineral density in the spine and hip compared to placebo. Further follow-up is necessary to evaluate the long-term clinical implications of this difference. C1 Mayo Clin, Jacksonville, FL 32224 USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Hotel Dieu Hlth Sci Hosp, St Catharines, ON, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. Natl Canc Inst Canada Clin Trials Grp, Kingston, ON, Canada. British Columbia Canc Agcy, Vancouver Canc Clin, Vancouver, BC V5Z 4E6, Canada. Mayo Clin, Rochester, MN USA. Inst Canc Res, Med Grp, Santa Monica, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Perez, EA (reprint author), Mayo Clin, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM perez.edith@mayo.edu NR 15 TC 196 Z9 203 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 1 PY 2006 VL 24 IS 22 BP 3629 EP 3635 DI 10.1200/JCO.2005.05.4882 PG 7 WC Oncology SC Oncology GA 069JY UT WOS:000239443400020 PM 16822845 ER PT J AU Cloughesy, TF Wen, PY Robins, HI Chang, SM Groves, MD Fink, KL Junck, L Schiff, D Abrey, L Gilbert, MR Lieberman, F Kuhn, J DeAngelis, LM Mehta, M Raizer, JJ Yung, WKA Aldape, K Wright, J Lamborn, KR Prados, MD AF Cloughesy, Timothy F. Wen, Patrick Y. Robins, H. Ian Chang, Susan M. Groves, Morris D. Fink, Karen L. Junck, Larry Schiff, David Abrey, Lauren Gilbert, Mark R. Lieberman, Frank Kuhn, John DeAngelis, Lisa M. Mehta, Minesh Raizer, Jeff J. Yung, W. K. Alfred Aldape, Ken Wright, John Lamborn, Kathleen R. Prados, Michael D. TI Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FARNESYL TRANSFERASE INHIBITOR; GLIOBLASTOMA-MULTIFORME; ADVANCED CANCER; R115777; PACLITAXEL; RAS; ANTICONVULSANTS; THERAPY; KINASE AB Purpose A phase 11 study was undertaken in patients with recurrent malignant glioma to determine the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, dosed at the respective maximum-tolerated dose (MTD) for patients receiving and not receiving enzyme-inducing antiepileptic drugs (EIAEDs). Because tipifarnib undergoes extensive hepatic metabolism, MTD is doubled in patients on EIAEDs. The population included 67 patients with glioblastoma multiforme (GBM) and an exploratory group of 22 patients with anaplastic glioma (AG). Patients and Methods Patients received tipifarnib (300 and 600 mg bid for 21 days every 4 weeks in non-EIAED and EIAED patients, respectively). All patients were assessable for efficacy and safety. Results Two AG patients (9.1%) and eight GBM patients (11.9%) had progression-free survival (PFS) more than 6 months. Among the latter eight GBM patients, six of 36 patients (16.7%; 95% Cl, 7% to 32%) were not receiving EIAEDs and two of 31 patients (6.5%; 95% Cl, 1% to 20%) were receiving EIAEDs. Four patients had partial responses in group A GBM and one patient had a partial response group B GBM. An exploratory comparison of PFS between GBM groups A and B was statistically significant (P = .01). Patients not receiving EIAEDs had a higher incidence and increased severity of hematologic events. However, the incidence and severity of rash (the previously determined dose-limiting toxicity in patients receiving EIAEDs) seemed similar in EIAED and non-EIAED subgroups. Conclusion Tipifarnib (300 mg bid for 21 days every 4 weeks) shows modest evidence of activity in patients with recurrent GBM who are not receiving EIAEDs and is generally well tolerated in this population. C1 Univ Calif Los Angeles, Neurooncol Program, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Neurooncol Serv, San Francisco, CA 94143 USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Univ Wisconsin Hosp, Madison, WI USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75235 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Michigan Hosp, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. RP Cloughesy, TF (reprint author), Univ Calif Los Angeles, Neurooncol Program, David Geffen Sch Med, 710 Westwood Plaza,Reed Bldg,Room 1-230, Los Angeles, CA 90095 USA. EM tcloughe@ucla.edu RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA62455-08, 5-U01CA62399-09, CA16672, CA62412, CA6242, CA62426, U01CA62399, U01CA62405, U01CA62407-08, U01CA62421-08, U01CA62422]; NCRR NIH HHS [M01 RR03186, M01-RR00042, M01-RR00056, M01-RR00079, M01-RR00633, M01-RR0865] NR 24 TC 104 Z9 105 U1 0 U2 5 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 1 PY 2006 VL 24 IS 22 BP 3651 EP 3656 DI 10.1200/JCO.2006.06.2323 PG 6 WC Oncology SC Oncology GA 069JY UT WOS:000239443400023 PM 16877733 ER PT J AU Biederman, J Petty, CR Faraone, SV Hirshfeld-Becker, DR Henin, A Brauer, L Kaufman, B Rosenbaum, JF AF Biederman, Joseph Petty, Carter R. Faraone, Stephen V. Hirshfeld-Becker, Dina R. Henin, Aude Brauer, Lindsay Kaufman, Bonnie Rosenbaum, Jerrold F. TI Antecedents to panic disorder in nonreferred adults SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEPARATION ANXIETY HYPOTHESIS; REGRESSION TREES CART; GENERAL-POPULATION; CHILDHOOD HISTORY; EARLY-ONSET; COMORBIDITY; CLASSIFICATION; AGORAPHOBIA; DEPRESSION; CHILDREN AB Objective: Previous work has shown that childhood anxiety disorders are unique antecedents for panic disorder. The current study examined both childhood and adult comorbid disorders as potential antecedent disorders to panic disorder in a large sample of nonreferred adults. Methods: Subjects were 1018 adults with (N = 58) and without (N = 960) panic disorder who were derived from a sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD); data were obtained from 1988 to 1996. Classification and regression trees (CART) analysis was used to examine anxiety and nonanxiety disorders antecedent to panic disorder. Results: CART analysis showed that separation anxiety disorder, social phobia, and simple phobia were unique predictors of subsequent panic disorder. Conclusion: These results support and expand previously reported findings in referred samples documenting that comorbid anxiety disorders are unique antecedent risk factors for panic disorder. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM Jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD36317]; NIMH NIH HHS [5R01MH50657] NR 42 TC 9 Z9 9 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2006 VL 67 IS 8 BP 1179 EP 1186 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 080MQ UT WOS:000240252400002 PM 16965194 ER PT J AU Houston, JP Ahl, J Meyers, AL Kaiser, CJ Tohen, M Baldessarini, RJ AF Houston, John P. Ahl, Jonna Meyers, Adam L. Kaiser, Christopher J. Tohen, Mauricio Baldessarini, Ross J. TI Reduced suicidal ideation in bipolar I disorder mixed-episode patients in a placebo-controlled trial of olanzapine combined with lithium or divalproex SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 157th Annual Meeting of the American-Psychiatric-Association CY MAY 01-06, 2004 CL New York, NY SP Amer Psychiat Assoc ID RATING-SCALE; DEPRESSIVE-MANIA; SOMATIC SYMPTOMS; RISK; SCHIZOPHRENIA; CLOZAPINE; BEHAVIOR; FLUOXETINE; PSYCHOSIS; METAANALYSIS AB Objective: To identify symptoms associated with suicidality in bipolar I disorder patients, and to assess suicide risk during treatment with olanzapine in combination with lithium or divalproex. Method: We used data from a study (conducted from September 1997 to October 2000) in which DSM-IV bipolar I manic or mixed-episode patients who were partially responsive to at least 2 weeks of lithium or divalproex monotherapy prior to study entry were randomly assigned to augmentation therapy with olanzapine (5-20 mg/day) or placebo. Among mixed-episode patients with residual suicidality (Hamilton Rating Scale for Depression-item 3 [HAM-D-3] score of 1 or above) at randomization to cotherapy, we identified items in the Young Mania Rating Scale, Positive and Negative Syndrome Scale, and Barnes Akathisia Rating Scale that correlated with HAM-D-3 scores. We used factor analysis of correlated items to identify symptom domains associated with suicidality ratings and assessed changes in symptom factors and HAM-D-3 scores during 6 weeks of combination therapy with olanzapine versus placebo. Results: In 58 mixed-episode patients, mean +/- SD HAM-D-3 scores averaged 1.36 +/- 0.55 after at least 2 weeks of initial mood stabilizer monotherapy prior to study entry. Factors associated with the HAM-D-3 appeared to represent somatic discomfort, agitated depression, and psychotic features. Combination therapy with olanzapine (N = 36) versus placebo (N = 22) differentially reduced HAM-D-3 scores by 58% versus 29% (p <.05) within 1 week, and all 3 associated symptom factors within 2 weeks by averages of 31% versus 12% (p <.05). Conclusions: Suicidality in adult, mixed-episode, bipolar I disorder patients was associated with somatic discomfort, agitated depression, and psychosis. Overall, these findings suggest that the addition of an atypical antipsychotic-antimanic agent in some bipolar disorder patients may help to reduce suicidal ideation. C1 Eli Lilly & Co, Lilly Technol Ctr, Lilly Res Labs, Indianapolis, IN 46221 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Int Bipolar Disorders Res Program, Mailman Res Ctr, McLean Div, Belmont, MA USA. RP Houston, JP (reprint author), Eli Lilly & Co, Lilly Technol Ctr, Lilly Res Labs, Drop Code 4133,1400 W Reymond St, Indianapolis, IN 46221 USA. EM houstonjp@lilly.com NR 44 TC 32 Z9 35 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2006 VL 67 IS 8 BP 1246 EP 1252 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 080MQ UT WOS:000240252400011 PM 16965203 ER PT J AU Hornberger, J Torriani, FJ Dieterich, DT Brau, N Sulkowski, MS Torres, MR Green, J Patel, K AF Hornberger, John Torriani, Francesca J. Dieterich, Douglas T. Brau, Norbert Sulkowski, Mark S. Torres, Maribel Rodriguez Green, Jesse Patel, Kavita TI Cost-effectiveness of peginterferon alfa-2a (40 kDa) plus ribavirin in patients with HIV and hepatitis C virus co-infection SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE HIV; economics; costs; cost-effectiveness; interferon; peginterferon alfa-2a; ribavirin ID ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; INTERFERON-ALPHA; MORTALITY; MORBIDITY; LIVER; POPULATION; CIRRHOSIS; SURVIVAL; DURATION AB Background: A multinational trial (APRICOT) showed that peginterferon alfa-2a (40 kDa) plus ribavirin is efficacious for treatment of HIV-HCV co-infection. The cost-effectiveness of treating these patients with peginterferon alfa-2a/ribavirin has yet to be explored from a US societal perspective. Objective: To predict the cost-effectiveness of peginterferon alfa-2a/ribavirin with interferon/ribavirin (IFN/RBV) or no treatment in HIV-HCV co-infected patients. Study design: A Markov model was constructed with liver progression estimates based on published literature. Sustained virological response and baseline characteristics of the reference case were based on APRICOT. Quality of life and costs in 2004 US dollars (US$) were based on literature estimates and discounted at 3%. Results: Peginterferon alfa-2a/ribavirin compared with IFN/RBV or no treatment is predicted to increase quality-adjusted life-years (QALYs) by 0.73 and 0.94 years, respectively, in HCV-genotype-1 patients. The incremental cost-effectiveness ratio of peginterferon alfa-2a/ribavirin compared with IFN/RBV and no treatment for all patients is respectively US$ 2082 and 5187/QALY gained. Conclusions: Anti-HCV treatment is predicted to decrease the risk of cirrhosis and increase quality-adjusted survival of HIV-HCV co-infected patients compared with IFN/RBV and no treatment. Peginterferon alfa-2a/ribavirin's cost per QALY gained relative to these options falls within the cost-effectiveness level of many health technologies commonly adopted in the US. (C) 2006 Elsevier B.V. All rights reserved. C1 SPHERE Inst Acumen LLC, Burlingame, CA 94010 USA. Dept Vet Affairs, Palo Alto, CA USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Fdn Invest Diego, Santurce, PR USA. Ponce Sch Med, Ponce, PR USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RP Hornberger, J (reprint author), SPHERE Inst Acumen LLC, 500 Airport Blvd,Suite 365, Burlingame, CA 94010 USA. EM jhornberger@sphereinstitute.org NR 45 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD AUG PY 2006 VL 36 IS 4 BP 283 EP 291 DI 10.1016/j.jcv.2006.04.008 PG 9 WC Virology SC Virology GA 075BR UT WOS:000239857700007 PM 16765638 ER PT J AU Schnurr, PP Hayes, AF Lunney, CA McFall, M Uddo, M AF Schnurr, Paula P. Hayes, Andrew F. Lunney, Carole A. McFall, Miles Uddo, Madeline TI Longitudinal analysis of the relationship between symptoms and quality of life in veterans treated for posttraumatic stress disorder SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; quality of life; military veterans; group psychotherapy ID ANXIETY DISORDERS; GROUP-THERAPY; TRAUMA; PTSD; INJURY; TRIAL AB This study examined how change in posttraumatic stress disorder (PTSD) symptoms relates to change in quality of life. The sample consisted of 325 male Vietnam veterans with chronic PTSD who participated in a randomized trial of group psychotherapy. Latent growth modeling was used to test for synchronous effects of PTSD symptom change on psychosocial and physical health-related quality of life within the same time period and lagged effects of initial PTSD symptom change on later change in quality of life. PTSD symptoms were associated with reduced quality of life before treatment. There were synchronous effects of symptom change on change in quality of life but no significant lagged effects. Results indicate the importance of measuring quality of life in future investigations of PTSD treatment. C1 US Vet Affairs Med Ctr, Natl Ctr PostTraumat Stress Disorder, White River Jct, VT 05009 USA. Dartmouth Coll Sch Med, Dept Psychiat, Dartmouth, NS, Canada. Ohio State Univ, Sch Commun, Columbus, OH 43210 USA. Univ Washington, Sch Med, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. New Orleans VA Med Ctr, New Orleans, LA USA. RP Schnurr, PP (reprint author), US Vet Affairs Med Ctr, Natl Ctr PostTraumat Stress Disorder, 116D, White River Jct, VT 05009 USA. EM paula.schnurr@dartmouth.edu RI Hayes, Andrew/A-5936-2008; Lunney, Carole/A-1366-2010 OI Hayes, Andrew/0000-0002-8329-1696; Lunney, Carole/0000-0002-0077-1281 NR 31 TC 86 Z9 87 U1 0 U2 15 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2006 VL 74 IS 4 BP 707 EP 713 DI 10.1037/0022-006X.74.4.707 PG 7 WC Psychology, Clinical SC Psychology GA 071NM UT WOS:000239608900008 PM 16881778 ER PT J AU Foschi, F Izard, J Sasaki, H Sambri, V Prati, C Muller, R Stashenko, P AF Foschi, F. Izard, J. Sasaki, H. Sambri, V. Prati, C. Mueller, R. Stashenko, P. TI Treponema denticola in disseminating endodontic infections SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE periapical lesion; Tannerella forsythia; Porphyromonas gingivalis; disseminating infection; micro-computed tomography ID POLYMERASE-CHAIN-REACTION; CORONARY-HEART-DISEASE; PORPHYROMONAS-GINGIVALIS; PERIODONTAL-DISEASE; BONE DESTRUCTION; RED COMPLEX; MICE; ASSOCIATION; PENETRATION; SAMPLES AB Treponema denticola is a consensus periodontal pathogen that has recently been associated with endodontic pathology. In this study, the effect of mono-infection of the dental pulp with T. denticola and with polymicrobial "red-complex" organisms (RC) (Porphyromonas gingivalis, Tannerella forsythia, and T. denticola) in inducing disseminating infections in wild-type (WT) and severe-combined-immunodeficiency (SCID) mice was analyzed. After 21 days, a high incidence (5/10) of orofacial abscesses was observed in SCID mice mono-infected with T. denticola, whereas abscesses were rare in SCID mice infected with the red-complex organisms or in wild-type mice. Splenomegaly was present in all groups, but only mono-infected SCID mice had weight loss. T. denticola DNA was detected in the spleen, heart, and brain of mono-infected SCID mice and in the spleen from mono-infected wildtype mice, which also had more periapical bone resorption. The results indicate that T. denticola has high pathogenicity, including dissemination to distant organs, further substantiating its potential importance in oral and linked systemic conditions. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Univ Bologna, Dept Oral Sci, Endodont Unit, I-40126 Bologna, Italy. Forsyth Inst, Dept Mol Genet, Boston, MA USA. Univ Bologna, Osped S Orsola, DMCSS, Microbiol Sect, I-40126 Bologna, Italy. Univ Zurich, CH-8006 Zurich, Switzerland. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pstashenko@forsyth.org RI Muller, Ralph/A-1198-2008; Izard, Jacques/A-6074-2012; Foschi, Federico /E-7531-2012; OI Muller, Ralph/0000-0002-5811-7725; Prati, Carlo/0000-0001-8163-8628; Izard, Jacques/0000-0002-5904-5436 FU NIDCR NIH HHS [DE-11664, R01 DE011664, R01 DE011664-04] NR 30 TC 27 Z9 27 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD AUG PY 2006 VL 85 IS 8 BP 761 EP 765 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 073XK UT WOS:000239775800014 PM 16861296 ER PT J AU Nagurney, JT Feldman, D Cahill, DP Gatha, NM Koroshetz, WJ AF Nagurney, John T. Feldman, David Cahill, Daniel P. Gatha, Nehal M. Koroshetz, Walter J. TI Unusual visual symptoms in a patient with bilateral vertebral artery dissection: A case report SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE vertebral artery dissection; migraine; visual symptoms; diagnosis AB We present a previously unreported set of symptoms in a patient found to have bilateral vertebral dissections. Although visual symptoms are common in vertebral dissection, their pattern does not typically mimic those that commonly precede or accompany migraine headache. When they do occur, they usually take the form of diplopia or blurred vision. The patient we describe had visual symptoms that varied over three episodes of headache and included transient visual field loss and scintillations ("lightning bolts"), both common in migraine. However, our patient's new visual symptoms represented a change in pattern from those that had accompanied her previous migraines. This detailed history-taking prompted an evaluation for an etiology other than migraine and prevented a further delay in diagnosis and treatment. (C) 2006 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02115 USA. Washington Hosp Ctr, Dept Emergency Med, Washington, DC 20010 USA. Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. Albany Med Coll, Albany, NY 12208 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, 55 Fruit St, Boston, MA 02115 USA. OI Cahill, Daniel/0000-0003-2552-6546 NR 12 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2006 VL 31 IS 2 BP 169 EP 171 DI 10.1016/j.jemermed.2005.09.014 PG 3 WC Emergency Medicine SC Emergency Medicine GA 067UL UT WOS:000239328000007 PM 17044579 ER PT J AU Collins, JJ Brown, D Fix, M Nagurney, JT Nadel, E Shewakramani, S White, B Miller, R Sellas, M AF Collins, John J. Brown, David Fix, Megan Nagurney, J. Tobias Nadel, Eric Shewakramani, Sanjay White, Benjamin Miller, Robert Sellas, Monique TI Septic shock and community-acquired MRSA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; RISK-FACTORS; INFECTIONS; PREVALENCE; SKIN C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Bulfinch 105, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2006 VL 31 IS 2 BP 211 EP 214 DI 10.1016/j.jemermed.2006.05.007 PG 4 WC Emergency Medicine SC Emergency Medicine GA 067UL UT WOS:000239328000013 PM 17044585 ER PT J AU Eisner, BH Gargollo, PC Dretler, SP AF Eisner, B. H. Gargollo, P. C. Dretler, S. P. TI 119 uses of the stone cone during ureteroscopic laser lithotripsy SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Kidney Stone Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD AUG PY 2006 VL 20 SU 1 BP A115 EP A115 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 075ST UT WOS:000239906200444 ER PT J AU Larson, B Lance, M Sommers, V Jaffs, M William, E Thames, L AF Larson, Benjumin Lance, Mynderse Sommers, V. Jaffs, M. William, Evans Thames, Larson TI Blood pressure surges during office-based transurethral microwave thermotherapy treatments of the prostate SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Cleveland, OH 44106 USA. Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. SW Florida Urol Assoc, Ft Myers, FL USA. Inst Med Res, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD AUG PY 2006 VL 20 SU 1 BP A59 EP A59 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 075ST UT WOS:000239906200234 ER PT J AU Matin, SF Ahrar, K Cadeddu, JA Gervais, DA McGovern, FJ Zagoria, RA Uzzo, RG Haaga, J Resnick, MI Kaouk, J Gill, IS AF Matin, S. F. Ahrar, K. Cadeddu, J. A. Gervais, D. A. McGovern, F. J. Zagoria, R. A. Uzzo, R. G. Haaga, J. Resnick, M. I. Kaouk, J. Gill, I. S. TI Residual and recurrent disease following renal energy-ablative therapy: Implications for management a multi-institutional study SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD AUG PY 2006 VL 20 SU 1 BP A11 EP A11 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 075ST UT WOS:000239906200044 ER PT J AU Kripalani, S Paasche-Orlow, MK Parker, RM Saha, S AF Kripalani, Sunil Paasche-Orlow, Michael K. Parker, Ruth M. Saha, Somnath TI Advancing the field of health literacy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID ADHERENCE C1 Emory Univ, Sch Med, Div Gen Med, Atlanta, GA 30303 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Kripalani, S (reprint author), Emory Univ, Sch Med, Div Gen Med, 49 Jesse Hill Jr Dr SE, Atlanta, GA 30303 USA. EM skripal@emory.edu OI Paasche-Orlow, Michael/0000-0002-9276-7190 NR 6 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2006 VL 21 IS 8 BP 804 EP 805 DI 10.1111/j.1525-1497.2006.00568.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 061QZ UT WOS:000238888800002 ER PT J AU Saha, S AF Saha, Somnath TI Improving literacy as a means to reducing health disparities SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID MORTALITY; INCOME; POLICIES C1 Oregon Hlth Sci Univ, Dept Med, Portland VA Med Ctr, Gen Internal Med Sect,Portland VAMC P3MED, Portland, OR 97239 USA. RP Saha, S (reprint author), Oregon Hlth Sci Univ, Dept Med, Portland VA Med Ctr, Gen Internal Med Sect,Portland VAMC P3MED, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sahas@ohsu.edu NR 18 TC 26 Z9 26 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2006 VL 21 IS 8 BP 893 EP 895 DI 10.1111/j.1525-1497.2006.00546.x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 061QZ UT WOS:000238888800020 PM 16881955 ER PT J AU Scalapino, KJ Tang, QZ Bluestone, JA Bonyhadi, ML Daikh, DI AF Scalapino, Kenneth J. Tang, Qizhi Bluestone, Jeffrey A. Bonyhadi, Mark L. Daikh, David I. TI Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo, expanded regulatory T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VERSUS-HOST-DISEASE; IN-VITRO; AUTOIMMUNE ENCEPHALOMYELITIS; CD25(+); TOLERANCE; INTERLEUKIN-2; ERYTHEMATOSUS; GLOMERULONEPHRITIS; DAMAGE AB An increasing number of studies indicate that a subset of CD4(+) T cells with regulatory capacity (regulatory T cells; T-regs) can function to control organ-specific autoimmune disease. To determine whether abnormalities of thymic-derived T,,g, play a role in systemic lupus erythematosus, we evaluated T-reg prevalence and function in (New Zealand Black X New Zealand White)F-1 (B/W) lupus-prone mice. To explore the potential of T-g to suppress disease, we evaluated the effect of adoptive transfer of purified, ex vivo expanded thymic-derived T-regs on the progression of renal disease. We found that although the prevalence of Tregs is reduced in regional lymph nodes and spleen of prediseased B/W mice compared with age-matched non-autoimmune mice, these cells increase in number in older diseased mice. In addition, the ability of these cells to proliferate in vitro was comparable to those purified from non-autoimmune control animals. Purified CD4(+)CD25(+)CD62L(high) B/W T-regs were expanded ex vivo 80-fold, resulting in cells with a stable suppressor phenotype. Adoptive transfer of these exogenously expanded cells reduced the rate at which mice developed renal disease; a second transfer after treated animals had developed proteinuria further slowed the progression of renal disease and significantly improved survival. These studies indicate that thymic-derived T-regs may have a significant role in the control of autoimmunity in lupus-prone B/W mice, and augmentation of these cells may constitute a novel therapeutic approach for systemic lupus erythematosus. C1 Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, Ctr Diabet, Dept Med, San Francisco, CA 94121 USA. Xcyte, Seattle, WA 98104 USA. RP Daikh, DI (reprint author), Univ Calif San Francisco, Dept Med, Div Rheumatol, Arthrit Immunol 111R,4150 Clement St, San Francisco, CA 94121 USA. EM daikh@itsa.ucsf.edu NR 29 TC 128 Z9 138 U1 3 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2006 VL 177 IS 3 BP 1451 EP 1459 PG 9 WC Immunology SC Immunology GA 065DT UT WOS:000239140300017 PM 16849451 ER PT J AU Barrington, RA Borde, M Rao, AJ Carroll, MC AF Barrington, Robert A. Borde, Madhuri Rao, Anjana Carroll, Michael C. TI Involvement of NFAT1 in B cell self-tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL; ANTIGEN-RECEPTOR; LYMPHOCYTES-B; IN-VIVO; CALCINEURIN; TRANSCRIPTION; ACTIVATION; ELIMINATION; INDUCTION; APOPTOSIS AB B cells from anti-lysozyme Ig/soluble lysozyme double-transgenic mice are chronically exposed to self-Ag in the periphery, resulting in an anergic phenotype. Chronic exposure to self-Ag leads to nuclear translocation of NFAT1 and NFAT2, suggesting that they are involved in anergy. To directly test a role for NFAT1 in B cell anergy, NFAT1-deficient mice were crossed with antilysozyme Ig transgenic mice. As expected, B cell anergy was evident in the presence of self-Ag based on reduced serum antilysozyme levels, percentage and number of mature B cells, and reduced B cell responsiveness. By contrast, B cell anergy was relieved in NFAT1(-/-) mice expressing soluble self-Ag. Bone marrow development was equivalent in NFAT1-sufficient and -deficient mice, suggesting that loss of anergy in the latter is due to selection later in development. Taken together, these studies provide direct evidence that the transcription factor NFAT1 is involved in B cell anergy. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu FU NHLBI NIH HHS [HL066987]; NIAID NIH HHS [AI039246-1A1, 2R01AI048213-06] NR 41 TC 16 Z9 16 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2006 VL 177 IS 3 BP 1510 EP 1515 PG 6 WC Immunology SC Immunology GA 065DT UT WOS:000239140300023 PM 16849457 ER PT J AU Bachmann, MP Bartsch, H Gross, JK Maier, SM Gross, TF Workman, JL James, JA Farris, AD Jung, B Franke, C Conrad, K Schmitz, M Buttner, C Buyon, JP Semsei, M Harley, JB Rieber, EP AF Bachmann, Michael P. Bartsch, Holger Gross, Joanne K. Maier, Shannon M. Gross, Timothy F. Workman, Jennifer L. James, Judith A. Farris, A. Darise Jung, Bettina Franke, Claudia Conrad, Karsten Schmitz, Marc Buettner, Cordula Buyon, Jill P. Semsei, Mre Harley, John B. Rieber, E. Peter TI Autoimmunity as a result of escape from RNA surveillance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERNAL TRANSLATION INITIATION; TERMINATION FACTOR LA; AUTOANTIGEN LA/SS-B; MESSENGER-RNA; POLYMERASE-III; IN-VITRO; TRANSCRIPTION TERMINATION; POLIOVIRUS RNA; VIRUS-RNA; SS-B AB In previous studies, we detected a frame shift mutation in the gene encoding the autoantigen La of a patient with systemic lupus erythematosus. The mutant La mRNA contains a premature termination codon. mRNAs that prematurely terminate translation should be eliminated by RNA quality control mechanisms. As we find Abs specific for the mutant La form in similar to 30% of sera from anti-La-positive patients, we expected that mutant La mRNAs circumvent RNA control and the expression of mutant La protein could become harmful. Indeed, real-time PCR, immunostaining, and immunoblotting data of mice transgenic for the mutant La form show that mutant La mRNAs are not repressed in these animals and are translated to mutant La protein. In addition to the mutant La protein, we detected a minor portion of native human La in the mutant La-transgenic mice. Therefore, ribosomal frame shifting may allow the mutant La mRNA to escape from RNA control. Interestingly, expression of the mutant La mRNA results in a lupus-like disease in the experimental mice. Consequently, escape of mutant La mRNA from RNA control can have two effects: it 1) results in the expression of an immunogenic (neo)epitope, and 2) predisposes to autoimmunity. C1 Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Immunol, D-01307 Dresden, Germany. Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. NYU, Sch Med, Hosp Joint Dis, New York, NY 10003 USA. Univ Debrecen, Dept Med 3, Med & Hlth Sci Ctr, Debrecen, Hungary. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA. RP Bachmann, MP (reprint author), Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Immunol, Fiedlerstr 42, D-01307 Dresden, Germany. EM michael.bachmann@mailbox.tu-dresden.de RI Bachmann, Michael/E-8850-2010 OI Bachmann, Michael/0000-0002-8029-5755 FU NCRR NIH HHS [IP20RR15577, P20 RR015577, P20 RR020143, RR020143]; NIAID NIH HHS [AI053747, AI054117, AI131584, AI24717, AI48097, AI51647, K02 AI051647, R01 AI024717, R01 AI031584, R01 AI048097, R21 AI053747, R37 AI024717, R41 AI054117]; NIAMS NIH HHS [P50 AR048940, AR049084, AR42460, AR48940, P01 AR049084, R01 AR042460]; NIDCR NIH HHS [DE015223, R01 DE015223]; NIGMS NIH HHS [GM63497, R01 GM063497] NR 39 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2006 VL 177 IS 3 BP 1698 EP 1707 PG 10 WC Immunology SC Immunology GA 065DT UT WOS:000239140300045 PM 16849479 ER PT J AU Hsieh, MF Lai, SL Chen, JP Sung, JM Lin, YL Wu-Hsieh, BA Gerard, C Luster, A Liao, F AF Hsieh, Ming-Fang Lai, Szu-Liang Chen, Jia-Perng Sung, Jui-Ming Lin, Yi-g Lin Wu-Hsieh, Betty A. Gerard, Craig Luster, Andrew Liao, Fang TI Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CD8(+) T-CELLS; GAMMA-INDUCIBLE PROTEIN-10; CHEMOKINE EXPRESSION; IN-VIVO; HOST-DEFENSE; HEMORRHAGIC-FEVER; IMMUNE-RESPONSES; INTERFERON-GAMMA; VIRAL-INFECTION AB We examined the extent to which CXCR3 mediates resistance to dengue infection. Following intracerebral infection with dengue virus, CXCR3-deficient (CXCR3(-/-)) mice showed significantly higher mortality rates than wild-type (WT) mice; moreover, surviving CXCR3(-/-) mice, but not WT mice, often developed severe hind-limb paralysis. The brains of CXCR3-/- mice showed higher viral loads than those of WT mice, and quantitative analysis using real-time PCR, flow cytometry, and immunohistochemistry revealed fewer T cells, CD8(+) T cells in particular, in the brains of CXCR3(-/)- mice. This suggests that recruitment of effector T cells to sites of dengue infection was diminished in CXCR3-/- mice, which impaired elimination of the virus from the brain and thus increased the likelihood of paralysis and/or death. These results indicate that CXCR3 plays a protective rather than an immunopathological role in dengue virus infection. In studies to identify critical CXCR3 ligands, CXCL10/IFN-inducible protein 10-deficient (CXCL10/IP-10(-/-)) mice infected with dengue virus showed a higher mortality rate than that of the CXCR3(-/-) mice. Although CXCL10/IP-10, CXCL9/monokine induced by IFN-gamma, and CXCL11/IFN-inducible T cell a chemoattractant share a single receptor and all three of these chemokines are induced by dengue virus infection, the latter two could not compensate for, the absence of CXCL10/IP-10 in this in vivo model. Our results suggest that both CXCR3 and CXCLIO/IP-10 contribute to resistance against primary dengue virus infection and that chemokines that are indistinguishable in in vitro assays differ in their activities in vivo. C1 Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 112, Taiwan. Natl Taiwan Univ, Coll Med, Grad Inst Immunol, Taipei 10764, Taiwan. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Liao, F (reprint author), Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. EM fl9z@ibms.sinica.edu.tw OI WU-HSIEH, BETTY AN-YE/0000-0003-1522-2055 NR 69 TC 82 Z9 84 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2006 VL 177 IS 3 BP 1855 EP 1863 PG 9 WC Immunology SC Immunology GA 065DT UT WOS:000239140300063 PM 16849497 ER PT J AU Banda, NK Thurman, JM Kraus, D Wood, A Carroll, MC Arend, WP Holers, VM AF Banda, Nirmal K. Thurman, Joshua M. Kraus, Damian Wood, Allyson Carroll, Michael C. Arend, William P. Holers, V. Michael TI Alternative complement pathway activation is essential for inflammation and joint destruction in the passive transfer model of collagen-induced arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE IMMUNE-SYSTEM; RHEUMATOID-ARTHRITIS; RENAL-DISEASE; MRL/LPR MICE; FACTOR B; FACTOR-H; PROGRESSION; INHIBITION; DEFICIENCY; INITIATION AB Activation of each complement initiation pathway (classical, alternative, and lectin) can lead to the generation of bioactive fragments with resulting inflammation in target organs. The objective of the current study was to determine the role of specific complement activation pathways in the pathogenesis of experimental anti-type II collagen mAb-passive transfer arthritis. C57BL/6 mice were used that were genetically deficient in either the alternative pathway protein factor B (Bf(-/-)) or in the classical pathway component C4 (C4(-/-)). Clinical disease activity was markedly decreased in Bf(-/-) compared with wild-type (WT) mice (0.5 +/- 0.22 (n = 6) in Bf(-/-) vs 8.83 +/- 0.41 (n = 6) in WT mice (p < 0.0001)). Disease activity scores were not different between C4(-/-) and WT mice. Analyses of joints showed that C3 deposition, inflammation, parmus, cartilage, and bone damage scores were all significantly less in Bf(-/-) as compared with WT mice. There were significant decreases in mRNA levels of C3, C4, CR2, CR3, C3aR, and C5aR in the knees of Bf(-/-) as compared with C4(-/-) and WT mice with arthritis; mRNA levels for complement regulatory proteins did not differ between the three strains. These results indicate that the alternative pathway is absolutely required for the induction of arthritis following injection of anti-collagen Abs. The mechanisms by which these target organ-specific mAbs bypass the requirements for engagement of the classical pathway remain to be defined but do not appear to involve a lack of alternative pathway regulatory proteins. C1 Univ Colorado, Hlth Sci Ctr, Div Rheumatol, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Nephrol & Hypertens, Denver, CO 80262 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Holers, VM (reprint author), Univ Colorado, Hlth Sci Ctr, Div Rheumatol, Dept Med, 4200 E 9th Ave,B-115, Denver, CO 80262 USA. EM Michael.Holers@uchsc.edu FU NIAID NIH HHS [AI39246, AI53570]; NIAMS NIH HHS [AR51749] NR 40 TC 77 Z9 80 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2006 VL 177 IS 3 BP 1904 EP 1912 PG 9 WC Immunology SC Immunology GA 065DT UT WOS:000239140300069 PM 16849503 ER PT J AU Levy, O Coughlin, M Cronstein, BN Roy, RM Desai, A Wessels, MR AF Levy, Ofer Coughlin, Melissa Cronstein, Bruce N. Roy, Rene M. Desai, Avani Wessels, Michael R. TI The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTORS; IN-VIVO; INNATE IMMUNITY; A(3) RECEPTORS; CYTOKINE PRODUCTION; ADENYLYL-CYCLASE; MONOCYTIC CELLS; CUTTING EDGE; CORD BLOOD AB Human newborns are susceptible to microbial infection and mount poor vaccine responses, yet the mechanisms underlying their susceptibility are incompletely defined. We have previously reported that despite normal basal expression of TLRs and associated signaling intermediates, human neonatal cord blood monocytes demonstrate severe impairment in TNF-alpha production in response to triacylated (TLR 2/1) and diacylated (TLR 2/6) bacterial lipopeptides (BLPs). We now demonstrate that in marked contrast, BLP-induced synthesis of IL-6, a cytokine with anti-inflammatory and Th2-polarizing properties, is actually greater in neonates than adults. Remarkably, newborn blood plasma confers substantially reduced BLP-induced monocyte synthesis of TNF-a, while preserving IL-6 synthesis, reflecting the presence in neonatal blood plasma of a soluble, low molecular mass inhibitory factor (< 10 kDa) that we identify as adenosine, an endogenous purine metabolite with immunomodulatory properties. The neonatal adenosine system also inhibits TNF-alpha production in response to whole microbial particles known to express TLR2 agonist activity, including Listeria monocytogenes, Escherichia coli (that express BLPs), and zymosan particles. Selective inhibition of neonatal TNF-alpha production is due to the distinct neonatal adenosine system, including relatively high adenosine concentrations in neonatal blood plasma and heightened sensitivity of neonatal mononuclear cells to adenosine A3 receptor-mediated accumulation of cAMP, a second messenger that inhibits TLR-mediated TNF-alpha synthesis but preserves IL-6 production. We conclude that the distinct adenosine system of newborns polarizes TLR-mediated cytokine production during the perinatal period and may thereby modulate their innate and adaptive immune responses. C1 Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NYU, Sch Med, Dept Med, New York, NY 10016 USA. RP Levy, O (reprint author), Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA. EM ofer.levy@childrens.harvard.edu FU NIAID NIH HHS [K08 AI050583, K08 AI50583-01, R01 AI067353-01A1, R01 AI067353] NR 64 TC 128 Z9 130 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2006 VL 177 IS 3 BP 1956 EP 1966 PG 11 WC Immunology SC Immunology GA 065DT UT WOS:000239140300075 PM 16849509 ER PT J AU Kim, SZ Song, WJ Nyhan, WL Mandell, R Shih, VE AF Kim, S. Z. Song, W. J. Nyhan, W. L. Mandell, R. Shih, V. E. TI Long-term neurologic follow up of HHH syndrome in 4 cases SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Korea Genet Res Ctr, Cheong Ju City, South Korea. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 48 EP 48 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100166 ER PT J AU Venugopal, B Kennedy, J Curcio-Morelli, C Falardeau, J LaPlante, JM Vassilev, PM Slaugenhaupt, SA AF Venugopal, B. Kennedy, J. Curcio-Morelli, C. Falardeau, J. LaPlante, J. M. Vassilev, P. M. Slaugenhaupt, S. A. TI Novel interaction of heat shock cognate protein 70 (Hsc70) with mucolipin-1, the protein responsible for mucolipidosis type IV SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 76 EP 76 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100278 ER PT J AU Wattanasirichaigoon, D Khowsathit, P Visudtibhan, A Suthutvoravut, U Charoenpipop, D Kim, SZ Levy, HL Shih, VE AF Wattanasirichaigoon, Duangrurdee Khowsathit, Pongsak Visudtibhan, Anannit Suthutvoravut, Umaporn Charoenpipop, Dussadee Kim, Sook Z. Levy, Harvey L. Shih, Vivian E. TI Pericardial effusion in primary systemic carnitine deficiency SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article C1 Mahidol Univ, Dept Pediat, Fac Med, Ramathibodi Hosp, Bangkok 10700, Thailand. Mahidol Univ, Res Ctr, Fac Med, Ramathibodi Hosp, Bangkok 10700, Thailand. Korea Genet Res Ctr, Cheong Ju City, Chungbuk, South Korea. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wattanasirichaigoon, D (reprint author), Mahidol Univ, Dept Pediat, Fac Med, Ramathibodi Hosp, Bangkok 10700, Thailand. EM radwc@mahidol.ac.th NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 IS 4 BP 589 EP 589 DI 10.1007/s1545-006-0335-7 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 078MH UT WOS:000240107400019 PM 16830263 ER PT J AU Vockel, M Liew, CW Kreienkamp, HJ Brandner, JM AF Vockel, M. Liew, C. W. Kreienkamp, H. J. Brandner, J. M. TI Regulation of tight junctions by somatostatin receptor 3 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Society-of-Dermatology-Research (ESDR) CY SEP 06-07, 2006 CL Paris, FRANCE SP European Soc Dermatol Res C1 Univ Hosp Hamburg, Dept Human Genet, Dept Dermatol & Venerol, Hamburg, Germany. Joslin Diabet Ctr, Boston, MA 02215 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2006 VL 126 SU 3 BP 18 EP 18 PG 1 WC Dermatology SC Dermatology GA 117RY UT WOS:000242891900092 ER PT J AU Salter, SA Batra, RS Rohrer, TE Kohli, N Kimball, AB AF Salter, Sharon A. Batra, Ritu S. Rohrer, Thomas E. Kohli, Neeraj Kimball, Alexa B. TI Striae and pelvic relaxation: Two disorders of connective tissue with a strong association SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID ORGAN PROLAPSE; SWEDISH POPULATION; GENITAL PROLAPSE; WOMEN; GRAVIDARUM AB Pelvic relaxation, a weakening of pelvic support structures, is an under- reported condition that affects a multitude of women. In the United States alone, more than 338,000 procedures for prolapse are performed annually. Decreased collagen content has been noted in the tissues of women affected by this condition. Interestingly, biopsy specimens of women with striae also show a diminution of collagen. Using self-reported anonymous data, we compared the prevalence of striae in women with and without pelvic relaxation to see if an association between these two disorders of connective tissue existed. More than half the women with prolapse ( 54.7%) ( n = 41) reported striae, whereas only 25.0% of women in the non- prolapse group ( n 8) reported striae ( P < 0.01). Multivariate logistic regression analysis confirmed striae as a significant risk factor for the development of clinical prolapse ( odds ratio 3.12, P < 0.05). There appears to be a strong association between the presence of striae and the development of pelvic relaxation, which is unrelated to conventionally cited risk factors, such as age, weight, number of pregnancies, or postmenopausal status. C1 Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urogynecol, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. SkinCare Phys, Chestnut Hill, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Brigham & Womens Hosp, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA. EM akimball@partners.org NR 17 TC 15 Z9 15 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2006 VL 126 IS 8 BP 1745 EP 1748 DI 10.1038/sj.jid.5700258 PG 4 WC Dermatology SC Dermatology GA 096EB UT WOS:000241359100011 PM 16557237 ER PT J AU Underhill, HR Kerwin, WS Hatsukami, TS Yuan, C AF Underhill, Hunter R. Kerwin, William S. Hatsukami, Thomas S. Yuan, Chun TI Automated measurement of mean wall thickness in the common carotid artery by MRI: A comparison to intima-media thickness by B-mode ultrasound SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE carotid artery MRI; atherosclerosis; intima-media thickness; stastical shape modelling; B-mode ultrasound ID HIGH-RESOLUTION MRI; IN-VIVO; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS; PLAQUE; TRIAL; REPRODUCIBILITY; HEMORRHAGE; ACCURACY; STROKE AB Purpose: To determine whether the mean wall thickness (MWT) of the common carotid artery (CCA) measured by MRI is comparable to B-mode ultrasound (US) measurement of the intima-media thickness (IMT), an established marker of cardiovascular risk. Materials and Methods: As part of the two-year ORION trial, 43 patients with 16-79% stenosis by duplex US underwent high-resolution MRI and B-mode US examinations of their carotid arteries. Twenty-eight carotid arteries were identified as having both sufficient proximal coverage and adequate image quality of the CCA on MRI and a corresponding US. A novel algorithm utilizing statistical shape modeling was developed to automatically detect and measure MWT to within subpixel accuracy. The interrater and interscan reproducibility of the MWT measurement was computed as the root-mean-square (RMS) difference. The MWT and IMT measurements were compared via the Pearson correlation coefficient. Results: The MWT and IMT had a high Pearson correlation coefficient (r = 0.93; P < 0.001). The RMS difference between readers and between scans was 0.01 mm and 0.04 mm,respectively. Our automated algorithm correctly identified the lumen in 28 cases (100%) and the outer-wall boundary in 26 cases (93%). Conclusion: Automated measurements of the MWT by MRI are reproducible and have a high correlation with the IMT by B-mode US. C1 Univ Washington, Dept Radiol, Vasc Imaging Lab, Seattle, WA 98109 USA. Univ Washington, Dept Surg, Seattle, WA 98109 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98109 USA. RP Underhill, HR (reprint author), Univ Washington, Dept Radiol, Vasc Imaging Lab, 815 Mercer St,Box 358050, Seattle, WA 98109 USA. EM hunterru@gmail.com FU NHLBI NIH HHS [T32 HL07828] NR 30 TC 36 Z9 36 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD AUG PY 2006 VL 24 IS 2 BP 379 EP 387 DI 10.1002/jmri.20636 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 068YG UT WOS:000239410300017 PM 16786590 ER PT J AU Rodriguez, KL Young, AJ AF Rodriguez, K. L. Young, A. J. TI Perceptions of patients on the utility or futility of end-of-life treatment SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID MEDICAL FUTILITY; ADVANCE DIRECTIVES; CARE; RESOURCE; DECIDES; TERM AB Background and objectives: Definitions of medical futility, offered by healthcare professionals, bioethicists and other experts, have been rigorously debated by many investigators, but the perceptions of patients of futility have been explored only by a few. Patients were allowed to discuss their concerns about end-of-life care, so that their ideas about treatment futility or utility could be extrapolated by us. Methods: In this cross-sectional study, in-depth, semistructured interviews were conducted with 30 elderly people who were receiving outpatient care in a large, urban Veterans Affairs medical centre in the US. Each of their healthcare providers was also interviewed. Participants were asked to consider four terms commonly used in advance directive forms (ie, life-sustaining treatment, terminal condition, state of permanent unconsciousness and decision-making capacity) and to discuss what these terms meant to them. Audiotapes of the open-ended interviews were transcribed and responses were coded and categorised by constant comparison, a commonly used qualitative method. Results: The following four factors were taken into account by the participants when discussing end-of-life interventions and outcomes: (1) expected quality of life; (2) emotional and financial costs of treatment; (3) likelihood of treatment success; and (4) expected effect on longevity. C onclusions: Although the terms "utility'' or "futility'' were not generally used by the participants, segments of speech indicating their perceptions of these terms were identified. Treatment was not always discussed in the same way by patients and providers, but seemed to reflect the same four concerns. Therefore, it may be fruitful for providers to focus on these concerns when discussing end-of-life treatment options with their patients. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Memphis, Dept Commun, Memphis, TN 38152 USA. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 151CU,Univ Dr C,Bldg 28,MB-1A129, Pittsburgh, PA 15240 USA. EM Rodriguez@med.va.gov NR 37 TC 19 Z9 20 U1 2 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD AUG 1 PY 2006 VL 32 IS 8 BP 444 EP 449 DI 10.1136/jme.2005.014118 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 068HK UT WOS:000239363800003 PM 16877622 ER PT J AU Song, BW Sodroski, J AF Song, Byeongwoon Sodroski, Joseph TI Characterization of primate TRIM5alpha variants SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 49 BP 291 EP 291 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300060 ER PT J AU Whitney, JB Jiang, SS Mirshahidi, S Goins, LM Ibegbu, C Frankel, F Lieberman, J McClure, HM Raybourne, RB Ruprecht, RM AF Whitney, James B. Jiang, Shisong Mirshahidi, Saied Goins, Lauren M. Ibegbu, Chris Frankel, Fred Lieberman, Judy McClure, Harold M. Raybourne, Richard B. Ruprecht, Ruth M. TI Recombinant Listeria vectors as candidate oral aids vaccines: Primate studies SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. Ctr Blood Res, Boston, MA 02115 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. US FDA, Immunobiol Branch, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 113 BP 314 EP 315 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300124 ER PT J AU von Gegerfelt, A Valentin, A Patel, V Morrow, M Alicea, C Rosati, M Marthas, M Ruprecht, R Felber, BK Pavlakis, GN AF von Gegerfelt, Agneta Valentin, Antonio Patel, Vainav Morrow, Matthew Alicea, Candido Rosati, Margherita Marthas, Marta Ruprecht, Ruth Felber, Barbara K. Pavlakis, George N. TI Preservation of SIV-specific subset of cells with central memory phenotype SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Frederick, MD 21702 USA. Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Dana Farber Canc Inst, 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 122 BP 318 EP 318 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300133 ER PT J AU McCaslin, SE Rogers, CE Metzler, TJ Best, SR Weiss, DS Fagan, JA Liberman, A Marmar, CR AF McCaslin, Shannon E. Rogers, Cynthia E. Metzler, Thomas J. Best, Suzanne R. Weiss, Daniel S. Fagan, Jeffrey A. Liberman, Akiva Marmar, Charles R. TI The impact of personal threat on police officers' responses to critical incident stressors SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE police; personal threat; traumatic stress; peritraumatic dissociation; peritraumatic distress ID EMERGENCY SERVICES PERSONNEL; POSTTRAUMATIC-STRESS; PERITRAUMATIC DISSOCIATION; PSYCHOLOGICAL DISTRESS; EVENT SCALE; SYMPTOMS; DISORDER; EXPOSURE AB The relationship of type of critical incident (CI) stressor with peritraumatic responses and posttraumatic stress disorder symptoms was examined in police. Officers (N = 662) provided narratives of their most distressing CI experienced during police service and completed measures of related peritraumatic responses and posttraumatic stress disorder symptoms. Narratives were reliably rated (kappa = .80-1.0) on seven categories emerging from a series of factor analyses of a measure of critical incident stressors. Additional analysis revealed that the classification of primary narrative features required only five categories (personal life threat, duty-related violence, encountering physical or sexual assault victims, exposure to civilian death, other). When analyzed by further collapsing these five categories into high versus low personal threat, officers whose narratives contained high personal threat reported more peritraumatic dissociation, peritraumatic emotional distress, and current hyperarousal symptoms. Results suggest that greater personal threat during a CI may place an officer at greater risk for subsequent distress. C1 San Francisco VA Med Ctr, PTSD Res Program, Psychiat Serv 116P, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. No Calif Inst Res & Educ, San Francisco, CA USA. Washington Univ, St Louis, MO USA. Columbia Univ, New York, NY USA. Natl Inst Justice, Washington, DC USA. RP McCaslin, SE (reprint author), San Francisco VA Med Ctr, PTSD Res Program, Psychiat Serv 116P, 4150 Clement St, San Francisco, CA 94121 USA. EM shannon.mccaslin@ucsf.edu FU NIMH NIH HHS [MH56350-01A1] NR 33 TC 24 Z9 24 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD AUG PY 2006 VL 194 IS 8 BP 591 EP 597 DI 10.1097/01.nmd.0000230641.43013.68 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 076SH UT WOS:000239977500006 PM 16909067 ER PT J AU Hicks, C Sorocco, D Levin, M AF Hicks, Caitlin Sorocco, Debra Levin, Michael TI Automated analysis of behavior: A computer-controlled system for drug screening and the investigation of learning SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE automated behavior analysis; learning; memory; testing; screening ID FEEDING-BEHAVIOR; INTRACELLULAR PH; MEMORY TRANSFER; DUGESIA-DOROTOCEPHALA; CONDITIONED RESPONSE; PLANARIAN OCELLUS; FREEZING BEHAVIOR; SMALL-MOLECULE; MODEL SYSTEM; REGENERATION AB Efforts to understand cognition will be greatly facilitated by computerized systems that enable the automated analysis of animal behavior. A number of controversies in the invertebrate learning field have resulted from difficulties inherent in manual experiments. Driven by the necessity to overcome these problems during investigation of neural function in planarian flatworms and frog larvae, we designed and developed a prototype for an inexpensive, flexible system that enables automated control and analysis of behavior and learning. Applicable to a variety of small animals such as flatworms and zebralish, this system allows automated analysis of innate behavior, as well as of learning and memory in a plethora of conditioning paradigms. We present here the schematics of a basic prototype, which overcomes experimenter effects and operator tedium, enabling a large number of animals to be analyzed with transparent on-line access to primary data. A scaled-up version of this technology represents an efficient methodology to screen pharmacological and genetic libraries for novel neuroactive reagents of basic and biomedical relevance. (c) 2006 Wiley Periodicals, Inc. C1 Forsyth Inst, Forsyth Ctr Regenerat & Dev Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Forsyth Inst, Forsyth Ctr Regenerat & Dev Biol, 75 Francis St, Boston, MA 02115 USA. EM mlevin@forsyth.org RI Hicks, Caitlin/E-8849-2012; OI Hicks, Caitlin/0000-0001-7638-1936 FU NIGMS NIH HHS [GM-068483-A1] NR 96 TC 29 Z9 34 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD AUG PY 2006 VL 66 IS 9 BP 977 EP 990 DI 10.1002/neu.20290 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 070SS UT WOS:000239544900007 PM 16779826 ER PT J AU Caselli, A Spallone, V Marfia, GA Battista, C Pachatz, C Veves, A Uccioli, L AF Caselli, A. Spallone, V. Marfia, G. A. Battista, C. Pachatz, C. Veves, A. Uccioli, L. TI Validation of the nerve axon reflex for the assessment of small nerve fibre dysfunction SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 05-09, 2004 CL Munich, GERMANY SP European Assoc Study Diabet ID DIABETIC-PATIENTS; ORTHOSTATIC HYPOTENSION; PERIPHERAL NEUROPATHY; SKIN BIOPSY; VASODILATION; MULTICENTER; THRESHOLD; TOOL AB Objective: To validate nerve-axon reflex-related vasodilatation as an objective method to evaluate C-nociceptive fibre function by comparing it with the standard diagnostic criteria. Methods: Neuropathy was evaluated in 41 patients with diabetes (26 men and 15 women) without peripheral vascular disease by assessing the Neuropathy Symptom Score, the Neuropathy Disability Score (NDS), the vibration perception threshold (VPT), the heat detection threshold (HDT), nerve conduction parameters and standard cardiovascular tests. The neurovascular response to 1% acetylcholine (Ach) iontophoresis was measured at the forearm and at both feet by laser flowmetry. An age-matched and sex-matched control group of 10 healthy people was also included. Results: Significant correlations were observed between the neurovascular response at the foot and HDT (r(s) = -0.658; p < 0.0001), NDS (r(s) = -0.665; p < 0.0001), VPT (r(s) = -0.548; p = 0.0005), tibial nerve conduction velocity (r(s) = 0.631; p = 0.0002), sural nerve amplitude (r(s) = 0.581; p = 0.0002) and autonomic function tests. According to the NDS, in patients with diabetes who had mild, moderate or severe neuropathy, a significantly lower neurovascular response was seen at the foot than in patients without neuropathy and controls. A neurovascular response < 50% was found to be highly sensitive (90%), with a good specificity (74%), in identifying patients with diabetic neuropathy. Conclusion: Small-fibre dysfunction can be diagnosed reliably with neurovascular response assessment. This response is already reduced in the early stages of peripheral neuropathy, supporting the hypothesis that small-fibre impairment is an early event in the natural history of diabetic neuropathy. C1 Univ Roma Tor Vergata, Dept Internal Med, I-00133 Rome, Italy. Univ Roma Tor Vergata, Dept Neurol Sci, I-00133 Rome, Italy. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Joslin Beth Israel Deaconess Foot Ctr,M, Boston, MA USA. RP Caselli, A (reprint author), Univ Roma Tor Vergata, Dept Internal Med, Viale Oxford 81, I-00133 Rome, Italy. EM dracaselli@yahoo.it RI Marfia, Girolama Alessandra/G-5389-2012 NR 34 TC 23 Z9 24 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD AUG PY 2006 VL 77 IS 8 BP 927 EP 932 DI 10.1136/jnnp.2005.069609 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 063RP UT WOS:000239037600008 PM 16624842 ER PT J AU Bruce, BB Zhang, X Kedar, S Newman, NJ Biousse, V AF Bruce, B. B. Zhang, X. Kedar, S. Newman, N. J. Biousse, V. TI Traumatic homonymous hemianopia SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID VISUAL-FIELD DEFECTS; REHABILITATION; PERIMETRY; GOLDMANN; INJURY AB Objective: To describe the characteristics of patients with homonymous hemianopia from traumatic brain injury (TBI) seen in our unit between 1989 and 2004. Methods: Only patients with a history of TBI, who had detailed clinical information and results of neuroimaging, were included in our study. Demographic characteristics, clinical features, types of visual field defects, location of lesion and evolution of visual field defects were recorded. Results: Of the 880 patients with homonymous hemianopia seen in our unit, 103 patients (112 with homonymous hemianopia) had TBI (74 men and 29 women, mean age 30.7 (SD 15.3) years). Median time from injury to initial visual field testing was 5 (range 0.5-360) months. In all, 64 (57.1%) patients sustained injuries that were motor vehicle-related; 19 (17%) violence-related; 17 (15.2%) due to falls; and 12 (10.7%) because of other blunt head trauma. Visual field defects included complete homonymous hemianopia in 44 (39.3%) patients and incomplete homonymous hemianopia in 68 (60.7%) patients. The lesion was occipital in 14 (12.5%) patients, associated with optic radiation in 26 (23.2%) and the optic tract in 12 (10.7%), and multiple in 60 (53.6%). Conclusion: Most cases of homonymous hemianopia from TBI were motor vehicle-related. Patients were younger, more often male, and had multiple brain lesions more often than patients with homonymous hemianopia from causes other than TBI. A median delay of 5 months was observed before the documentation of the homonymous hemianopia, which may have a major effect on the success of rehabilitation and driving training in these young patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. RP Biousse, V (reprint author), Emory Eye Ctr, Neuroophthalmol Unit, 1365 B Clifton Rd NE, Atlanta, GA 30322 USA. EM vbiouss@emory.edu RI KEDAR, SACHIN/B-2579-2008; OI Bruce, Beau/0000-0003-3003-2962; Kedar, Sachin/0000-0002-7293-5556 FU NEI NIH HHS [P30-EY06360] NR 21 TC 17 Z9 17 U1 2 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD AUG PY 2006 VL 77 IS 8 BP 986 EP 988 DI 10.1136/jnnp.2006.088799 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 063RP UT WOS:000239037600026 PM 16574725 ER PT J AU Mann, MA Das, S Zhang, JH Wagner, M Fischbach, GD AF Mann, Mary Anne Das, Saumya Zhang, Jinghua Wagner, Meredith Fischbach, Gerald D. TI Neuregulin effect on quantal content dissociated from effect on miniature endplate potential amplitude SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID BUNGAROTOXIN-TREATED RATS; ACETYLCHOLINE-RECEPTOR TRANSCRIPTION; PRESYNAPTIC TRANSMITTER RELEASE; EPSILON-SUBUNIT GENE; NEUROMUSCULAR-JUNCTION; DIFFERENTIAL EXPRESSION; NEUROTRANSMITTER RELEASE; RETROGRADE SIGNAL; MYASTHENIA-GRAVIS; UP-REGULATION AB Members of the neuregulin family of signaling proteins increase transcription of acetylcholine receptor ( AChR) subunit genes in muscle fibers and the number of AChRs in the muscle membrane. In adult mice heterozygous for targeted deletion of type I neuregulins (Ig-NRG(+/-)), postsynaptic AChR density was decreased and transmitter release was increased. We examined the relationship between functional AChR density and ACh release in postnatal day 7 (P7), P14, and adult NRG-deficient mice. Here we report that changes in postsynaptic sensitivity and transmitter release are not temporally coupled during postnatal development in Ig-NRG-deficient mice. Although miniature endplate potential (MEPP) amplitude was decreased compared with control in P7 Ig-NRG(+/-) mice, quantum content was not increased. Quantum content was increased in adult heterozygotes despite normal MEPP amplitudes. Thus, during postnatal maturation, both quantal size and quantum content were influenced by decreased Ig-NRG expression, although the effects were dissociated in time. C1 Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Cardiac Arrhythmia, Boston, MA 02114 USA. RP Mann, MA (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pharmacol, 630 W 168th St,BB1102, New York, NY 10032 USA. EM mam2012@columbia.edu NR 54 TC 2 Z9 2 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2006 VL 96 IS 2 BP 671 EP 676 DI 10.1152/jn.00225.2006 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 062VW UT WOS:000238974700019 PM 16835362 ER PT J AU Polanczyk, MJ Hopke, C Vandenbark, AA Offner, H AF Polanczyk, Magdalena J. Hopke, Corwyn Vandenbark, Arthur A. Offner, Halina TI Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of Treg cells, and enhanced expression of the PD-1 costimulatory pathway SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE estrogen; Treg; costimulation; dendritic cells; PD-1 ID DENDRITIC CELLS; MULTIPLE-SCLEROSIS; PROGRAMMED DEATH-1; B7 FAMILY; RECEPTOR; ANTIGEN; MICE; 17-BETA-ESTRADIOL; AUTOIMMUNITY; LYMPHOCYTES AB Estrogen (E2)-induced immunomodulation involves dual effects on antigen-presenting cells (APC) and CD4(+)CD25(+) regulatory T cells (Treg) but not a direct effect on effector T cells. In this report, we further investigated the effects of E2 on APC and Treg function. We found that E2 treatment in vivo strongly reduced recovery of APC from the peritoneal cavity and inhibited induction of the inflammatory cytokines interleukin (IL)-12 and interferon-gamma but enhanced secretion of IL-10. Moreover, E2-conditioned bone marrow-derived dendritic cells (BM-DC) could both enhance Treg activity and directly inhibit responder T cells in the absence of Treg cells. We examined whether this E2-induced inhibitory activity of BM-DC might involve costimulation through the recently described PD-1 pathway. Both E2 and pregnancy markedly enhanced PD-1 expression in several types of APC, including macrophages, B cells, and especially dendritic cells (DC). Similarly to E2-induced enhancement of FoxP-3 expression and experimental autoimmune encephalomyelitis protection, E2-induced enhancement of PD-1(+) cells was also mediated through estrogen receptor alpha (Esr1) in DC and macrophages but not in B cells. Based on antibody inhibition studies, PD-1 interaction with its ligands, PDL-1 and especially PDL-2, could mediate either positive or negative regulatory signaling in both mature and immature E2-conditioned DC, depending, respectively, on a relatively high (10:1) or low (1:1) ratio of T cells:BM-DC. These novel findings indicate that E2-induced immunomodulation is mediated in part through potentiation in BM-DC of the PD-1 costimulatory pathway. (c) 2006 Wiley-Liss, Inc. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Agr Univ Warsaw, Fac Vet Med, Dept Food Hyg, Warsaw, Poland. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D-31,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NINDS NIH HHS [NS49210, NS23444, NS45445] NR 35 TC 73 Z9 78 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 1 PY 2006 VL 84 IS 2 BP 370 EP 378 DI 10.1002/jnr.20881 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 069NY UT WOS:000239456700014 PM 16676326 ER PT J AU Abukawa, H Kaban, LB Williams, WB Terada, S Vacanti, JP Troulis, MJ AF Abukawa, Haru Kaban, Leonard B. Williams, W. Bradford Terada, Shinichi Vacanti, Joseph P. Troulis, Maria J. TI Effect of interferon-alpha-2b on porcine mesenchymal stem cells SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 10-14, 2003 CL Orlando, FL SP Amer Assoc Oral & Maxillofacial Surg ID LIFE-THREATENING HEMANGIOMAS; ALFA-2A THERAPY; SPONTANEOUS REGENERATION; ANTIANGIOGENIC THERAPY; OSTEOCLAST FORMATION; RECEPTOR EXPRESSION; ALPHA-INTERFERON; IN-VITRO; BONE; INFANCY AB Purpose: Patients undergoing enucleation and adjuvant interferon therapy for giant cell jaw tumors have been observed to exhibit exuberant bone formation in the resultant defects. We hypothesize that interferon promotes bone formation by enhancing mesenchymal stem cell (MSC) differentiation and by stimulating osteoblasts. This is a preliminary study to determine the effects of interferon on porcine mesenchymal stem cells (pMSCs) in culture. Materials and Methods: Isolated pMSCs were grown under the following conditions: 1) MSCs alone (negative control); 2) MSCs + osteogenic supplements (positive control); and 3) MSCs + interferon (experimental). Cell cultures were evaluated morphologically, by quantitative DNA analysis, and quantitative and qualitative alkaline phosphatase analysis. Results: Cells treated with interferon exhibited a slower but constant proliferation rate, did not clump, and produced more alkaline phosphatase as compared with the negative control. Conclusion: The data indicate that interferon may act to differentiate MSCs into osteoblasts and to stimulate metabolic activity while not increasing the proliferation rate. (C) 2006 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Skeletal Biol Res Ctr, Minimally Invas Oral & Maxillofacial Surg Program, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tissue Engn & Organ Fabricat Lab, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Skeletal Biol Res Ctr, Minimally Invas Oral & Maxillofacial Surg Program, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. EM mtroulis@partners.org FU NIDCR NIH HHS [K23-DE. 14070-01] NR 39 TC 17 Z9 17 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2006 VL 64 IS 8 BP 1214 EP 1220 DI 10.1016/j.joms.2006.04.006 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 070UE UT WOS:000239549400007 PM 16860212 ER PT J AU Hsu, HP Zanella, JM Peckham, SM Spector, M AF Hsu, H. -P. Zanella, J. M. Peckham, S. M. Spector, M. TI Comparing ectopic bone growth induced by rhBMP-2 on an absorbable collagen sponge in rat and rabbit models SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE ectopic bone growth; rhBMP-2; rabbit models; rat models ID POSTEROLATERAL SPINE FUSION; MORPHOGENETIC PROTEIN-2; INTERBODY FUSION; NONHUMAN PRIMATE; DELIVERY; CARRIER; MATRIX; OSTEOINDUCTION; RELEASE AB Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) is currently employed as an autograft replacement for spinal fusion. The morphogen is incorporated onto its carrier, an absorbable collagen sponge (ACS), in the operating room. Although the effectiveness of the rhBMP-2/ACS implant in stimulating bone formation in human subjects has now been well established, further investigations of its use are necessary to deepen our understanding of its performance. The objective of the present study was to determine whether fluid released from the rhBMP-2/ACS implant could induce bone growth in tissue sites away from the implant site. We first measured the amount of protein in the fluid released from the rhBMP-2-soaked ACS during intraoperative handling. Variables included soak time and degree of compression. In the compression group that most closely approximated intraoperative conditions, more than 95% of the rhBMP-2 protein was retained by the ACS following a 15-min. soak time. This in vitro study was followed by an in vivo ectopic implant experiment using rat and rabbit models. The animal investigation compared the amount of bone induced by rhBMP-2 solution alone versus the de novo bone formation induced by rhBMP-2/ACS implants with varying concentrations of rhBMP-2. No ossicles were found at the sites where rhBMP-2 solution was injected in either animal species. Twenty-two of the 24 subcutaneous sites in the rats implanted with the rhBMP-2/ACS constructs displayed the presence of the typical 4- and 12-week ossicle. There were no noticeable differences in the size and shape of the ossicles after 4 and 12 weeks. There was a greater percentage of implant sites without ossicles in the rabbits, compared to the rats. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Medtron Sofamor Danek, Memphis, TN 38132 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Boston Campus,Room D1-152,Mail Stop 151 Res,150 S, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu NR 28 TC 38 Z9 41 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD AUG PY 2006 VL 24 IS 8 BP 1660 EP 1669 DI 10.1002/jor.20204 PG 10 WC Orthopedics SC Orthopedics GA 068HO UT WOS:000239364300009 PM 16779816 ER PT J AU Penrod, JD Deb, P Luhrs, C Dellenbaugh, C Zhu, CW Hochman, T Maciejewski, ML Granieri, E Morrison, RS AF Penrod, Joan D. Deb, Partha Luhrs, Carol Dellenbaugh, Cornelia Zhu, Carolyn W. Hochman, Tsivia Maciejewski, Matthew L. Granieri, Evelyn Morrison, R. Sean TI Cost and utilization outcomes of patients receiving hospital-based palliative care consultation SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; PROPENSITY SCORE METHODS; END; PERSPECTIVES; CAREGIVERS; MEDICINE; SUPPORT; MODELS; GROWTH; TRIAL AB Objective: To compare per them total direct, ancillary (laboratory and radiology) and pharmacy costs of palliative care (PC) compared to usual care (UC) patients during a terminal hospitalization; to examine the association between PC and ICU admission. Design: Retrospective, observational cost analysis using a VA (payer) perspective. Setting: Two urban VA medical centers. Measurements: Demographic and health characteristics of 314 veterans admitted during two years were obtained from VA administrative data. Hospital costs came from the VA cost accounting system. Analysis: Generalized linear models (GLM) were estimated for total direct, ancillary and pharmacy costs. Predictors included patient age, principal diagnosis, comorbidity, whether patient stay was medical or surgical, site and whether the patient was seen by the palliative care consultation team. A probit regression was used to analyze probability of ICU admission. Propensity score matching was used to improve balance in observed covariates. Results: PC patients were 42 percentage points (95% CI, -556% to -31%) less likely to be admitted to ICU. Total direct costs per day were $239 (95% CI, -387 to -122) lower and ancillary costs were $98 (95% CI, -133 to -57) lower than costs for UC patients. There was no difference in pharmacy costs. The results were similar using propensity score matching. Conclusion: PC was asssociated with significantly lower likelihood of ICU use and lower inpatient costs compared to UC. Our findings coupled with those indicating better patient and family outcomes with PC suggest both a cost and quality incentive for hospitals to develop PC programs. C1 CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, James J Peters VA Med Ctr, Program Res Serious Phys & Mental Illness, New York, NY 10029 USA. CUNY Hunter Coll, Dept Econ, New York, NY 10021 USA. VA NY Harbor Healthcare Syst, Brooklyn, NY USA. James J Peters VA Med Ctr, Program Res Serious Phys & Mental Ill, Bronx, NY USA. James J Peters VA Med Ctr, Bronx NY Harbor VA Geriatr Res Educ & Clin Ctr, Bronx, NY USA. Univ Washington, Dept Hlth Serv, Vet Affairs Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98195 USA. CUNY Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA. RP Penrod, JD (reprint author), CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, James J Peters VA Med Ctr, Program Res Serious Phys & Mental Illness, New York, NY 10029 USA. EM joan.penrod@mssm.edu FU NIA NIH HHS [K24 AG022345] NR 42 TC 119 Z9 119 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG PY 2006 VL 9 IS 4 BP 855 EP 860 DI 10.1089/jpm.2006.9.855 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 078AT UT WOS:000240074000010 PM 16910799 ER PT J AU Fromme, EK Bascom, PB Smith, MD Tolle, SW Hanson, L Hickam, DH Osborne, ML AF Fromme, Erik K. Bascom, Paul B. Smith, M. D. Tolle, Susan W. Hanson, Lissi Hickam, David H. Osborne, Molly L. TI Survival, mortality, and location of death for patients seen by a hospital-based palliative care team SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; LIFE-SUSTAINING TREATMENT; HOUSE CALLS; SERVICE; OREGON; CONSULTATION; READMISSIONS; QUALITY AB Background: Little is known about patient outcomes after discharge planning by inpatient palliative care teams. A major difficulty is that successful discharge planning often effectively limits or ends the team's relationship with the patient and family. The goal of this study was to gather a clearer picture of what happened to our palliative care consult patients after discharge. Methods: This was a longitudinal survey of all patients seen over a one year period by the inpatient palliative care team at Oregon Health & Science University (OHSU). Data were recorded by team members at the time of consultation and supplemented by data from administrative databases and death certificates. Results: The team provided consults to 292 unique patients: 60% were younger than age 65, 39% were female, and 16% were members of an ethnic or racial minority. Almost three quarters of patients carried a non-cancer diagnosis. Of the 292 patients, 37% died in hospital and 63% were discharged alive, either to home (54%), nursing facilities (20%), or inpatient hospice (26%). Of the 183 patients discharged alive, 38% died within 2 weeks, 32% died between 2 weeks and 6 months, 25% were alive at 6 months, and 4% were unknown. Of note, only 10% of patients seen by the consult service were readmitted to OSHU within 30 days, and only 5% of those discharged alive from OHSU ultimately died in an acute care hospital. Discussion: We characterized patient outcomes following inpatient palliative care consultation: where patients are discharged, how long they live, and where they die. Two thirds of patients were able to be discharged, even when death occurred within two weeks. The low rates of readmission and death in an acute care hospital support that the decision to discharge the patients was reasonable and the discharge plan was adequate. Hospital based palliative care teams can play an important and unique role in discharge planning-allowing even patients very near death to leave the hospital if they wish. C1 Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Dept Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med, Div Gen Med & Geriatr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Fromme, EK (reprint author), Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Dept Med, 3181 SW Sam Jackson Pk Rd,L586, Portland, OR 97239 USA. EM frommee@ohsu.edu NR 35 TC 38 Z9 38 U1 2 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG PY 2006 VL 9 IS 4 BP 903 EP 911 DI 10.1089/jpm.2006.9.903 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 078AT UT WOS:000240074000016 PM 16910805 ER PT J AU Cohen, LM Moss, AH Wetsbord, SD Germain, MJ AF Cohen, Lewis M. Moss, Alvin H. Wetsbord, Steven D. Germain, Michael J. TI Renal palliative care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID QUALITY-OF-LIFE; HOSPITALIZED MEDICAL PATIENTS; SLEEP-APNEA SYNDROME; HEMODIALYSIS-PATIENTS; UREMIC PRURITUS; ERECTILE DYSFUNCTION; DIALYSIS PATIENTS; PERITONEAL-DIALYSIS; RISK-FACTORS; SUBTOTAL PARATHYROIDECTOMY AB Patients with chronic kidney disease have a shortened life expectancy and carry a high symptom burden. Clinicians need sophisticated expertise in pain and symptom management and skills in communication to meet the many needs of this population. This article reviews the literature and discusses prognosis, ethical and legal considerations, symptoms, treatment, and end-of-life issues. The field of nephrology is shifting from an exclusive focus on increasing survival to one that provides greater attention to quality of life. There is an opportunity to integrate many of the advances of palliative medicine into the comprehensive treatment of these patients. C1 Baystate Med Ctr, Renal Palliat Care Initiat, Springfield, MA 01199 USA. W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Nephrol Sect, Morgantown, WV 26506 USA. W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Ctr Hlth Eth & Law, Morgantown, WV 26506 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Cohen, LM (reprint author), Baystate Med Ctr, Renal Palliat Care Initiat, 759 Chestnut St,S2669, Springfield, MA 01199 USA. EM lewis.cohen@bhs.org NR 125 TC 51 Z9 53 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG PY 2006 VL 9 IS 4 BP 977 EP 992 DI 10.1089/jpm.2006.9.977 PG 16 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 078AT UT WOS:000240074000024 PM 16910813 ER PT J AU Misra, M Levitsky, LL AF Misra, Madhusmita Levitsky, Lynne L. TI Intermittent growth attenuation: Is this a sign of craniopharyngioma? SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHILDHOOD CRANIOPHARYNGIOMA; WESSEX GROWTH; CHILDREN; RELIABILITY; HEIGHT; TUMORS AB We present two young children eventually diagnosed with large craniopharyngiomas, who had a normal growth velocity for several years following an initial short period of growth attenuation. These cases suggest the need for a low threshold to undertake hormonal evaluation of patients who present with a past history of growth attenuation. C1 Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Pediat Endocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org NR 13 TC 0 Z9 0 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD AUG PY 2006 VL 19 IS 8 BP 1033 EP 1038 PG 6 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 084HW UT WOS:000240525000011 PM 16995589 ER PT J AU Rumbo, C Fawaz, RL Emre, SH Suchy, FJ Kerkar, N Morotti, RA Shneider, BL AF Rumbo, Carolina Fawaz, Rima L. Emre, Sukru H. Suchy, Frederick J. Kerkar, Nanda Morotti, Raffaella A. Shneider, Benjamin L. TI Hepatitis C in children: A quaternary referral center perspective SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE cirrhosis interferon; ribavirin; pegylated; transplant liver ID INTERFERON-ALPHA; PLUS RIBAVIRIN; KIDNEY-TRANSPLANT; VIRUS-INFECTION; THERAPY; LONG; LIVER; PHARMACOKINETICS; ADOLESCENTS; COMBINATION AB Introduction: Chronic hepatitis C virus (HCV) infection affects 0.3% of children in the United States, and the general impression is that it has a benign course in childhood. We analyzed a pediatric population with chronic HCV in a quaternary referral center. Material and Methods: This is a retrospective clinical review comprising all patients with chronic HCV referred to the Pediatric Liver/Liver Transplant Program between January 1999 and December 2004. Results: Ninety-one patients (52% female; mean age, 9 years) were assessed. Eight-three percent of the patients were genotype 1. Twenty-one patients received/are receiving interferon and ribavirin for chronic HCV (treatment indications-advanced disease, 9; clinical trial, 6; genotype 2, 2; social, 2; prerenal transplant, 1). Eight (53%) of 15 patients, who have completed therapy and follow-up, achieved sustained viral response. Seven of 91 patients had cirrhosis at presentation (mean age, 11.7 years). Four underwent liver transplantation, all experienced HCV recurrence, 2 died, 1 was retransplanted, and 1 has compensated cirrhosis. Conclusion: Although, in general, HCV in children has a slow progression, there are cases with an accelerated course and early development of cirrhosis requiring liver transplant. Hepatitis C virus recurs universally after transplant, and its prognosis is usually poor; therefore, the most promising long-term approach is to clear this infection before transplantation. C1 Mt Sinai Sch Med, Div Pediat Hepatol, Dept Pediat, Beijing 100029, Peoples R China. Mt Sinai Sch Med, RecantilMiller Transplantat Inst, Beijing 100029, Peoples R China. Massachusetts Gen Hosp, Div Pediat Gastroenterol, Boston, MA 02114 USA. Mt Sinai Sch Med, Dept Surg, Beijing 100029, Peoples R China. Mt Sinai Sch Med, Dept Pathol, Beijing 100029, Peoples R China. RP Shneider, BL (reprint author), Mt Sinai Sch Med, Div Pediat Hepatol, Dept Pediat, 1 Gustave L Levy Pl,Box 1656, Beijing 100029, Peoples R China. EM Benjamin.Shneider@mssm.edu NR 43 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2006 VL 43 IS 2 BP 209 EP 216 DI 10.1097/01.mpg.0000228117.52229.32 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 070RU UT WOS:000239542200012 PM 16877987 ER PT J AU Hoover, K Piotrowski, J St Pierre, K Katz, A Goldstein, AM AF Hoover, Kevin Piotrowski, Julie St. Pierre, Kristin Katz, Aubrey Goldstein, Allan M. TI Simultaneous gastric and small intestinal trichobezoars - a hairy problem SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE trichobezoar; gastric outlet obstruction; small bowel obstruction ID SMALL-BOWEL OBSTRUCTION; RAPUNZEL-SYNDROME; DIAGNOSIS; ENDOSCOPY; BEZOAR AB A trichobezoar represents a mass of accumulated hair within the gastrointestinal tract. Isolated gastric trichobezoars, those with extension into the duodenum, and small intestinal trichobezoars have all been described. However, the presence of discrete gastric and intestinal trichobezoars has been rarely presented in the literature. This case report describes synchronous trichobezoars in the stomach and jejunum in a 9-year-old girl presenting with abdominal pain, anorexia, and vomiting. This case emphasizes the role of radiographic imaging in the diagnosis of trichobezoars and the importance of a complete clinical evaluation of the small bowel at the time of removal of an obstructing gastric bezoar. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Gastroenterol, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. EM agoldstein@partners.org NR 17 TC 17 Z9 17 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 2006 VL 41 IS 8 BP 1495 EP 1497 DI 10.1016/j.jpedsurg.2006.04.003 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 071UO UT WOS:000239629600030 PM 16863865 ER PT J AU Gunay-Aygun, M Avner, ED Bacallao, RL Choyke, PL Flynn, JT Germino, GG Guay-Woodford, L Harris, P Heller, T Ingelfinger, J Kaskel, F Kleta, R LaRusso, NF Mohan, P Pazour, GJ Shneider, BL Torres, VE Wilson, P Zak, C Zhou, J Gahl, WA AF Gunay-Aygun, Meral Avner, Ellis D. Bacallao, Robert L. Choyke, Peter L. Flynn, Joseph T. Germino, Gregory G. Guay-Woodford, Lisa Harris, Peter Heller, Theo Ingelfinger, Julie Kaskel, Frederick Kleta, Robert LaRusso, Nicholas F. Mohan, Parvathi Pazour, Gregory J. Shneider, Benjamin L. Torres, Vicente E. Wilson, Patricia Zak, Colleen Zhou, Jing Gahl, William A. TI Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis: Summary statement of a first National Institutes of Health/Office of Rare Diseases Conference SO JOURNAL OF PEDIATRICS LA English DT Article ID PKHD1 MUTATIONS; PRIMARY CILIA; PROTEIN; ARPKD; GENE; PATHOGENESIS; FIBROCYSTIN; MECHANISMS; EXPRESSION; DIAGNOSIS C1 NHGRI, NIH, Mol Imaging Program, NIDDK, Bethesda, MD 20892 USA. Med Coll Wisconsin, Childrens Hosp Wisconsin, Milwaukee, WI 53226 USA. Indiana Univ, Sch Med, Bloomington, IN 47405 USA. Albert Einstein Coll Med, Childrens Hosp Montefiore, New York, NY USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Univ Alabama, Tuscaloosa, AL 35487 USA. Mayo Clin, Rochester, MN USA. Harvard Univ, Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Inst Med, Autosomal Recess Polycyst Kidney Dis Congenital H, Boston, MA 02115 USA. Harvard Univ, Inst Med, Dept Internal Med, Boston, MA 02115 USA. George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. RP Gunay-Aygun, M (reprint author), NHGRI, NIH, Mol Imaging Program, NIDDK, 10 Ctr Dr Bldg 10,Room 10C103A, Bethesda, MD 20892 USA. EM mgaygun@mail.nih.gov OI Bacallao, Robert/0000-0002-5703-5701; Germino, Gregory/0000-0002-3609-5588; Pazour, Gregory/0000-0002-6285-8796 FU Intramural NIH HHS [Z99 HG999999] NR 35 TC 40 Z9 44 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 2006 VL 149 IS 2 BP 159 EP 164 DI 10.1016/j.jpeds.2006.03.014 PG 6 WC Pediatrics SC Pediatrics GA 073JG UT WOS:000239738300006 PM 16887426 ER PT J AU Erdie-Lalena, CR Holm, VA Kelly, PC Frayo, RS Cummings, DE AF Erdie-Lalena, Christine R. Holm, Vanja A. Kelly, Patrick C. Frayo, R. Scott Cummings, David E. TI Ghrelin levels in young children with Prader-Willi syndrome SO JOURNAL OF PEDIATRICS LA English DT Article ID GROWTH-HORMONE DEFICIENCY; FASTING PLASMA GHRELIN; BODY-MASS INDEX; FOOD-INTAKE; CIRCULATING GHRELIN; UNIPARENTAL DISOMY; INSULIN-RESISTANCE; OBESE SUBJECTS; ACTIVE FORM; SECRETION AB Objective To explore the hypothesis that high ghrelin levels contribute to obesity in Prader-Willi syndrome (PWS), we assessed whether the increased levels observed in older persons with PWS exist in very young children, before the onset of hyperphagia. Study design We measured ghrelin levels in nine children with PWS (17-60 months of age) and eight healthy control subjects of equivalent body mass index (BMI), age, and sex. Results PWS and control groups had equivalent BMI (16.8 +/- 1.4 vs 16.1 +/- 0.9 kg/m(2), respectively; P = .24), age (37.8 +/- 15.4 vs 50.3 +/- 17.7 months; P = .14), and sex. PWS and control groups also had equivalent fasting levels of total ghrelin (787 242 vs 716 135 pg/mL, respectively; P = .24), bioactive ghrelin (102 +/- 35 vs 91 +/- 23 pg/mL; P = .45), insulin, and glucose. Ghrelin correlated negatively with BMI among controls (r = -0.760, P = .029) but not PWS (r = 0.015, P = .97). Conclusions Children < 5 years of age with PWS, who had not yet developed hyperphagia or excessive obesity, had normal ghrelin levels, in contrast with the hyperghrelinemia of older, hyperphagic people with PWS. It is possible that ghrelin levels increase suddenly before hyperphagia develops. C1 Univ Washington, VA Puget Sound Hlth Care Syst, SIII Endo, Dept Med,Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Madigan Army Med Ctr, Dept Pediat, Div Dev & Behav Pediat, Ft Lewis, WA USA. Univ Washington, Sch Med, Ctr Human Dev & Disabil, Dept Pediat, Seattle, WA 98195 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, SIII Endo, Dept Med,Div Metab Endocrinol & Nutr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM davidec@u.washington.edu FU NIDDK NIH HHS [R01 DK61516, P01 DK68384] NR 54 TC 29 Z9 33 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 2006 VL 149 IS 2 BP 199 EP 204 DI 10.1016/j.jpeds.2006.04.011 PG 6 WC Pediatrics SC Pediatrics GA 073JG UT WOS:000239738300013 PM 16887433 ER PT J AU Brody, AL AF Brody, AL TI Functional brain imaging of tobacco use and dependence SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Review DE tobacco dependence; functional magnetic resonance imaging; positron emission tomography; autoradiography; prefrontal cortex; review ID NICOTINIC ACETYLCHOLINE-RECEPTORS; CEREBRAL-BLOOD-FLOW; VENTRAL TEGMENTAL AREA; INDUCED DOPAMINE RELEASE; MONOAMINE-OXIDASE-B; ANTERIOR CINGULATE CORTEX; RAT NUCLEUS-ACCUMBENS; FREELY-MOVING RATS; CIGARETTE-SMOKING; CHOLINERGIC-RECEPTORS AB While most cigarette smokers endorse a desire to quit smoking, only about 14% to 49% will achieve abstinence after 6 months or more of treatment. A greater understanding of the effects of smoking on brain function may (in conjunction with other lines of research) result in improved pharmacological (and behavioral) interventions. Many research groups have examined the effects of acute and chronic nicotine/cigarette exposure on brain activity using functional imaging; the purpose of this paper is to synthesize findings from such studies and present a coherent model of brain function in smokers. Responses to acute administration of nicotine/smoking include: a reduction in global brain activity; activation of the prefrontal cortex, thalamus, and visual system; activation of the thalamus and visual cortex during visual cognitive tasks; and increased dopamine (DA) concentration in the ventral striatum/nucleus accumbens. Responses to chronic nicotine/cigarette exposure include decreased monoamine oxidase (MAO) A and B activity in the basal ganglia and a reduction in alpha(4)beta(2) nicotinic acetylcholine receptor (nAChR) availability in the thalamus and putamen. Taken together, these findings indicate that smoking enhances neurotransmission through cortico-basal ganglia-thalamic circuits either by direct stimulation of nAChRs, indirect stimulation via DA release or MAO inhibition, or a combination of these factors. Activation of this circuitry may be responsible for the effects of smoking seen in tobacco dependent subjects, such as improvements in attentional performance, mood, anxiety, and irritability. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Res Dept, Los Angeles, CA USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU NIDA NIH HHS [R01 DA020872, R01 DA015059, R01 DA015059-04, R01 DA020872-01, R01 DA15059] NR 172 TC 101 Z9 104 U1 2 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD AUG PY 2006 VL 40 IS 5 BP 404 EP 418 DI 10.1016/j.jpsychires.2005.04.012 PG 15 WC Psychiatry SC Psychiatry GA 059ZB UT WOS:000238769600004 PM 15979645 ER PT J AU Kratochvil, CJ Wilens, TE Greenhill, LL Gao, HT Baker, KD Feldman, PD Gelowitz, DL AF Kratochvil, Christopher J. Wilens, Timothy E. Greenhill, Laurence L. Gao, Haitao Baker, Kurt D. Feldman, Peter D. Gelowitz, Douglas L. TI Effects of long-term atomoxetine treatment for young children with attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE atomoxetine; attention-deficit/hyperactivity disorder; pediatric patients ID ONCE-DAILY ATOMOXETINE; DEFICIT HYPERACTIVITY DISORDER; PRESCHOOL-CHILDREN; OPEN-LABEL; DOUBLE-BLIND; ADHD; METHYLPHENIDATE; EFFICACY; TRIAL; COMORBIDITY AB Objective: The purpose of this 13-study (seven double-blind/placebo-controlled, six open-label) meta-analysis is to determine the effectiveness and tolerability of long-term atomoxetine treatment among young children with attention-deficit/hyperactivity disorder (ADHD). Method: Data were pooled from 6- and 7-year-olds (N = 272) who met DSM-1V criteria for ADHD, received atomoxetine treatment, and were enrolled in clinical trials of >= 2 years. Of these, 97 subjects reached the 24-month time point, providing data for long-term trend analysis of safety and effectiveness. Results: Effectiveness for most subjects was maintained over long-term treatment, as demonstrated by total scores and total T scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version, investigator administered and scored. During the 2-year period, 25.7% discontinued because of lack of effectiveness, but adverse events were clinically minor and transient, and only 4.0% of children discontinued because of an adverse event. Notable effects on growth were seen during early phases of the study, with attenuation occurring by the 2-year time point. Statistically significant increases in pulse and blood pressure and decreases in cardiac PR interval were seen, but no changes were deemed both statistically significant and clinically meaningful among any vital signs, electrocardiographic measures, or laboratory tests. Conclusion: Long-term atomoxetine treatment appears generally well tolerated and effective in the treatment of young children with ADHD. C1 Univ Nebraska, Coll Med, Omaha, NE 68198 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. Lilly Res Labs, Indianapolis, IN USA. RP Kratochvil, CJ (reprint author), Univ Nebraska, Coll Med, 9855-81 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ckratoch@unmc.edu NR 42 TC 78 Z9 89 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2006 VL 45 IS 8 BP 919 EP 927 DI 10.1097/01.chi0000222788.34229.68 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 067GS UT WOS:000239290500005 PM 16865034 ER PT J AU Kratochvil, CJ Kazura, A Deas, D Martin, CA Dosh, T Wilens, TE AF Kratochvil, Christopher J. Kazura, Alessandra Deas, Deborah Martin, Catherine A. Dosh, Tyanne Wilens, Timothy E. TI Pharmacological management of a teen with significant alcohol use and depression SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID ADOLESCENT ALCOHOLICS; MAJOR DEPRESSION; DOUBLE-BLIND; EFFICACY; PLACEBO; TRIAL; DISORDERS; BUPROPION C1 Univ Nebraska, Med Ctr, Dept Psychiat, Omaha, NE 68198 USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Bradley Hasbro Childrens Res Ctr, Providence, RI 02912 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Kentucky, Dept Psychiat, Lexington, KY USA. Univ Kentucky, Coll Med, Lexington, KY USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kratochvil, CJ (reprint author), Univ Nebraska, Med Ctr, Dept Psychiat, 985581 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ckratoch@unmc.edu NR 14 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2006 VL 45 IS 8 BP 1011 EP 1015 DI 10.1097/01.chi.00002224332.93442.d5 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 067GS UT WOS:000239290500016 PM 16865045 ER PT J AU Schlozman, S Falzone, R AF Schlozman, Steven Falzone, Richard TI Everything bad is good for you: How today's popular culture is actually making us smarter. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cambridge Hlth Alliance, Cambridge, MA USA. RP Schlozman, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2006 VL 45 IS 8 BP 1017 EP 1019 DI 10.1097/01.chi.0000227884.96145.e1 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 067GS UT WOS:000239290500018 ER PT J AU Tierney, E Kimball, AB AF Tierney, Emily Kimball, Alexa Boer TI Median dermatology base incomes in senior academia and practice are comparable, but a significant income gap exists at junior levels SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Academy-of-Dermatology CY FEB 18-22, 2005 CL New Orleans, LA SP Amer Acad Dermatol ID CHOICE AB Background: The perception that dermatologists in practice have substantially higher incomes than in academics is often cited as the primary reason people choose to practice Outside academic institutions. Objective. We sought to compare the incomes of dermatologists in academics versus various practice settings. Methods: Data from various surveys of dermatologists from 2002 to 2004 were adjusted for annual inflation to the year 2004 and compared. Benefits and bonuses were not included. The income level of clinical instructors, who are 7.0% of all academic dermatology faculty, were not available for inclusion. Results. Median dermatology faculty income (combined average of assistant, associate, and professor levels) was $192,267, 12.0% less than the median practice income of $215,303. There was substantial variation across regions, institutions, and types of nonacademic practice. Median starting incomes for dermatology residency graduates were comparable in practice across Multiple data sources ($182,116-$200,000) and private universities ($189,336); however, both were significantly higher than median starting incomes in public universities ($83,349). Limitations: This study relied on self-reported data. Although all attempts were made to use comparable information, variances in how data were collected and classified may exist. Conclusions: Initial income for those entering practice is equivalent to those entering academia in private universities; however, incomes for both of these groups are 2- to 3-fold higher than those entering academia in public universities. This discrepancy may discourage some recent trainees, some of whom have high debt and high expenses, from entering the field of academic dermatology. Because incomes in academia increase predictably with increasing rank, overall self-reported incomes for established dermatologists in practice and senior academia are comparable. C1 Tufts Univ, Sch Med, Dept Internal Med, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Unit Res Trials Skin, 221 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM harvardskinstudies@partners.org NR 21 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2006 VL 55 IS 2 BP 213 EP 219 DI 10.1016/j.jaad.2006.01.044 PG 7 WC Dermatology SC Dermatology GA 068VY UT WOS:000239403800002 PM 16844501 ER PT J AU Mahlberg, MJ McGinnis, KS Draft, KS Fakharzadeh, SS AF Mahlberg, Matthew J. McGinnis, Karen S. Draft, Karla S. Fakharzadeh, Steven S. TI Multiple eccrine poromas in the setting of total body irradiation and immunosuppression SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SKIN-CANCER; P53 PROTEIN; POROCARCINOMA; EXPRESSION; TUMORS; CHILD AB Eccrine poromas are benign, adnexal tumors that most often occur as a solitary lesion on the palm or sole. The occurrence of multiple eccrine poromas is extremely rare. In this report, we describe the development of several eccrine poromas in an acral distribution in a 42-year-old man. Before the appearance of these tumors, the patient had received total body irradiation and allogeneic bone marrow transplantation for treatment of acute lymphocytic leukemia. As a complication of the bone marrow transplant, the patient developed chronic graft-versus-host disease, which was treated with immunosuppressive therapy. We discuss this patient and review the available literature regarding multiple eccrine poromas. C1 Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. NYU, Sch Med, New York, NY USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Fakharzadeh, SS (reprint author), 415 Curie Blvd,Room 235 B,Clin Res Bldg, Philadelphia, PA 19104 USA. EM ssf@mail.med.upenn.edu NR 21 TC 13 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2006 VL 55 IS 2 SU S BP S46 EP S49 DI 10.1016/j.jaad.2006.02.052 PG 4 WC Dermatology SC Dermatology GA 069RA UT WOS:000239464700011 PM 16843124 ER PT J AU Millett, PJ Clavert, P Hatch, GFR Warner, JJP AF Millett, Peter J. Clavert, Philippe Hatch, G. F. Rick, III Warner, Jon J. P. TI Recurrent posterior shoulder instability SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID ROTATOR INTERVAL CAPSULE; GLENOHUMERAL JOINT; MULTIDIRECTIONAL INSTABILITY; THERMAL CAPSULORRHAPHY; DELTOID MUSCLE; FOLLOW-UP; SUBLUXATION; STABILITY; SHIFT; COMPLICATIONS AB Recurrent posterior shoulder instability is an uncommon condition. it is often unrecognized, leading to incorrect diagnoses, delays in diagnosis, and even missed diagnoses. Posterior instability encompasses a wide spectrum of pathology, ranging from unidirectional posterior subluxation to multidirectional instability to locked posterior dislocations. Nonsurgical treatment of posterior shoulder instability is successful in most cases; however, surgical intervention is indicated when conservative treatment fails. For optimal results, the surgeon must accurately define the pattern of instability and address all soft-tissue and bony injuries present at the time of surgery. Arthroscopic treatment of posterior shoulder instability has increased application, and a variety of techniques has been described to manage posterior glenohumeral instability related to posterior capsulolabral injury. C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Cambridge, MA 02138 USA. CHRU Hautepierre, Dept Orthopaed, Strasbourg, France. USC Keck Sch Med, Dept Orthopaed Surg, Los Angeles, CA USA. RP Millett, PJ (reprint author), Steadman Hawkins Clin, 181 W Meadow Dr, Vail, CO 81657 USA. NR 39 TC 37 Z9 37 U1 0 U2 6 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD AUG PY 2006 VL 14 IS 8 BP 464 EP 476 PG 13 WC Orthopedics SC Orthopedics GA 072XW UT WOS:000239707500004 PM 16885478 ER PT J AU Cannon, CP Benjamin, AS Murphy, SA Mega, JL Braunwald, E AF Cannon, Christopher P. Steinberg, Benjamin A. Murphy, Sabina A. Mega, Jessica L. Braunwald, Eugene TI Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; DENSITY-LIPOPROTEIN CHOLESTEROL; PLACEBO-CONTROLLED TRIAL; ACUTE CORONARY SYNDROMES; TREATMENT PANEL-III; HIGH-RISK PATIENTS; MYOCARDIAL-INFARCTION; HEART-DISEASE; ATORVASTATIN; PREVENTION AB OBJECTIVES The purpose of this study was to conduct a meta-analysis that compares the reduction of cardiovascular outcomes with high-dose statin therapy versus standard dosing. BACKGROUND Debate exists regarding the merit of more intensive lipid lowering with high-dose statin therapy as compared with standard-dose therapy. METHODS We searched PubMed and article references for randomized controlled trials of intensive versus standard-dose statin therapy enrolling more than 1,000 patients with either stable coronary heart disease or acute coronary syndromes. Four trials were identified: the TNT (Treating to New Targets) and the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid-Lowering) trials involved patients with stable cardiovascular disease, and the PROVE IT-TIMI-22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy Thrombolysis in Myocardial Infarction-22) and A-to-Z (Aggrastat-to-Zocor) trials involved patients with acute coronary syndromes. We carried out a meta-analysis of the relative odds on the basis of a fixed-effects model using the Mantel-Haenszel method for the major outcomes of death and cardiovascular events. RESULTS A total of 27,548 patients were enrolled in the 4 large trials. The combined analysis yielded a significant 16% odds reduction in coronary death or myocardial infarction (p < 0.00001), as well as a significant 16% odds reduction of coronary death or any cardiovascular event (p < 0.00001). No difference was observed in total or non-cardiovascular mortality, but a trend toward decreased cardiovascular mortality (odds reduction 12%, p = 0.054) was observed. CONCLUSIONS Intensive lipid lowering with high-dose statin therapy provides a significant benefit over standard-dose therapy for preventing predominantly non-fatal cardiovascular events. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 23 TC 362 Z9 383 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 1 PY 2006 VL 48 IS 3 BP 438 EP 445 DI 10.1016/j.jacc.2006.04.070 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 068VB UT WOS:000239401500004 PM 16875966 ER PT J AU Foster, NM McGory, ML Zingmond, DS Ko, CY AF Foster, Nova M. McGory, Marcia L. Zingmond, David S. Ko, Clifford Y. TI Small bowel obstruction: A population-based appraisal SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg ID NATURAL-HISTORY; MANAGEMENT; OPERATION; DEATH AB BACKGROUND: Small bowel obstruction (SBO) is a common reason for surgical consultation, but little is known about the natural history of SBO. We performed a population-based analysis to evaluate SBO frequency, type of operation, and longterm outcomes. STUDY DESIGN: Using the California Inpatient File, we identified all patients admitted in 1997 with a diagnosis of SBO. Patients were excluded if they had a diagnosis of bowel obstruction in the previous 6 years (1991 to 1996). Of the remaining cohort, the natural history of SBO over the subsequent 5 years (1998 to 2002) was analyzed. Index hospitalization outcomes (eg, surgical versus nonsurgical management, length of stay, in-hospital mortality), and longterm outcomes, including SBO readmissions and 1-year mortality, were evaluated. RESULTS: We identified 32,583 patients with an index admission for SBO in 1997; 24% had surgery during the index admission. The distribution of surgical procedures was: 38% lysis of adhesions, 38% hernia repair, 18% small bowel resection with lysis of adhesions, and 6% small bowel resection with hernia repair. Patients who underwent operations during index admission had longer lengths of stay, lower mortality, fewer SBO readmissions, and longer time to readmission than patients treated nonsurgically. Regardless of treatment during the index admission, 81% of surviving patients had no additional SBO readmissions over the subsequent 5 years. CONCLUSIONS: Most of the 32,583 patients requiring admission for index SBO in 1997 were treated nonsurgically, and few of these patients were readmitted. This is the first longitudinal population-based analysis of SBO evaluating surgical versus nonsurgical management and outcomes, including mortality and readmissions. C1 Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ctr Surg Outcomes & Qual, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP McGory, ML (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ctr Surg Outcomes & Qual, 10833 Le Conte Ave,72-215 Ctr Hlth Sci,Box 956904, Los Angeles, CA 90095 USA. NR 12 TC 71 Z9 74 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2006 VL 203 IS 2 BP 170 EP 176 DI 10.1016/j.jamcollsurg.2006.04.020 PG 7 WC Surgery SC Surgery GA 071ZP UT WOS:000239642700004 PM 16864029 ER PT J AU Sarr, MG Warshaw, AL McFadden, DW Souba, WW AF Sarr, Michael G. Warshaw, Andrew L. McFadden, David W. Souba, Wiley W. TI Future of surgery journals: Good or bad? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg C1 Mayo Clin, Dept Surg, Coll Med, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. W Virginia Univ, Dept Surg, Morgantown, WV 26506 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Surg, Hershey, PA 17033 USA. RP Sarr, MG (reprint author), Mayo Clin, Dept Surg, Coll Med, AL 2-435,200 1st St SW, Rochester, MN 55905 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2006 VL 203 IS 2 BP 192 EP + DI 10.1016/j.jamcollsurg.2006.04.008 PG 6 WC Surgery SC Surgery GA 071ZP UT WOS:000239642700007 PM 16864032 ER PT J AU Fang, MC Go, AS Hylek, EM Chang, Y Henault, LE Jensvold, NG Singer, DE AF Fang, Margaret C. Go, Alan S. Hylek, Elaine M. Chang, Yuchiao Henault, Lori E. Jensvold, Nancy G. Singer, Daniel E. TI Age and the risk of warfarin-associated hemorrhage: The anticoagulation and risk factors in atrial fibrillation study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc DE aging; anticoagulation; hemorrhage; atrial fibrillation ID BLEEDING COMPLICATIONS; STROKE PREVENTION; MAJOR HEMORRHAGE; THERAPY; INTENSITY; SEVERITY; TRIALS AB OBJECTIVES: To assess whether older age is independently associated with hemorrhage risk in patients with atrial fibrillation, whether or not they are taking warfarin therapy. DESIGN: Cohort study. SETTING: Integrated healthcare delivery system. PARTICIPANTS: Thirteen thousand five hundred fifty-nine adults with nonvalvular atrial fibrillation. MEASUREMENTS: Patient data were collected from automated clinical and administrative databases using previously validated search algorithms. Medical charts were reviewed from patients hospitalized were for major hemorrhage (intracranial, fatal, requiring >= 2 units of transfused blood, or involving a critical anatomic site). Age was categorized into four categories (< 60, 60-69, 70-79, and >= 80), and multivariable Poisson regression was used to assess whether major hemorrhage rates increased with age, stratified by warfarin use and adjusted for other clinical risk factors for hemorrhage. RESULTS: A total of 170 major hemorrhages were identified during 15,300 person-years of warfarin therapy and 162 major hemorrhages during 15,530 person-years off warfarin therapy. Hemorrhage rates rose with older age, with an average increase in hemorrhage rate of 1.2 (95% confidence interval (CI) 1.0-1.4) per older age category in patients taking warfarin and 1.5 (95% CI = 1.3-1.8) in those not taking warfarin. Intracranial hemorrhage rates were significantly higher in those aged 80 and older (adjusted rate ratio = 1.8, 95% CI = 1.1-3.1 for those taking warfarin, adjusted rate ratio = 4.7, 95% Cl = 2.4-9.2 for those not taking warfarin) than in those younger than 80. CONCLUSION: Older age increases the risk of major hemorrhage, particularly intracranial hemorrhage, in patients with atrial fibrillation, whether or not they are taking warfarin. Hemorrhage rates were generally comparable with those reported in previous randomized trials, indicating that carefully monitored warfarin therapy can be used with reasonable safety in older patients. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Boston Univ, Sch Med, Gen Internal Med & Clin Epidemiol Unit, Boston, MA 02215 USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Fang, MC (reprint author), Univ Calif San Francisco, 533 Parnassus Ave,Box 0131, San Francisco, CA 94143 USA. EM mfang@medicine.ucsf.edu FU NIA NIH HHS [AG15478, K23 AG028978, R01 AG015478] NR 29 TC 122 Z9 124 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2006 VL 54 IS 8 BP 1231 EP 1236 DI 10.1111/j.1532-5415.2006.00828.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 076MC UT WOS:000239961400010 PM 16913990 ER PT J AU Roman, MJ Naqvi, TZ Gardin, JM Gerhard-Herman, M Jaff, M Mohler, E AF Roman, Mary J. Naqvi, Tasneern Z. Gardin, Julius M. Gerhard-Herman, Marie Jaff, Michael Mohler, Emile TI Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: A report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID INTIMA-MEDIA THICKNESS; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE ATHEROSCLEROSIS; ENDOTHELIUM-DEPENDENT DILATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CAROTID WALL THICKNESS; HEALTHY-YOUNG ADULTS; BRACHIAL-ARTERY; ESSENTIAL-HYPERTENSION; POSTMENOPAUSAL WOMEN AB Noninvasive measures of atherosclerosis have emerged as adjuncts to standard cardiovascular disease (CVD) risk factors in an attempt to refine risk stratification and the need for more aggressive preventive strategies. Two such approaches, carotid artery imaging and brachial artery reactivity testing (BART), are ultrasound based. Numerous carotid artery imaging protocols have been used, and methodologic aspects are described in detail in this review. The panel recommends that protocols: (1) use end-diastolic (minimum dimension) images for intimal-medial thickness (IMT) measurements; (2) provide separate categorization of plaque presence and IMT; (3) avoid use of a single upper limit of normal for IMT because the measure varies with age, sex, and race; and (4) incorporate lumen measurement, particularly when serial measurements are performed to account for changes in distending pressure. Protocols may vary in the number of segments wherein IMT is measured, whether near wall is measured in addition to far wall, and whether IMT measurements are derived from B-mode or M-mode images, depending on the application. BART is a technique that requires meticulous attention to patient preparation and methodologic detail. Its application is substantially more challenging than is carotid imaging and remains largely a research technique that is not readily translated into routine clinical practice. C1 Cornell Univ, Weill Med Coll, New York, NY USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. St John Hosp & Med Ctr, Detroit, MI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn Hlth Syst, Philadelphia, PA USA. RP Roman, MJ (reprint author), Amer Soc Echocardiog, 1500 Sunday Dr,Suite 102, Raleigh, NC 27607 USA. NR 94 TC 82 Z9 93 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD AUG PY 2006 VL 19 IS 8 BP 943 EP 954 DI 10.1016/j.echo.2006.04.020 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 076DA UT WOS:000239936000002 PM 16880089 ER PT J AU Gerhard-Herman, M Gardin, JM Jaff, M Mohler, E Roman, M Naqvi, TZ AF Gerhard-Herman, Marie Gardin, Julius M. Jaff, Michael Mohler, Emile Roman, Mary Naqvi, Tasneem Z. TI Guidelines for noninvasive vascular laboratory testing: A report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; ASSISTED DUPLEX SONOGRAPHY; LONG-TERM PATENCY; CAROTID-ARTERY; FOLLOW-UP; FEMOROPOPLITEAL ANGIOPLASTY; DOPPLER ULTRASOUND; LOWER-EXTREMITIES; STENOSIS; ENDARTERECTOMY AB Accompanying the rapid growth of interest in percutaneous vascular interventions, there has been increasing interest among cardiologists in performing noninvasive vascular testing using ultrasound. In an attempt to provide recommendations on the best practices in vascular laboratory testing, this report has been prepared by a writing group from the American Society of Echocardiography (ASE) and the Society of Vascular Medicine and Biology. The document summarizes principles integral to vascular duplex ultrasound-including color Doppler, spectral Doppler waveform analysis, power Doppler, and the use of contrast. Appropriate indications and interpretation of carotid artery, renal artery, abdominal aorta, and peripheral artery ultrasound imaging are described. A dedicated section summarizes noninvasive techniques for physiologic vascular testing of the lower extremity arteries-including measurement of segmental pressures and pulse volume plethysmography. The use of exercise testing in the evaluation of peripheral artery disease, ultrasound evaluation of the lower extremities after percutaneous revascularization, and the diagnosis and management of iatrogenic pseudoaneurysm (PSA) is also discussed. A section on the important topic of vascular laboratory accreditation is included. Finally, additional details regarding proper technique for performance of the various vascular tests and procedures are included in the Appendix. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. St John Hosp & Med Ctr, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn Hlth Syst, Philadelphia, PA USA. Cornell Univ, Weill Med Coll, New York, NY USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Gerhard-Herman, M (reprint author), Amer Soc Echocardiog, 1500 Sunday Dr,Suite 102, Raleigh, NC 27607 USA. NR 51 TC 42 Z9 42 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD AUG PY 2006 VL 19 IS 8 BP 955 EP 972 DI 10.1016/j.echo.2006.04.019 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 076DA UT WOS:000239936000003 PM 16880090 ER PT J AU Vallet, M Picard, N Loffing-Cueni, D Fysekidis, M Bloch-Faure, M Deschenes, G Breton, S Meneton, P Loffing, J Aronson, PS Chambrey, R Eladari, D AF Vallet, Marion Picard, Nicolas Loffing-Cueni, Dominique Fysekidis, Marinos Bloch-Faure, May Deschenes, Georges Breton, Sylvie Meneton, Pierre Loffing, Johannes Aronson, Peter S. Chambrey, Regine Eladari, Dominique TI Pendrin regulation in mouse kidney primarily is chloride-dependent SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID THICK ASCENDING LIMB; COLLECTING DUCT; ACID-BASE; SENSITIVE HYPERTENSION; INTERCALATED CELLS; EXCHANGER PENDRIN; NACL RESTRICTION; TIME-COURSE; SODIUM; RAT AB Recent studies indicate that pendrin, an apical Cl-/HCO3- exchanger, mediates chloride reabsorption in the connecting tubule and the cortical collecting duct and therefore is involved in extracellular fluid volume regulation. The purpose of this study was to test whether pendrin is regulated in vivo primarily by factors that are associated with changes in renal chloride transport, by aldosterone, or by the combination of both determinants. For achievement of this goal, pendrin protein abundance was studied by semiquantitative immunoblotting in different mouse models with altered aldosterone secretion or tubular chloride transport, including NaCl loading, hydrochlorothiazide administration, NaCl co-transporter knockout mice, and mice with Liddle's mutation. The parallel regulation of the aldosterone-regulated epithelial sodium channel (ENaC) was examined as a control for biologic effects of aldosterone. Major changes in pendrin protein expression were found in experimental models that are associated with altered renal chloride transport, whereas no significant changes were detected in pendrin protein abundance in models with altered aldosterone secretion. Moreover, in response to hydrochlorothiazide administration, pendrin was downregulated despite a marked secondary hyperaldosteronism. In contrast, a-ENaC was markedly upregulated, and the molecular weight of a large fraction of gamma-ENaC subunits was shifted from 85 to 70 kD, consistent with previous results from rat models with elevated plasma aldosterone levels. These results suggest that factors that are associated with changes in distal chloride delivery govern pendrin expression in the connecting tubule and cortical collecting duct. C1 INSERM, U 652, IFR58, Inst Cordeliers, F-75006 Paris, France. Univ Paris Descartes, Fac Med Rene Descartes, Paris, France. Univ Paris 06, UMR 7134, CNRS, F-75252 Paris 05, France. Hop Necker Enfants Malad, Dept Physiol, AP HP, Paris, France. Univ Fribourg, Dept Med, Unit Anat, CH-1700 Fribourg, Switzerland. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Chambrey, R (reprint author), INSERM, U 652, IFR58, Inst Cordeliers, 15 Rue Ecole Med, F-75006 Paris, France. EM chambrey@ccr.jussieu.fr; eladari@ccr.jussieu.fr RI Picard, Nicolas/B-6677-2012 OI Picard, Nicolas/0000-0002-1695-3389 FU NIDDK NIH HHS [DK17433, DK38452, DK33793, R37 DK033793] NR 37 TC 64 Z9 64 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2006 VL 17 IS 8 BP 2153 EP 2163 DI 10.1681/ASN.2005101054 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 069LV UT WOS:000239449000016 PM 16825334 ER PT J AU Johansen, KL Painter, PL Sakkas, GK Gordon, P Doyle, J Shubert, T AF Johansen, Kirsten L. Painter, Patricia L. Sakkas, Giorgos K. Gordon, Patricia Doyle, Julie Shubert, Tiffany TI Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: A randomized, controlled trial SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; MORTALITY; DIALYSIS; CAPACITY; STRENGTH; ANEMIA; HEALTH AB Patients who are on hemodialysis commonly experience muscle wasting and weakness, which have a negative effect on physical functioning and quality of life. The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis. A randomized 2 X 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California, San Francisco-affiliated dialysis units. Interventions included double-blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights. Primary outcomes included change in lean body mass (LBM) measured by dual-energy x-ray absorptiometry, quadriceps muscle cross-sectional area measured by magnetic resonance imaging, and knee extensor muscle strength. Secondary outcomes included changes in physical performance, self-reported physical functioning, and physical activity. Sixty-eight patients completed the study. Patients who received nandrolone decanoate increased their LBM by 3.1 +/- 2.2 kg (P < 0.0001). Exercise did not result in a significant increase in LBM. Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise (P = 0.01) and to nandrolone (P < 0.0001) in an additive manner. Patients who exercised increased their strength in a training-specific fashion, and exercise was associated with an improvement in self-reported physical functioning (P = 0.04 compared with nonexercising groups). Nandrolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis. Further studies are needed to determine whether these interventions improve survival. C1 San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. Univ Thessaly, Dept Med, Thessaly, Greece. No Calif Inst Res & Educ, San Francisco, CA USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU NIDDK NIH HHS [DK-56182] NR 25 TC 164 Z9 172 U1 1 U2 9 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 AUG PY 2006 VL 17 IS 8 BP 2307 EP 2314 DI 10.1681/ASN.2006010034 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 069LV UT WOS:000239449000033 PM 16825332 ER PT J AU Shih, KS Tsai, WF Wu, CJ Mudgal, C AF Shih, Kao-Shang Tsai, Wun-Fu Wu, Chun-Jen Mudgal, Chaitanya TI Simultaneous dislocation of the carpometacarpal and metacarpophalangeal joints of the thumb in a motorcyclist SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Article DE carpometacarpal; dislocation; metacarpophalangeal joints; thumb ID METACARPO-PHALANGEAL JOINTS; INTERPHALANGEAL AB Combined dislocation of more than one joint in a single finger is a rare injury. An amateur motorcyclist sustained simultaneous closed dislocation of the carpometacarpal and metacarpophalangeal joints of the thumb as an isolated injury after falling from his motorcycle during an abrupt stop from high speed. The dislocated joints were reduced by closed means on the day of injury. After 18 months, the functional result of his right thumb was excellent. The mechanism of injury and management of this uncommon motorcycle injury is reported. C1 Far Eastern Mem Hosp, Dept Emergency Med, Taipei 220, Taiwan. Far Eastern Mem Hosp, Div Orthopaed Surg, Dept Surg, Taipei 220, Taiwan. Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. Massachusetts Gen Hosp, Orthoped Hand Serv, Boston, MA 02114 USA. RP Wu, CJ (reprint author), Far Eastern Mem Hosp, Dept Emergency Med, 21 Nan Ya S Rd,Sect 2, Taipei 220, Taiwan. EM soe123@ms22.hinet.net NR 17 TC 3 Z9 5 U1 0 U2 0 PU SCIENTIFIC COMMUNICATIONS INTERNATIONAL LTD. PI TAIPEI PA NO 1, CHANG-TE ST, TAIPEI, 100, TAIWAN SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD AUG PY 2006 VL 105 IS 8 BP 670 EP 673 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 080MP UT WOS:000240252300009 PM 16935769 ER PT J AU Gibson, CM Zorkun, C Molhoek, P Zmudka, K Greenberg, M Mueller, H Wesdorp, J Louwerenburg, H Niederman, A Westenburg, J Bikkina, M Batty, J de Winter, J Murphy, SA McCabe, CH AF Gibson, CM Zorkun, C Molhoek, P Zmudka, K Greenberg, M Mueller, H Wesdorp, J Louwerenburg, H Niederman, A Westenburg, J Bikkina, M Batty, J de Winter, J Murphy, SA McCabe, CH TI Dose escalation trial of the efficacy, safety, and pharmacokinetics of a novel fibrinolytic agent, BB-10153, in patients with ST elevation MI: Results of the TIMI 31 trial SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE fibrinolytic; ST elevation myocardial infarction; TIMI Flow Grade; TIMI frame count ID MYOCARDIAL-INFARCTION TIMI; THROMBIN-ACTIVATABLE PLASMINOGEN; THROMBOLYSIS; THERAPY AB Background: Currently available fibrinolytic agents are limited by their ability to restore normal blood flow in only half of patients, the risk of reocclusion, and the risk of intracranial hemorrhage. The genetically engineered agent BB-10153 is activated by thrombin, not plasminogen activator enzymes, which limits its activity to the site of thrombus which may in turn reduce the risk of systemic bleeding. BB-10153 also has a relatively long half-life of 3-4 hours, which may also limit the potential for early reocclusion [1, 2]. Methods: The study was a phase II, open-label, multi-center, dose escalation, single-dose administration study to determine the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of BB-10153 in ST segment elevation MI (STEMI). STEMI patients (n = 50) received a single dose of BB-10153 at one of six dose levels (1.0, 2.0, 3.0, 5.0, 7.5 and 10 mg/kg). The primary endpoint was TIMI flow grade (TFG) 3 at 60 minutes following the intravenous bolus of BB-10153. Results: Mean area under the curve for drug concentration ranged from 48.0 mu g center dot h/mL in the 1 mg/kg dose group to 788.6 mu g center dot h/mL in the 10 mg/kg dose group. Likewise, mean C-max generally increased with dose over the entire dose range, from 4.9 mu g/mL in the 1 mg/kg dose group to 139.6 mu g/mL in the 10 mg/kg dose group. The mean apparent terminal half-life (t1/2) was 4.4 hours (range 2.2 to 7.6 hours). Few patients in the 1-3 mg/kg dosage groups achieved TFG 3 on the one-hour post-dose angiogram (4/20, 20%), and no patients achieved complete ST segment resolution. The 5, 7.5 and 10 mg/kg doses were associated with similar rates of TIMI grade 3 flow of approximately three per seven patients. Pooling TFG 3 data from the 5, 7.5 and 10 mg/kg groups yielded a TIMI grade 3 flow rate of 34% (n = 10/29; range 29-43%). No patients experienced 30-day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during the study. One patient experienced recurrent angina and developed recurrent myocardial ischemia requiring urgent revascularization. Three patients sustained TIMI major bleeding events (one in 1 mg/kg group, two in 7.5 mg/kg group), six patients sustained TIMI minor bleeds (one in the 2, 3, 7.5 and 10 mg/kg groups, two in the 5 mg/kg group), two patients sustained TIMI minimal bleeds (one in each of the 2 and 10 mg/kg groups) and no patients sustained intracranial hemorrhage (ICH). Conclusion: In a dose escalation study of a single intravenous bolus, the novel fibrinolytic agent, BB-10153 was associated with a rise in the mean area under the curve and C-max for drug concentration over the dose range 1 to 10 mg/kg. Higher doses were associated with a range of TIMI grade 3 flow of 29-43%, and no patients experienced 30-day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during the study. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. John Paul II Hosp, Krakow, Poland. Med Spectrum Twente, Enschede, Netherlands. Montefiore Med Ctr, New York, NY USA. Spaarne Ziekenhuis, Heemstede, Netherlands. N Ridge Med Ctr, Ft Lauderdale, FL USA. Scheperziekenhuis, Emmen, Netherlands. St Josephs Med Ctr, Paterson, NJ USA. New Mexico Heart Inst, Albuquerque, NM USA. Tweesteden Ziekenhuis, Tilberg, Netherlands. RP Gibson, CM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org NR 11 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD AUG PY 2006 VL 22 IS 1 BP 13 EP 21 DI 10.1007/s11239-006-8080-1 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 055JE UT WOS:000238445600002 PM 16786228 ER PT J AU Mega, JL Morrow, DA Cannon, CP Murphy, S Cairns, R Ridker, PM Braunwald, E AF Mega, JL Morrow, DA Cannon, CP Murphy, S Cairns, R Ridker, PM Braunwald, E TI Cholesterol, C-reactive protein, and cerebrovascular events following intensive and moderate statin therapy SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE C-reactive protein; cerebrovascular event; cholesterol; hydroxymethylglutaryl-CoA reductase inhibitors ID RANDOMIZED CONTROLLED-TRIAL; ACUTE CORONARY SYNDROMES; ISCHEMIC-STROKE; MYOCARDIAL-INFARCTION; REDUCTASE INHIBITORS; PLASMA-CONCENTRATION; SERUM-CHOLESTEROL; HEART-DISEASE; RISK-FACTOR; PRAVASTATIN AB Background: While statins have been shown to reduce cerebrovascular events (CVE), the relationship between cholesterol, C-reactive protein (CRP), and CVE in patients treated with different statin strategies is still being explored. Methods: PROVE IT-TIMI 22 was a randomized trial of intensive (atorvastatin 80 mg/day) and moderate (pravastatin 40 mg/day) statin therapy in 4,162 patients with acute coronary syndromes followed for an average of 24 months; serial biomarkers allowed for an assessment of the lipid and non-lipid effects of statins as they relate to CVE. Results: In this study, 45 patients on intensive statin therapy and 40 patients on moderate statin therapy had a CVE during the study period (2.1% v. 1.9%, P = 0.62). While the lipid profiles of patients with and without CVE were similar, those with CVE had higher CRP levels at 30 days and 4 months (2.7 v. 1.9, 2.4 v. 1.7 mg/L; P = 0.012, P = 0.005). Day 30 CRP remained an independent predictor of CVE after adjusting for age, development of atrial fibrillation, diabetes, and prior CVE. Patients with low density lipoprotein (LDL) levels < 70 mg/dL and >= 70 mg/dL had similar rates of CVE, while patients with CRP < 2 mg/L tended to have lower event rates when compared to those with higher levels. The lowest rates of CVE were seen in patients who had LDL < 70 mg/dL and CRP < 2 mg/L. Conclusion: In PROVE IT - TIMI 22, achieved LDL levels did not appear to independently impact the rate of CVE. In contrast, patients with elevated CRP levels were at higher risk of stroke or transient ischemic attack, reinforcing the link between inflammation and CVE. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, Boston, MA USA. Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Nottingham Clin Res Grp, Nottingham, England. RP Mega, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, 55 Fruit St,GRB 804, Boston, MA USA. EM jmega@partners.org NR 33 TC 15 Z9 17 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD AUG PY 2006 VL 22 IS 1 BP 71 EP 76 DI 10.1007/s11239-006-8081-0 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 055JE UT WOS:000238445600010 PM 16786236 ER PT J AU Padfield, KE Zhang, QH Gopalan, S Tzika, AA Mindrinos, MN Tompkins, RG Rahme, LG AF Padfield, Katie E. Zhang, Qunhao Gopalan, Suresh Tzika, A. Aria Mindrinos, Michael N. Tompkins, Ronald G. Rahme, Laurence G. TI Local and distant burn injury alter immuno-inflammatory gene expression in skeletal muscle SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE muscle; burn; inflammation; systemic inflammatory response ID LEUKEMIA INHIBITORY FACTOR; MULTIPLE ORGAN FAILURE; ACUTE-PHASE RESPONSE; THERMAL-INJURY; OXIDATIVE STRESS; SIGNALING PATHWAY; CYTOKINES; DYSFUNCTION; ACTIVATION; PROTEINS AB Background. Severe burn trauma mediates immune dysfunction, infection, and multiple organ dysfunction syndrome. We are investigating the immuno-inflammatory response by characterizing gene expression changes in skeletal muscle after local and distant burn injury. Methods. Male CDI mice in three experimental groups, control (unburned), hind limb (local burn), and 30% total body surface area (distant burn), were killed between 6 hours and 10 days post-burn; and changes in gastrocnemius muscle global gene expression were assessed using microarrays. Results. The 35 immuno-inflammatory genes are differentially expressed in both models, with an additional 20 and 30 genes specific to distant and local burn, respectively. These genes encode chemokines, oxidative-stress, complement, and defense/immune functions. Conclusion. Burn mediates a common systemic response, independent of the site or extent of injury, and also specific responses to local versus distant trauma. A transcriptome profile of genes that initiate and sustain systemic inflammation has been identified. C1 Massachusetts Gen Hosp, Shriners Burns Inst, Dept Surg, Mol Surg Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Rahme, LG (reprint author), Massachusetts Gen Hosp, Shriners Burns Inst, Dept Surg, Mol Surg Lab, Thier 340,50 Blossom St, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu FU NIGMS NIH HHS [U54 GM-62119-03] NR 39 TC 12 Z9 13 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 AUG PY 2006 VL 61 IS 2 BP 280 EP 292 DI 10.1097/01.ta.0000230567.56797.6c PG 13 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 075UW UT WOS:000239911800009 PM 16917440 ER PT J AU Simpson, T Jakupcak, M Luterek, JA AF Simpson, Tracy Jakupcak, Matthew Luterek, Jane A. TI Fear and avoidance of internal experiences among patients with substance use disorders and PTSD: The centrality of anxiety sensitivity SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; THOUGHT CONTROL QUESTIONNAIRE; PSYCHOMETRIC PROPERTIES; TRAIT ANXIETY; ALCOHOL-USE; HYPERVENTILATION; ALEXITHYMIA; TRAUMA; SCALE; EXPECTANCIES AB This study evaluated anxiety sensitivity, cognitive avoidance, and alexithymia and their relationship to posttraumatic stress disorder (PTSD) and alcohol use indices concurrently and prospectively in an outpatient substance abuse treatment sample that screened positive for PTSD (N=58). Anxiety sensitivity accounted for substantial variance in the PTSD clusters, reexperiencing. avoidance, and hyperarousal, both concurrently and prospectively. Cognitive avoidance accounted for additional variance with concurrent PTSD avoidance symptoms. Anxiety sensitivity and cognitive avoidance were largely not associated with alcohol use indices. Alexithymia was largely redundant with cognitive avoidance and was, therefore, not included in the regression analyses. Theoretical and treatment implications of these findings are discussed in the context of individuals with dually diagnosed PTSD and substance abuse disorders. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Dept Vet Affairs, Off Acad Affiliat,VA MIRECC Fellowship Program Ad, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Simpson, T (reprint author), 1660 S Columbia Way 1160MHC, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov NR 58 TC 23 Z9 23 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2006 VL 19 IS 4 BP 481 EP 491 DI 10.1002/jts.20128 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 084FO UT WOS:000240518000006 PM 16929503 ER PT J AU Hinton, DE Chhean, D Pich, V Hofmann, SG Barlow, DH AF Hinton, Devon E. Chhean, Dara Pich, Vuth Hofmann, Stefan G. Barlow, David H. TI Tinnitus among Cambodian refugees: Relationship to PTSD severity SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID PANIC-ATTACKS; ANXIETY; SCALE; DEPRESSION; DISORDER; THERAPY AB Consecutive Cambodian refugees attending a psychiatric clinic were assessed for the presence and severity of current tinnitus (i.e., at least one episode in the last month). Fifty percent(521104) of surveyed patients had tinnitus. Among the tinnitus patients, posttraumatic stress disorder (PTSD) rates were significantly more elevated than among nontinnitus patients (OR = 13.5; 95% CI= 5.8 to 39.4), as were Clinician-Administered PTSD Scale (CAPS) scores. In a hierarchical regression among tinnitus patients (n = 52), tinnitus-related trauma associations and catastrophic cognitions accounted for variability in CAPS severity beyond a measure of tinnitus severity. Among tinnitus patients, tinnitus-related trauma associations and catastrophic cognitions mediated the effect of tinnitus severity on CAPS severity. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Southeast Asian Clin, Arbour Counseling Serv, Lowell, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Univ, Ctr Anxiety Disorders, Boston, MA USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 16 TC 41 Z9 41 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2006 VL 19 IS 4 BP 541 EP 546 DI 10.1002/jts.20138 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 084FO UT WOS:000240518000011 PM 16929509 ER PT J AU Zimering, R Gulliver, SB Knight, J Munroe, J Keane, TM AF Zimering, Rose Gulliver, Suzy B. Knight, Jeffrey Munroe, James Keane, Terence M. TI Posttraumatic stress disorder in disaster relief workers following direct and indirect trauma exposure to ground zero SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ADMINISTERED PTSD SCALE; PSYCHOMETRIC PROPERTIES; TERRORIST ATTACKS; INVENTORY; SEPTEMBER-11; CONSISTENCY; DEPRESSION; ANXIETY; EVENTS AB The present study compared rates of posttraumatic stress disorder (PTSD) in relief workers at the World Trade Center collapse from two sources: direct exposure to the disaster site and indirect exposure through survivor narratives. Standardized clinical interviews for PTSD were conducted with 109 relief workers 6-8 months after the September 11th terrorist attacks. Rates of acute PTSD from direct and indirect exposure to traumatic stressors were 6.4% and 4.69%, respectively. The findings suggest that indirect exposures can lead to PTSD even when Criterion A1 of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR; American Psychiatric Association, 2000, p. 463), i.e., "experienced by a family member or other close associate" is not met. Further research is necessary to define precisely the parameters of indirect traumatic exposure that may be linked to the development of PTSD. C1 VA Boston Healthcare Syst, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Zimering, R (reprint author), VA Boston Healthcare Syst, 251 Causeway St, Boston, MA 02114 USA. EM rose.zimering@va.gov FU NIMH NIH HHS [R01MH66353] NR 14 TC 30 Z9 30 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2006 VL 19 IS 4 BP 553 EP 557 DI 10.1002/jts.20143 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 084FO UT WOS:000240518000013 PM 16929511 ER PT J AU Yannucci, J Manola, J Garnick, MB Bhat, G Bubley, GJ AF Yannucci, Jennifer Manola, Judi Garnick, Marc B. Bhat, Gajanan Bubley, Glenn J. TI The effect of androgen deprivation therapy on fasting serum lipid and glucose parameters SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; androgen antagonists; glucose; lipids ID PROSTATE-CANCER; BODY-COMPOSITION; OPEN-LABEL; MEN; CARCINOMA; REPLACEMENT; MULTICENTER; METABOLISM; MORTALITY; ADJUVANT AB Purpose: Although prostate cancer specific mortality is decreasing, there is little effect on overall mortality in this population, suggesting the possibility of an increased risk of death from nonprostate cancer related causes. Androgen deprivation therapy could adversely affect cardiovascular health. We investigated changes in lipid and glucose during androgen deprivation therapy. Materials and Methods: We performed an exploratory analysis of pooled data from 3 prospective clinical trials aimed at achieving medical castration by comparing the gonadotropin releasing hormone antagonist abarelix, the gonadotropin releasing hormone agonist leuprolide acetate and leuprolide acetate plus the antiandrogen bicalutamide. Most patients were treated in the neoadjuvant setting or because of biochemical recurrence. Fasting serum lipid, glucose and hemoglobin A1C were determined in 1,102 men at baseline, and on treatment days 85 and 169, In the current study men were categorized into 3 treatment groups according to the type of androgen deprivation therapy, that is leuprolide acetate, leuprolide acetate plus bicalutamide or abarelix, and statin therapy. Results: Significant increases in total cholesterol, triglyceride and high density lipoprotein-cholesterol were observed in patients on leuprolide acetate or abarelix but not in patients on leuprolide acetate plus bicalutamide. Consistent changes in low density lipoprotein-cholesterol were not detected. Increased total cholesterol was usually due to an increase in high density lipoprotein-cholesterol. Hemoglobin A1C increased from baseline to day 85 only and there were no significant changes in fasting glucose measurements. The type of androgen deprivation therapy did not affect these parameters. Conclusions: Short-term androgen deprivation therapy affects serum lipid and hemoglobin A1C independent of statin therapy. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston & Praecis Pharmaceut Inc, Waltham, MA USA. RP Bubley, GJ (reprint author), Beth Israel Deaconess Med Ctr, HIM Room,1049 E Campus,330 Brookline Ave, Boston, MA 02215 USA. EM gbubley@bidmc.harvard.edu NR 20 TC 38 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 2006 VL 176 IS 2 BP 520 EP 525 DI 10.1016/j.juro.2006.03.057 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 063KZ UT WOS:000239018400024 PM 16813881 ER PT J AU Subramanya, AR Yang, CL McCormick, JA Ellison, DH AF Subramanya, A. R. Yang, C-L McCormick, J. A. Ellison, D. H. TI WNK kinases regulate sodium chloride and potassium transport by the aldosterone-sensitive distal nephron SO KIDNEY INTERNATIONAL LA English DT Review DE WNK; NCC; ROMK; ENaC; distal convoluted tubule ID ACTIVATES SGK1; MUTANT WNK4; HYPERTENSION; HYPERKALEMIA; ISOFORM; CHANNEL; PSEUDOHYPOALDOSTERONISM; COTRANSPORTERS; PERMEABILITY; REABSORPTION AB With-No-Lysine [K] (WNKs) are a recently discovered family of serine/threonine protein kinases that contain a uniquely structured catalytic domain. Mutations in the genes encoding two family members, WNK1 and WNK4, cause a chloride-dependent, thiazide-sensitive inherited syndrome of hypertension and hyperkalemia. Over the past 5 years, physiologic studies have demonstrated that these proteins regulate transcellular and paracellular epithelial ion flux. In this mini review, we discuss WNK1 and WNK4 gene products and their regulatory effects on sodium chloride and potassium handling in the aldosterone-sensitive distal nephron. Experimental observations regarding the effects of these proteins on transport processes mediated by the thiazide-sensitive Na-Cl co-transporter, the epithelial sodium channel, the renal outer medullary potassium channel, and the paracellular pathway integrate into a model that suggests an essential role for WNKs in coordinating renal Na-Cl reabsorption and K+ secretion. C1 Oregon Hlth Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Ellison, DH (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Nephrol & Hypertens, PP262,33134 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM ellisond@ohsu.edu OI Ellison, David/0000-0003-2915-265X FU NIDDK NIH HHS [DK51496, F32-DK72895] NR 28 TC 46 Z9 47 U1 2 U2 8 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 AUG PY 2006 VL 70 IS 4 BP 630 EP 634 DI 10.1038/sj.ki.5001634 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 077FW UT WOS:000240015100010 PM 16820787 ER PT J AU Wong, JS AF Wong, Julia S. TI Is radiotherapy boost needed in young patients with ductal carcinoma-in-situ? SO LANCET ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; RADIATION; TRIAL; RECURRENCE; WOMEN C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Wong, JS (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM jwong@lroc.harvard.edu NR 10 TC 4 Z9 4 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2006 VL 7 IS 8 BP 615 EP 617 DI 10.1016/S1470-2045(06)70771-9 PG 3 WC Oncology SC Oncology GA 071RR UT WOS:000239620000004 PM 16887475 ER PT J AU Kuperberg, GR Caplan, D Sitnikova, T Eddy, M Holcomb, PJ AF Kuperberg, Gina R. Caplan, David Sitnikova, Tatiana Eddy, Marianna Holcomb, Phillip J. TI Neural correlates of processing syntactic, semantic, and thematic relationships in sentences SO LANGUAGE AND COGNITIVE PROCESSES LA English DT Article ID EVENT-RELATED POTENTIALS; BRAIN POTENTIALS; AMBIGUITY RESOLUTION; WORKING-MEMORY; POSITIVE SHIFT; EYE-MOVEMENTS; TIME-COURSE; INFORMATION; INTEGRATION; ANOMALIES AB Event-related potentials were measured as subjects read sentences presented word by word. A small N400 and a robust P600 effect were elicited by verbs that assigned the thematic role of Agent to their preceding noun-phrase argument when this argument was inanimate in nature. The amplitude of the P600, but not the N400, was modulated by the transitivity of the critical verbs and by plausibility ratings of passivised versions of these sentences (reflecting the fit between the critical verb and the inanimate noun-phrase as the verb's Theme). The P600 was similar in scalp distribution although smaller in amplitude, than that elicited by verbs with morphosyntactic violations. Pragmatically unlikely verbs that did not violate thematic constraints elicited a larger N400 but no P600 effect. These findings support the theory that the cost of syntactic processing on a verb is influenced by the precise thematic relationships between that verb and its preceding arguments. C1 Tufts Univ, Dept Psychol, Medford, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Tufts Univ, Dept Psychol, Medford, MA USA. RP Kuperberg, GR (reprint author), Psychiat Neurosci Program, CNY-2 Bldg 149,MGH East,13th St, Charlestown, MA 02129 USA. EM kuperber@nmr.mgh.harvard.edu NR 66 TC 71 Z9 73 U1 1 U2 9 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0169-0965 J9 LANG COGNITIVE PROC JI Lang. Cogn. Process. PD AUG PY 2006 VL 21 IS 5 BP 489 EP 530 DI 10.1080/01690960500094279 PG 42 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA 081ZM UT WOS:000240356100001 ER PT J AU Hadlock, TA Greenfield, LJ Wernick-Robinson, M Cheney, ML AF Hadlock, Tessa A. Greenfield, Laura J. Wernick-Robinson, Mara Cheney, Mack L. TI Multimodality approach to management of the paralyzed face SO LARYNGOSCOPE LA English DT Article DE facial paralysis; Bell's Palsy; chemodenervation; botulinum toxin; brow ptosis; fascia lata sling; cross-face nerve graft ID FACIAL PARALYSIS; MUSCLE TRANSPLANTATION; BOTULINUM TOXIN; REANIMATION; PALSY; RECONSTRUCTION; TRANSPOSITION AB Objectives: Despite the ability of facial reanimation techniques to introduce meaningful movement to the paralyzed face, dynamic methods do not address all zones of the face. Our objective was to retrospectively review outcomes after multimodality management of the patient with facial paralysis, to describe several novel surgical methods that introduce subtle improvements in static facial balance, and to present an algorithm for comprehensive management of the paralyzed face. Methods/Results: Three hundred thirty-seven patients with facial paralysis were seen and treated in a busy facial nerve center setting over a 3-year period using a range of standard muscle transfers, physical therapy, chemodenervation with botulinum toxin, and static surgical techniques. Three adjunct techniques emerged as novel and useful procedures that more fully addressed facial balance issues than existing techniques. Of patients proceeding with physical therapy, greater than 80% of patients experienced a benefit, and 97% of those who proceeded with botulinum toxin therapy experienced a benefit. Conclusions: Facial paralysis is best managed using a multimodality approach that includes surgical interventions, physical therapy, and chemo-deneveration. We describe three adjunctive surgical techniques for management of the paralyzed face and present a comprehensive algorithm for management of the paralyzed face. That may provide improved function and cosmesis in all zones of the paralyzed face. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 15 TC 42 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 2006 VL 116 IS 8 BP 1385 EP 1389 DI 10.1097/01.mlg.0000225980.38147.c6 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 071RN UT WOS:000239619500013 PM 16885741 ER PT J AU Griffith, AJ Yang, Y Pryor, SP Park, HJ Jabs, EW Nadol, JB Russell, LJ Wasserman, DI Richard, G Adams, JC Merchant, SN AF Griffith, Andrew J. Yang, Yandan Pryor, Shannon P. Park, Hong-Joon Jabs, Ethylin Wang Nadol, Joseph B., Jr. Russell, Laura J. Wasserman, Daniel I. Richard, Gabriele Adams, Joe C. Merchant, Saumil N. TI Cochleosaccular dysplasia associated with a connexin 26 mutation in keratitis-ichthyosis-deafness syndrome SO LARYNGOSCOPE LA English DT Article DE Scheibe dysplasia; cochleosaccular dysplasia; connexin 26; GJB2; hearing; KID syndrome ID HEARING IMPAIRMENT; KID SYNDROME; HISTOPATHOLOGY; EXPRESSION AB Objective: The objective of this study was to characterize the temporal bone phenotype associated with a mutation of GJB2 (encoding connexin 26). Study Design: The authors conducted correlative clinical, molecular genetic, and postmortem histopathologic analysis. Methods: The study subject was a male infant with keratitis-ichthyosis-deafness (KID) syndrome. We performed a nucleotide sequence analysis of GJB2 and a histopathologic analysis of the temporal bones. Results: The subject was heterozygous for G45E, a previously reported KID syndrome mutation of GJB2. The primary inner ear abnormality was dysplasia of the cochlear and saccular neuroepithelium. Conclusions: GJB2 mutations can cause deafness in KID syndrome, and possibly in other GJB2 mutant phenotypes, by disrupting cochlear differentiation. C1 NIDCD, Sect Gene Struct & Funct, NIH, Bethesda, MD USA. NIDCD, Hearing Sect, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Inst Med Genet, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. McGill Univ, Montreal Childrens Hosp, Dept Pediat, Montreal, PQ H3H 1P3, Canada. Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. RP Griffith, AJ (reprint author), 5 Res Court,Room 2A-01, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov OI Jabs, Ethylin/0000-0001-8983-5466 FU NIDCD NIH HHS [1Z01 DC 000064-02, Z01 DC000064, 1Z01 DC 000060-02, Z01 DC000060, R01 DC003929]; PHS HHS [NIH 13849] NR 15 TC 32 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 2006 VL 116 IS 8 BP 1404 EP 1408 DI 10.1097/01.mlg.0000224549.75161.ca PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 071RN UT WOS:000239619500016 PM 16885744 ER PT J AU Smith, SM Johnson, JL Niedzwiecki, D Eder, JP Canellos, G Cheson, BD Bartlett, NL AF Smith, Sonali M. Johnson, Jeffrey L. Niedzwiecki, Donna Eder, J. Paul Canellos, George Cheson, Bruce D. Bartlett, Nancy L. CA Cancer Leukemia Group B TI Sequential doxorubicin and topotecan in relapsed/refractory aggressive non-Hodgkin's lymphoma: Results of CALGB 59906 SO LEUKEMIA & LYMPHOMA LA English DT Article DE aggressive lymphoma; camptothecins; relapsed lymphoma; topoisomerase inhibitors ID BONE-MARROW TRANSPLANTATION; PHASE-II; CHEMOTHERAPY; ETOPOSIDE; CAMPTOTHECINS; CANCER; LINE AB Topoisomerase enzymes are critical components of genomic replication and function to minimize torsional stress on DNA. Sequential administration of a topoisomerase II inhibitor followed by a topoisomerase I inhibitor is potentially synergistic due to increased target enzyme levels. Patients with relapsed or refractory aggressive non- Hodgkin's lymphomas ( NHL) were eligible for this phase II study of doxorubicin 25 mg/ m 2 intravenous ( IV) on day 1 and topotecan 1.75 mg/ m 2/ day IV on days 3 - 5, every 21 days. The trial objectives included the overall response rate, progression- free survival, and toxicity. Twenty- six patients were enrolled and 25 patients are assessable for toxicity and response. The median age was 58 ( range 23 - 74) years. The patients had received a median of two ( range one to five) prior regimens, including five patients with a prior stem cell transplant. Five patients ( 20%, 95% confidence interval 0.07, 0.42) responded with two ( 8%) complete remissions and three ( 12%) partial remissions; an additional four ( 16%) patients had stable disease. Both patients achieving a complete remission had Burkitt's lymphoma. There were no treatment- related deaths. In conclusion, the combination of doxorubicin and topotecan is well tolerated and has modest activity in relapsed/ refractory NHL, with occasional patients having a prolonged remission. The activity in Burkitt's lymphoma should be investigated further. C1 Univ Chicago, Chicago, IL 60637 USA. Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Washington, DC USA. Washington Univ, St Louis, MO USA. RP Smith, SM (reprint author), Univ Chicago, 5841 S Maryland Ave,MC2115, Chicago, IL 60637 USA. EM smsmith@medicine.bsd.uchicago.edu FU NCI NIH HHS [CA12046, CA33601, CA03927, CA31946, CA04326, CA07968, CA77440, CA86726, CA08025, CA41287, CA77658] NR 21 TC 4 Z9 5 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 2006 VL 47 IS 8 BP 1511 EP 1517 DI 10.1080/10428190600581385 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 083DH UT WOS:000240435600015 PM 16966261 ER PT J AU Moore, SDP Offor, O Ferry, JA Amrein, PC Morton, CC Dal Cin, P AF Moore, Steven D. P. Offor, Onyinye Ferry, Judith A. Amrein, Philip C. Morton, Cynthia C. Dal Cin, Paola TI ELF4 is fused to ERG in a case of acute myeloid leukemia with a t(X; 21)(q25-26; q22) SO LEUKEMIA RESEARCH LA English DT Article DE AML; ERG; ELF4; fusion; SAM/pointed domain; ETS domain ID ETS TRANSCRIPTION FACTOR; CHROMOSOMAL TRANSLOCATION; BINDING PROTEIN; GENE; MEF; FUSION; TLS/FUS; FAMILY; CANCER; RNA AB We report a novel chromosomal translocation in AML, t(X;21)(q25-26;q22), resulting in a fusion transcript between two ETS domain family members, ELF4 (at Xq25) and ERG (at 2 1 q22). ERG has been associated previously with other fusion partners, specifically FUS and EWSR1, and implicated in both AML and Ewing's sarcoma. RT-PCR analysis of RNA isolated from bone marrow samples from the patient demonstrates that the translocation occurs within intron 1 of ERG isoform, 1 (ERG-1) and intron 2 of ELF4 resulting in an in-frame fusion joining exon 2 from ELF4 with exon 2 of ERG. This is the first reported case of an ELF4-ERG fusion and identification of the specific ERG exon involved in the fusion that differentiates ERG isoforms. In addition, this case also directly implicates a new role for ELF4 in cancer. (c) 2005 Elsevier Ltd. All rights reserved. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, HematolOncol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dal Cin, P (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM pdalcin@partners.org FU NCI NIH HHS [P30 CA006516] NR 21 TC 11 Z9 13 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 AUG PY 2006 VL 30 IS 8 BP 1037 EP 1042 DI 10.1016/j.leukres.2005.10.014 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 062IA UT WOS:000238936600018 PM 16303180 ER PT J AU Belani, CP Pereira, JR von Pawel, J Pluzanska, A Gorbounova, V Kaukel, E Mattson, KV Ramlau, R Szczesna, A Fidias, P Millward, M Fossella, F AF Belani, Chandra P. Pereira, Jose R. von Pawel, Joachim Pluzanska, Anna Gorbounova, Vera Kaukel, Eckhard Mattson, Karin V. Ramlau, Rodryg Szczesna, Aleksandra Fidias, Panos Millward, Michael Fossella, Frank CA TAX 326 study grp TI Effect of chemotherapy for advanced non-small cell lung cancer on patients' quality of life - A randomized controlled trial SO LUNG CANCER LA English DT Article DE docetaxel; cisplatin; carboplatin; vinorelbine ID PHASE-III TRIAL; VINORELBINE PLUS CISPLATIN; ONCOLOGY-GROUP TRIAL; SUPPORTIVE CARE; CLINICAL-TRIALS; DOCETAXEL PLUS; GEMCITABINE; METAANALYSIS; CARBOPLATIN; MULTICENTER AB Background: Patients with advanced non-small cell lung cancer (NSCLC) do not have curative treatment options; therefore, treatments should prolong survival and improve quality of life (QoL). We compared the effect on QoL of two docetaxel-platinum regimens with vinorelbine-cisplatin. Methods: QoL was assessed by the Lung Cancer Symptom Scale (LCSS) and the general EuroQoL five-dimensional questionnaire (EQ-5D) in 926 chemotherapy-naive patients with stages IIIB to IV NSCLC. Patients were randomly assigned to receive: docetaxel 75 mg/m(2) plus cisplatin 75 mg/m(2), every 3 weeks (DC); docetaxel 75 mg/m(2) and carboplatin 6 mg/ml min, every 3 weeks (DCb); or vinorelbine 25 mg/m(2)/week plus cisplatin 100 mg/m(2), every 4 weeks (VC). Results: Overall, patients treated with either docetaxel-containing regimen had better QoL than VC-treated patients (LCSS global item "QoL today": P = 0.064 for DC and P = 0.016 for DCb versus VC; EQ-5D global item "health state today": P = 0.016 for DC and P < 0.001 for DCb versus VC). DC-treated patients experienced improved pain relief compared with VC (P = 0.033), whereas pain relief with DCb and VC was similar. Patients treated with either docetaxel regimen had more favorable changes in performance status (P = 0.065 for DC and P < 0.001 for DCb versus VC) and mean weight loss (0.06 kg, gain of 0.08 kg, and 2.27 kg for DC, DCb, and VC, respectively; P < 0.001 for both DC versus VC and DCb versus VC). Conclusion: The TAX 326 study shows that docetaxel-platinum regimens relieve symptoms and improve QoL inpatients with advanced NSCLC. DCb and DC were superior to VC in all QoL outcomes assessed except for the difference between DC and VC in LCSS "QoL today", which was not significant. (C) 2006 Elsevier Ireland Ltd. All, rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Western Australia, Sir Charles Gairdner Hosp, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. Massachusetts Gen Hosp, Ctr Thorac Canc, Div Hematol & Med Oncol, Boston, MA 02114 USA. Reg Lung Dis Hosp, PL-05400 Otwock, Poland. Reg Lung Dis Ctr, PL-60569 Poznan, Poland. Univ Helsinki, Cent Hosp, Dept Internal Med, FIN-00290 Helsinki, Finland. AK Harbug, Hamburg, Germany. Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. M Kopernik Mem Hosp, Lodz, Poland. Asklepios Fachklin Munchen Gauting, D-82131 Gauting, Germany. Inst Canc Arnaldo Vieira de Carvalho, BR-01221020 Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Lung & Thorac Malignancies Program, Univ Pittsburgh Canc Inst, Pittsburgh, PA 15232 USA. RP Fossella, F (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd,Box 432, Houston, TX 77030 USA. EM ffossell@mdanderson.org RI Millward, Michael/H-5456-2014; OI Belani, Chandra/0000-0001-5049-5329 NR 29 TC 38 Z9 40 U1 0 U2 2 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 AUG PY 2006 VL 53 IS 2 BP 231 EP 239 DI 10.1016/j.lungcan.2006.05.003 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 068DC UT WOS:000239351300014 PM 16787687 ER PT J AU Wittenberg, E Lichter, EL Ganz, ML McCloskey, LA AF Wittenberg, Eve Lichter, Erika L. Ganz, Michael L. McCloskey, Laura A. TI Community preferences for health states associated with intimate partner violence SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Meeting of the American-Academy-of-Health-Services-Research CY 2005 CL Boston, MA SP Amer Acad Hlth Serv Res DE domestic violence; intimate partner violence; utility; quality of life ID QUALITY-OF-LIFE; CONSEQUENCES; SF-12; SCORES; WOMEN; SF-36; VALUATIONS; UTILITIES; OUTCOMES; SCALES AB Background: One in 4 women is affected by intimate partner violence in her lifetime. This article reports on a cross-sectional survey to estimate community preferences for health states resulting from intimate partner violence. Methods: A secondary analysis was conducted of data from a convenience sample of 93 abused and 138 nonabused women (231 total) recruited for in-person interviews from hospital outpatient department waiting rooms in metropolitan Boston, Massachusetts. SF-12 data were converted to utilities to describe community-perspective preferences for health states associated with intimate partner violence. Linear regression analysis was used to explore the association between violence and utility while controlling for other health and demographic factors. Results: Median utility for intimate partner violence was between 0.58 and 0.63 on a scale of 0 (equivalent to death) to 1.0 (equivalent to optimal health), with a range from 0.64 to 0.66 for less severe violence to 0.53 to 0.62 for more severe violence. The data do not reveal whether violence itself is responsible for lower utility or whether a constellation of factors contributes to disutility experienced by women victims of abuse. Discussion: The utility of health states experienced by women exposed to intimate partner violence is substantially diminished compared with optimal health and even other health conditions. These values quantify the substantial negative health impact of the experience of intimate partner violence in terms that allow comparison across diseases. They can be used in cost-effectiveness analyses to identify the benefits and potential returns from resources allocated to violence prevention and intervention efforts. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Maine Bur Hlth, Augusta, ME USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Univ Penn, Sch Social Policy & Practice, Dept Social Work, Philadelphia, PA 19104 USA. RP Wittenberg, E (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Marrimac St,10th Floor, Boston, MA 02114 USA. EM eve@mgh-ita.org FU AHRQ HHS [R01 HS011088] NR 36 TC 7 Z9 7 U1 1 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 AUG PY 2006 VL 44 IS 8 BP 738 EP 744 DI 10.1097/01.mlr.0000215860.58954.86 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 068FE UT WOS:000239357200006 PM 16862035 ER PT J AU Conigliaro, J Justice, AC Gordon, AJ Bryant, K AF Conigliaro, Joseph Justice, Amy C. Gordon, Adam J. Bryant, Kendall CA VACS Alcohol Behavior Change Res G TI Role of alcohol in determining human immunodeficiency virus (HIV)-relevant outcomes - A conceptual model to guide the implementation of evidence-based interventions into practice SO MEDICAL CARE LA English DT Editorial Material ID HIV-INFECTION; SUBSTANCE USE; ANTIRETROVIRAL MEDICATIONS; REPORTED ADHERENCE; SEXUAL-BEHAVIOR; RISK BEHAVIOR; USE DISORDERS; CONSUMPTION; PREDICTORS; DRINKING C1 Univ Kentucky, Program Qual Safety & Patient Rights, Dept Med, Lexington, KY 40536 USA. Yale Univ, VA Connecticut Healthcare Syst, New Haven, CT USA. Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NIAAA, Rockville, MD 20852 USA. RP Conigliaro, J (reprint author), Univ Kentucky, Program Qual Safety & Patient Rights, Dept Med, 800 Rose St,N118, Lexington, KY 40536 USA. EM jconigliaro@uky.edu FU NIAAA NIH HHS [U01-AA13566] NR 45 TC 32 Z9 33 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 2006 VL 44 IS 8 SU 2 BP S1 EP S6 DI 10.1097/01.mlr.0000223659.36369.cf PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 069IB UT WOS:000239438500001 PM 16849963 ER PT J AU Fultz, SL Skanderson, M Mole, LA Gandhi, N Bryant, K Crystal, S Justice, AC AF Fultz, Shawn L. Skanderson, Melissa Mole, Larry A. Gandhi, Neel Bryant, Kendall Crystal, Stephen Justice, Amy C. TI Development and verification of a "virtual" cohort using the national VA health information system SO MEDICAL CARE LA English DT Article DE cohort studies; databases; HIV; information systems; validation studies; veterans ID HUMAN-IMMUNODEFICIENCY-VIRUS; ADMINISTRATIVE DATA; MEDICAID CLAIMS; DRUG-USERS; VETERANS; AIDS; SCHIZOPHRENIA; MORTALITY; HOSPITALIZATION; BENEFICIARIES AB Background: The VA's integrated electronic medical record makes it possible to create a "virtual" cohort of veterans with and without HIV infection to monitor trends in utilization, toxicity, and outcomes. Objectives: We sought to develop a virtual cohort of HIV-infected veterans by adapting an existing algorithm, verifying this algorithm against independent clinical data, and finally identifying demographically-similar HIV-uninfected comparators. Research Design: Subjects were identified from VA administrative data in fiscal years 1998-2003 using a modified existing algorithm, then linked with Immunology Case Registry (ICR, the VA's HIV registry) and Pharmacy Benefits Management (centralized database of outpatient prescriptions) to verify accuracy of identification. The algorithm was modified to maximize positive predictive value (PPV) against ICR. Finally, 2 HIV-uninfected comparators were matched to each HIV-infected subject. Results: Using a single HIV code, 30,564 subjects were identified (positive predictive value 69%). Modification to require > 1 outpatient or I inpatient code improved the positive predictive value to 88%. The lack of confirmatory laboratory and pharmacy data for the majority of subjects with a single outpatient code also supported this change. Of subjects identified with the modified algorithm, 89% had confirmatory evidence. When the modified algorithm was applied to fiscal years 1997-2004, 33,420 HIV-infected subjects were identified. Two HIV-uninfected comparators were matched to each subject for an overall cohort sample of 100,260. Conclusions: In the HAART era, HIV-related codes are sufficient for identifying HIV-infected subjects from administrative data when patients with a single outpatient code are excluded. A large cohort of HIV-infected subjects and matched comparators can be identified from existing VA administrative datasets. C1 VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. Yale Univ, Sch Med, New Haven, CT USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Qual Management Publ Hlth, VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Emory Univ, Sch Med, Atlanta, GA USA. NIAAA, NIH, Bethesda, MD USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. RP Justice, AC (reprint author), VA Connecticut Healthcare Syst, Bldg 35A,Room 2-212 11 ACSLG,950 Campbell Ave, West Haven, CT 06516 USA. EM amy.justice2@va.gov FU NIA NIH HHS [K08 AG00826]; PHS HHS [U01-13566] NR 27 TC 101 Z9 102 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 2006 VL 44 IS 8 SU 2 BP S25 EP S30 DI 10.1097/01.mlr.0000223670.00890.74 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 069IB UT WOS:000239438500004 PM 16849965 ER PT J AU Gordon, AJ McGinnis, KA Conigliaro, J Rodriguez-Barradas, MC Rabeneck, L Justice, AC AF Gordon, Adam J. McGinnis, Kathleen A. Conigliaro, Joseph Rodriguez-Barradas, Maria C. Rabeneck, Linda Justice, Amy C. CA VACS 3 Project Team TI Associations between alcohol use and homelessness with healthcare utilization among human immunodeficiency virus-infected veterans SO MEDICAL CARE LA English DT Article DE homelessness; HIV; alcoholism and addictive behavior; utilization ID URBAN HOMELESS; UNITED-STATES; SERVICES UTILIZATION; PROTEASE INHIBITORS; SHELTER UTILIZATION; HOUSING STATUS; HIV-INFECTION; MENTAL-HEALTH; AGING COHORT; RISK-FACTORS AB Background: Alcohol use is a frequent root cause of homelessness, and both homelessness and alcohol use influence the quality and quantity of interactions with health care providers. Objective: The objectives of this study are to compare rates of homelessness and alcohol use in a cohort of human immunodeficiency virus (HIV)-infected persons and to evaluate the influence of homelessness and alcohol use on utilization of health services. Research Design and Measures: Data were obtained from the Veterans Aging Cohort 3-Site Study, a cohort study of 881 HIV-infected veterans at 3 VA hospitals. In a baseline survey, we assessed current and past history of homelessness and levels of alcohol consumption. Health care service utilization (ambulatory visits, emergency room visits, and hospital admissions) for the preceding 6 months was determined by self-report and VA administrative records. Logistic regression was used to assess whether homelessness and drinking variables were associated with health care visits in the past 6 months. Results: Among HIV-infected veterans with complete data (n = 839), 62 (7%) were currently homeless, and 212 (25.3%) had a past, but not current, history of homelessness. Among the currently homeless, 36% reported alcohol consumption, 34% were hazardous drinkers, 46% were binge drinkers, and 26% had a diagnosis of alcohol abuse. When adjusting for age, severity of HIV disease, and use of illicit drugs, hazardous drinking (adjusted odds ratio [AOR] 0.68, 95% confidence interval [CI] 0.49-0.93) and current homelessness (AOR 0.56, 95% CI 0.32-0.97) were associated with less than 2 outpatient clinic visits. HIV-infected veterans who were homeless in the past were more likely to be hospitalized in the prior 6 months than those never homeless (AOR 1.51, 95% CI 1.07-2.11). Conclusions: Although homeless HIV-infected veterans tend to use inpatient services more than nonhomeless HIV infected veterans, they were less likely to achieve optimum outpatient care. Alcohol use complicates the effect of homelessness on adherence to outpatient care and is associated with increased inpatient utilization among HIV-infected veterans. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA USA. Univ Kentucky, Albert B Chandler Med Ctr, Lexington, KY 40536 USA. Houston VA Med Ctr, Houston, TX USA. Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada. Yale Univ, VA Connecticut Healthcare Syst, New Haven, CT USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 28,Mailcode 151-C,Univ Dr C, Pittsburgh, PA 15240 USA. EM adam.gordon@va.gov FU NIA NIH HHS [K23 AG00826-03]; NIAAA NIH HHS [U01 AA13566-02] NR 39 TC 17 Z9 17 U1 3 U2 4 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 AUG PY 2006 VL 44 IS 8 SU 2 BP S37 EP S43 DI 10.1097/01.mlr.0000223705.00175.3d PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 069IB UT WOS:000239438500006 PM 16849967 ER PT J AU Justice, AC Dombrowski, E Conigliaro, J Fultz, SL Gibson, D Madenwald, T Goulet, J Simberkoff, M Butt, AA Rimland, D Rodriguez-Barradas, MC Gibert, CL Oursler, KAK Brown, S Leaf, DA Goetz, MB Bryant, K AF Justice, Amy C. Dombrowski, Elizabeth Conigliaro, Joseph Fultz, Shawn L. Gibson, Deborah Madenwald, Tamra Goulet, Joseph Simberkoff, Michael Butt, Adeel A. Rimland, David Rodriguez-Barradas, Maria C. Gibert, Cynthia L. Oursler, Kris Ann K. Brown, Sheldon Leaf, David A. Goetz, Matthew B. Bryant, Kendall TI Veterans Aging Cohort Study (VACS) - Overview and description SO MEDICAL CARE LA English DT Article DE HIV/AIDS; alcohol; aging veterans; data management/research design ID MITOCHONDRIAL ASPARTATE-AMINOTRANSFERASE; PRIMARY-CARE; PSYCHOMETRIC PROPERTIES; ALCOHOL-CONSUMPTION; REPORTED ADHERENCE; CLINICAL-TRIALS; DISORDERS; AFFAIRS; RELIABILITY; VALIDATION AB Background: The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study. Objectives: We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample. Research Design: We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection. Measures: Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA "paperless" electronic medical record system. Results: More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age-race-site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control. Conclusions: VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions. C1 VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. Yale Univ, Sch Med, Sect Gen Med, New Haven, CT USA. Yale Univ, Sch Med, Dept Internal Med, Program Aging, New Haven, CT 06510 USA. Univ Kentucky, Med Ctr, Lexington, KY USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NYU, Sch Med, New York, NY USA. VA New York Harbor Healthcare Syst, New York, NY USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Emory Univ, Sch Med, Atlanta, GA USA. VA Med Ctr, Atlanta, GA USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey VAMC, Houston, TX USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. VA Med Ctr, Washington, DC USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Baltimore VA Med Ctr, Baltimore, MD USA. Bronx Vet Adm Med Ctr, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NIAAA, HIV AIDS Res, Rockville, MD 20852 USA. RP Justice, AC (reprint author), VA Connecticut Healthcare Syst, Bldg 35A,Room 212,950 Campbell Ave 11-ACLSG, West Haven, CT 06516 USA. EM amy.justice2@va.gov FU NIA NIH HHS [K23 AG024896, K23 AG024896-01A2]; NIAAA NIH HHS [U01 AA 13566, U01 AA013566] NR 43 TC 121 Z9 121 U1 2 U2 6 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 AUG PY 2006 VL 44 IS 8 SU 2 BP S13 EP S24 DI 10.1097/01.mlr.0000223741.02074.66 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 069IB UT WOS:000239438500003 PM 16849964 ER PT J AU Justice, AC Lasky, E McGinnis, KA Skanderson, M Conigliaro, J Fultz, SL Crothers, K Rabeneck, L Rodriguez-Barradas, M Weissman, SB Bryant, K AF Justice, Amy C. Lasky, Elaine McGinnis, Kathleen A. Skanderson, Melissa Conigliaro, Joseph Fultz, Shawn L. Crothers, Kristina Rabeneck, Linda Rodriguez-Barradas, Maria Weissman, Sharon B. Bryant, Kendall CA VACS 3 Project Team TI Medical disease and alcohol use among veterans with human immunodeficiency infection - A comparison of disease measurement strategies SO MEDICAL CARE LA English DT Article DE alcohol; HIV; comorbid disease; ICD-9 codes; chart review ID CANCER THERAPY; HIV-INFECTION; ADMINISTRATIVE DATA; USE DISORDERS; AGING COHORT; PRIMARY-CARE; EPIDEMIOLOGY; CONSUMPTION; OUTCOMES; TIME AB Background: Many people with human immunodeficiency (HIV) infection drink alcohol. We asked whether level of exposure to alcohol is associated with medical disease in a linear,or nonlinear manner, whether the association depends upon the proximity of alcohol use, and whether it varies by source used to measure disease (chart review vs. ICD-9 Diagnostic Codes). Methods: The Veterans Aging 3 Site Cohort Study (VACS 3) enrolled 881 veterans, 86% of all HIV-positive patients seen, at 3 VA sites from June 23, 1999, to July 28, 2000. To maximize the sensitivity for alcohol exposure, alcohol use was measured combining data from patient self-report, chart review, and ICD-9 codes. We assigned the greatest exposure level reported from any source. Alcohol use within the past 12 months was considered current. Data on comorbid and AIDS-defining medical diseases were collected via chart review and ICD-9 diagnostic codes. The association of alcohol use (level and timing) and disease was modeled only for diseases demonstrating >= 10% prevalence. Linearity was compared with nonlinearity of association using nested multivariate models and the likelihood ratio test. All multivariate models were adjusted for age, CD4 cell count, viral load, intravenous drug use, exercise, and smoking. Results: Of 881 subjects enrolled, 866 (98%) had sufficient data for multivariate analyses, and 876 (99%) had sufficient data for comparison of chart review with ICD-9 Diagnostic Codes. Of the 866, 42 (5%) were lifetime abstainers; 247 (29%) were past drinkers; and 577 (671/6) were current users. Among the 824 reporting past or current alcohol use, 341 (41%) drank in moderation, 192 (23%) drank hazardously, and 291 (35%) carried a diagnosis of abuse or dependence. ICD-9 codes showed limited sensitivity, but overall agreement with chart review was good for 15 of 20 diseases (kappa > 0.4). The following diseases demonstrated a >= 10% prevalence with both measures (hepatitis C, hypertension, diabetes, obstructive lung disease, candidiasis, and bacterial pneumonia). All of these were associated with alcohol use (P < 0.05). Hepatitis C, hypertension, obstructive lung disease, candidiasis, and bacterial pneumonia demonstrated linear associations with level of alcohol use (P < 0.03). Past alcohol use increased the risk of hepatitis C and diabetes after adjustment for level of exposure (P < 0.01). With the exception of candidiasis, the associations between level and timing of alcohol use were similar when measured by ICD-9 codes or by chart review. Conclusions: Past and current use of alcohol is common among those with HIV infection. Estimates of disease risk associated with alcohol use based upon ICD-9 Diagnostic Codes appear similar to those based upon chart review. After adjustment for level of alcohol exposure, past use is associated with similar (or higher) prevalence of disease as among current drinkers. Finally, level of alcohol use is linearly associated with medical disease. We find no evidence of a "safe" level of consumption among those with HIV infection. C1 VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. Yale Univ, Sch Med, Sect Gen Med, New Haven, CT USA. Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Kentucky, Med Ctr, Lexington, KY USA. Univ Toronto, Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey VAMC, Houston, TX USA. Hosp St Raphael, Haelen Ctr, New Haven, CT USA. NIAAA, HIV AIDS Res, Bethesda, MD USA. RP Justice, AC (reprint author), VA Connecticut Healthcare Syst, Bldg 35A,Room 212,950 Campbell Ave 11-ACLSG, West Haven, CT 06516 USA. EM amy.justice2@va.gov NR 45 TC 92 Z9 95 U1 2 U2 4 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 AUG PY 2006 VL 44 IS 8 SU 2 BP S52 EP S60 DI 10.1097/01.mlr.0000228003.08925.8c PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 069IB UT WOS:000239438500008 PM 16849969 ER PT J AU Kraemer, KL McGinnis, KA Skanderson, M Cook, R Gordon, A Conigliaro, J Shen, YJ Fiellin, DA Justice, AC AF Kraemer, Kevin L. McGinnis, Kathleen A. Skanderson, Melissa Cook, Robert Gordon, Adam Conigliaro, Joseph Shen, Yujing Fiellin, David A. Justice, Amy C. TI Alcohol problems and health care services use in human immunodeficiency virus (HIV)-infected and HIV-uninfected veterans SO MEDICAL CARE LA English DT Article DE alcohol; drinking; HIV disease/AIDS; health services; utilization ID SUBSTANCE-ABUSE TREATMENT; AGING COHORT 3-SITE; UNITED-STATES; MEDICAL-CARE; PROBLEM DRINKING; EMERGENCY-ROOM; COST; INFECTION; ORGANIZATION; DISORDERS AB Background: Although alcohol problems are common in human immunodeficiency virus (HIV)-infected patients, their impact on health care services use in HIV-infected patients is not well understood. Objective: We sought to examine the association between alcohol problems and health care services use in HIV-infected and HIV-uninfected patients. Design, Setting, and Subjects: We undertook a prospective analysis of 16,048 HIV-infected veterans and 32,096 age-, race-, gender-, and region-matched HIV-uninfected controls identified through the national Veterans Affairs electronic administrative medical record database. We identified subjects with alcohol problems using ICD-9-CM codes for alcohol diagnoses and/or alcohol-related complications. Main Outcome Measures: We measured outpatient visits, emergency department visits, and inpatient hospitalizations over 12 months of follow-up. Results: In adjusted analyses, HIV-infected veterans with alcohol problems were significantly more likely than HIV-uninfected veterans without alcohol problems to have at least I outpatient visit and at least I inpatient hospitalization and, among those with any health services use, to have significantly greater rates for outpatient visits (Incidence rate ratio [IRR] 2.17; 95% confidence interval [CI] 2.06-2.28; P < 0.001), emergency department visits (IRR 1.46; 95% CI 1.35-1.58; P < 0.001), and inpatient hospitalizations (IRR 1.46; 95% CI 1.30-1.64; P < 0.001). The incidence rates for outpatient visits, mental health visits, emergency department visits, and inpatient hospitalizations were significantly higher in HIV-infected veterans with alcohol problems than in HIV-infected veterans without alcohol problems. We did not find a consistent interaction effect between alcohol problems and HIV status. Conclusion: Alcohol problems are associated with greater outpatient, emergency department, and inpatient healthcare utilization in HIV-infected and HIV-uninfected veterans. However alcohol does not appear to have a stronger effect on health services use in HIV-infected veterans compared with HIV-uninfected veterans. C1 Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Vet Aging Cohort Study Ctr, Pittsburgh, PA USA. Univ Kentucky, Med Ctr, Lexington, KY USA. Lexington VA Med Ctr, Lexington, KY USA. Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. Yale Univ, Sch Med, Div Gen Internal Med, New Haven, CT USA. W Haven VA Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, West Haven, CT USA. RP Kraemer, KL (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM kraemerkl@upmc.edu FU NIAAA NIH HHS [U01 AA 13566] NR 31 TC 24 Z9 24 U1 5 U2 6 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 AUG PY 2006 VL 44 IS 8 SU 2 BP S44 EP S51 DI 10.1097/01.mlr.0000223703.91275.78 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 069IB UT WOS:000239438500007 PM 16849968 ER PT J AU Wright, SM Levine, RB Beasley, B Haidet, P Gress, TW Caccamese, S Brady, D Marwaha, A Kern, DE AF Wright, Scott M. Levine, Rachel B. Beasley, Brent Haidet, Paul Gress, Todd W. Caccamese, Suzanne Brady, Donald Marwaha, Ajay Kern, David E. TI Personal growth and its correlates during residency training SO MEDICAL EDUCATION LA English DT Article DE multicentre study [publication type]; internship and residency, organisation & administration; education, medical, undergraduate, organisation & administration; staff development; United States; cross-sectional studies; questionnaires ID SELF-AWARENESS; MEDICAL RESIDENCY; PATIENT-CARE; PHYSICIANS; STRESS; INTERNSHIP; ERRORS AB OBJECTIVES To explore the characteristics of and factors associated with personal growth during residency training. METHODS In 2003, 359 house officers on 7 internal medicine residency training programmes in the USA were surveyed about their training experiences and issues related to their personal growth. Factor analysis and internal reliability testing were used to develop a 'personal growth scale'. Logistic regression models were then used to identify independent associations between individual variables and 'high' versus 'low' personal growth scores. RESULTS A total of 281 house officers (80%) responded. The personal growth scale had a Cronbach's alpha of 0.81. Factors that were independently associated with achieving high amounts of personal growth during residency training included: agreeing that reflection is important during residency training (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.1-7.4); being male (OR 2.6, 95% CI 1.4-4.5); being non-white (OR 2.2, 95% CI 1.3-3.9); having a strong desire to develop personally and professionally (OR 2.2, 95% CI 1.1-4.1), and feeling highly supported by one's programme director (OR 2.1, 95% CI 1.2-3.9). Independent predictors of scoring below the median on the personal growth scale included feeling emotionally isolated at work (OR 0.4, 95% CI 0.2-0.7) and noting that negative or disappointing experiences had been powerful (OR 0.4, 95% CI 0.2-0.9). CONCLUSIONS Disparate amounts of personal growth occur among trainees during residency training. Residency programmes interested in promoting personal growth among their trainees may wish to focus on modifiable factors that are associated with personal growth, such as fostering supportive relationships and encouraging reflection. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Div Gen Internal Med, Baltimore, MD 21224 USA. Univ Missouri, Dept Med, Kansas City, MO 64110 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Marshall Univ, Dept Med, Huntington, WV USA. Greater Baltimore Med Ctr, Baltimore, MD USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. York Hosp, York, PA USA. RP Wright, SM (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Div Gen Internal Med, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM smwright@jhmi.edu NR 32 TC 19 Z9 19 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0308-0110 J9 MED EDUC JI Med. Educ. PD AUG PY 2006 VL 40 IS 8 BP 737 EP 745 DI 10.1111/j.1365-2929.2006.02499.x PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 067XI UT WOS:000239335500005 PM 16869918 ER PT J AU Yoshida, H Svoboda, AC Orton, CG AF Yoshida, Hiro Svoboda, Albert C., Jr. Orton, Colin G. TI Within the next five years CT colonography will make conventional colonoscopy obsolete for colon cancer screening SO MEDICAL PHYSICS LA English DT Editorial Material ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; TO-BACK COLONOSCOPIES; COLORECTAL-CANCER; VIRTUAL COLONOSCOPY; MISS RATES; POLYPS; POPULATION; CHALLENGES; CAD C1 Massachusetts Gen Hosp, Image Anal Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Sansum Diabet Res Inst, Santa Barbara, CA 93105 USA. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, Image Anal Lab, Boston, MA 02114 USA. EM Yoshida.Hiro@mgh.harvard.edu; asvoboda@earthlink.net NR 23 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2006 VL 33 IS 8 BP 2679 EP 2682 DI 10.1118/1.2189710 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 074ZZ UT WOS:000239852800001 PM 16964844 ER PT J AU Coolens, C Evans, PM Seco, J Webb, S Blackall, JM Rietzel, E Chen, GTY AF Coolens, Catherine Evans, Phil M. Seco, Joao Webb, Steve Blackall, Jane M. Rietzel, Eike Chen, George T. Y. TI The susceptibility of IMRT dose distributions to intrafraction organ motion: An investigation into smoothing filters derived from four dimensional computed tomography data SO MEDICAL PHYSICS LA English DT Article DE IMRT; organ motion; deformable image registration; treatment uncertainty ID INTENSITY-MODULATED BEAMS; INDUCED LIVER-DISEASE; RESPIRATORY MOTION; HEPATOCELLULAR-CARCINOMA; CONFORMAL RADIOTHERAPY; DELIVERY; IMAGES; CT; CONSTRAINTS; ULTRASOUND AB This study investigated the sensitivity of static planning of intensity-modulated beams (IMBs) to intrafraction deformable organ motion and assessed whether smoothing of the IMBs at the treatment-planning stage can reduce this sensitivity. The study was performed with a 4D computed tomography (CT) data set for an IMRT treatment of a patient with liver cancer. Fluence profiles obtained from inverse-planning calculations on a standard reference CT scan were redelivered on a CT scan from the 4D data set at a different part of the breathing cycle. The use of a nonrigid registration model on the 4D data set additionally enabled detailed analysis of the overall intrafraction motion effects on the IMRT delivery during free breathing. Smoothing filters were then applied to the beam profiles within the optimization process to investigate whether this could reduce the sensitivity of IMBs to intrafraction organ motion. In addition, optimal fluence profiles from calculations on each individual phase of the breathing cycle were averaged to mimic the convolution of a static dose distribution with a motion probability kernel and assess its usefulness. Results from nonrigid registrations of the CT scan data showed a maximum liver motion of 7 mm in superior-inferior direction for this patient. Dose-volume histogram (DVH) comparison indicated a systematic shift when planning treatment on a motion-frozen, standard CT scan but delivering over a full breathing cycle. The ratio of the dose to 50% of the normal liver to 50% of the planning target volume (PTV) changed up to 28% between different phases. Smoothing beam profiles with a median-window filter did not overcome the substantial shift in dose due to a difference in breathing phase between planning and delivery of treatment. Averaging of optimal beam profiles at different phases of the breathing cycle mainly resulted in an increase in dose to the organs at risk (OAR) and did not seem beneficial to compensate for organ motion compared with using a large margin. Additionally, the results emphasized the need for 4D CT scans when aiming to reduce the internal margin (IM). Using only a single planning scan introduces a systematic shift in the dose distribution during delivery. Smoothing beam profiles either based on a single scan or over the different breathing phases was not beneficial for reducing this shift. (C) 2006 American Association of Physicists in Medicine. C1 Inst Canc Res, Joint Dept Phys, Surrey SM2 5PT, England. Royal Marsden NHS Fdn Trust, Surrey SM2 5PT, England. UCL, Dept Comp Sci, Ctr Med Image Comp, London WC1E 6BT, England. Massachusetts Gen Hosp, Radiotherapy Grp, Boston, MA 02114 USA. RP Coolens, C (reprint author), Royal Marsden NHS Fdn Trust, Dept Phys, Fulham Rd, London SW3 6JJ, England. EM catherine.coolens@icr.ac.uk RI Evans, Philip/A-6257-2009; Seco, Joao/J-4451-2012 NR 31 TC 16 Z9 16 U1 1 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2006 VL 33 IS 8 BP 2809 EP 2818 DI 10.1118/1.2219329 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 074ZZ UT WOS:000239852800015 PM 16964857 ER PT J AU Howlett, KF Sakamoto, K Yu, HY Goodyear, LJ Hargreaves, M AF Howlett, Kirsten F. Sakamoto, Kei Yu, Haiyan Goodyear, Laurie J. Hargreaves, Mark TI Insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID KINASE-ACTIVITY; IN-VIVO; PHOSPHOINOSITIDE 3-KINASE; GLUCOSE-TRANSPORT; TIME-COURSE; IRS-2; MICE; SENSITIVITY; DISRUPTION; METABOLISM AB Exercise increases skeletal muscle insulin action but the underlying mechanisms mediating this are equivocal. In mouse skeletal muscle, prior exercise enhances insulin-stimulated insulin receptor substrate-2 (IRS-2) signaling (Diabetes 2002;51:479-83), but it is unknown if this also occurs in humans. Hyperinsulinemic-euglycemic clamps were performed on 7 untrained males at rest and immediately after 60 minutes of cycling exercise at similar to 75% V-O2peak- Muscle biopsies were obtained at basal, immediately after exercise, and at 30 and 120 minutes of hyperinsulinemia. Insulin infusion increased (P < .05) insulin receptor tyrosine phosphorylation similarly in both the rest and exercise trials. Under resting conditions, insulin infusion resulted in a small, but non-statistically significant increase in IRS-2-associated phosphatidylinositol 3 (PI 3)-kinase activity over basal levels. Exercise per se decreased (P < .05) IRS-2-associated PI 3-kinase activity. After exercise, insulin-stimulated IRS-2-associated PI 3-kinase activity tended to increase at 30 minutes and further increased (P < .05) at 120 minutes when compared with the resting trial. Insulin increased (P < .05) Akt Ser(473) and GSK-3 alpha/beta Ser(21)/Ser(9) phosphorylation in both trials, with the response tending to be higher in the exercise trial. In conclusion, in the immediate period after an acute bout of exercise, insulin-stimulated IRS-2 signaling is enhanced in human skeletal muscle. (c) 2006 Elsevier Inc. All rights reserved. C1 Deakin Univ, Sch Exercise & Nutr Sci, Ctr Phys Activ & Nutr, Burwood, Vic 3125, Australia. Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Melbourne, Dept Physiol, Parkville, Vic 3010, Australia. RP Howlett, KF (reprint author), Deakin Univ, Sch Exercise & Nutr Sci, Ctr Phys Activ & Nutr, Burwood, Vic 3125, Australia. EM kirsten.howlett@deakin.edu.au OI Hargreaves, Mark/0000-0002-3694-5335; Howlett, Kirsten/0000-0002-8571-4867 FU NIAMS NIH HHS [AR45670, AR42238] NR 32 TC 28 Z9 31 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2006 VL 55 IS 8 BP 1046 EP 1052 DI 10.1016/j.metabol.2006.03.016 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 067GG UT WOS:000239289300010 PM 16839840 ER PT J AU Clancy, CJ Nguyen, MH Alandoerffer, R Cheng, SJ Iczkowski, K Richardson, M Graybil, JR AF Clancy, Cornelius J. Nguyen, M. Hong Alandoerffer, Ruth Cheng, Shaoji Iczkowski, Kenneth Richardson, Malcolm Graybil, John R. TI Cryptococcus neoformans var. grubii isolates recovered from persons with AIDS demonstrate a wide range of virulence during murine meningoencephalitis that correlates with the expression of certain virulence factors SO MICROBIOLOGY-SGM LA English DT Article ID CAPSULE-ASSOCIATED GENE; PHOSPHOLIPASE-ACTIVITY; HUMAN MONOCYTES; IN-VITRO; STRAINS; MICE; POLYSACCHARIDE; SECRETION; INFECTION; MELANIN AB Cryptococcus neoformans is a common cause of meningoencephalitis among AIDS patients. Several C. neoformans virulence factors have been identified, but the relative importance of particular factors is unknown. This study examined the corrrelation of the virulence of 18 C. neoformans var. grubii isolates from AIDS patients with the expression of several well-described virulence factors. The LD50 at 15 days after intracranial inoculation of ICR mice was < 100 c.f.u. for 22% of isolates, 100-1000 for 28 %, 1000-10000 for 11 % and > 20 000 for 39 %. Higher cryptococcal concentrations in brains were noted for isolates with lower LD50 (P= 0(.)002). In survival studies, no immunocompetent BALB/c mice (nul-) infected with 3 x LD50 of three virulent isolates (LD50 = 62, 99, 1280) survived beyond 23 days, whereas 100 %, 90 % and 90 % of mice infected with 20 000 c.f.u. of three hypovinulent isolates (LD50 > 20 000) survived for 60 days (P < 0(.)0001). Even among BALB/c nude (nu/nu) mice, survival rates over 60 days were 100%, 70%and 50%, respectively, for the hypovirulent isolates. Growth rate at 37 degrees C and capsule size within brains correlated with LD50 by univariate (P=0(.)0001 and 0(.)028, respectively) and multivariate (P= 0(.)017 and 0(.)016, respectively) analyses. There was no correlation between LD50 and capsule size in vitro, phospholipase activity, melanin formation, proteinase activity and fluconazole MIC. In conclusion, AIDS patients are susceptible to infection by C. neoformans isolates of wide-ranging virulence, including isolates that are markedly hypovirulent. The virulence of a given isolate reflects a composite of factors rather than the contribution of a dominant factor. Growth at 37 degrees C and capsule size in vivo make particularly important contributions. C1 VA Med Ctr, Gainesville, FL USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32611 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Univ Florida, Coll Med, Dept Med, Div Infect Dis, Gainesville, FL 32611 USA. RP Clancy, CJ (reprint author), Univ Florida, Coll Med, Dept Med, Div Infect Dis, Gainesville, FL 32611 USA. EM clancyn@medicine.ufl.edu OI Richardson, Malcolm/0000-0001-5672-9552 NR 53 TC 21 Z9 21 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD AUG PY 2006 VL 152 BP 2247 EP 2255 DI 10.1099/mic.0.28798-0 PN 8 PG 9 WC Microbiology SC Microbiology GA 074PF UT WOS:000239823600006 PM 16849791 ER PT J AU Ogino, S Brahmandam, M Kawasaki, T Kirkner, GJ Loda, M Fuchs, CS AF Ogino, Shuji Brahmandam, Mohan Kawasaki, Takako Kirkner, Gregory J. Loda, Massimo Fuchs, Charles S. TI Epigenetic profiling of synchronous colorectal neoplasias by quantitative DNA methylation analysis SO MODERN PATHOLOGY LA English DT Article DE colon cancer; adenoma; epigenetics; methyLight; hypermethylation; CIMP ID CPG ISLAND HYPERMETHYLATION; COLON-CANCER; PROMOTER HYPERMETHYLATION; PHENOTYPE; CARCINOMAS; MUTATIONS; TUMORS; METHYLTRANSFERASE; ADENOCARCINOMA; TUMORIGENESIS AB Transcriptional inactivation of tumor-suppressor genes by promoter CpG island methylation is thought to be an important mechanism in human carcinogenesis. The CpG island methylator phenotype (CIMP) with extensive promoter methylation appears to be a distinct epigenetic subtype of colorectal carcinoma. Most previous studies on CpG island methylation in colorectal carcinoma used methylation-specific PCR, which may detect low levels of DNA methylation with little or no biological significance. In contrast, quantitative DNA methylation assays have been shown to provide useful information beyond that which can be achieved with methylation-specific PCR. Synchronous neoplasias provide a unique model for investigators to examine molecular alterations in multistep tumorigenesis within one individual. However, no study to date has quantified DNA methylation of CIMP-specific promoters in synchronous colorectal neoplasias. Utilizing real-time PCR (MethyLight), we quantified DNA methylation in five CIMP-specific gene promoters [CACNA1G (calcium channel, voltage-dependent, T type alpha-1G subunit), CDKN2A (p16/INK4A), CRABP1 (cellular retinoic acid binding protein-1), MLH1 and NEUROG1 ( neurogenin 1)] and MGMT in six synchronous carcinoma pairs (12 carcinomas) and eight synchronous carcinoma and adenoma pairs (16 tumors). We found that while some synchronous tumor pairs showed discordant promoter methylation patterns, other tumor pairs showed similar, but not exactly identical, patterns of promoter methylation. All but two pairs showed concordant patterns of CIMP status (CIMP positive vs CIMP negative) (P = 0.05 in cancer pairs). BRAF mutations were present in only CIMP-positive tumors. A high degree of microsatellite instability (MSI-H) was observed in both CIMP-positive and CIMP-negative tumors. KRAS mutations were not concordant in any synchronous neoplasia pair. In conclusion, epigenetic alterations at CIMP-specific promoter CpG islands in synchronous colorectal neoplasias likely have both random and nonrandom components. C1 Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, 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. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075-13, P01 CA87969-03] NR 34 TC 24 Z9 26 U1 0 U2 3 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 AUG PY 2006 VL 19 IS 8 BP 1083 EP 1090 DI 10.1038/modpathol.3800618 PG 8 WC Pathology SC Pathology GA 066AF UT WOS:000239200900008 PM 16699497 ER PT J AU Colvin, RA Campanella, GSV Manice, LA Luster, AD AF Colvin, Richard A. Campanella, Gabriele S. V. Manice, Lindsay A. Luster, Andrew D. TI CXCR3 requires tyrosine sulfation for ligand binding and a second extracellular loop arginine residue for ligand-induced chemotaxis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR3; CELL-ALPHA-CHEMOATTRACTANT; BOWEL ALLOGRAFT-REJECTION; IFN-INDUCIBLE PROTEIN-10; T-CELLS; DIFFERENTIAL EXPRESSION; AMINO-TERMINUS; MOLECULAR CHARACTERIZATION; MULTIPLE-SCLEROSIS; HIV-1 ENTRY AB CXCR3 is a G-protein-coupled seven-transmembrane domain chemokine receptor that plays an important role in effector T-cell and NK cell trafficking. Three gamma interferon-inducible chemokines activate CXCR3: CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-TAC). Here, we identify extracellular domains of CXCR3 that are required for ligand binding and activation. We found that CXCR3 is sulfated on its N terminus and that sulfation is required for binding and activation by all three ligands. We also found that the proximal 16 amino acid residues of the N terminus are required for CXCL10 and CXCL11 binding and activation but not CXCL9 activation. In addition, we found that residue 8216 in the second extracellular loop is required for CXCR3-mediated chemotaxis and calcium mobilization but is not required for ligand binding or ligand-induced CXCR3 internalization. Finally, charged residues in the extracellular loops contribute to the receptor-ligand interaction. These findings demonstrate that chemokine activation of CXCR3 involves both high-affinity ligand-binding interactions with negatively charged residues in the extracellular domains of CXCR3 and a lower-affinity receptor-activating interaction in the second extracellular loop. This lower-affinity interaction is necessary to induce chemotaxis but not ligand-induced CXCR3 internalization, further suggesting that different domains of CXCR3 mediate distinct functions. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, 149 13th St,Room 8031, Charlestown, MA 02129 USA. EM aluster@partners.org FU NCI NIH HHS [R01 CA069212, R01 CA69212]; NIAID NIH HHS [K08 AI50147]; NIDDK NIH HHS [R01 DK07449, P01 DK050305, P01 DK50305, T32 DK007449] NR 50 TC 72 Z9 74 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2006 VL 26 IS 15 BP 5838 EP 5849 DI 10.1128/MCB.00556-06 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 067FG UT WOS:000239286600025 PM 16847335 ER PT J AU Ishida-Takahashi, R Rosario, F Gong, YS Kopp, K Stancheva, Z Chen, XH Feener, EP Myers, MG AF Ishida-Takahashi, Ryoko Rosario, Felicia Gong, Yusong Kopp, Keely Stancheva, Zlatina Chen, Xiaohong Feener, Edward P. Myers, Martin G., Jr. TI Phosphorylation of Jak2 on Ser(523) inhibits Jak2-dependent leptin receptor signaling (vol 26, pg 4063, 2006) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Ishida-Takahashi, R (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2006 VL 26 IS 16 BP 6309 EP 6309 DI 10.1128/MCB.01147-06 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 072PK UT WOS:000239685100034 ER PT J AU Law, B Quinti, L Choi, YD Weissleder, R Tung, CH AF Law, Benedict Quinti, Luisa Choi, Yongdoo Weissleder, Ralph Tung, Ching-Hsuan TI A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CELL-PENETRATING PEPTIDES; DELIVERY; APOPTOSIS AB A potent cytotoxic peptide (r7-kla) was synthesized by incorporating a mitochondrial membrane disrupting peptide, kla (klaklakklaklak), with a cell-penetrating domain, r7 (rrrrrrr). The IC50 of r7-kla (3.54 +/- 0.11 mu mol/L) was more than two orders of magnitude lower than that of kla. r7-kla induced cell death in both in vitro and in vivo environments, and showed rapid kinetics. Within minutes, the morphologic changes in cells and mitochondrial leakage were apparent by microscopy and was consistent with rapid apoptosis. Our results suggested that r7-kla is an apoptosis inducer and can be potentially used as an antitumor agent, especially when combined with the appropriate systemic delivery systems. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01 CA99385] NR 21 TC 57 Z9 58 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2006 VL 5 IS 8 BP 1944 EP 1949 DI 10.1158/1535-7163.MCT-05-0509 PG 6 WC Oncology SC Oncology GA 077KY UT WOS:000240029400006 PM 16928814 ER PT J AU Yuan, QA Simmons, HH Robinson, MK Russeva, M Marasco, WA Adams, GP AF Yuan, Qing-an Simmons, Heidi H. Robinson, Matthew K. Russeva, Maria Marasco, Wayne A. Adams, Gregory P. TI Development of engineered antibodies specific for the Mullerian inhibiting substance type II receptor: a promising candidate for targeted therapy of ovarian cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID IN-VIVO; MONOCLONAL-ANTIBODIES; SEXUAL DEVELOPMENT; CELL-GROWTH; HORMONE; EXPRESSION; DUCT; PHAGE; VITRO; MICE AB The Mullerian inhibiting substance type II receptor (MISIIR) is involved in Mullerian duct regression as part of the development of the male reproductive system. In adult females, MISIIR is present on ovarian surface epithelium and is frequently expressed on human epithelial ovarian cancer cells. Mullerian inhibiting substance has been found to be capable of inhibiting the growth of primary human ovarian cancer cells derived from ascites and ovarian cancer cell lines. This suggested to us that MISIIR could be an attractive target for antibody-based tumor targeting and growth inhibition strategies. Here, we describe the production of recombinant human MISIIR extracellular domain-human immunoglobulin Fc domain fusion proteins and their use as targets for the selection of MISIIR-specific human single-chain variable fragments (scFv) molecules from a human nonimmune scFv phage display library. The binding kinetics of the resulting anti-MISIIR scFv clones were characterized and two were employed as the basis for the construction of bivalent scFv:Fc antibody-based molecules. Both bound specifically to human ovarian carcinoma cells in flow cytometry assays and cross-reacted with mouse MISIIR. These results indicate that antibody-based constructs may provide a highly specific means of targeting MISIIR on human ovarian carcinoma cells for the purpose of diagnosing and treating this disease. C1 Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Ctr, Boston, MA USA. RP Adams, GP (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM gp_adams@fccc.edu FU NCI NIH HHS [P50 CA083638] NR 57 TC 16 Z9 19 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2006 VL 5 IS 8 BP 2096 EP 2105 DI 10.1158/1535-7163.MCT-06-0115 PG 10 WC Oncology SC Oncology GA 077KY UT WOS:000240029400023 PM 16928831 ER PT J AU Kudva, IT Krastins, B Sheng, HQ Griffin, RW Sarracino, DA Tarr, PI Hovde, CJ Calderwood, SB John, M AF Kudva, Indira T. Krastins, Bryan Sheng, Haiqing Griffin, Robert W. Sarracino, David A. Tarr, Phillip I. Hovde, Carolyn J. Calderwood, Stephen B. John, Manohar TI Proteomics-based expression library screening (PELS) - A novel method for rapidly defining microbial immunoproteomes SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID ESCHERICHIA-COLI O157-H7; INDUCED ANTIGEN TECHNOLOGY; GENOME SEQUENCE; IDENTIFICATION; INFECTION; ADHERENCE; PROTEINS; VACCINE; IHA AB Current methodologies for global identification of microbial proteins that elicit host humoral immune responses have several limitations and are not ideally suited for use in the postgenomic era. Here we describe a novel application of proteomics, proteomics-based expression library screening, to rapidly define microbial immunoproteomes. Proteomics-based expression library screening is broadly applicable to any cultivable, sequenced pathogen eliciting host antibody responses and hence is ideal for rapidly mining microbial proteomes for targets with diagnostic, prophylactic, and therapeutic potential. In this report, we demonstrate "proof-of-principle" by identifying 207 proteins of the Escherichia coli O157:H7 immunome in bovine reservoirs in only 3 weeks. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02114 USA. Harvard Univ, Partners Ctr Genet & Genom, Cambridge, MA 02139 USA. Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83844 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. RP John, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM mjohn1@partners.org FU NCRR NIH HHS [P20-RR16454, P20-RR15587]; NIAID NIH HHS [R21 AI055963-02, U54-AI57141, R21-AI055963, R21 AI055963]; NICHD NIH HHS [N01-HD03309]; NIDDK NIH HHS [R01 DK052081-10, R01 DK052081, R01-DK52081] NR 21 TC 10 Z9 12 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2006 VL 5 IS 8 BP 1514 EP 1519 DI 10.1074/mcp.T600013-MCP200 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 071UB UT WOS:000239627800013 PM 16737953 ER PT J AU Carroll, JS Brown, M AF Carroll, Jason S. Brown, Myles TI Estrogen receptor target gene: An evolving concept SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID BREAST-CANCER-CELLS; DIFFERENTIALLY EXPRESSED GENES; MYC ONCOGENE EXPRESSION; RESPONSE ELEMENTS; C-MYC; CHROMATIN IMMUNOPRECIPITATION; TRANSCRIPTIONAL REGULATION; PATHWAY ACTIVATION; ANDROGEN RECEPTOR; REGULATED GENE AB Estrogen receptor ( ER) functions as a transcription factor to induce gene expression events sufficient for cell division and breast cancer progression. A significant body of work exists on the identification of ER gene targets and the cofactors that contribute to these transcription events, yet surprisingly little is known of the cis-regulatory elements involved. In this review, we investigate the advances in technology that contribute to a comprehensive understanding of ER target genes and explore recent work identifying cis-regulatory domains that augment transcription of these targets. Specifically, we find that ER association with gene targets results from an association with the pioneer factor FoxA1, responsible for recruitment of ER to the genome. Recruitment of ER to the genome does not occur at promoter proximal regions, but instead involves distal enhancer elements that function to tether the ER complex to the target gene promoters. These advances in technology permit a more detailed investigation of ER activity and may aid in the development of superior drug interventions. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol & Cellular Oncol,Dept Med Oncol, Boston, MA 02115 USA. RP Brown, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol & Cellular Oncol,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 NR 70 TC 153 Z9 166 U1 1 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 2006 VL 20 IS 8 BP 1707 EP 1714 DI 10.1210/me.2005-0334 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 067CC UT WOS:000239277700001 PM 16396959 ER PT J AU Carney, SA Chen, J Burns, CG Xiong, KM Peterson, RE Heideman, W AF Carney, Sara A. Chen, Jing Burns, C. Geoffrey Xiong, Kong M. Peterson, Richard E. Heideman, Warren TI Aryl hydrocarbon receptor activation produces heart-specific transcriptional and toxic responses in developing zebrafish SO MOLECULAR PHARMACOLOGY LA English DT Article ID EARLY LIFE STAGES; CHICK-EMBRYO; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TOXICITY; DEFICIENT MICE; DEVELOPMENTAL TOXICITY; INTRACELLULAR CALCIUM; NUCLEAR TRANSLOCATOR; CIRCULATION FAILURE; MICROARRAY ANALYSIS; GENE-EXPRESSION AB Proper regulation of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, is required for normal vertebrate cardiovascular development. AHR hyperactivation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during zebrafish (Danio rerio) development results in altered heart morphology and function, culminating in death. To identify genes that may cause cardiac toxicity, we analyzed the transcriptional response to TCDD in zebrafish hearts. Zebrafish larvae were exposed to TCDD for 1 h at 72 h after fertilization (hpf), and the hearts were extracted for microarray analysis at 1, 2, 4, and 12 h after exposure (73, 74, 76, and 84 h postfertilization). The remaining body tissue was also collected at each time for comparison. TCDD rapidly induced expression in 42 genes within 1 to 2 h of exposure. These genes function in xenobiotic metabolism, proliferation, heart contractility, and pathways that regulate heart development. Furthermore, these expression changes preceded signs of cardiovascular toxicity, characterized by decreased stroke volume, peripheral blood flow, and a halt in heart growth. This identifies strong candidates for important AHR target genes. It is noteworthy that the TCDD-induced transcriptional response in the hearts of zebrafish larvae was substantially different from that induced in the rest of the body tissues. One of the biggest differences included a cluster of genes that were down-regulated 12 h after exposure in heart tissue, but not in the body samples. More than 70% of the transcripts in this heart-specific cluster promote cellular growth and proliferation. Thus, the developing heart stands out as being responsive to TCDD at both the level of toxicity and gene expression. C1 Univ Wisconsin, Sch Pharm, Mol & Environm Toxicol Program, Madison, WI 53705 USA. Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Heideman, W (reprint author), Univ Wisconsin, Sch Pharm, Mol & Environm Toxicol Program, 5111 Rennebohm Hall,777 Highland Ave, Madison, WI 53705 USA. EM wheidema@wisc.edu RI Chen, Jing/D-7353-2011 FU NIA NIH HHS [K01 AG023562]; NIEHS NIH HHS [R01-ES012716, T32-ES07015] NR 65 TC 90 Z9 97 U1 0 U2 13 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 2006 VL 70 IS 2 BP 549 EP 561 DI 10.1124/mol.106.025304 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 064VM UT WOS:000239117900016 PM 16714409 ER PT J AU Shugart, YY Samuels, J Willour, VL Grados, MA D Greenberg, B Knowles, JA T McCracken, J Rauch, SL Murphy, DL Wang, Y Pinto, A Fyer, AJ Piacentini, J Pauls, DL Cullen, B Page, J Rasmussen, SA Bienvenu, OJ Hoehn-Saric, R Valle, D Liang, KY Riddle, MA Nestadt, G AF Shugart, Y. Y. Samuels, J. Willour, V. L. Grados, M. A. D Greenberg, B. Knowles, J. A. T McCracken, J. Rauch, S. L. Murphy, D. L. Wang, Y. Pinto, A. Fyer, A. J. Piacentini, J. Pauls, D. L. Cullen, B. Page, J. Rasmussen, S. A. Bienvenu, O. J. Hoehn-Saric, R. Valle, D. Liang, K. -Y Riddle, M. A. Nestadt, G. TI Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q SO MOLECULAR PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; genome-wide scan; covariate based linkage analysis; simulation; age of onset ID COMPLEX SEGREGATION ANALYSIS; GENOTYPING ERRORS; FAMILY; ADOLESCENTS; STATISTICS; RATIONALE; GENETICS; CHILDREN; PROBANDS; HISTORY AB Obsessive-compulsive disorder (OCD) is the tenth most disabling medical condition worldwide. Twin and family studies implicate a genetic etiology for this disorder, although specific genes have yet to be identified. Here, we present the first large-scale model-free linkage analysis of both extended and nuclear families using both 'broad' (definite and probable diagnoses) and 'narrow' (definite only) definitions of OCD. We conducted a genome-scan analysis of 219 families collected as part of the OCD Collaborative Genetics Study. Suggestive linkage signals were revealed by multipoint analysis on chromosomes 3q27-28 (P = 0.0003), 6q (P = 0.003), 7p (P = 0.001), 1q (P = 0.003), and 15q (P = 0.006). Using the 'broad' OCD definition, we observed the strongest evidence for linkage on chromosome 3q27-28. The maximum overall Kong and Cox LODall score (2.67) occurred at D3S1262 and D3S2398, and simulation based P-values for these two signals were 0.0003 and 0.0004, respectively, although for both signals, the simulation-based genome-wide significance levels were 0.055. Covariate-linkage analyses implicated a possible role of gene(s) on chromosome 1 in increasing the risk for an earlier onset form of OCD. We are currently pursuing fine mapping in the five regions giving suggestive signals, with a particular focus on 3q27-28. Given probable etiologic heterogeneity in OCD, mapping gene(s) involved in the disorder may be enhanced by replication studies, large-scale family-based linkage studies, and the application of novel statistical methods. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21287 USA. Univ Bristol, Dept Social Med, Bristol, Avon, England. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21287 USA. Kennedy Krieger Inst, Baltimore, MD USA. Brown Univ, Sch Med, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Behav Sci & Pediat, Baltimore, MD USA. RP Shugart, YY (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21287 USA. EM yyao@jhsph.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NCRR NIH HHS [RR 00052]; NIMH NIH HHS [7K23MH066284, K23-MH64543, R01 MH50214] NR 36 TC 84 Z9 87 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD AUG PY 2006 VL 11 IS 8 BP 763 EP 770 DI 10.1038/sj.mp.4001847 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 067NL UT WOS:000239309800009 PM 16755275 ER PT J AU Wiviott, SD Cannon, CP AF Wiviott, Stephen D. Cannon, Christopher P. TI Update on lipid-lowering therapy and LDL-cholesterol targets SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Review DE acute coronary syndrome; cholesterol; HMG-CoA reductase inhibitors; LDL; lipid lowering ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; LOW-DENSITY-LIPOPROTEIN; PLACEBO-CONTROLLED TRIAL; INTENSIVE STATIN THERAPY; HIGH BLOOD CHOLESTEROL; C-REACTIVE PROTEIN; NCEP EXPERT PANEL; HMG-COA REDUCTASE; TO-Z TRIAL AB Serum cholesterol has long been recognized as an important risk factor for the development and progression of atherosclerotic vascular disease. For more than 30 years, improved outcomes with lipid lowering have been demonstrated. As a result of these data, the National Heart, Lung, and Blood Institute (NHLBI) convened the National Cholesterol Education Program-Adult Treatment Panel I (NCEP ATP I). This panel and similar ones around the world have served to set the standards for lipid lowering in clinical practice. Subsequent revisions of these standards (NCEP ATP II and III) have led to greater focus being placed on LDL, and targets for lowering LDL levels being based on patients' risk of subsequent coronary disease events. Since the publication of the NCEP ATP III guidelines, several large-scale clinical trials of cholesterol lowering have been conducted, the findings of which have the potential to impact on clinical practice standards. In this article we focus on current guidelines for lipid-lowering therapy, review the results and implications of important completed clinical trials, and consider the utility of additional targets for preventive therapy, such as C-reactive protein and HDL. We also consider the prospects for treatments in development and future goals. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. RP Wiviott, SD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div,TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 57 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD AUG PY 2006 VL 3 IS 8 BP 424 EP 436 DI 10.1038/ncpcardio0613 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 067ZD UT WOS:000239340400010 PM 16874355 ER PT J AU Selvaggi, K Abrahm, J AF Selvaggi, Kathy Abrahm, Janet TI Metastatic spinal cord compression: the hidden danger SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Article DE metastatic melanoma; pain; palliative care; spinal cord compression ID CANCER PAIN; PREVALENCE; TUMOR AB Background A 47-year-old male underwent resection of a left-shoulder melanoma in 1997. In November 2004 he was found to have multiple brain lesions and adrenal, lung, and bone metastases, and in January 2005 underwent resection of his symptomatic right parietal lobe lesion and subsequent whole-brain radiation. In February 2005 he experienced headaches and word-finding difficulty and was found to have four progressive brain lesions on MRI. These were resistant to conventional radiotherapy and were treated with stereotactic radiosurgery. The patient later developed an obstruction of the jejunum and underwent resection of multiple abdominal masses. In April 2005, the patient commenced temozolomide and underwent radiation therapy to the left arm for pain thought to be caused by an increase in size of his melanoma metastasis. In August 2005 the patient reported persistent and worsening arm pain, despite a further course of radiotherapy in June 2005. Investigations Physical examination including a thorough neurological examination, radiography, X-ray, CT scan, and MRI. Diagnosis Metastatic melanoma to the cervical spine (C7 vertebra) with spinal cord compression. Management Involved field radiotherapy, temozolomide, opioids, gabapentin, corticosteroids, and Cyberknife(R) therapy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Abrahm, J (reprint author), Dana Farber Canc Inst, 44 Binney St SW 420, Boston, MA 02115 USA. EM jabrahm@partners.org NR 16 TC 4 Z9 4 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD AUG PY 2006 VL 3 IS 8 BP 458 EP 461 DI 10.1038/ncponc0561 PG 4 WC Oncology SC Oncology GA 067ZK UT WOS:000239341100012 PM 16894391 ER PT J AU Kozak, KR Milne, GL D Morrow, J Cuiffo, BP AF Kozak, Kevin R. Milne, Ginger L. D Morrow, Jason Cuiffo, Barry P. TI Hypertrophic osteoarthropathy pathogenesis: a case highlighting the potential role for cyclo-oxygenase-2-derived prostaglandin E-2 SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Article DE clubbing; cyclo-oxygenase 2; hypertrophic osteoarthropathy; non-small-cell lung cancer; prostaglandin ID ENDOTHELIAL GROWTH-FACTOR; MAJOR URINARY METABOLITE; PULMONARY OSTEOARTHROPATHY; CYSTIC-FIBROSIS; PAMIDRONATE; PAIN; OCTREOTIDE; CANCER AB Background A 65-year-old woman presented with weakness, 9 kg weight loss, dysphagia, facial and bilateral upper-extremity swelling, and debilitating, bilateral lower-extremity pain. The patient had undergone a right upper lobectomy for a 5 mm, poorly differentiated adenocarcinoma of the lung 4 years previously. Medical history included chronic obstructive pulmonary disease (emphysema), hypertension, cerebrovascular disease and multinodular goiter. Surgical history included a right carotid endarterectomy. The patient's history was remarkable for 50+ pack-years of smoking. Investigations Physical examination, comprehensive metabolic panel and complete blood counts, CT, bone scintigraphy, quantification of urinary 11 alpha-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (also known as PGE-M). Diagnosis Recurrent non-small-cell lung cancer with adrenal metastasis, hypertrophic osteoarthropathy associated with non-small-cell lung cancer, and hyperprostaglandinuria. Management Rofecoxib 25 mg daily for hypertrophic osteoarthropathy, palliative external-beam radiation (44 Gy in 22 fractions) for mediastinal mass, palliative external-beam radiation (30 Gy in 12 fractions), followed 2 years later with radiofrequency ablation, for left adrenal metastasis. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Radiat Oncol Program, Boston, MA 02114 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Brockton Hosp, Brockton, MA USA. RP Kozak, KR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Radiat Oncol Program, 100 Blossom St,COX-3, Boston, MA 02114 USA. EM kkozak@partners.org RI Milne, Ginger/D-7648-2014 OI Milne, Ginger/0000-0003-3890-151X FU NCI NIH HHS [CA77839]; NCRR NIH HHS [RR00095]; NIDDK NIH HHS [DK48831]; NIGMS NIH HHS [GM15431] NR 20 TC 21 Z9 21 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD AUG PY 2006 VL 2 IS 8 BP 452 EP 456 DI 10.1038/ncprheum0252 PG 5 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 067YT UT WOS:000239339400011 PM 16932737 ER PT J AU Hu, H Wang, B Borde, M Nardone, J Maika, S Allred, L Tucker, PW Rao, A AF Hu, Hui Wang, Bin Borde, Madhuri Nardone, Julie Maika, Shan Allred, Laura Tucker, Philip W. Rao, Anjana TI Foxp1 is an essential transcriptional regulator of B cell development SO NATURE IMMUNOLOGY LA English DT Article ID COORDINATE REGULATION; V(D)J RECOMBINATION; HEAVY-CHAIN; BONE-MARROW; IG-BETA; GENE; EXPRESSION; DIFFERENTIATION; MOUSE; E2A AB Forkhead transcription factors are key participants in development and immune regulation. Here we demonstrate that absence of the gene encoding the forkhead transcription factor Foxp1 resulted in a profound defect in early B cell development. Foxp1 deficiency was associated with decreased expression of all B lineage genes in B220(+) fetal liver cells as well as with a block in the transition from pro-B cell to pre-B cell involving diminished expression of recombination-activating genes 1 and 2. Foxp1 bound to the Erag enhancer and was involved in controlling variable-(diversity)-joining recombination of the gene encoding immunoglobulin heavy chain in a B cell lineage - specific way. Our results identify Foxp1 as an essential participant in the transcriptional regulatory network of B lymphopoiesis. C1 Harvard Univ, Sch Med, CBRI Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. Univ Texas, Dept Mol Genet, Austin, TX 78712 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. RP Hu, H (reprint author), Harvard Univ, Sch Med, CBRI Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. EM hu@cbr.med.harvard.edu; arao@cbr.med.harvard.edu FU NCI NIH HHS [CA31534, CA42471, CA92318]; NHLBI NIH HHS [HL071160]; NIAID NIH HHS [AI44432, AI48213] NR 54 TC 177 Z9 186 U1 0 U2 5 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 AUG PY 2006 VL 7 IS 8 BP 819 EP 826 DI 10.1038/ni1358 PG 8 WC Immunology SC Immunology GA 065GH UT WOS:000239147200017 PM 16819554 ER PT J AU Pearce, G Angeli, V Randolph, GJ Junt, T von Andrian, U Schnittler, HJ Jessberger, R AF Pearce, Glen Angeli, Veronique Randolph, Gwendalyn J. Junt, Tobias von Andrian, Ulrich Schnittler, Hans-Joachim Jessberger, Rolf TI Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs SO NATURE IMMUNOLOGY LA English DT Article ID TRANSENDOTHELIAL MIGRATION; LEUKOCYTE FUNCTION; LYMPHOCYTES; NODES; NEUTROPHILS; CHEMOKINES; ADHESION; ACTIN; ACTIVATION; POLARITY AB The migration of B cells into secondary lymphoid organs is required for the generation of an effective immune response. Here we analyzed the involvement of SWAP-70, a Rac-interacting protein involved in actin rearrangement, in B cell entry into lymph nodes. We noted reduced migration of Swap70(-/-) B cells into lymph nodes in vivo. Swap70(-/-) B cells rolled and adhered, yet accumulated in lymph node high endothelial venules. This defect was not due to impaired integrin expression or chemotaxis. Instead, Swap70(-/-) B cells aberrantly regulated integrin-mediated adhesion. During attachment, Swap70(-/-) B cells showed defective polarization and did not form uropods or stabilize lamellipodia at a defined region. Thus, SWAP-70 selectively regulates processes essential for B cell entry into lymph nodes. C1 Tech Univ Dresden, Inst Physiol Chem, D-01307 Dresden, Germany. CUNY Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Tech Univ Dresden, Inst Physiol, D-01307 Dresden, Germany. RP Jessberger, R (reprint author), Tech Univ Dresden, Inst Physiol Chem, D-01307 Dresden, Germany. EM rolf.jessberger@tu-dresden.de RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL056949]; NIAID NIH HHS [AI49470] NR 47 TC 51 Z9 51 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 AUG PY 2006 VL 7 IS 8 BP 827 EP 834 DI 10.1038/ni1365 PG 8 WC Immunology SC Immunology GA 065GH UT WOS:000239147200018 PM 16845395 ER PT J AU Phan, UT T Waldron, T Springer, TA AF Phan, Uyen T. T Waldron, Travis Springer, Timothy A. TI Remodeling of the lectin-EGF-like domain interface in P- and L-selectin increases adhesiveness and shear resistance under hydrodynamic force SO NATURE IMMUNOLOGY LA English DT Article ID CELL-ADHESION; LIGAND RECOGNITION; LYMPHOCYTE RECIRCULATION; GLYCOPROTEIN LIGAND-1; LEUKOCYTE EMIGRATION; S128R POLYMORPHISM; CYTOPLASMIC DOMAIN; TRAFFIC SIGNALS; FLOW; RECEPTOR AB Crystal structures of the lectin and epidermal growth factor (EGF)-like domains of P-selectin show 'bent' and 'extended' conformations. An extended conformation would be 'favored' by forces exerted on a selectin bound at one end to a ligand and at the other end to a cell experiencing hydrodynamic drag forces. To determine whether the extended conformation has higher affinity for ligand, we introduced an N-glycosylation site to 'wedge open' the interface between the lectin and EGF-like domains of P-selectin. This alteration increased the affinity of P-selectin for its ligand P-selectin glycoprotein 1 (PSGL-1) and thereby the strength of P-selectin-mediated rolling adhesion. Similarly, an asparagine-to-glycine substitution in the lectin-EGF-like domain interface of L-selectin enhanced rolling adhesion under shear flow. Our results demonstrate that force, by 'favoring' an extended selectin conformation, can strengthen selectin-ligand bonds. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu FU NHLBI NIH HHS [HL-48675, P01 HL048675]; NIAID NIH HHS [F32 AI052851]; NIGMS NIH HHS [F32 GM073529] NR 50 TC 85 Z9 91 U1 0 U2 5 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 AUG PY 2006 VL 7 IS 8 BP 883 EP 889 DI 10.1038/ni1366 PG 7 WC Immunology SC Immunology GA 065GH UT WOS:000239147200025 PM 16845394 ER PT J AU Kerkela, R Grazette, L Yacobi, R Iliescu, C Patten, R Beahm, C Walters, B Shevtsov, S Pesant, S Clubb, FJ Rosenzweig, A Salomon, RN Van Etten, RA Alroy, J Durand, JB Force, T AF Kerkela, Risto Grazette, Luanda Yacobi, Rinat Iliescu, Cezar Patten, Richard Beahm, Cara Walters, Brian Shevtsov, Sergei Pesant, Stephanie Clubb, Fred J. Rosenzweig, Anthony Salomon, Robert N. Van Etten, Richard A. Alroy, Joseph Durand, Jean-Bernard Force, Thomas TI Cardiotoxicity of the cancer therapeutic agent imatinib mesylate SO NATURE MEDICINE LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; ABL TYROSINE KINASE; CHRONIC MYELOGENOUS LEUKEMIA; HER2-POSITIVE BREAST-CANCER; UNFOLDED PROTEIN RESPONSE; CHRONIC MYELOID-LEUKEMIA; NEURONAL CELL-DEATH; N-TERMINAL KINASE; C-ABL; ADJUVANT CHEMOTHERAPY AB Imatinib mesylate (Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia. Here we report ten individuals who developed severe congestive heart failure while on imatinib and we show that imatinib-treated mice develop left ventricular contractile dysfunction. Transmission electron micrographs from humans and mice treated with imatinib show mitochondrial abnormalities and accumulation of membrane whorls in both vacuoles and the sarco-(endo-) plasmic reticulum, findings suggestive of a toxic myopathy. With imatinib treatment, cardiomyocytes in culture show activation of the endoplasmic reticulum (ER) stress response, collapse of the mitochondrial membrane potential, release of cytochrome c into the cytosol, reduction in cellular ATP content and cell death. Retroviral gene transfer of an imatinib-resistant mutant of c-Abl, alleviation of ER stress or inhibition of Jun amino-terminal kinases, which are activated as a consequence of ER stress, largely rescues cardiomyocytes from imatinib-induced death. Thus, cardiotoxicity is an unanticipated side effect of inhibition of c-Abl by imatinib. C1 Thomas Jefferson Univ, Jefferson Med Coll, Ctr Translat Med, Philadelphia, PA 19107 USA. Tufts Univ, New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, Houston, TX 77030 USA. Texas Heart Inst, Dept Cardiovasc Pathol, Houston, TX 77030 USA. Tufts Univ, Cummings Sch Vet Med, North Grafton, MA 01536 USA. RP Force, T (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Ctr Translat Med, 1025 Walnut St, Philadelphia, PA 19107 USA. EM thomas.force@jefferson.edu OI Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [HL67371] NR 49 TC 656 Z9 686 U1 3 U2 34 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2006 VL 12 IS 8 BP 908 EP 916 DI 10.1038/nm1446 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 071TS UT WOS:000239626200021 PM 16862153 ER PT J AU Engelman, JA Luo, J Cantley, LC AF Engelman, Jeffrey A. Luo, Ji Cantley, Lewis C. TI The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism SO NATURE REVIEWS GENETICS LA English DT Review ID TUMOR-SUPPRESSOR GENE; SQUAMOUS-CELL CARCINOMA; SEVERE INSULIN-RESISTANCE; MAMMARY EPITHELIAL-CELLS; LYSOSOME-LIKE VACUOLE; PHOSPHOINOSITIDE 3-KINASE; PROTEIN-KINASE; PIK3CA GENE; PROSTATE-CANCER; SKELETAL-MUSCLE AB Phosphatidylinositol 3-kinases (PI3Ks) evolved from a single enzyme that regulates vesicle trafficking in unicellular eukaryotes into a family of enzymes that regulate cellular metabolism and growth in multicellular organisms. In this review, we examine how the PI3K pathway has evolved to control these fundamental processes, and how this pathway is in turn regulated by intricate feedback and crosstalk mechanisms. In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases. C1 Harvard Univ, Sch Dent Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Dent Med, Dept Syst Biol, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 166 TC 1435 Z9 1479 U1 20 U2 149 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD AUG PY 2006 VL 7 IS 8 BP 606 EP 619 DI 10.1038/nrg1879 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 064VR UT WOS:000239118400013 PM 16847462 ER PT J AU Phoon, RKS Kitching, AR Luster, AD Holdsworth, SR AF Phoon, R. K. S. Kitching, A. R. Luster, A. D. Holdsworth, S. R. TI INTRINSIC RENAL CELL PRODUCTION OF IFN-GAMMA-INDUCIBLE PROTEIN-10 (IP-10, CXCL10) NEGATIVELY REGULATES THE DEVELOPMENT OF EXPERIMENTAL CRESCENTIC GLOMERULONEPHRITIS SO NEPHROLOGY LA English DT Meeting Abstract C1 [Phoon, R. K. S.; Kitching, A. R.; Holdsworth, S. R.] Monash Univ, Clayton, Vic 3800, Australia. [Luster, A. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD AUG PY 2006 VL 11 SU 2 BP A2 EP A2 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27ZZ UT WOS:000208652400006 ER PT J AU Imam, SZ Karahalil, B Hogue, BA Souza-Pinto, NC Bohr, VA AF Imam, SZ Karahalil, B Hogue, BA Souza-Pinto, NC Bohr, VA TI Mitochondrial and nuclear DNA-repair capacity of various brain regions in mouse is altered in an age-dependent manner SO NEUROBIOLOGY OF AGING LA English DT Article DE DNA repair; glycosylases; mitochondria; aging; neurodegeneration ID OXIDATIVE DAMAGE; ALZHEIMERS-DISEASE; AGING BRAIN; LYASE ACTIVITY; STRESS; GLYCOSYLASES; RESTRICTION; INCREASES; CHEMISTRY; DELETIONS AB Aging is associated with increased susceptibility to neuronal loss and disruption of cerebral function either as a component of senescence, or as a consequence of neurodegenerative disease or stroke. Here we report differential changes in the repair of oxidative DNA damage in various brain regions during aging. We evaluated mitochondrial and nuclear incision activities of oxoguanine DNA glycosylase (OGG1), uracil DNA glycosylase (UDG) and the endonuclease Ill homologue (NTH1) in the caudate nucleus (CN), frontal cortex (FC), hippocampus (Hip), cerebellum (CE) and brain stem (BS) of 6- and 18-month-old male C5781/6 mice. We observed a significant age-dependent decrease in incision activities of all three glycosylases in the mitochondria of all brain regions, whereas variable patterns of changes were seen in nuclei. No age- or region-specific changes were observed in the mitochondrial repair synthesis incorporation of uracil-initiated base-excision repair (BER). We did not observe any age or region dependent differences in levels of BER proteins among the five brain regions. In summary, our data suggest that a decreased efficiency of mitochondrial BER-glycosylases and increased oxidative damage to mitochondrial DNA might contribute to the normal aging process. These data provide a novel characterization of oxidative DNA damage processing in different brain regions implicated in various neurodegenerative disorders, and suggest that this process is regulated in an age-dependent manner. Manipulation of DNA repair mechanisms may provide a strategy to prevent neuronal loss during age-dependent neurodegenerative disorders. (c) 2005 Elsevier Inc. All rights reserved. C1 NIA, Gerontol Res Ctr, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Gazi Univ, Fac Pharm, Dept Toxicol, TR-06330 Ankara, Turkey. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. RP Bohr, VA (reprint author), NIA, Gerontol Res Ctr, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 34 TC 110 Z9 113 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD AUG PY 2006 VL 27 IS 8 BP 1129 EP 1136 DI 10.1016/j.neurobiolaging.2005.06.002 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 057YV UT WOS:000238632000011 PM 16005114 ER PT J AU Mendez, MF McMurtray, A Licht, E Shapira, JS Saul, RE Miller, BL AF Mendez, Mario F. McMurtray, Aaron Licht, Eliot Shapira, Jill S. Saul, Ronald E. Miller, Bruce L. TI The scale for emotional blunting in patients with frontotemporal dementia SO NEUROCASE LA English DT Article ID ALZHEIMERS-DISEASE; PICKS-DISEASE; CLINICAL-FEATURES; TEMPORAL VARIANTS; PREFRONTAL CORTEX; WORK GROUP; CRITERIA; DEGENERATION; DIAGNOSIS; CONSENSUS AB Emotional blunting may underlie many of the behavioral features of frontotemporal dementia (FTD). The Scale for Emotional Blunting (SEB) was evaluated in 12 patients with early FTD, 12 patients with Alzheimer's disease (AD), and 12 normal controls. There were overall group differences on the SEB, and the FTD patients had greater emotional blunting than the AD patients. The SEB had good inter-rater reliability and a sensitivity of 92%, and a specificity of 83.5% for FTD. These findings suggest that the SEB may be a good instrument for the early detection and quantification of emotional blunting in patient with FTD. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit, 691-116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU NIA NIH HHS [AG19724-01, P01 AG019724] NR 31 TC 10 Z9 12 U1 4 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PD AUG PY 2006 VL 12 IS 4 BP 242 EP 246 DI 10.1080/13554790600910375 PG 5 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 087NS UT WOS:000240749700008 PM 17000595 ER PT J AU Han, X Jovicich, J Salat, D van der Kouwe, A Quinn, B Czanner, S Busa, E Pacheco, J Albert, M Killiany, R Maguire, P Rosas, D Makris, N Dale, A Dickerson, B Fischl, B AF Han, Xiao Jovicich, Jorge Salat, David van der Kouwe, Andre Quinn, Brian Czanner, Silvester Busa, Evelina Pacheco, Jenni Albert, Marilyn Killiany, Ronald Maguire, Paul Rosas, Diana Makris, Nikos Dale, Anders Dickerson, Bradford Fischl, Bruce TI Reliability of MRI-derived measurements of human cerebral cortical thickness: The effects of field strength, scanner upgrade and manufacturer SO NEUROIMAGE LA English DT Article DE cortical thickness; structural MRI; cerebral cortex; morphology ID MAGNETIC-RESONANCE IMAGES; GRAY-MATTER LOSS; ALZHEIMERS-DISEASE; BRAIN SEGMENTATION; COORDINATE SYSTEM; CORTEX; SURFACE; SCHIZOPHRENIA; ATROPHY; HETEROGENEITY AB In vivo MRI-derived measurements of human cerebral cortex thickness are providing novel insights into normal and abnormal neuroanatomy, but little is known about their reliability. We investigated how the reliability of cortical thickness measurements is affected by MRI instrument-related factors, including scanner field strength, manufacturer, upgrade and pulse sequence. Several data processing factors were also studied. Two test-retest data sets were analyzed: 1) 15 healthy older subjects scanned four times at 2-week intervals on three scanners; 2) 5 subjects scanned before and after a major scanner upgrade. Within-scanner variability of global cortical thickness measurements was < 0.03 mm, and the point-wise standard deviation of measurement error was approximately 0.12 mm. Variability was 0.15 mm and 0.17 mm in average, respectively, for cross-scanner (Siemens/GE) and cross-field strength (1.5 T/3 T) comparisons. Scanner upgrade did not increase variability nor introduce bias. Measurements across field strength, however, were slightly biased (thicker at 3 T). The number of (single vs. multiple averaged) acquisitions had a negligible effect on reliability, but the use of a different pulse sequence had a larger impact, as did different parameters employed in data processing. Sample size estimates indicate that regional cortical thickness difference of 0.2 min between two different groups could be identified with as few as 7 subjects per group, and a difference of 0.1 min could be detected with 26 subjects per group. These results demonstrate that MRI-derived cortical thickness measures are highly reliable when MRI instrument and data processing factors are controlled but that it is important to consider these factors in the design of multi-site or longitudinal studies, such as clinical drug trials. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02129 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21288 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. Pfizer Global Res & Dev, Groton, CT 06340 USA. Massachusetts Gen Hosp, Ctr Morphomet Anal, Boston, MA 02129 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. MIT, CSAIL, Cambridge, MA 02142 USA. RP Fischl, B (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM fischl@nmr.mgh.harvard.edu RI Jovicich, Jorge/D-2293-2010; Dale, Anders/A-5180-2010; OI Jovicich, Jorge/0000-0001-9504-7503 FU NCRR NIH HHS [P41 RR 14075, R01 RR 16594-01A1, U24 RR 021382]; NIA NIH HHS [K23 AG 22509, P01 AG 04953] NR 48 TC 625 Z9 629 U1 3 U2 30 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 1 PY 2006 VL 32 IS 1 BP 180 EP 194 DI 10.1016/j.neuroimage.2006.02.051 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 070NY UT WOS:000239530700020 PM 16651008 ER PT J AU Martuza, RL AF Martuza, Robert L. TI Preliminary individualized chemotherapy for malignant astrocytomas based on O-6-methylguanine-deoxyribonucleic acid methyltransferase methylation analysis - Commentary SO NEUROLOGIA MEDICO-CHIRURGICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Martuza, RL (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN NEUROSURGICAL SOC PI TOKYO PA C/O AKAMON-MAE IWATA BLDG, 5-27-8 HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0470-8105 J9 NEUROL MED-CHIR JI Neurol. Med.-Chir. PD AUG PY 2006 VL 46 IS 8 BP 394 EP 394 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 073HG UT WOS:000239733000010 ER PT J AU Kang, PB Krishnamoorthy, KS Jones, RM Shapiro, FD Darras, BT AF Kang, P. B. Krishnamoorthy, K. S. Jones, R. M. Shapiro, F. D. Darras, B. T. TI Atypical presentations of spinal muscular atrophy type III (Kugelberg-Welander disease) SO NEUROMUSCULAR DISORDERS LA English DT Article; Proceedings Paper CT 10th International Congress of the World-Muscle-Society CY SEP 28-OCT 10, 2005 CL Iguassu Falls, BRAZIL SP World Muscle Soc DE spinal muscular atrophy; Kugelberg-Welander disease; survival motor neuron; anterior horn cell; electromyography AB Spinal muscular atrophy type III (SMA III, Kugelberg-Welander disease) typically presents with symmetric proximal weakness, areflexia, and hypotonia. We present four children with spinal muscular atrophy type III who had atypical phenotypes. Three patients clearly had asymmetric weakness at presentation and two had upper motor neuron signs in the lower extremities (one patient had both features). Two of the patients had prolonged evaluations before the diagnosis was made. All patients had Gowers signs and two had pes planus. In patients with proximal muscle weakness the presence of asymmetrical weakness, upper motor neuron signs, or both, may be compatible with spinal muscular atrophy type III. The diagnosis of spinal muscular atrophy should be considered when other possibilities have been excluded. (C) 2006 Elsevier B.V. All rights reserved. C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Darras, BT (reprint author), Childrens Hosp, Dept Neurol, Fegan 11,300 Longwood Ave, Boston, MA 02115 USA. EM basil.darras@childrens.harvard.edu NR 10 TC 3 Z9 4 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD AUG PY 2006 VL 16 IS 8 BP 492 EP 494 DI 10.1016/j.nmd.2006.05.004 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 101RV UT WOS:000241759100003 PM 16797181 ER PT J AU Herbert, A Liu, CY Karamohamed, S Liu, J Manning, A Fox, CS Meigs, JB Cupples, LA AF Herbert, Alan Liu, Chunyu Karamohamed, Samer Liu, Jun Manning, Alisa Fox, Caroline S. Meigs, James B. Cupples, L. Adrienne TI BMI modifies associations of IL-6 genotypes with insulin resistance: The Framingham Study SO OBESITY LA English DT Article DE interleukin-6; insulin resistance; type 2 diabetes; genetics; epidemiology ID HOMEOSTASIS MODEL ASSESSMENT; TYPE-2 DIABETES-MELLITUS; PROMOTER POLYMORPHISM; GLUCOSE-TOLERANCE; INFLAMMATORY MARKERS; INTERLEUKIN-6; SENSITIVITY; C-174G; RISK; POPULATION AB Objective: The - 174 interleukin (IL)-6 gene polymorphism has been proposed as a risk factor for type 2 diabetes, but data are conflicting. Because white fat is a major source of IL-6 in resting individuals, we tested the hypothesis that BMI modifies the association among the IL-6 genotype, insulin resistance (IR) (measured using the homeostasis model), and risk of diabetes. Research Methods and Procedures: Outcomes were assessed in a community-based cohort study of 1525 adults (mean age, 55.6 years; 753 men), who participated in the Framingham Offspring Study during the 1991 to 1995 examinations. Results: We found a significant interaction between IL-6 genotype and BMI on levels of IR in men (p < 0.0001), with obese homozygotes for the minor C allele being most resistant. The IL-6-BMI interaction was not significant (p = 0.46) in women. Among men with the CC genotype, increasing BMI was associated with increased prevalence of diabetes [odds ratio (OR) per unit increase in BMI, 1.30; 95% confidence interval (CI), 1.11 to 1.50] but not among those with the GG (OR, 1.10; 95% Cl, 0.98 to 1.22) or GC genotype (OR, 1.05; 95% Cl, 0.97 to 1.14). Discussion: The - 174 IL-6 promoter polymorphism modifies the association of obesity with IR and diabetes risk in men. Weight loss regimens targeted at reducing the risk of diabetes may be of particular benefit for men with a - 174 IL-6 CC genotype. C1 Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study Genet Lab, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, NHLBI,Framingham Heart Study, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Gen Div, Boston, MA 02114 USA. RP Cupples, LA (reprint author), Boston Univ, Sch Med, Dept Biostat, 715 Albany St, Boston, MA 02118 USA. EM adrienne@bu.edu FU NHLBI NIH HHS [HL64753, HL076784, N01-HC-25195] NR 28 TC 24 Z9 24 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD AUG PY 2006 VL 14 IS 8 BP 1454 EP 1461 DI 10.1038/oby.2006.165 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 087OR UT WOS:000240752200020 PM 16988089 ER PT J AU Wolfberg, AJ Growdon, WB Feltmate, CM Goldstein, DR Genest, DR Chinchilla, ME Berkowitz, RS Lieberman, ES AF Wolfberg, Adam J. Growdon, Whitfield B. Feltmate, Colleen M. Goldstein, Donald R. Genest, David R. Chinchilla, Manuel E. Berkowitz, Ross S. Lieberman, Ellice S. TI Low risk of relapse after achieving undetectable hCG levels in women with partial molar pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID GESTATIONAL TROPHOBLASTIC DISEASE; PARTIAL HYDATIDIFORM MOLE; TUMORS; MANAGEMENT; DIAGNOSIS AB OBJECTIVE: We evaluated the risk of gestational trophoblastic neoplasia (GTN) for women with partial molar pregnancy whose human chorionic gonadotropin (hCG) levels fall spontaneously to undetectable levels using a sensitive hCG assay. METHODS: We analyzed data from the New England Trophoblastic Disease Center to estimate the risk of GTN among 284 women with partial molar pregnancy and at least 6 months of gonadotropin follow-up. RESULTS: None of the 238 women with complete gonadotropin follow-up and a spontaneous decline in serum hCG levels to undetectable levels subsequently developed GTN (95% confidence interval 0-1.6%). CONCLUSION: If these results are replicated at other institutions with longstanding experience managing partial molar pregnancies, it may be reasonable to abbreviate clinical follow-up for women with partial molar pregnancy whose serum hCG levels spontaneously decline to an undetectable level. C1 New England Trophoblast Dis Ctr, Trophoblast Tumor Registry, Boston, MA USA. Brigham & Womens Hosp, Div Gynecol Oncol, Div Clin & Epidemiol Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wolfberg, AJ (reprint author), 310 Waverley Ave, Newton, MA 02458 USA. EM adam.wolfberg@childrens.harvard.edu NR 15 TC 24 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 2006 VL 108 IS 2 BP 393 EP 396 DI 10.1097/01.AOG.0000227754.12848.4e PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XO UT WOS:000246768900022 PM 16880311 ER PT J AU Nadol, JB AF Nadol, Joseph B., Jr. TI Revision mastoidectomy SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID CHRONIC OTITIS-MEDIA; CANAL WALL; TYMPANOMASTOID SURGERY; ADITUS BLOCK; CHOLESTEATOMA; MANAGEMENT; FLAP AB The first three priorities in surgery for chronic otitis media are (1) the elimination of progressive disease to produce a safe and dry ear, (2) modification of the anatomy of the tympanomastoid compartment to prevent recurrent disease, and (3) reconstruction of the hearing mechanism. The indications for revision following mastoidectomy for chronic otitis media thus involve failure to achieve any of these goals, including recurrent cholesteatoma, recurrent suppuration, recurrent perforation, or recurrent or residual conductive hearing loss. The focus of this article is the management of recurrent cholesteatoma or suppuration; that is, failure to achieve either of the first two priorities. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM joseph_nadol@meei.harvard.edu NR 25 TC 14 Z9 17 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD AUG PY 2006 VL 39 IS 4 BP 723 EP + DI 10.1016/j.ote.2006.05.003 PG 20 WC Otorhinolaryngology SC Otorhinolaryngology GA 078DF UT WOS:000240080900006 PM 16895781 ER PT J AU Boseley, ME Hartnick, CJ AF Boseley, Mark E. Hartnick, Christopher J. TI Pediatric partial cricotracheal resection: A new technique for the posterior cricoid anastomosis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID PRIMARY TRACHEAL ANASTOMOSIS; SUBGLOTTIC STENOSIS; CHILDREN; LARYNGEAL; AIRWAY; RECONSTRUCTION AB OBJECTIVE: Partial cricotracheal resection has become a more popular procedure in the pediatric population as a treatment for severe subglottic stenosis. We describe a new technique for the posterior cricoid anastomosis. STUDY DESIGN AND SETTING: This is a case series of 4 pediatric patients with a Myer-Cotton grade III or IV subglottic stensosis. SETTING: Tertiary care hospital with a pediatric intensive care unit. RESULTS: All 4 patients were decannulated and there were no observed complications to include posterior mucosal dehiscence and/or recurrent laryngeal nerve injury. CONCLUSIONS: Placing sutures through the cricoid cartilage is technically less difficult than previously described techniques for treating subglottic stenosis near the undersurface of the true vocal folds and affords a more stable posterior mucosal suture line. SIGNIFICANCE: This technique provides a surgical means to treat high subglottic stenosis that closely approximates the true vocal folds by enabling a stable posterior mucosa to mucosa apposition. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 17 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 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2006 VL 135 IS 2 BP 318 EP 322 DI 10.1016/j.otohns.2006.03.022 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 074EJ UT WOS:000239795200027 PM 16890090 ER PT J AU Nicolau, T Northrop, C Eavey, T AF Nicolau, Yamileth Northrop, Clarinda Eavey, Roland TI Tuberculous otitis in infants: Temporal bone histopathology and clinical extrapolation SO OTOLOGY & NEUROTOLOGY LA English DT Article DE tuberculosis; tuberculous mastoiditis; tuberculous otitis media ID MIDDLE-EAR TUBERCULOSIS; FACIAL PALSY; MEDIA; MASTOIDITIS; OTOMASTOIDITIS; EXPERIENCE; DIAGNOSIS; CHILDREN; SURGERY; CT AB Hypothesis: The study of infant temporal bones with tuberculosis (TB) of the middle ear and mastoid could provide information to assist with clinical diagnosis in this population. Background: The TB pandemic has become a critical global public health problem. With the rising incidence of the disease, otolaryngologists might encounter an increased frequency of otologic TB. Pediatric temporal bone reports of TB are rare. Methods: Light microscopic examination was performed on both temporal bones from an infant who died as a result of miliary TB. Results: The tympanic membranes were thickened with dilated blood vessels, yet were intact without perforations. Purulence, granulation tissue, and classic tubercles were observed in the middle ears and mastoids. Serous labyrinthitis and inflammatory cells surrounding the Cranial Nerve VIII in the internal auditory canal were observed in the inner ear. Conclusion: The histological findings suggest that a clinical presentation of infantile tuberculous otitis media and mastoiditis could be a patient with otoscopic findings consistent with common otitis media with an intact tympanic membrane, likely in conjunction with inner ear symptoms. Lacking the classic finding of multiple tympanic membrane perforations, tuberculous otitis might be underappreciated in this population. C1 Harvard Univ, Sch Med, Dept Genet, Pediat Otolaryngol Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Temporal Bone Fdn, Boston, MA USA. RP Nicolau, T (reprint author), Harvard Univ, Sch Med, Dept Genet, Pediat Otolaryngol Serv, NRB-256,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ynicolau@genetics.med.harvard.edu NR 58 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD AUG PY 2006 VL 27 IS 5 BP 667 EP 671 PG 5 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 070ND UT WOS:000239528500016 ER PT J AU Takeuchi, T Minami, Y Iijima, T Kameya, T Asamura, H Noguchi, M AF Takeuchi, Tomoyo Minami, Yuko Iijima, Tatsuo Kameya, Toru Asamura, Hisao Noguchi, Masayuki TI Characteristics of loss of heterozygosity in large cell neuroendocrine carcinomas of the lung and small cell lung carcinomas SO PATHOLOGY INTERNATIONAL LA English DT Article DE 22q13.3; 3p14.2; large cell neuroendocrine carcinoma; loss of heterozygosity; small cell lung carcinoma ID GENETIC CHANGES; EARLY-STAGE; FHIT GENE; CANCER; SPECTRUM; REGIONS; 3P14.2 AB Large cell neuroendocrine carcinoma (LCNEC) of the lung is a new entity. Besides morphological characteristics, its molecular biological features have been investigated by many researchers and compared to those of other neuroendocrine carcinomas, small cell lung carcinoma (SCLC) and carcinoid tumor (CT). However, there are few reports that show the significantly different genetic characteristics between them. The purpose of the present paper was to study the frequency of loss of heterozygosity (LOH) at chromosome 3p (3p14.2) in 38 neuroendocrine carcinomas of the lung (13 LCNEC, 11 SCLC and 14 CT) and 10 large cell carcinomas (LCC). The frequencies of LOH at 3p14.2 were 69.2% in LCNEC, 81.8% in SCLC, 50.0% in LCC and 7.14% in CT. Those at 22q13.3 were 30.8% in LCNEC, 72.7% in SCLC, 45.5% in LCC and 7.14% in CT. In particular, the frequency of SCLC with LOH at both 3p14.2 and 22q13.3 (63.6%) was significantly higher than that of LCNEC (15.4%). LCNEC and SCLC had different characteristics of LOH patterns at 3p14.2 and 22q13.3. The combined analysis of the LOH at 3p14.2 and 22q13.3 is thought to be useful for differential diagnosis between LCNEC and SCLC. C1 Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Tsukuba, Ibaraki 3058575, Japan. Shizuoka Canc Ctr, Dept Pathol, Shizuoka, Japan. Natl Canc Ctr, Dept Thorac Surg, Tokyo, Japan. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Noguchi, M (reprint author), Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM nmasayuk@md.tsukuba.ac.jp NR 19 TC 7 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD AUG PY 2006 VL 56 IS 8 BP 434 EP 439 DI 10.1111/j.1440-1827.2006.01985.x PG 6 WC Pathology SC Pathology GA 061SI UT WOS:000238892300003 PM 16872437 ER PT J AU Winterkorn, EB Daouk, GH Anupindi, S Thiele, EA AF Winterkorn, Elisabeth B. Daouk, Ghaleb H. Anupindi, Sudha Thiele, Elizabeth A. TI Tuberous sclerosis complex and renal angiomyolipoma: case report and review of the literature SO PEDIATRIC NEPHROLOGY LA English DT Review DE tuberous sclerosis complex; angiomyolipoma; selective arterial embolization ID MAMMALIAN TARGET; MANAGEMENT; RAPAMYCIN; MANIFESTATIONS; PATHOGENESIS; DIAGNOSIS; PATHWAY; LESIONS; KIDNEY AB A 5-year-old boy with a known diagnosis of tuberous sclerosis complex was found to have an enlarging renal mass on routine ultrasound. He was diagnosed with an angiomyolipoma ( AML) and scheduled for close observation. Follow-up magnetic resonance imaging demonstrated the AML to be significantly enlarged and hypervascular. Selective arterial embolization of the tumor was performed, which resulted in an appropriate decrease in tumor size. Angiomyolipoma is a known and well-described complication of the tuberous sclerosis complex that is usually found among patients in their adolescent and adult years. The case presented here illustrates the need for early and repeated renal imaging of younger pediatric patients with tuberous sclerosis. Our experience adds to the literature on young pediatric patients requiring embolization for treatment of large renal angiomyolipomas. C1 Herscot Ctr Tuberous Sclerosis Complex, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat Nephrol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat Radiol, Boston, MA USA. RP Thiele, EA (reprint author), Herscot Ctr Tuberous Sclerosis Complex, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 27 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD AUG PY 2006 VL 21 IS 8 BP 1189 EP 1193 DI 10.1007/s00467-006-0133-3 PG 5 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 074NC UT WOS:000239818100022 PM 16791610 ER PT J AU Ullrich, NJ Marcus, K Pomeroy, SL Turner, CD Zimmerman, MA Lehmann, LE Scott, RM Gounmerova, L Gillan, E Kieran, MW Chi, SN AF Ullrich, Nicole J. Marcus, Karen Pomeroy, Scott L. Turner, Christopher D. Zimmerman, MaryAnn Lehmann, Leslie E. Scott, R. Michael Gounmerova, Liliana Gillan, Eileen Kieran, Mark W. Chi, Susan N. TI Transverse myelitis after therapy for primitive neuroectodermal tumors SO PEDIATRIC NEUROLOGY LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; STEM-CELL RESCUE; BONE-MARROW-TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; CERVICAL SPINAL-CORD; PEDIATRIC BRAIN-TUMORS; RADIATION MYELITIS; YOUNG-CHILDREN; CHILDHOOD; RECURRENT AB Traditional therapy for malignant primitive neuroectodermal tumors in children includes surgery, multiagent chemotherapy, and radiation. Given the poor prognosis with conventional therapy alone, newer treatment approaches have incorporated high-dose chemotherapy followed by autologous stem cell rescue. Treatment with chemotherapy and radiation is not without unanticipated and unwanted side effects. Specifically, radiation-induced damage to the central nervous system can occur, though the frequency is thought to be acceptably low. This report describes two cases of treatment-related transverse myelitis in patients who received induction chemotherapy and craniospinal irradiation followed by high-dose chemotherapy with autologous stem cell rescue. Other patients treated with a similar strategy but different sequence and timing of treatment did not experience symptoms of myelitis, suggesting that the specific timing of radiation in relationship to the chemotherapy may be of critical importance. (c) 2006 by Elsevier Inc. All rights reserved. C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Connecticut Childrens Med Ctr, Dept Pediat Hematol & Oncol, Hartford, CT USA. RP Ullrich, NJ (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM nicole.ullrich@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 31 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD AUG PY 2006 VL 35 IS 2 BP 122 EP 125 DI 10.1016/j.pediatrneurol.2006.01.013 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 072UG UT WOS:000239697900008 PM 16876009 ER PT J AU Kinane, TB Murphy, J Bass, JL Corwin, MJ AF Kinane, T. Bernard Murphy, Joan Bass, Joel L. Corwin, Michael J. TI Comparison of respiratory physiologic features when infants are placed in car safety seats or car beds SO PEDIATRICS LA English DT Article DE apnea; car seats; car beds ID PRETERM INFANTS; AIRWAY-OBSTRUCTION; OXYGEN-SATURATION; PREMATURE-INFANTS; HEALTHY INFANTS; NEWBORN-INFANTS; TRANSPORTATION; RISK; TERM AB OBJECTIVE. The objective of this study was to compare the respiratory physiologic features of healthy term infants placed in either a car bed or a car safety seat. METHODS. Within the first 1 week of life, 67 healthy term infants were recruited and assigned randomly to be monitored in either a car bed ( 33 infants) or a car safety seat ( 34 infants). Physiologic data, including oxygen saturation and frequency and type of apnea, were obtained and analyzed in a blinded manner. RESULTS. The groups spent similar amounts of time in the devices ( car bed: 71.6 minutes; car seat: 74.2 minutes). The mean oxygen saturation values were not different between the groups ( car bed: 97.1%; car seat: 97.3%). The percentages of time with oxygen saturation of < 95% were also similar for the 2 groups ( car bed: 18.3%; car seat: 11.8%). In both groups, a number of infants spent high percentages of study time with oxygen saturation of < 95%. The 6 infants with the most time at this level were all in the car safety seat group (54% - 63% of study time). Values for the 6 infants in the car bed group with the most time at this level were lower ( 20% - 42%). This difference in the duration of oxygen saturation of < 95% was not statistically significant. The mean end-tidal carbon dioxide levels and the numbers of episodes of apnea were similar for the 2 groups. CONCLUSIONS. The respiratory physiologic features of infants in the 2 car safety devices were observed to be similar. Of note, substantial periods of time with oxygen saturation of < 95% were surprisingly common in both groups. C1 Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA 02115 USA. Newton Wellesley Hosp, Dept Pediat, Boston, MA USA. Boston Univ, Sch Med, Boston Med Ctr, Dept Pediat, Boston, MA 02118 USA. RP Kinane, TB (reprint author), Massachusetts Gen Hosp Children, Pediat Pulm Unit, 55 Fruit St, Boston, MA 02114 USA. EM tkinane@partners.org OI Corwin, Michael/0000-0002-6591-209X NR 16 TC 14 Z9 14 U1 0 U2 0 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 AUG PY 2006 VL 118 IS 2 BP 522 EP 527 DI 10.1542/peds.2005-2712 PG 6 WC Pediatrics SC Pediatrics GA 069IW UT WOS:000239440600011 PM 16882803 ER PT J AU Fischer, MA Vogeli, C Stedman, M Kaushal, R Ferris, T Weissman, JS AF Fischer, Michael A. Vogeli, Christine Stedman, Margaret Kaushal, Rainu Ferris, Timothy Weissman, Joel S. TI Impact of electronic prescribing on use of generic medications SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 602 BP S280 EP S280 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200603 ER PT J AU Fischer, MA Vogeli, C Stedman, M Sands, DZ Kaushal, R Weissman, JS AF Fischer, Michael A. Vogeli, Christine Stedman, Margaret Sands, Daniel Z. Kaushal, Rainu Weissman, Joel S. TI Adoption of electronic prescribing in US community-based medical practices SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 219 BP S103 EP S103 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200220 ER PT J AU Kimmel, SE Chen, Z Price, M Parker, CS Metlay, JP Christie, JD Brensinger, CM Newcomb, CW Samaha, FF Gross, R AF Kimmel, Stephen E. Chen, Zhen Price, Maureen Parker, Catherine S. Metlay, Joshua P. Christie, Jason D. Brensinger, Colleen M. Newcomb, Craig W. Samaha, Frederick F. Gross, Robert TI The effects of adherence on anticoagulation control with warfarin SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 111 BP S52 EP S53 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200112 ER PT J AU Louik, C Lin, AE Werler, MM Hernandez-Diaz, S Mitchell, AA AF Louik, Carol Lin, Angela E. Werler, Martha M. Hernandez-Diaz, Sonia Mitchell, Allen A. TI First trimester exposure to SSRIs and the risk of birth defects SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 173 BP S81 EP S82 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200174 ER PT J AU Meropol, SB Glick, HA Asch, DA AF Meropol, Sharon B. Glick, Henry A. Asch, David A. TI Alternative strategies for diagnosis and treatment of pediatric acute otitis media SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 643 BP S299 EP S299 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200644 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 Olanzapine in the treatment of acute mania in adolescents with bipolar I disorder; A 3-week randomized double-blind placebo-controlled study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract 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 JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 648 BP S301 EP S302 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200649 ER PT J AU Faber, JJ Anderson, DF Jonker, SS Davis, LE Giraud, GD AF Faber, J. J. Anderson, D. F. Jonker, S. S. Davis, L. E. Giraud, G. D. TI Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep SO PLACENTA LA English DT Article DE fetal arterial pressure; fetal placental flow; fetal placental resistance; plasma ID BLOOD-FLOW; RESPONSES; CIRCULATION; PRESSURE AB Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515 +/- 217 (SD) ml of fluid and 93.2 +/- 12.0 g of protein. Fetal plasma protein concentrations increased from 34.2 +/- 2.3 to 77.0 +/- 9.7 g/l (P < 0.0001). Fetal arterial blood pressures rose from 42 +/- 3 to 59 +/- 4 mmHg (P < 0.01) and venous pressures rose from 2.2 +/- 0.5 to 4.8 +/- 0.8 mmHg (P < 0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627 +/- 299 ml/min and 552 +/- 221 ml/min) while fetal umbilical resistance increased from 0.077 +/- 0.038 to 0.115 +/- 0.053 mmHg min/ml (P < 0.01). On day 7, plasma renin activity had fallen from 6.7 +/- 4.2 ng/(ml/h) at preinfusion control to 0.6 +/- 0.6 ng/(ml/h) (P < 0.05) and plasma anglotensin-II concentration had fallen from 33.2 +/- 26.6 to 6.2 +/- 3.9 pg/ml, although this fall was not statistically significant (P = 0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow. C1 Oregon Hlth Sci Univ, Sch Med, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Sch Med, Dept Obstet & Gynecol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Giraud, GD (reprint author), Oregon Hlth Sci Univ, Heart Res Ctr, Sch Med, L334, Portland, OR 97239 USA. EM giraudg@ohsu.edu OI Jonker, Sonnet/0000-0002-1097-2562 FU NICHD NIH HHS [5P01-HD34430, 5R01-HD37376] NR 13 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD AUG PY 2006 VL 27 IS 8 BP 876 EP 881 DI 10.1016/j.placenta.2005.09.003 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 062XU UT WOS:000238981000012 PM 16289267 ER PT J AU Haynes, C Oldfield, CJ Ji, F Klitgord, N Cusick, ME Radivojac, P Uversky, VN Vidal, M Iakoucheva, LM AF Haynes, Chad Oldfield, Christopher J. Ji, Fei Klitgord, Niels Cusick, Michael E. Radivojac, Predrag Uversky, Vladimir N. Vidal, Marc Iakoucheva, Lilia M. TI Intrinsic disorder is a common feature of hub proteins from four eukaryotic interactomes SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID INTERACTION NETWORKS; UNSTRUCTURED PROTEINS; GENE ONTOLOGY; SACCHAROMYCES-CEREVISIAE; INTERACTION MAP; DATABASE; BINDING; RECOGNITION; PREDICTIONS; PROTEOME AB Recent proteome-wide screening approaches have provided a wealth of information about interacting proteins in various organisms. To test for a potential association between protein connectivity and the amount of predicted structural disorder, the disorder propensities of proteins with various numbers of interacting partners from four eukaryotic organisms (Caenorhabditis elegans, Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens) were investigated. The results of PONDR VL-XT disorder analysis show that for all four studied organisms, hub proteins, defined here as those that interact with >= 10 partners, are significantly more disordered than end proteins, defined here as those that interact with just one partner. The proportion of predicted disordered residues, the average disorder score, and the number of predicted disordered regions of various lengths were higher overall in hubs than in ends. A binary classification of hubs and ends into ordered and disordered subclasses using the consensus prediction method showed a significant enrichment of wholly disordered proteins and a significant depletion of wholly ordered proteins in hubs relative to ends in worm, fly, and human. The functional annotation of yeast hubs and ends using GO categories and the correlation of these annotations with disorder predictions demonstrate that proteins with regulation, transcription, and development annotations are enriched in disorder, whereas proteins with catalytic activity, transport, and membrane localization annotations are depleted in disorder. The results of this study demonstrate that intrinsic structural disorder is a distinctive and common characteristic of eukaryotic hub proteins, and that disorder may serve as a determinant of protein interactivity. C1 Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Indiana Univ, Sch Informat, Bloomington, IN USA. Russian Acad Sci, Inst Biol Instrumentat, Moscow, Russia. RP Iakoucheva, LM (reprint author), Rockefeller Univ, Lab Stat Genet, 1230 York Ave, New York, NY 10021 USA. EM lilia@rockefeller.edu RI Klitgord, Niels/B-5121-2009; Uversky, Vladimir/F-4515-2011; OI Uversky, Vladimir/0000-0002-4037-5857; Iakoucheva, Lilia/0000-0002-4542-5219 FU NCI NIH HHS [CA105405, CA112952, R33 CA105405, U54 CA112952] NR 52 TC 306 Z9 308 U1 1 U2 24 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD AUG PY 2006 VL 2 IS 8 BP 890 EP 901 AR e100 DI 10.1371/journal.pcbi.0020100 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 077DE UT WOS:000240007100005 PM 16884331 ER PT J AU Haake, DA AF Haake, David A. TI Molecular epidemiology of leptospirosis in the Amazon SO PLOS MEDICINE LA English DT Editorial Material ID PATHOGENIC LEPTOSPIRA C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. RP Haake, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. EM dhaake@ucla.edu FU NIAID NIH HHS [R01 AI034431, R21 AI034431, R01 AI034431-09, AI-34431, R29 AI034431] NR 11 TC 1 Z9 1 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD AUG PY 2006 VL 3 IS 8 BP 1214 EP 1215 AR e302 DI 10.1371/journal.pmed.0030302 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 079YG UT WOS:000240213200008 PM 16933961 ER PT J AU Goveas, JS Caroff, SN AF Goveas, Joseph S. Caroff, Stanley N. TI Post-ictal symptoms and neuroleptic malignant syndrome SO PSYCHIATRIC ANNALS LA English DT Article ID NONCONVULSIVE STATUS EPILEPTICUS; CATATONIA; EPILEPSY C1 Franciscan Skemp Healthcare Mayo Hlth Syst, Dept Psychiat, La Crosse, WI USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Inpatient Psychiat Serv, Philadelphia, PA USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2006 VL 36 IS 8 BP 530 EP 534 PG 5 WC Psychiatry SC Psychiatry GA 072UN UT WOS:000239698600003 ER PT J AU Perlick, DA Rosenheck, RA Kaczynski, R Swartz, MS Canive, JM Lieberman, JA AF Perlick, Deborah A. Rosenheck, Robert A. Kaczynski, Richard Swartz, Marvin S. Canive, Jose M. Lieberman, Jeffrey A. TI Components and correlates of family burden in schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article ID CLINICAL ANTIPSYCHOTIC TRIALS; EFFECTIVENESS CATIE PROJECT; SOCIAL SUPPORT; MENTAL-HEALTH; ALZHEIMERS-DISEASE; CAREGIVER BURDEN; SPOUSE CAREGIVERS; RATING-SCALE; STRESS; RELATIVES AB Objective: Components and correlates of caregiver burden in schizophrenia were studied. Methods: The family caregivers of 623 ( 43 percent) of 1,460 patients with schizophrenia enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) were interviewed about resources they provided and experiences with patient behavior over the previous month. Patients were independently evaluated on symptoms, quality of life, neurocognition, medication side effects, and service use. Factor analysis reduced the caregiver data into four orthogonal factors assessing perceptions of patient problem behavior, patient impairment in activities of daily living, patient helpfulness, and resource demands and disruptions in the caregiver's personal routine. Results: Hierarchical regression analyses demonstrated differential correlates of burden for each factor, explaining 34 percent of variance each for problem behavior and resource demands and disruption, 21 percent for impairment in activities of daily living, and 38 percent for patient helpfulness. Demographic characteristics and patient symptoms explained the greatest proportion of variance, whereas quality of life and service use explained modest variance and patient neurocognition and medication side effects were not significantly associated with burden. Conclusions: Results underscore the need for continued intervention with family members after the acute inpatient phase of treatment to address the impacts of symptoms as well as incorporation of skills training into consumer treatment programs to improve consumer contributions to household maintenance. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. W Haven Vet Affairs Med Ctr, NE Program, Evaluat Ctr, West Haven, CT USA. Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06520 USA. Yale Univ, Dept Epidemiol, Sch Med, New Haven, CT 06520 USA. Yale Univ, Dept Publ Hlth, Sch Med, New Haven, CT 06520 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. New Mexico VA Hlth Care Syst, Albuquerque, NM USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. RP Perlick, DA (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM deborah.perlick@mssm.edu FU NIMH NIH HHS [N01-MH-90001] NR 64 TC 50 Z9 54 U1 3 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 AUG PY 2006 VL 57 IS 8 BP 1117 EP 1125 DI 10.1176/appi.ps.57.8.1117 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 067NF UT WOS:000239309200008 PM 16870962 ER PT J AU Weiss, AP Henderson, DC Weilburg, JB Goff, DC Meigs, JB Cagliero, E Grant, RW AF Weiss, Anthony P. Henderson, David C. Weilburg, Jeffrey B. Goff, Donald C. Meigs, James B. Cagliero, Enrico Grant, Richard W. TI Treatment of cardiac risk factors among patients with schizophrenia and diabetes SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-DISORDERS; EXCESS MORTALITY; MULTIFACTORIAL INTERVENTION; CARDIOVASCULAR-DISEASE; MEDICAL-CARE; THERAPY; DISPARITIES; ADHERENCE; MELLITUS; QUALITY AB Objective: The appropriateness and effectiveness of the outpatient medical management of cardiac risk factors for patients with diabetes who had a diagnosis of schizophrenia or a related psychotic syndrome were examined. Methods: In a cross-sectional analysis of 4,236 patients with diabetes, ICD- 9 billing codes were used to identify 214 patients with schizophrenia or a schizophrenia-related syndrome. Measures of treatment appropriateness and effectiveness for the management of cardiac risk factors ( control of blood sugar, blood pressure, and lipids) were assessed for this group and compared with measures from patients with diabetes but no severe mental illness (N=3,594). Odds ratios were adjusted for between-group differences in gender, race, age, and clinic setting. Results: There were no statistically significant between-group differences on any of the five measures of treatment appropriateness, indicating that patients with schizophrenia received a similar regimen of medical treatment for cardiac factors. However, two of the seven measures of treatment effectiveness indicated significant deficiencies, with fewer patients with schizophrenia meeting the clinical quality benchmarks for cholesterol and low-density lipoprotein control. This disparity may have been caused by factors other than the measured treatment appropriateness variables, including the prescription of older lipid-lowering agents and a higher rate of missed appointments in the group with schizophrenia. Conclusions: Effective lipid control may be more difficult to attain for at least some patients with schizophrenia. Given that population's high rates of cardiovascular mortality, additional research to clarify the barriers to effective lipid management is essential. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM aweiss@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23-DK-067452]; NIMH NIH HHS [K23-MH-067019] NR 32 TC 34 Z9 37 U1 1 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 AUG PY 2006 VL 57 IS 8 BP 1145 EP 1152 DI 10.1176/appi.ps.57.8.1145 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 067NF UT WOS:000239309200012 PM 16870966 ER PT J AU Glahn, DC Barrett, J Bearden, CE Mintz, J Green, MF Monkul, ES Najt, P Soares, JC Velligan, DI AF Glahn, David C. Barrett, Jennifer Bearden, Carrie E. Mintz, Jim Green, Michael F. Monkul, E. Serap Najt, Pablo Soares, Jair C. Velligan, Dawn I. TI Dissociable mechanisms for memory impairment in bipolar disorder and schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; WORKING-MEMORY; NEUROCOGNITIVE FUNCTION; RATING-SCALE; I DISORDER; STRATEGIES; TASKS; ENDOPHENOTYPES; METAANALYSIS; INFORMATION AB Background. Although memory deficits are consistently reported in schizophrenia and bipolar disorder, the mechanisms underlying these impairments are poorly understood. Clarifying the nature and degree of overlap in memory deficits between the two illnesses could help to distinguish brain systems disrupted in these illnesses, and indicate cognitive remediation strategies to improve patient outcomes. Method. We examined performance on a non-verbal memory task in clinically stable out-patients with bipolar disorder (n = 40), schizophrenia (n = 40), and healthy comparison subjects (n = 40). This task includes conditions in which distinct mnemonic strategies-namely, using context to organize familiar stimuli or using holistic representation of novel stimuli - facilitate performance. Result. When compared to a reference condition, bipolar patients had deficits consistent with organizational dysfunction and poor detection of novel information. Although patients with schizophrenia performed worse than the other groups, they were only differentially impaired when organizational demands were significant. Task performance was not correlated with severity of clinical symptomatology. Conclusions. This pattern of distinct memory impairments implies disturbances in partially overlapping neural systems in bipolar disorder and schizophrenia. Evidence of impairment in detection of novel stimuli that is unique to bipolar disorder suggests that, while the absolute level of cognitive dysfunction is less severe in bipolar disorder as compared to schizophrenia, subtle disruptions in memory are present. These findings can be used to plan targeted cognitive remediation programs by helping patients to capitalize on intact functions and to learn new strategies that they do not employ without training. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Glahn, DC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr,Mail Code 7792, San Antonio, TX 78229 USA. EM glahn@uthscsa.edu RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NCRR NIH HHS [M01 RR 01346]; NIMH NIH HHS [MH 62850] NR 46 TC 21 Z9 21 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2006 VL 36 IS 8 BP 1085 EP 1095 DI 10.1017/S0033291706007902 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 074QO UT WOS:000239827100005 PM 16734948 ER PT J AU Biederman, J Petty, C Hirshfeld-Becker, DR Henin, A Faraone, SV Dang, D Jakubowski, A Rosenbaum, JF AF Biederman, Joseph Petty, Carter Hirshfeld-Becker, Dina R. Henin, Aude Faraone, Stephen V. Dang, Danielle Jakubowski, Aleksandra Rosenbaum, Jerrold F. TI A controlled longitudinal 5-year follow-up study of children at high and low risk for panic disorder and major depression SO PSYCHOLOGICAL MEDICINE LA English DT Article ID CHILDHOOD ANXIETY DISORDERS; PRESCHOOL-CHILDREN; PSYCHIATRIC-DISORDERS; YOUNG-CHILDREN; PARENTS; FAMILY; COMORBIDITY; ADOLESCENTS; AGORAPHOBIA; SAMPLE AB Background. To evaluate the longitudinal course of psychiatric disorders in children of parents with panic disorder (PD) and major depression (MD) as they transition through the period of risk from childhood into adolescence. Method. Over a 5-year follow-up, we compared psychiatric disorders in four groups of children: (1) offspring of parents with PD plus MD (n = 136); (2) offspring of parents with PD without MD (n = 27); (3) offspring of parents with MD but without PD (n = 53); and (4) offspring of non-PD non-MD parents (n = 103). Results. Parental PD was significantly associated with increased risk for anxiety disorders, irrespective of parental MD. Parental MD was associated with increased risk for MD, disruptive behavior disorders, and deficits in psychosocial functioning, irrespective of parental PD. Conclusions. These longitudinal findings confirm and extend previous cross-sectional results documenting significant associations between PD and MD in parents and patterns of psychopathology and dysfunction in their offspring. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit,Pediat Psychopharmaco, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Biederman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit,Pediat Psychopharmaco, YAW 6A,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-47077-05] NR 46 TC 36 Z9 36 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2006 VL 36 IS 8 BP 1141 EP 1152 DI 10.1017/S0033291706007781 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 074QO UT WOS:000239827100010 PM 16700966 ER PT J AU Bar, M Neta, M AF Bar, Moshe Neta, Maital TI Humans prefer curved visual objects SO PSYCHOLOGICAL SCIENCE LA English DT Article ID SOCIAL-PERCEPTION; FACILITATION; RECOGNITION; STIMULI; DESIGN AB People constantly make snap judgments about objects encountered in the environment. Such rapid judgments must be based on the physical properties of the targets, but the nature of these properties is yet unknown. We hypothesized that sharp transitions in contour might convey a sense of threat, and therefore trigger a negative bias. Our results were consistent with this hypothesis. The type of contour a visual object possesses-whether the contour is sharp angled or curved-has a critical influence on people's attitude toward that object. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, Boston, MA 02129 USA. RP Bar, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, 149 13th St, Boston, MA 02129 USA. EM bar@nmr.mgh.harvard.edu FU NINDS NIH HHS [NS44319-01] NR 16 TC 139 Z9 140 U1 3 U2 38 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD AUG PY 2006 VL 17 IS 8 BP 645 EP 648 DI 10.1111/j.1467-9280.2006.01759.x PG 4 WC Psychology, Multidisciplinary SC Psychology GA 069YU UT WOS:000239486500001 PM 16913943 ER PT J AU Inslicht, SS Marmar, CR Neylan, TC Metzler, TJ Hart, SL Otte, C McCaslin, SE Larkin, GL Hyman, KB Baum, A AF Inslicht, Sabra S. Marmar, Charles R. Neylan, Thomas C. Metzler, Thomas J. Hart, Stacey L. Otte, Christian McCaslin, Shannon E. Larkin, G. Luke Hyman, Kelly B. Baum, Andrew TI Increased cortisol in women with intimate partner violence-related posttraumatic stress disorder SO PSYCHONEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE posttraumatic stress disorder; cortisol; HPA axis; epinephrine; norepinephrine; intimate partner violence ID 24-HOUR URINARY CORTISOL; MOTOR-VEHICLE ACCIDENTS; MIDDLE-AGED WOMEN; PLASMA NOREPINEPHRINE; CEREBROSPINAL-FLUID; DEPRESSED-PATIENTS; SALIVARY CORTISOL; DOMESTIC VIOLENCE; COMMUNITY SAMPLE; CATECHOLAMINES AB Background: Alterations of hypothalamic-pituitary-adrenal (HPA) axis function and sympathetic-ad renal activity have been proposed as key factors in biological models of posttraumatic stress disorder (PTSD). Methods: We examined neuroendocrine function in female survivors of intimate partner violence (IPV) with lifetime (current or remitted) PTSD (n=29) and in women who were exposed to IPV but never developed PTSD (n=20). Salivary cortisol was collected as a marker of HPA axis function at 1, 4, 9, and 11 h after awakening. Platelet epinephrine and norepinephrine were assayed as markers of sympathetic-adrenal activation. Results: Women with lifetime PTSD had significantly higher cortisol. levels across the day compared to abuse-exposed participants without PTSD, after controlling for age, depression, severity, and latency of abuse. There were no significant group differences in levels of platelet catecholamines. Conclusions: Elevated cortisol levels may be a biomarker of IPV-related lifetime PTSD, reflecting tong-tasting changes associated with trauma-exposure or possibly a reflection of risk for PTSD in women. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Canc Inst, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. Affairs Med Ctr, Dept Vet Affairs, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Hosp Hamburg Eppendorf, Dept Psychiat & Psychotherapy, D-20246 Hamburg, Germany. Univ Texas, Mem Hosp, SW Med Ctr, Dept Surg,Div Emergency Med, Dallas, TX 75390 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equit Res & Promot, Pittsburgh, PA 15240 USA. RP Inslicht, SS (reprint author), Univ Pittsburgh, Dept Psychol, Sennott Sq,3rd Floor,210 S Bouquet St, Pittsburgh, PA 15260 USA. EM sabra.inslicht@ucsf.edu RI Hart, Stacey/E-4819-2011; OI LARKIN, GREGORY LUKE/0000-0002-8655-7824 FU NIMH NIH HHS [MH54837]; NIOSH CDC HHS [OH3306] NR 75 TC 49 Z9 50 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD AUG PY 2006 VL 31 IS 7 BP 825 EP 838 DI 10.1016/j.psyneuen.2006.03.007 PG 14 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 069UW UT WOS:000239475100004 PM 16716530 ER PT J AU Kern, RS Green, MF Cornblatt, BA Owen, JR McQuade, RD Carson, WH Ali, M Marcus, R AF Kern, Robert S. Green, Michael F. Cornblatt, Barbara A. Owen, J. Randall McQuade, Robert D. Carson, William H. Ali, Mirza Marcus, Ron TI The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine SO PSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; aripiprazole; olanzapine; neurocognition; learning; memory; dopamine; agonists ID NEUROPSYCHOLOGICAL CHANGE; SCHIZOAFFECTIVE DISORDER; ANTIPSYCHOTIC TREATMENT; PROPENSITY SCORE; PARTIAL AGONIST; SCHIZOPHRENIA; RISPERIDONE; CLOZAPINE; MEMORY; HALOPERIDOL AB Rationale Cognitive deficits are a core feature of schizophrenia. As a target of intervention, improvements in cognition may lead to improvements in functional outcome. Objectives The present paper is the first report, to our knowledge, on the neurocognitive effects of aripiprazole. Unlike other second-generation antipsychotics, aripiprazole is a D-2 and D-3 receptor partial agonist. It is unknown what effects this unusual pharmacological profile may yield on neurocognition. Materials and methods The present open-label study included data on 169 patients with schizophrenia or schizoaffective disorder who were randomly treated with aripiprazole or olanzapine. Subjects received a neurocognitive battery at baseline, week 8, and 26. Results The aripiprazole group had a significantly greater dropout rate than the olanzapine group. Neurocognitive data were reduced through a principal components analysis that yielded a three-factor solution. The factors were general cognitive functioning, executive functioning, and verbal learning. For general cognitive functioning, both groups improved from baseline and the effects were relatively stable over the 26-week protocol. There were no differential treatment effects. For executive functioning, neither group improved significantly from baseline. For verbal learning, the aripiprazole group improved significantly from baseline to the 8th and 26th week of assessment, and there was a between-group effect favoring aripiprazole over olanzapine that was largely attributable to the differences in performance within the 8th week. Separate analyses were conducted for a measure of sustained attention (Continuous Performance Test-Identical Pairs). There were no differential treatment effects on this measure. Conclusions The findings from this open-label study suggest that the neurocognitive effects of aripiprazole are at least as good as those of olanzapine. C1 VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA. Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs VISN 22, Los Angeles, CA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Zucker Hillside Hosp, N Shore Long Isl Jewish Med Ctr, Glen Oaks, NY USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Otsuka Amer Pharmaceut Inc, Princeton, NJ USA. Otsuka Maryland Res Inst, Rockville, MD USA. RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare Ctr, 11301 Wilshire Blvd,MIRECC 210A, Los Angeles, CA 90073 USA. EM rkern@ucla.edu NR 51 TC 80 Z9 86 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 2006 VL 187 IS 3 BP 312 EP 320 DI 10.1007/s00213-006-0428-x PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 082VQ UT WOS:000240415700009 PM 16810506 ER PT J AU Harvey, PD Green, MF Bowie, C Loebel, A AF Harvey, Philip D. Green, Michael F. Bowie, Christopher Loebel, Antony TI The dimensions of clinical and cognitive change in schizophrenia: evidence for independence of improvements SO PSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; clinical effectiveness; cognitive function; antipsychotic; treatment ID ACUTELY ILL INPATIENTS; DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER; 1ST-EPISODE PSYCHOSIS; SUPPORTED EMPLOYMENT; FACTORIAL STRUCTURE; NEGATIVE SYMPTOMS; RATING-SCALE; OLANZAPINE; ZIPRASIDONE AB Background As cognitive impairments are related to deficits in everyday functioning in schizophrenia, treatment of these impairments may have the potential to reduce these functional deficits. To determine if treatments truly reduce cognitive impairment, it is important to discriminate direct cognitive effects of treatment from generalized treatment benefits on the multiple clinical dimensions of schizophrenia. Thus, this study used a database from an existing clinical trial and examined the relationships between changes in clinical symptoms and cognitive deficits with several different strategies. Materials and methods Two hundred and seventy stable but symptomatic outpatients with schizophrenia entered a study where they were switched from previous treatment to open-label ziprasidone. The present data are from the 6-month endpoint (n=184). Patients were examined at baseline and the 6-month endpoint with ratings of clinical symptoms based on the Positive and Negative Syndrome Scale (PANSS) and a neuropsychological (NP) assessment battery including aspects of cognitive functioning known to be related to functional outcome in schizophrenia. Results Changes on the individual PANSS items and NP test scores were examined with two separate principal components analyses, revealing four dimensions of clinical change (psychosis, negative symptoms, affective symptoms, and agitation) and two dimensions of NP improvement. Pearson correlations between changes in the (1) factors derived from the analyses, (2) individual NP items based the four clinical dimensions of change, and (3) the 30 PANSS items and the two NP dimensions of change suggested minimal relationships (largest r=0.15). Implications This sample was selected because previous findings suggested that clinical and NP symptoms of schizophrenia significantly improved from baseline after a switch to ziprasidone treatment. While four dimensions of change in clinical symptoms and two dimensions of cognitive improvements were identified, clinical changes, regardless of how they were defined, were not related to NP improvements. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Univ Calif Los Angeles, VA Greater Los Angles Healthcare Syst, Inst Neuropsychiat, Los Angeles, CA USA. Pfizer Inc, New York, NY 10016 USA. RP Harvey, PD (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, 1425 Madison Ave, New York, NY 10029 USA. EM philipdharvey1@cs.com NR 44 TC 29 Z9 34 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 2006 VL 187 IS 3 BP 356 EP 363 DI 10.1007/s00213-006-0432-1 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 082VQ UT WOS:000240415700013 PM 16783539 ER PT J AU Lorenz, KA Cunningham, WE Spritzer, KL Hays, RD AF Lorenz, Karl A. Cunningham, William E. Spritzer, Karen L. Hays, Ron D. TI Changes in symptoms and health-related quality of life in a nationally representative sample of adults in treatment for HIV SO QUALITY OF LIFE RESEARCH LA English DT Article DE health; longitudinal studies; quality of life; symptoms ID LOW-PREVALENCE DISEASES; MENTAL-HEALTH; SERVICES UTILIZATION; PROBABILITY SAMPLES; COST; ASSOCIATIONS; PERFORMANCE; OUTPATIENTS; INFECTION; CARE AB Patient-centered measures of functioning and well-being are needed to monitor and improve health for HIV-infected persons. We estimated the associations between HRQOL and symptoms over time in HIV-infected persons, adjusting for demographic and clinical characteristics using a longitudinal study of a nationally representative cohort of 2267 patients in care for HIV infection surveyed in 1996 and again in 1998. We used two global measures of HRQOL (overall health and overall quality of life) scored to have a mean of 50 and standard deviation of 10 in the sample. The total number of symptoms decreased (-1.29, p < 0.001 for the difference), and overall health (1.09, p < 0.001 for the difference) and overall quality of life (1.31, p < 0.001 for the difference) improved over the period. Controlling for baseline symptoms and HRQOL, each additional symptom at follow-up (B=-1.14, p < 0.001) was associated with worsened overall health and worsened overall quality of life (B=-0.95, p < 0.001). The association of two additional symptoms with lower global HRQOL was similar in magnitude to the effect of having significant depressive symptoms or the diagnosis of AIDS. In conclusion, among HIV-infected patients, symptoms are significantly related to HRQOL over time. The functioning and well-being of patients with HIV is inextricably linked to the symptoms they experience. C1 VA Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Div Gen Internal Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Lorenz, KA (reprint author), VA Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Div Gen Internal Med, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM karl.lorenz@med.va.gov RI Hays, Ronald/D-5629-2013 FU AHRQ HHS [U-01HS08578]; ASC OASH HHS [R01AS10227]; NIA NIH HHS [AG-02-004]; NIMHD NIH HHS [P20-MD00148-01] NR 20 TC 45 Z9 48 U1 2 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD AUG PY 2006 VL 15 IS 6 BP 951 EP 958 DI 10.1007/s11136-005-6010-x PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 073CE UT WOS:000239719400002 PM 16900276 ER PT J AU Seiden, SC Galvan, C Lamm, R AF Seiden, S. C. Galvan, C. Lamm, R. TI Role of medical students in preventing patient harm and enhancing patient safety SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID ETHICAL ISSUES; ERRORS; CARE; EMERGENCY; PERFORMANCE; ENVIRONMENT; PHYSICIANS; RESIDENTS; ATTITUDES; EDUCATION AB Background: Substantial efforts are focused on the high prevalence of patient harm due to medical errors and the mechanisms to prevent them. The potential role of the medical student as a valuable member of the team in preventing patient harm has, however, often been overlooked. Methods: Four cases are presented from two US academic health centers in which medical students prevented or were in a position to prevent patient harm from occurring. The authors directly participated in each case. Results: The types of harm prevented included averting non-sterile conditions, missing medications, mitigating exposure to highly contagious patients, and respecting patients' "do not resuscitate'' requests. Conclusion: Medical students are often overlooked as valuable participants in ensuring patient safety. These cases show that medical students may be an untapped resource for medical error prevention. Medical students should be trained to recognize errors and to speak up when errors occur. Those supervising students should welcome and encourage students to actively communicate observed errors and near misses and should work to eliminate all intimidation by medical hierarchy that can prevent students from being safety advocates. C1 Univ Chicago, Comer Childrens Hosp, Dept Pediat, Chicago, IL 60637 USA. Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. Brigham & Womens Hosp, Harvard Affiliated Emergency Residency, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Seiden, SC (reprint author), Univ Chicago, Comer Childrens Hosp, Dept Pediat, 5721 S Maryland Ave,MC8016, Chicago, IL 60637 USA. EM seiden@uchicago.edu NR 48 TC 35 Z9 37 U1 1 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD AUG PY 2006 VL 15 IS 4 BP 272 EP 276 DI 10.1136/qshc.2006.018044 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 069OS UT WOS:000239458700011 PM 16885252 ER PT J AU Kobayashi, H Pian-Smith, M Sato, M Sawa, R Takeshita, T Raemer, D AF Kobayashi, H. Pian-Smith, M. Sato, M. Sawa, R. Takeshita, T. Raemer, D. TI A cross-cultural survey of residents' perceived barriers in questioning/challenging authority SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID RESPONSE BIAS; COMMUNICATION FAILURES; ATTENDING PHYSICIANS; RESOURCE-MANAGEMENT; CLASSIFICATION; EDUCATION AB Objectives: To identify perceived barriers to residents' questioning or challenging their seniors, to determine how these barriers affect decisions, and to assess how these barriers differ across cultures. Method: A written questionnaire was administered to residents in teaching hospitals in the US and Japan to assess factors affecting residents' willingness to question or challenge their superiors. The responses were analyzed for statistical significance of differences between the two cultures and to determine the importance of issues affecting decisions. Results: Questionnaires were completed by 175 US and 65 Japanese residents, with an overall response rate of 71%. Trainees from both countries believe that questioning and challenging contribute to safety. The perceived importance of specific beliefs about the workplace differed across cultures in seven out of 22 questions. Residents' decisions to make a challenge were related to the relationships and perceived response of the superiors. There was no statistical difference between the US and Japanese residents in terms of the threshold for challenging their seniors. Conclusion: We have identified attributes of residents' beliefs of communication, including several cross-cultural differences in the importance of values and issues affecting one's decision to question or challenge. In contrast, there was no difference in the threshold for challenging seniors by the Japanese and US residents studied. Changes in organizational and professional culture may be as important, if not more so, than national culture to encourage "speaking up''. Residents should be encouraged to overcome barriers to challenging, and training programs should foster improved relationships and communication between trainers and trainees. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Nippon Med Coll, Grad Sch Med, Tokyo 113, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. Ctr Med Simulat, Boston, MA USA. RP Kobayashi, H (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM hajime2004@post.harvard.edu NR 19 TC 37 Z9 37 U1 1 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD AUG PY 2006 VL 15 IS 4 BP 277 EP 283 DI 10.1136/qshc.2005.017368 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 069OS UT WOS:000239458700012 PM 16885253 ER PT J AU Thrall, JH AF Thrall, James H. TI Education and cultural development of the health care workforce - Part II. Opportunities for nonprofessional workers SO RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ-FND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 9 TC 2 Z9 2 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 AUG PY 2006 VL 240 IS 2 BP 311 EP 314 DI 10.1148/radiol.2402060601 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 066PO UT WOS:000239242600002 PM 16864662 ER PT J AU Blanchard, K Colbert, JA Kopans, DB Moore, R Halpern, EF Hughes, KS Smith, BL Tanabe, KK Michaelson, JS AF Blanchard, Karen Colbert, James A. Kopans, Daniel B. Moore, Richard Halpern, Elkan F. Hughes, Kevin S. Smith, Barbara L. Tanabe, Kenneth K. Michaelson, James S. TI Long-term risk of false-positive screening results and subsequent biopsy as a function of mammography use SO RADIOLOGY LA English DT Article ID BREAST-CANCER; UNITED-STATES; CARCINOMA; WOMEN; SURVIVAL; PATTERNS; INTERVAL; HISTORY; OLDER AB Purpose: To retrospectively determine the long-term risk of false-positive mammographic assessments and to evaluate the effect of screening regularity on the risk of false-positive events. Materials and Methods: Institutional review board approval was obtained, and informed consent was waived. Retrospective analysis was performed for the occurrence of false-positive assessments among 83 511 women who underwent 314 185 mammographic examinations from January 1, 1985, to February 19, 2002. Data were collected from a database that had been assembled prospectively. Two categories of false-positive events were examined: biopsies that did not reveal cancer and false-positive mammographic assessments. Rates of false-positive events were compared by using a chi(2) analysis, and 95% confidence limits were calculated. Because comparisons of multiple pairs were considered, all P values that demonstrated statistical significance exceeded the requirement of the Bonferroni correction. Results: While the overall rates of biopsies that did not reveal cancer and of false-positive mammographic assessments were similar to those found in other studies, most of the burden of false-positive events was borne by women who underwent intermittent screening. Long-term rates of false-positive events were lower among women who underwent regular screening than among those who underwent intermittent screening. In the 5-year group, 2.9% of women who underwent five mammographic examinations over the next 5 years had biopsy results that did not reveal cancer, whereas 4.6% of women who underwent three mammographic examinations over the next 5 years had biopsy results that did not reveal cancer. For women who underwent regular screening, the risk of undergoing biopsies that did not reveal cancer declined over time to 0.25% per year after several years of screening, a value that is lower than the risk of these events among women who did not undergo screening. The rate of false-positive mammographic assessments was also lower for women who underwent regular screening than for those who underwent intermittent screening. Conclusion: Prompt annual attendance for mammographic screening reduces the occurrence of false- positive mammographic results. (c) RSNA, 2006. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Michaelson, JS (reprint author), Massachusetts Gen Hosp, Dept Surg, Yawkey 7939,55 Fruit St, Boston, MA 02114 USA. EM michaelj@helix.mgh.harvard.edu NR 31 TC 16 Z9 16 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 AUG PY 2006 VL 240 IS 2 BP 335 EP 342 DI 10.1148/radiol.2402050107 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 066PO UT WOS:000239242600005 PM 16864665 ER PT J AU Uppot, RN Sahani, DV Hahn, PF Kalra, MK Saini, SS Mueller, PR AF Uppot, Raul N. Sahani, Dushyant V. Hahn, Peter F. Kalra, Mannudeep K. Saini, Sanjay S. Mueller, Peter R. TI Effect of obesity on image quality: Fifteen-year longitudinal study for evaluation of dictated radiology reports SO RADIOLOGY LA English DT Article AB Purpose: To retrospectively assess the effect of obesity on image quality, as determined from dictated radiology reports filed between 1989 and 2003. Materials and Methods: Institutional review board approval was obtained for this HIPAA-compliant study; informed consent was not required. Electronic records were searched for radiology reports with the phrase "limited due to body habitus" (hereafter, "habitus limited") filed between 1989 and 2003; reports were retrospectively reviewed. Habitus limited was qualified as the search phrase by auditing radiologic images and patient weights. Trends in the number of habitus-limited reports were calculated for each year, and linear regression analysis was performed. The number of habitus-limited reports was also compared between modalities within a year and within each modality across 15 years. The trend was correlated with the prevalence of obesity in Massachusetts by using the Pearson correlation coefficient. Results: There was a significant difference (P < .001) between the weight of patients with habitus-limited reports and the weight of patients with reports that were not habitus limited. Overall, 7778 (0.15%) of 5 253 014 reports were habitus limited. Between 1989 and 2003, there was a linear increase of 0.010% per year (95% confidence interval: 0.007%, 0.013%; P < .001). There was a positive correlation between the increased number of habitus-limited reports and the increased prevalence of obese individuals in Massachusetts between 1991 and 2001. The modality most commonly associated with habitus-limited reports was abdominal ultrasonography. Conclusion: There was a small but progressive increase in the number of habitus-limited radiology reports between 1989 and 2003. (c) RSNA, 2006. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent Rad, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Radiol, Emory Healthcare, Atlanta, GA USA. RP Uppot, RN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent Rad, 55 Fruit St,White 270, Boston, MA 02114 USA. EM ruppot@partners.org NR 6 TC 40 Z9 40 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 AUG PY 2006 VL 240 IS 2 BP 435 EP 439 DI 10.1148/radiol.2402051110 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 066PO UT WOS:000239242600015 PM 16801372 ER PT J AU Hahn, PF Blake, MA Boland, GWL AF Hahn, Peter F. Blake, Michael A. Boland, Giles W. L. TI Adrenal lesions: Attenuation measurement differences between CT scanners SO RADIOLOGY LA English DT Article; Proceedings Paper CT 90th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 28-DEC 03, 2004 CL Chicago, IL SP Radiol Soc N Amer ID ENHANCED CT; MASSES; ADENOMAS; INCIDENTALOMAS; NONADENOMAS AB Purpose: To retrospectively compare unenhanced computed tomographic scans of the same adrenal lesion obtained with two different manufacturers' multidetector scanners to assess whether there are differences in attenuation measurements. Materials and Methods: The study was approved by the local ethical committee, which waived patient consent, and was conducted in compliance with HIPAA. Electronic searching revealed patients with adrenal nodules scanned with both a Siemens 16-detector row scanner and one of eight GE Medical Systems multi-detector row scanners between January 2000 and September 2004 without the use of intravenous contrast material. Lesions were characterized by using histologic findings, fat content, or size stability. Size stability for 6 months was required unless both scans were obtained within 21 days of each other. Two radiologists independently measured lesion attenuation for regression analysis. Lesions considered benign (<= 10 HU) on one scan and indeterminate (<= 10 HU) on the other were separately analyzed, and technical parameters of scanning were compared. Results: There were 47 patients (27 men, 20 women; age range, 40-86 years; mean age, 64 years) with four metastases, 42 adenomas, and one myelolipoma (long-axis length, 10-85 mm; mean, 24 mm). GE scans were obtained with four-detector row scanners (n=32), an eight-detector row scanner (n=2), and 16=detector row scanners (n=13). Correlation between the two readers was 0.99 for both Siemens and GE scan attenuation measurements. The slope of regression lines for both readers plotting GE attenuation (y-axis) against Siemens attenuation (x-axis) was less than 1, which indicated a slight but statistically significant tendency for GE scans to have lower attenuations than do Siemens scans. For both readers, there were more lesions indeterminate (<= 10 HU) on Siemens scans but benign (<= 10 HU) on GE scans than the reverse (McNemar test, P <.02 for reader 1, not significant for reader 2). Average Siemens and GE scan technical parameters were similar. Conclusion: There are only slight differences in attenuation of adrenal nodules measured on scans obtained with different scanners. (c) RSNA, 2006. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hahn, PF (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM phahn@partners.org NR 12 TC 25 Z9 26 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 AUG PY 2006 VL 240 IS 2 BP 458 EP 463 DI 10.1148/radiol.2402042120 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 066PO UT WOS:000239242600018 PM 16801368 ER PT J AU Saam, T Cai, J Ma, L Cai, YQ Ferguson, MS Polissar, NL Hatsukami, TS Yuan, C AF Saam, Tobias Cai, Jianming Ma, Lin Cai, You-Quan Ferguson, Marina S. Polissar, Nayak L. Hatsukami, Thomas S. Yuan, Chun TI Comparison of symptomatic and asymptomatic atherosclerotic carotid plaque features with in vivo MR imaging SO RADIOLOGY LA English DT Article ID SUDDEN CORONARY DEATH; INTRAPLAQUE HEMORRHAGE; INVERSION-RECOVERY; CEREBRAL-ISCHEMIA; ARTERY STENOSIS; RUPTURE; LESIONS; CLASSIFICATION; PROGRESSION; IDENTIFICATION AB Purpose: To retrospectively determine if in vivo magnetic resonance (MR) imaging can simultaneously depict differences between symptomatic and asymptomatic carotid atherosclerotic plaque. Materials and Methods: Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Twenty-three patients (21 men, two women; mean age, 66.1 years +/- 11.0 [standard deviation]) with unilateral symptomatic carotid disease underwent 1.5-T time-of-flight MR angiography and 1.5-T T1-, intermediate-, and T2-weighted MR imaging. Both carotid arteries were reviewed. One observer recorded quantitative and morphologic information, which included measurement of the area of the lumen, artery wall, and main plaque components; fibrous cap status (thick, thin, or ruptured); American Heart Association (AHA) lesion type (types I-VIII); and location (juxtaluminal vs intraplaque) and type of hemorrhage. Plaques associated with neurologic symptoms and asymptomatic plaques were compared with Wilcoxon signed rank and McNemar tests. Results: Compared with asymptomatic plaques, symptomatic plaques had a higher incidence of fibrous cap rupture (P=.007), juxtaluminal hemorrhage or thrombus (P=.039), type I hemorrhage (P=.021), and complicated AHA type VI lesions (P=-.004) and a lower incidence of uncomplicated AHA type IV and V lesions (P=.005). Symptomatic plaques also had larger hemorrhage (P=.003) and loose matrix (P=.014) areas and a smaller lumen area (P=.008). No significant differences between symptomatic and asymptomatic plaques were found for quantitative measurements of the lipid-rich necrotic core, calcification, and the vessel wall or for the occurrence of intraplaque hemorrhage or type II hemorrhage. Conclusion: This study revealed significant differences between symptomatic and asymptomatic plaques in the same patient. (c) RSNA, 2006. C1 Univ Washington, Dept Radiol, Seattle, WA 98109 USA. Univ Washington, Dept Surg, Seattle, WA 98109 USA. Peoples Liberat Army Gen Hosp, Dept Radiol, Beijing, Peoples R China. Mt Whisper Light Stat Consulting, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Saam, T (reprint author), Univ Washington, Dept Radiol, 815 Mercer St,Box 358050, Seattle, WA 98109 USA. EM Tobias.Saam@med.uni-muenchen.de FU NHLBI NIH HHS [P01 HL072262, P01HL072262, R01 HL056874, R01 HL073401, R01HL073401, R01HL56874] NR 36 TC 122 Z9 134 U1 1 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2006 VL 240 IS 2 BP 464 EP 472 DI 10.1148/radiol.2402050390 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 066PO UT WOS:000239242600019 PM 16864672 ER PT J AU Chen, JW Sans, MQ Bogdanov, A Weissleder, R AF Chen, John W. Sans, Manel Querol Bogdanov, Alexei, Jr. Weissleder, Ralph TI Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates SO RADIOLOGY LA English DT Article ID RISK-ASSESSMENT STRATEGIES; VULNERABLE PATIENT; HYPOCHLOROUS ACID; OXIDATION; NEUTROPHILS; ATHEROSCLEROSIS; ACTIVATION; PLAQUE; INFLAMMATION; POLYMORPHISM AB Purpose: To evaluate whether contrast agents for molecular magnetic resonance (MR) imaging can demonstrate the in vivo activity of myeloperoxidase, an enzyme that is secreted by stimulated polymorphonuclear leukocytes, monocytes, and macrophages during inflammation. Materials and Methods: Animal experiments were approved by the animal care committee. Protocols for the procurement and use of human blood were approved by the institutional review board. Informed consent was obtained from each donor, and HIPAA guidelines were followed for humans. Two paramagnetic myeloperoxidase substrates-that is, gadolinium-5-hydroxytryptamide-tetraazacyclododecane tetraacetic acid (Gd-5-HT-DOTA) and Gd-bis-5-HT-diethylenetriaminepentaacetic acid (Gd-bis-5-HT-DTPA)-were synthesized. Indium 111-labeled bis-5-HT-DTPA was used to determine biodistribution and target localization. A total of 22 mice were used in three models. In the first model, human myeloperoxidase was embedded in a basement membrane matrix gel and was injected intramuscularly. In the second model, lipopolysaccharide (LPS) from Escherichia coli was embedded in a basement membrane matrix gel and was injected intramuscularly to induce endogenous myeloperoxidase secretion. In the third model, LPS was injected intramuscularly to induce myositis. Statistical significance was calculated for contrast-to-noise ratio (CNR) curves by using the Kolmogorov-Smirnov test. Results: After the administration of Gd-bis-5-HT-DTPA, strong MR signal enhancement (up to 2.5-fold increase in CNR, P <.001) was observed in vivo for implants that contained human myeloperoxidase. In the LPS-induced myositis model, a smaller visible difference was seen (1.3-fold increase in CNR, P <.001), which was consistent with the fact that endogenous mouse myeloperoxidase is only about 10%-20% as active as human myeloperoxidase. Prolonged contrast material enhancement was observed in the myeloperoxidase-containing areas that were injected with Gd-5-HT-DOTA or Gd-bis5-HT-DTPA but was not observed in areas that were injected with Gd-DTPA or Gd-dopamine-DOTA (P <.05). Single photon emission computed tomography combined with computed tomography was used to confirm the increased retention of contrast agents at sites that contained human myeloperoxidase, and the results of biodistribution studies demonstrated a more than fourfold increase radio-tracer accumulation at these sites. Conclusion: Human and mouse myeloperoxidase activity in myeloperoxidase implants and inflamed tissues can be visualized and reported in vivo by using myeloperoxidase-sensitive "smart" molecular imaging probes. (c) RSNA, 2006. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Chen, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 5404 Bldg 149,13th St, Charlestown, MA 02129 USA. EM chenjo@helix.mgh.harvard.edu FU NCI NIH HHS [R24-CA92782, P50-CA86355]; NHLBI NIH HHS [R01-HL078641]; NIBIB NIH HHS [R01 EB000858] NR 32 TC 97 Z9 100 U1 2 U2 15 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2006 VL 240 IS 2 BP 473 EP 481 DI 10.1148/radiol.2402050994 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 066PO UT WOS:000239242600020 PM 16864673 ER PT J AU Benditt, JO Hess, DR AF Benditt, Joshua O. Hess, Dean R. TI Respiratory care and neuromuscular disease SO RESPIRATORY CARE LA English DT Editorial Material C1 Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Benditt, JO (reprint author), Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD AUG PY 2006 VL 51 IS 8 SI SI BP 828 EP 828 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 073AX UT WOS:000239715800001 ER PT J AU Brown, R DiMarco, AF Hoit, JD Garshick, E AF Brown, Robert DiMarco, Anthony F. Hoit, Jeannette D. Garshick, Eric TI Respiratory dysfunction and management in spinal cord injury SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 37th Conference on Neuromuscular Disease in Respiratory and Critical Care Medicine CY MAR 17-19, 2006 CL Ixtapa, MEXICO DE spinal cord injury; respiratory failure; diaphragm; rib cage; airway clearance ID INTRAMUSCULAR DIAPHRAGM ELECTRODES; PROVIDE ARTIFICIAL-VENTILATION; PRESSURE-VOLUME CURVE; LONG-TERM SURVIVAL; PULMONARY-FUNCTION; PHRENIC-NERVE; RIB CAGE; CERVICAL CORD; TETRAPLEGIC PATIENTS; INTERCOSTAL MUSCLES AB Respiratory dysfunction is a major cause of morbidity and mortality in spinal cord injury (SCI), which causes impairment of respiratory muscles, reduced vital capacity, ineffective cough, reduction in lung and chest wall compliance, and excess oxygen cost of breathing due to distortion of the respiratory system. Severely affected individuals may require assisted ventilation, which can cause problems with speech production. Appropriate candidates can sometimes be liberated from mechanical ventilation by phrenic-nerve pacing and pacing of the external intercostal muscles. Partial recovery of respiratory-muscle performance occurs spontaneously. The eventual vital capacity depends on the extent of spontaneous recovery, years since injury, smoking, a history of chest injury or surgery, and maximum inspiratory pressure. Also, respiratory-muscle training and abdominal binders improve performance of the respiratory muscles. For patients on long-term ventilation, speech production is difficult. Often, practitioners are reluctant to deflate the tracheostomy tube cuff to allow speech production. Yet cuff-deflation can be done safely. Standard ventilator settings produce poor speech quality. Recent studies demonstrated vast improvement with long inspiratory time and positive end-expiratory pressure. Abdominal binders improve speech quality in patients with phrenic-nerve pacers. Recent data show that the level and completeness of injury and older age at the time of injury may not be related directly to mortality in SCI, which suggests that the care of SCI has improved. The data indicate that independent predictors of all-cause mortality include diabetes mellitus, heart disease, cigarette smoking, and percent-of-predicted forced expiratory volume in the first second. An important clinical problem in SCI is weak cough, which causes retention of secretions during infections. Methods for secretion clearance include chest physical therapy, spontaneous cough, suctioning, cough assistance by forced compression of the abdomen ("quad cough"), and mechanical insufflation-exsufflation. Recently described but not yet available for general use is activation of the abdominal muscles via an epidural electrode placed at spinal cord level T9-L1. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Metrohlth Med Ctr, Rammelkamp Res Ctr, Cleveland, OH USA. Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. Univ Arizona, Dept Speech Language & Hearing Sci, Tucson, AZ USA. Vet Affairs Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, R (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM rbrown5@partners.org FU NICHD NIH HHS [R01 HD042141, R01 HD042141-05, R01 HD42141] NR 114 TC 125 Z9 133 U1 2 U2 10 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD AUG PY 2006 VL 51 IS 8 SI SI BP 853 EP 868 PG 16 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 073AX UT WOS:000239715800006 PM 16867197 ER PT J AU Hess, DR AF Hess, Dean R. TI Noninvasive ventilation in neuromuscular disease: Equipment and application SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 37th Conference on Neuromuscular Disease in Respiratory and Critical Care Medicine CY MAR 17-19, 2006 CL Ixtapa, MEXICO DE bi-level ventilation; body ventilator; mask ventilation; mouthpiece ventilation; neuromuscular disease; noninvasive positive-pressure ventilation ID POSITIVE-PRESSURE VENTILATION; CHRONIC RESPIRATORY-FAILURE; PROPORTIONAL ASSIST VENTILATION; OBSTRUCTIVE PULMONARY-DISEASE; 2 DIFFERENT MODES; QUALITY-OF-LIFE; FULL FACE MASK; SUPPORT VENTILATION; AIRWAY PRESSURE; MECHANICAL VENTILATION AB Noninvasive support of ventilation is commonly needed in patients with neuromuscular disease. Body ventilators, which are used rarely, function by applying intermittent negative pressure to the thorax or abdomen. More commonly, noninvasive positive-pressure ventilation (NPPV) is used. This therapy can be applied with a variety of interfaces, ventilators, and ventilator settings. The patient interface has a major impact on comfort during NPPV. The most commonly used interfaces are nasal masks and oronasal masks. Other interfaces include nasal pillows, total face masks, helmets, and mouthpieces. Theoretically, any ventilator can be attached to a mask rather than an artificial airway. Portable pressure ventilators (bi-level positive airway pressure) are available specifically to provide NPPV and are commonly used to provide this therapy. Selection of NPPV settings in patients with neuromuscular disease is often done empirically and is symptom-based. Selection of settings can also be based on the results of physiologic studies or sleep studies. The use of NPPV in this patient population is likely to expand, particularly with increasing evidence that it is life-prolonging in patients with diseases such as amyotrophic lateral sclerosis. Appropriate selection of equipment and settings for NPPV is paramount to the success of this therapy. C1 Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 82 TC 40 Z9 41 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD AUG PY 2006 VL 51 IS 8 SI SI BP 896 EP 911 PG 16 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 073AX UT WOS:000239715800012 PM 16867200 ER PT J AU El-Serag, HB Tran, T Richardson, P Ergun, G AF El-Serag, Hashem B. Tran, Thomas Richardson, Peter Ergun, Gulchin TI Anthropometric correlates of intragastric pressure SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE BMI; GERD; obesity; risk factor; waist circumference ID GASTROESOPHAGEAL-REFLUX DISEASE; BODY-MASS INDEX; RISK-FACTORS; ESOPHAGUS; OBESITY; ADENOCARCINOMA; ASSOCIATION; PREGNANCY; SYMPTOMS; ASCITES AB Objective. Obesity may increase intra-abdominal pressure on the stomach leading to an increase in intragastric pressure, which in turn induces lower esophageal sphincter relaxation, with subsequent reflux. However, the association between anthropometric measures of total body as well as abdominal obesity and intragastric pressure has not been examined. Material and methods. This prospective cross-sectional study included consecutive patients undergoing manometry at an open access Reflux Center. Standardized measurements of body-weight, height, and waist and hip circumference were prospectively obtained. To assess the intragastric pressure, the perfusion port levels of the catheter were verified to be at the same vertical height (0 mmHg) inside the patient as they were outside the patient during calibration. Correlation between gastric pressure and anthropometric measures was calculated and adjusted for demographic features and presenting symptoms. Results. A total of 322 patients (67% women) with a mean age of 52.5 years were enrolled. The mean values for weight, height, and body mass index (BMI) were 77.2 kg, 168 cm, and 27.5 kg/m(2), respectively (range 16.0-52.0, median 27.0). The mean intragastric pressure was 2.9 cm H2O (SD: 1.7). There was a weak, positive correlation between gastric pressure and both BMI (r = 0.11, p = 0.05) and waist circumference (r = 0.11, p = 0.06). The associations between gastric pressure and both BMI and waist circumference were relatively unaffected by adjusting for several variables including age, indications for manometry, race, and gender in a multivariable linear regression model. For each unit increase in BMI, there was approximately a 10% increase in intragastric pressure. Conclusions. In this study of consecutive patients with wide-ranging BMI values, there was a weak, positive correlation between intragastric pressure and both BMI and waist circumference. This indicates that obesity operates to increase the risk of gastroesophageal reflux disease (GERD) at least partly by increasing intragastric pressure. C1 Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 16 TC 70 Z9 75 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD AUG PY 2006 VL 41 IS 8 BP 887 EP 891 DI 10.1080/00365520500535402 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 067BH UT WOS:000239275100003 PM 16803686 ER PT J AU Chien, K AF Chien, Kenneth TI Making a play at regrowing hearts SO SCIENTIST LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; BONE-MARROW-CELLS; STEM-CELLS; CARDIAC REPAIR; FOLLOW-UP; TRANSPLANTATION; REGENERATION; ASTAMI AB For patients with chronic degenerative diseases such as heart failure, regenerative medicine holds great promise. Results from clinical trials on cardiovascular stem cell therapy have shown a range of efficacy from minimal, to transient, to no improvement in global cardiac function. Lessons learned from these and other ongoing clinical trials can be used to design better experimental strategies. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Stem Cell Inst Program, Boston, MA USA. Harvard Univ, Dept Cell Biol, Boston, MA 02115 USA. RP Chien, K (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM kchien@partners.org NR 17 TC 2 Z9 2 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 400 MARKET ST, STE 1250, PHILADELPHIA, PA 19106 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD AUG PY 2006 VL 20 IS 8 BP 34 EP 39 PG 6 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 066IO UT WOS:000239223100015 ER PT J AU Gottlieb, DJ Redline, S Nieto, FJ Baldwin, CM Newman, AB Resnick, HE Punjabi, NM AF Gottlieb, Daniel J. Redline, Susan Nieto, F. Javier Baldwin, Carol M. Newman, Anne B. Resnick, Helaine E. Punjabi, Naresh M. TI Association of usual sleep duration with hypertension: The sleep heart health study SO SLEEP LA English DT Article DE hypertension; sleep deprivation; epidemiology ID BLOOD-PRESSURE; INSUFFICIENT SLEEP; ALAMEDA-COUNTY; MORTALITY; INSOMNIA; WOMEN; DISEASE; RISK; TIME AB Study Objectives: Limited experimental data suggest that sleep restriction acutely elevates blood pressure; however, little is known about the relationship between usual sleep duration and hypertension, This study assesses the relationship between usual sleep duration and hypertension in a community-based cohort. Design: Cross-sectional observational study. Setting: The Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing. Participants: Two thousand eight hundred thirteen men and 3097 women, aged 40 to 100 years. Interventions: None. Measurements and Results: Usual weekday and weekend sleep durations were obtained by questionnaire, and their weighted average were categorized as less than 6, 6 to less than 7, 7 to less than 8, 8 to less than 9, and 9 or more hours per night. Hypertension was defined as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or use of medication to treat hypertension. The relationship between sleep duration and hypertension was examined using categorical logistic regression with adjustment for age, sex, race, apnea-hypopnea index, and body mass index. Compared to subjects sleeping 7 to less than 8 hours per night, those sleeping less than 6 and between 6 and 7 hours per night had adjusted odds ratios for hypertension of 1.66 (95% confidence interval 1.35-2.04) and 1.19 (1.02-1.39), respectively, whereas those sleeping between 8 and 9 and 9 or more hours per night had adjusted odds ratios for hypertension of 1.19 (1.04-1.37) and 1.30 (1.04-1.62), respectively (p <.0001 for association of sleep duration with hypertension). These associations persisted when analyses were further adjusted for caffeine and alcohol consumption, current smoking, insomnia symptoms, depression symptoms, sleep efficiency, and prevalent diabetes mellitus or cardiovascular disease. Conclusions: Usual sleep duration above or below the median of 7 to less than 8 hours per night is associated with an increased prevalence of hypertension, particularly at the extreme of less than 6 hours per night. C1 Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Wisconsin, Madison, WI 53706 USA. Arizona State Univ, Coll Nursing SW Borderlands, Tempe, AZ 85287 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. MedStar Res Inst, Hyattsville, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Gottlieb, DJ (reprint author), Boston Univ, Sch Med, Ctr Pulm, 715 Albany St,R-304, Boston, MA 02118 USA. EM dgottlieb@lung.bumc.bu.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Baldwin, Carol/0000-0002-0732-2307 FU NHLBI NIH HHS [U01HL64360, HL53938-07S1, U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL53938, U01HL53940, U01HL53941, U01HL63429, U01HL63463] NR 28 TC 363 Z9 370 U1 6 U2 32 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD AUG 1 PY 2006 VL 29 IS 8 BP 1009 EP 1014 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 077RB UT WOS:000240046400003 PM 16944668 ER PT J AU Morgenthaler, TI Kapen, S Lee-Chiong, T Alessi, C Boehlecke, B Brown, T Coleman, J Friedman, L Kapur, V Owens, J Pancer, J Swick, T AF Morgenthaler, Timothy I. Kapen, Sheldon Lee-Chiong, Teofilo Alessi, Cathy Boehlecke, Brian Brown, Terry Coleman, Jack Friedman, Leah Kapur, Vishesh Owens, Judith Pancer, Jeffrey Swick, Todd TI Practice parameters for the medical therapy of obstructive sleep apnea SO SLEEP LA English DT Article DE obstructive sleep apnea; medical therapy; weight reduction; bariatric surgery; positional therapy; supplementary oxygen; selective serotonergic uptake inhibitors ID POSITIVE AIRWAY PRESSURE; HORMONE-REPLACEMENT THERAPY; BARIATRIC SURGERY; HYPOPNEA SYNDROME; WEIGHT-LOSS; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND; NASAL CPAP; APNEA/HYPOPNEA SYNDROME; DAYTIME SLEEPINESS AB Therapies for obstructive sleep apnea other than positive airway pressure, oral appliances, and surgical modifications of the upper airway are reviewed in this practice parameter. Several of these therapies such as weight loss and positional therapy hold some promise. Others, such as serotonergic agents, may gain credibility in the future but lack well-designed clinical trials. No practice parameters could be developed for a number of possible therapeutic modalities that had little or no evidence-based data on which to form a conclusion. The role of an organized, targeted weight-loss program either as a single therapy or as a supplement to PAP needs to be clarified. Although bariatric surgery is increasingly performed for refractory medically complicated obesity, its long-term effectiveness in treatment of obstructive sleep apnea in morbidly obese patients is not yet demonstrated. Positional therapy, or methods for preventing sleep in the supine position, has probably been undenutilized due to lack of easily measured predictive factors and randomized controlled trials. C1 Mayo Clin, Sleep Disorders Ctr, Rochester, MN 55905 USA. Detroit VA Med Ctr, Detroit, MI USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Sepulveda, CA USA. Univ N Carolina, Chapel Hill, NC 27515 USA. St Joseph Mem Hosp, Murphysboro, IL USA. Stanford Univ, Stanford, CA 94305 USA. Univ Washington, Seattle, WA 98195 USA. Rhode Isl Hosp, Providence, RI 02903 USA. Houston Sleep Ctr, Houston, TX USA. RP Morgenthaler, TI (reprint author), Mayo Clin, Sleep Disorders Ctr, 200 1st St SW, Rochester, MN 55905 USA. EM thaler.timothy@mayo.edu RI Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Morgenthaler, Timothy/0000-0002-2614-3793 NR 64 TC 99 Z9 103 U1 1 U2 3 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD AUG 1 PY 2006 VL 29 IS 8 BP 1031 EP 1035 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 077RB UT WOS:000240046400006 PM 16944671 ER PT J AU McCarthy, JR Jaffer, FA Weissleder, R AF McCarthy, Jason R. Jaffer, Farouc A. Weissleder, Ralph TI A macrophage-targeted theranostic nanoparticle for biomedical applications SO SMALL LA English DT Article DE drug design; iron; macrophages; nanoparticles; photosensitizers ID SUPERPARAMAGNETIC IRON-OXIDE; PHOTODYNAMIC THERAPY; ATHEROSCLEROTIC PLAQUES; MOTEXAFIN LUTETIUM; TAT PEPTIDE; HEMATOPORPHYRIN; CONJUGATION; DELIVERY; CELL; PHOTOANGIOPLASTY C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP McCarthy, JR (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM jason_mccarthy@hms.harvard.edu; weissleder@helix.mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NCI NIH HHS [P50 CA86355, T32 CA79443]; NHLBI NIH HHS [R01 HL080731] NR 40 TC 100 Z9 103 U1 4 U2 46 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-6810 J9 SMALL JI Small PD AUG PY 2006 VL 2 IS 8-9 BP 983 EP 987 DI 10.1002/smll.200600139 PG 5 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 073BN UT WOS:000239717500006 PM 17193154 ER PT J AU Reiser, RF Rocheford, EC Armstrong, CJ AF Reiser, Raoul F., II Rocheford, Erik C. Armstrong, Casey J. TI Building a better understanding of basic mechanical principles through analysis of the vertical jump SO STRENGTH AND CONDITIONING JOURNAL LA English DT Article DE countermovement; biomechanics; mechanics; vertical jump ID COUNTERMOVEMENT JUMP; SQUAT JUMP; HEIGHT; POWER AB An understanding of the basic mechanical principles governing movement is essential for the development of training programs, performance improvement, and injury prevention. The goal of this article is to review these principles through an analysis of the vertical jump. C1 Colorado State Univ, Hlth & Exercise Sci Dept, Ft Collins, CO 80523 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Colorado, Boulder, CO 80309 USA. RP Reiser, RF (reprint author), Colorado State Univ, Hlth & Exercise Sci Dept, Ft Collins, CO 80523 USA. NR 21 TC 14 Z9 14 U1 2 U2 27 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1524-1602 J9 STRENGTH COND J JI Strength Cond. J. PD AUG PY 2006 VL 28 IS 4 BP 70 EP 80 DI 10.1519/1533-4295(2006)028[0070:BABUOB]2.0.CO;2 PG 11 WC Sport Sciences SC Sport Sciences GA 078HF UT WOS:000240092600011 ER PT J AU Malin, JL Ko, C Ayanian, JZ Harrington, D Nerenz, DR Kahn, KL Ganther-Urmie, J Catalano, PJ Zaslavsky, AM Wallace, RB Guadagnoli, E Arora, NK Roudier, MD Ganz, PA AF Malin, Jennifer L. Ko, Clifford Ayanian, John Z. Harrington, David Nerenz, David R. Kahn, Katherine L. Ganther-Urmie, Julie Catalano, Paul J. Zaslavsky, Alan M. Wallace, Robert B. Guadagnoli, Edward Arora, Neeraj K. Roudier, Maryse D. Ganz, Patricia A. TI Understanding cancer patients' experience and outcomes: development and pilot study of the Cancer Care Outcomes Research and Surveillance patient survey SO SUPPORTIVE CARE IN CANCER LA English DT Article DE quality of health care; patterns of care; outcome assessment; process assessment; patient satisfaction; decision making; health disparities ID QUALITY-OF-LIFE; METASTATIC LUNG-CANCER; FUNCTIONAL LIVING INDEX; FORM HEALTH SURVEY; COLORECTAL-CANCER; CLINICAL-TRIALS; ADJUVANT CHEMOTHERAPY; RACIAL-DIFFERENCES; PROSTATE-CANCER; AGE AB Goals of work: The National Cancer Institute's Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium is conducting a population-based study of newly diagnosed patients with lung and colorectal cancer to describe the experience of persons living with cancer and to understand which barriers present the most significant obstacles to their receipt of appropriate care. The keystone to this effort is the baseline patient survey administered approximately 4 months after diagnosis. Patients and methods: We developed a survey to obtain information from patients newly diagnosed with lung and colorectal cancer about their personal characteristics, decision making, experience of care, and outcomes. We conducted a pilot study to evaluate the feasibility of a lengthy and clinically detailed interview in a convenience sample of patients within 8 months of diagnosis (n=71). Main results: The median length of the interviews was 75 min for patients with lung cancer (range 43-130) and 82 min for patients with colorectal cancer (range 46-119). Most patients had received some form of treatment for their cancer: 66.1% had undergone surgery, 28.2% had received radiation therapy, and 54.9% were treated with chemotherapy. In addition, 26.7% reported their overall health was less than 70 on a 0-100 scale, demonstrating that patients with substantial health impairment were able to complete the survey. Conclusions: A clinically detailed survey of newly diagnosed lung and colorectal cancer patients is feasible. A modified version of this survey is being fielded by the CanCORS Consortium and should provide much needed population-based data regarding patients' experiences across the continuum of cancer care and their outcomes. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med Hlth Serv Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Amgen Corp, Thousand Oaks, CA 91320 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Henry Ford Hlth Syst, Ctr Hlth Serv Res, Detroit, MI USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Natl Canc Inst, Outcomes Res Branch, ARP, DCCPS, Bethesda, MD USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Malin, JL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med Hlth Serv Res, Los Angeles, CA 90024 USA. EM jmalin@amgen.com FU NCI NIH HHS [U01 CA93348, U01 CA93329, U01 CA93332, U01 CA93326, U01 CA93344, U01 CA93324, U01 CA93339] NR 62 TC 61 Z9 61 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD AUG PY 2006 VL 14 IS 8 BP 837 EP 848 DI 10.1007/s00520-005-0902-8 PG 12 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 063MV UT WOS:000239023400008 PM 16482448 ER PT J AU Hawn, MT Itani, KM Giobbie-Hurder, A McCarthy, M Jonasson, O Neumayer, LA AF Hawn, Mary T. Itani, Kamal M. Giobbie-Hurder, Anita McCarthy, Martin, Jr. Jonasson, Olga Neumayer, Leigh A. TI Patient-reported outcomes after inguinal herniorrhaphy SO SURGERY LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Society-of-University-Surgewons/1st Annual Academic Surgical Congress CY FEB 07-11, 2006 CL San Diego, CA SP Assoc Acad Surg, Soc Univ Surg ID RANDOMIZED CONTROLLED TRIAL; QUALITY-OF-LIFE; HERNIA REPAIR; CHRONIC PAIN; CLINICAL-TRIAL; GROIN HERNIA; MESH REPAIR; LICHTENSTEIN; SURGERY AB Background. Patient-reported outcomes (PRO) reflect the functional outcomes of inguinal hemiorrhaphy. We studied the effect of hernia recurrence and complications on PRO for participants in the Veterans Affairs trial of Open or Laparoscopic Repair of Inguinal Hernia. Methods. Analyzed PRO included (1) the Medical Outcomes Study Short Form 36, version 2, (2) the Surgical Pain Scale, (3) the Activities Assessment Scale, and (4) patient satisfaction. Recurrences and complications were recorded at follow-up visits. Complications were categorized by (1) hematoma/seroma, (2) orchitis, (3) neuralgia, and (4) other. Univariate and multivariable regression analyses identified variables significantly associated with postoperative PRO. Results. Of the 1603 patients with PRO data, 105 had a recurrence and 342 had a complication at 2 years. Multivariable analyses showed neuralgia (P < .0005) adversely affected all PRO, and recurrence (P < .05) affected Patient-reported Pain, activity, and satisfaction, but not the score for the Medical Outcomes Study Short Form 3. Patients with a recurrence after open repair had more pain than those with a recurrence after laparoscopic repair (P = .0001). Patients with other complications after loparoscopic repair reported more pain and less activity than those with other complications after open repair (P = .003 and P =.009, respectively). Conclusions. The effectiveness of inguinal herniorrhaphy should be measured by the rate of recurrence and neuralgia. Postoperative neuralgias have a deleterious effect on all patient-reported outcomes. C1 Univ Alabama, Birmingham VA Med Ctr, Deep S Cent Effectiveness Res, Birmingham, AL USA. Univ Alabama, Dept Surg, Birmingham, AL USA. Boston Univ, Dept Surg, Boston, MA 02215 USA. VA Boston Hlth Care Syst, Dept Surg, W Roxbury, MA USA. VA Cooperat Studies Program Coordinating Ctr, Hines, IL USA. Northwestern Univ, Feinberg Sch Med, Dept Preventat Med, Chicago, IL 60611 USA. Univ Illinois, Coll Med, Dept Surg, Chicago, IL 60680 USA. Univ Utah, VA Med Ctr, Salt Lake City, UT 84112 USA. Univ Utah, Dept Surg, Salt Lake City, UT 84112 USA. RP Neumayer, LA (reprint author), VAMC 112, 500 Foothill Dr, Salt Lake City, UT 84148 USA. EM neumayer@hsc.utah.edu NR 21 TC 24 Z9 26 U1 0 U2 2 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 AUG PY 2006 VL 140 IS 2 BP 198 EP 205 DI 10.1016/j.surg.2006.02.003 PG 8 WC Surgery SC Surgery GA 077PX UT WOS:000240043200010 PM 16904970 ER PT J AU Alam, HB Chen, Z Li, YQ Velmahos, G DeMoya, M Keller, CE Toruno, K Mehrani, T Rhee, P Spaniolas, K AF Alam, Hasan B. Chen, Zheng Li, Yongqing Velmahos, George DeMoya, Marc Keller, Christopher E. Toruno, Kevin Mehrani, Tina Rhee, Peter Spaniolas, Konstantinos TI Profound hypothermia is superior to ultraprofound hypothermia in improving survival in a swine model of lethal injuries SO SURGERY LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Society-of-University-Surgeons/1st Annual Academic Surgical Congress CY FEB 07-11, 2006 CL San Diego, CA SP Assoc Acad Surg, Soc Univ Surg ID CIRCULATORY ARREST; CARDIOPULMONARY BYPASS; HEMORRHAGE; DOGS; RESUSCITATION; METABOLISM; SURGERY; NEURONS; DEATH; FLOW AB Background. Rapid induction of profound hypothermia can improve survival from uncontrolled lethal hemorrhage. However, the optimal depth of hypothermia in this setting remains unknown. This experiment was designed to compare the impact of deep (15 degrees C), profound (10 degrees C), and ultraprofound (5 degrees C) hypothermia on survival and organ functions. Methods. Uncontrolled lethal hemorrhage was induced in 32 swine (80-120 lb) by creating an iliac artery and vein injury, followed 30 minutes later by laceration of the descending thoracic aorta. Hypothermia was induced rapidly (2 degrees C/min) by infusing cold organ preservation solution into the aorta through a thoracotomy. The experimental groups were (n = 8 Per group): a normothermic control, and 3 hypothermic groups in which the core temperature was reduced to 15 degrees C, 10 degrees C, and 5 degrees C Vascular injuries were repaired during 60 minutes of hypothermia. Animals were then rewarmed (0.5 degrees C/min) and resuscitated on cardiopulmonary bypass, and monitored for 6 weeks for neurologic deficits, cognitive function, and organ dysfunction. Results. All normothermic animals died, whereas 6-week survival rates for the 15 degrees C, 10 degrees C, and 5 degrees C groups were 62.5%, 8 7.5%, and 25%, respectively (P <.05: normothermic vs 15 degrees C and 10 degrees C; 10 degrees C vs 5 degrees C). The surviving animals,from the 15 degrees C and 10 degrees C groups were neurologically intact, displayed normal learning capacity, and had no long-term organ dysfunction. The survivors from the 5 T group displayed slower recovery and impaired cognitive functions. Conclusions. In. a model of lethal injuries, rapid induction of profound hypothermia can prevent death. The depth of hypothermia influences survival, with a better outcome associated with a core temperature of 10 degrees C compared with 5 degrees C. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02114 USA. Uniformed Serv Univ Hlth Sci, Trauma Res & Readiness Inst Surg, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Ctr Lab Anim Med, Bethesda, MD 20814 USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM hbalam@partners.org FU NHLBI NIH HHS [R01 HL71698] NR 27 TC 31 Z9 31 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2006 VL 140 IS 2 BP 307 EP 314 DI 10.1016/j.surg.2006.03.015 PG 8 WC Surgery SC Surgery GA 077PX UT WOS:000240043200024 PM 16904984 ER PT J AU Sands, BE AF Sands, Bruce E. TI New therapies for the treatment of inflammatory bowel disease SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID ACTIVE CROHNS-DISEASE; PLACEBO-CONTROLLED TRIAL; NECROSIS-FACTOR-ALPHA; RANDOMIZED CONTROLLED-TRIAL; SEVERE ULCERATIVE-COLITIS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; INTERCELLULAR-ADHESION MOLECULE-1; COLONY-STIMULATING FACTOR; MONOCLONAL-ANTIBODY CA2; TRICHURIS-SUIS THERAPY AB Medical therapy for inflammatory bowel diseases has evolved rapidly over the last decade with the adoption of immune modulators such as 6-mercaptopurine, azathioprine, and methotrexate, and the introduction of infliximab, a chimeric antitumor necrosis factor alpha antibody. Greater explication of the immune and inflammatory mechanisms underlying Crohn's disease and ulcerative colitis has facilitated an abundance of treatments with novel targets and mechanisms of action. These include biologics such as monoclonal antibodies, soluble receptors, cytokines and peptides; and small molecules, including organic compounds and antisense oligonucleotides; medical devices; and live agents with immune-modulating properties. Many of these are likely to reach clinicians in the coming years, increasing the need to understand their mechanisms, potential for efficacy, and possible pitfalls. C1 Massachusetts Gen Hosp, MGH Crohns & olitis Ctr, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, MGH Crohns & olitis Ctr, Gastrointestinal Unit, 165 cambridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org NR 70 TC 11 Z9 12 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD AUG PY 2006 VL 86 IS 4 BP 1045 EP + DI 10.1016/j.suc.2006.05.009 PG 21 WC Surgery SC Surgery GA 086CE UT WOS:000240649900015 PM 16905423 ER PT J AU Choi, JK Mandeville, JB Chen, YI Kim, YR Jenkins, BG AF Choi, JK Mandeville, JB Chen, YI Kim, YR Jenkins, BG TI High resolution spatial mapping of nicotine action using pharmacologic magnetic resonance imaging SO SYNAPSE LA English DT Article DE rats; choline; dopamine; MRI; cerebral blood volume; hemodynamics ID CEREBRAL GLUCOSE-UTILIZATION; RAT-BRAIN; TOBACCO SMOKERS; FUNCTIONAL MRI; BINDING-SITES; BLOOD-FLOW; ACTIVATION; SMOKING; SENSITIVITY; SUBUNIT AB Nicotine is one of the most addictive substances known. To better understand the mechanisms of action, we mapped the regional brain response to nicotine administration using pharmacologic magnetic resonance imaging (phMRI) in rats. We measured the regional response of relative cerebral blood volume (rCBV) in rats to a challenge of 0.07 mg/kg (0.43 mu mol/kg) of nicotine. The areas of the brain with significant and reproducible changes in the rCBV response were (in descending order of magnitude) infralimbic cortex, hippocampus (subiculum), agranular insular/pyriform cortex, visual cortex, interpeduncular area, nucleus accumbens, cingulate cortex, thalamus, and septum. This pattern of response is consistent with stimulation of both cholinergic and dopaminergic neuronal pathways and is consistent with the known behavioral properties of nicotine. The peak CBV response to nicotine occurred between 9 and 13 min depending upon brain region, and the average full width half-maximum of the rCBV response was 27 min. The high spatial and temporal resolution of the phMRI technique lends itself well to further, more detailed, studies of nicotine dynamics. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Jenkins, BG (reprint author), Harvard Univ, Sch Med, Dept Radiol, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bgj@nmr.mgh.harvard.edu FU NIDA NIH HHS [R01 DA16187, 5P01 DA09467] NR 25 TC 14 Z9 15 U1 0 U2 0 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 AUG PY 2006 VL 60 IS 2 BP 152 EP 157 DI 10.1002/syn.20284 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 052MT UT WOS:000238238500008 PM 16715493 ER PT J AU Stein, PD Beemath, A Goodman, LR Hales, CA Hull, RD Sostman, HD Weg, JG AF Stein, Paul D. Beemath, Afzal Goodman, Lawrence R. Hales, Charles A. Hull, Russell D. Sostman, H. Dirk Weg, John G. TI Outcome studies of pulmonary embolism versus accuracy: They do not equate SO THROMBOSIS AND HAEMOSTASIS LA English DT Editorial Material ID COMPUTED-TOMOGRAPHY; LOW-PROBABILITY; SCAN C1 St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI 48341 USA. Wayne State Univ, Dept Med, Detroit, MI 48202 USA. Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Calgary, Dept Med, Calgary, AB T2N 1N4, Canada. Weill Cornell Med Coll, Off Dean, Houston, TX USA. Methodist Hosp, Houston, TX 77030 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland Hosp, Dept Res, 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinp@trinity-health.org FU NHLBI NIH HHS [HL63928, HL63982, HL63940] NR 11 TC 9 Z9 9 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 2006 VL 96 IS 2 BP 107 EP 108 DI 10.1160/TH06-07-0363 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 075QK UT WOS:000239900100002 PM 16894448 ER PT J AU Husain, Z Almeciga, I Delgado, JC Clavijo, OP Castro, JE Belalcazar, V Pinto, C Zuniga, J Romero, V Yunis, EJ AF Husain, Zaheed Almeciga, Ingrid Delgado, Julio C. Clavijo, Olga P. Castro, Januario E. Belalcazar, Viviana Pinto, Clara Zuniga, Joaquin Romero, Viviana Yunis, Edmond J. TI Increased FasL expression correlates with apoptotic changes in granulocytes cultured with oxidized clozapine SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE apoptosis; clozapine; Fas; FasL; granulocytes; retinoic acid ID MAJOR HISTOCOMPATIBILITY COMPLEX; DIFFERENT ETHNIC-GROUPS; FC-GAMMA-RIII; INDUCED AGRANULOCYTOSIS; NEUTROPHIL APOPTOSIS; IN-VITRO; SODIUM-BUTYRATE; GENE-EXPRESSION; HL-60 CELLS; RECEPTOR AB Clozapine has been associated with a 1% incidence of agranulocytosis. The formation of an oxidized intermediate clozapine metabolite has been implicated in direct polymorphonuclear (PMN) toxicity. We utilized two separate systems to analyze the role of oxidized clozapine in inducing apoptosis in treated cells. Human PMN cells incubated with clozapine (0-10 mu M) in the presence of 0.1 mM H2O2 demonstrated a progressive decrease of surface CD16 expression along with increased apoptosis. RT-PCR analysis showed decreased CD16 but increased FasL gene expression in clozapine-treated PMN cells. No change in constitutive Fas expression was observed in treated cells. In HL-60 cells induced to differentiate with retinoic acid (RA), a similar increase in FasL expression, but no associated changes in CD16 gene expression, was observed following clozapine treatments. Our results demonstrate increased FasL gene expression in oxidized clozapine-induced apoptotic neutrophils suggesting that apoptosis in granulocytes treated with clozapine involves Fas/FasL interaction that initiates a cascade of events leading to clozapine-induced agranulocytosis. (c) 2006 Elsevier Inc. All rights reserved.. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Inst Nacl Enfermed Resp, Mexico City, DF, Mexico. RP Yunis, EJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM edmond_yunis@dfci.harvard.edu FU NHLBI NIH HHS [HL-29583]; NIMH NIH HHS [MH-47029] NR 44 TC 14 Z9 14 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG 1 PY 2006 VL 214 IS 3 BP 326 EP 334 DI 10.1016/j.taap.2006.01.008 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 070LJ UT WOS:000239523600013 PM 16510162 ER PT J AU Abdel-Wahab, OI Healy, B Dzik, WH AF Abdel-Wahab, Omar I. Healy, Brian Dzik, Walter H. TI Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities SO TRANSFUSION LA English DT Article ID CHRONIC LIVER-DISEASE; COAGULOPATHY; PLACEMENT; BIOPSY; AUDIT AB BACKGROUND: Fresh-frozen plasma (FFP) is frequently transfused to patients with mild prolongation of coagulation values under the assumption that FFP will correct the coagulopathy. There is little evidence to support this practice, however. To determine the effect of FFP on coagulation variables and correlation with bleeding in patients with mildly prolonged coagulation values, a prospective audit of all FFP transfusions at the Massachusetts General Hospital between September 2, 2004, and September 30, 2005, was performed. STUDY DESIGN AND METHODS: All patients transfused with FFP for a pretransfusion prothrombin time ( PT) between 13.1 and 17 seconds ( international normalized ratio [INR], 1.1-1.85) and with a follow-up PT-INR within 8 hours of transfusion were included. Of 1091 units of FFP transfused, follow-up coagulation values within 8 hours were available for 121 patients ( 324 units). RESULTS: Transfusion of FFP resulted in normalization of PT-INR values in 0.8 percent of patients (95% confidence interval [CI], 0.0020-0.045) and decreased the PT-INR value halfway to normalization in 15.0 percent of patients ( 95% CI, 0.097-0.225). Median decrease in PT was 0.20 seconds ( median decrease in INR, 0.07). Pretransfusion PT-INR, partial thromboplastin time, platelet count, and creatinine values had no correlation with red blood cell loss. CONCLUSION: It is concluded that transfusion of FFP for mild abnormalities of coagulation values results in partial normalization of PT in a minority of patients and fails to correct the PT in 99 percent of patients. C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Gray Jackson Bldg,Room 224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 20 TC 157 Z9 165 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2006 VL 46 IS 8 BP 1279 EP 1285 DI 10.1111/j.1537-2995.2006.00891.x PG 7 WC Hematology SC Hematology GA 066VZ UT WOS:000239259800005 PM 16934060 ER PT J AU Melanson, SEF Stowell, CP Flood, JG Lewandrowski, EL Zak, RJ Lewandrowski, KB AF Melanson, Stacy E. F. Stowell, Christopher P. Flood, James G. Lewandrowski, Elizabeth Lee Zak, Rychard J. Lewandrowski, Kent B. TI Does blood donor history accurately reflect the use of prescription medications? A comparison of donor history and serum toxicologic analysis SO TRANSFUSION LA English DT Article ID NONHEMOLYTIC TRANSFUSION REACTIONS; PHOTODIODE-ARRAY DETECTION; INJECTION-DRUG USERS; HEPATITIS-B; LIQUID-CHROMATOGRAPHY; SCREENING QUESTIONS; RISK BEHAVIORS; DONATED BLOOD; PREVALENCE; HIV AB Background: Blood donor screening is performed to accomplish several goals, including donor safety during collection and recipient safety during transfusion. Donors taking certain medications such as teratogens or platelet-inhibiting drugs are deferred from donation. Studies investigating the accuracy of the donor history are limited and only provide data on select groups of drugs. This study compares the results of an extended serum toxicology analysis to the medication use reported on the donor questionnaire. Study design and Methods: Whole-blood samples were collected from 108 volunteer blood donors. A serum toxicology analysis was performed with high-performance liquid chromatography with photodiode array detection. The results were compared to those reported on the donor history questionnaire. Results: The medication history was consistent with the reported medications in 96 (89%) donors. Serum toxicology testing detected medications that were not reported on the donor history form in 12 (11%) donors. Most of the donors who did not accurately report their medication use (8 or 67%) were taking psychotropic medications. Conclusion: Eleven percent of the donors did not fully disclose their recent medication history. Although none of the omitted medications would have been grounds for deferral, the finding of underreporting questions the reliability of donor screening. Despite a negative medication history, blood donor centers cannot assume that donors are medication-free. This study reveals a bias to omit psychotropic medications such as antidepressants and anxiolytics. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Lab Med,Dept Pathol, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Lab Med,Dept Pathol, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 33 TC 7 Z9 7 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2006 VL 46 IS 8 BP 1402 EP 1407 DI 10.1111/j.1537-2995.2006.00909.x PG 6 WC Hematology SC Hematology GA 066VZ UT WOS:000239259800023 PM 16934078 ER PT J AU Wong, WC Agrawal, N Pascual, M Anderson, DC Hirsch, HH Fujimoto, K Cardarelli, F Winkelmayer, WC Cosimi, AB Tolkoff-Rubin, N AF Wong, WC Agrawal, N Pascual, M Anderson, DC Hirsch, HH Fujimoto, K Cardarelli, F Winkelmayer, WC Cosimi, AB Tolkoff-Rubin, N TI Comparison of two dosages of thymoglobulin used as a short-course for induction in kidney transplantation SO TRANSPLANT INTERNATIONAL LA English DT Article DE antilymphocyte globulin; induction therapy; kidney transplantation; lymphocytes; thymoglobulin ID NONHUMAN PRIMATE MODEL; RENAL-TRANSPLANTATION; ANTITHYMOCYTE GLOBULIN; FOLLOW-UP; RECIPIENTS; THERAPY; NEPHROPATHY; RABBIT; TRIAL; IMMUNOSUPPRESSION AB Thymoglobulin is used effectively as an induction agent in kidney transplantation, but the optimal dose is not well established. We evaluated the degree and durability of T-cell clearances with two different thymoglobulin regimens in adult kidney transplant recipients (KTR). Seven KTR received a 3-day thymoglobulin-based induction of 1.0 mg/kg/day while nine received 1.5 mg/kg/day, in addition to maintenance immunosuppression. Lymphocyte subsets were monitored for 6 months. Renal function, infections and malignancies were monitored for 24 months. T-cell subsets were significantly lower by day 30 with the thymoglobulin 1.5 mg/kg/day regimen when compared with the 1.0 mg/kg/day regimen; this trend was sustained at 6-month (CD3(+): 438 +/- 254 vs. 1001 +/- 532 cells/mm(3), P = 0.016). Renal function between the two groups was not significantly different at 6- and 24-months post-transplant. One case of BK Virus viremia in the 1.5 mg/kg/day thymoglobulin group was detected. No acute rejection episodes, cytomegalovirus infections, or malignancies were noted in either group. Thymoglobulin induction was efficacious in both groups, but with a significantly sustained T-cell clearance in the 1.5 mg/kg/day regimen. A more profound T-cell clearance within the first 6 months postinduction therapy may translate into a decreased risk of immunological injury and improved long-term outcome after kidney transplantation. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CHU Vaudois, Transplant Ctr, CH-1011 Lausanne, Switzerland. Massachusetts Gen Hosp, Dept Immunopathol, Boston, MA 02114 USA. Univ Basel Hosp, Dept Infect Dis, CH-4031 Basel, Switzerland. Univ Parma, Clin Med & Nefrol, I-43100 Parma, Italy. Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharrmacoecon, Boston, MA 02115 USA. RP Wong, WC (reprint author), Massachusetts Gen Hosp, Renal Unit, POB MZ 70,55 Fruit St, Boston, MA 02114 USA. EM wwong@partners.org NR 25 TC 24 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD AUG PY 2006 VL 19 IS 8 BP 629 EP 635 DI 10.1111/j.1432-2277.2006.00270.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 059RX UT WOS:000238751000003 PM 16827679 ER PT J AU Efstathiou, JA Chen, MH Catalona, WJ McLeod, DG Carroll, PR Moul, JW Roehl, KA D'Amico, AV AF Efstathiou, Jason A. Chen, Ming-Hui Catalona, William J. McLeod, David G. Carroll, Peter R. Moul, Judd W. Roehl, Kimberly A. D'Amico, Anthony V. TI Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; RADIATION-THERAPY; ANDROGEN ABLATION; PRACTICE PATTERNS; ERA; PREDICTORS; DATABASE; PROGRAM AB Objectives. To compare the preoperative characteristics, postoperative prostate-specific antigen (PSA) doubling time (DT), and prostate cancer-specific mortality (PCSM) estimates after PSA failure in men diagnosed during a screening study versus a community referral population. A PSA-DT of less than 3 months is a surrogate endpoint for PCSM. Methods. From 1988 to 2002, 1492 of 9637 patients with clinically localized prostate cancer underwent radical prostatectomy and experienced PSA failure. They were either participating in a screening study (n = 841) or attended 1 of 44 community-based practices (n = 611). The distributions of PSA, Gleason score, tumor stage, and PSA-DT were compared using chi-square metric. The estimates of PCSM after PSA failure were compared using Gray's P value. Results. Compared with the community population, the annually screened men experiencing PSA failure had a lower PSA level at diagnosis (5.1 versus 9.5 ng/mL, P < 0.0001), were less likely to have Gleason score 7 to 10 cancer (25.1 % versus 42.1 %, P < 0.0001), and were more likely to have low-risk disease (64.5% versus 23.8%, P < 0.0001). Furthermore, the screened cohort had a reduction (P < 0.0001) in the proportion with a PSA-DT of less than 3, 3 to 5.99, and 6 to 11.99 months and a significant increase in the proportion with a PSA-DT of 12 months or longer. After a median follow-up of 4.5 and 4.1 years after PSA failure in the screened and community cohorts, respectively, the PCSM estimates were lower (P = 0.0002) in the screened cohort (10-year estimate 3.6% [95% confidence interval 1.3 to 5.8] versus 11.3% [95% confidence interval 5.9 to 17.4]). Conclusions. Patients diagnosed by annual prostate cancer screening appeared more likely to experience an indolent PSA recurrence and less likely to die of prostate cancer after PSA recurrence compared with patients referred from the community. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Urol Serv, Ctr Prostate Dis Res, Bethesda, MD USA. Walter Reed Army Med Ctr, Bethesda, MD USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Duke Univ, Med Ctr, Div Urol Surg, Durham, NC USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA. RP Efstathiou, JA (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,12, Boston, MA 02115 USA. EM jefstathiou@partners.org NR 30 TC 28 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 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2006 VL 68 IS 2 BP 342 EP 347 DI 10.1016/j.urology.2006.02.030 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 084WT UT WOS:000240565800025 PM 16904449 ER PT J AU Hurwitz, MD Schultz, D Richie, JP Wein, AJ Whittington, R Malkowicz, SB D'Amico, AV AF Hurwitz, Mark D. Schultz, Delray Richie, Jerome P. Wein, Alan J. Whittington, Richard Malkowicz, S. Bruce D'Amico, Anthony V. TI Radical prostatectomy for high-grade prostate cancer SO UROLOGY LA English DT Article ID THERAPY ONCOLOGY GROUP; BEAM RADIATION-THERAPY; BIOPSY GLEASON SCORE; PHASE-III TRIAL; ANDROGEN DEPRIVATION; CLINICAL UTILITY; RADIOTHERAPY; CARCINOMA; ADENOCARCINOMA; RECURRENCE AB Objectives. Patients with high-grade clinically localized disease often have disease beyond the prostate and, if so, are unlikely to benefit from radical prostatectomy in the long-term. The objective of this study was to assess whether use of other known prognostic factors could be helpful in defining which men with Gleason 8 to 10 prostate cancer are most likely to benefit from surgical management. Methods. A retrospective analysis was performed on men with biopsy Gleason 8 to 10 prostate cancer who underwent radical prostatectomy at two major university centers. No patients received hormonal therapy as part of initial treatment or adjuvant radiation therapy. Surgery was performed using a retropubic approach, and lymph node dissection was performed in all patients. Risk groups were defined based on prostate-specific antigen (PSA) value and percent positive biopsy cores (%PBC). A Cox proportional hazards analysis was performed to assess for differences in pretreatment prognostic factors. Kaplan-Meier curves were generated for each group, and then comparisons between groups were performed using log-rank analysis to assess for differences in 5-year actuarial freedom from biochemical failure. Results. Radical prostatectomy was performed on 196 patients between 1987 and 2002, of whom 168 had sufficient data for analysis. Median follow-up was 18 months (range, I to 130 months), with 31 patients at risk for more than 5 years. Patients with a PSA value of less than 10 ng/mL and %PBC of less than 50% had a 5-year actuarial biochemical control rate of 67% versus 23% for all other patients (P = 0.0001). Conclusions. PSA value and %PBC are useful in selecting patients with high-grade prostate cancer most likely to benefit by radical prostatectomy. C1 Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Hurwitz, MD (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM mhurwitz@lroc.harvard.edu NR 20 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2006 VL 68 IS 2 BP 367 EP 370 DI 10.1016/j.urology.2006.02.024 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 084WT UT WOS:000240565800030 PM 16904454 ER PT J AU Diaz-Griffero, F Vandegraaff, N Li, Y McGee-Estrada, K Stremlau, M Welikala, S Si, ZH Engelman, A Sodroski, J AF Diaz-Griffero, Felipe Vandegraaff, Nick Li, Yuan McGee-Estrada, Kathleen Stremlau, Matthew Welikala, Sohanya Si, Zhihai Engelman, Alan Sodroski, Joseph TI Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1 SO VIROLOGY LA English DT Article DE HIV; restriction factors; cyclophilin; capsid; uncoating; retrovirus; reverse transcription; tropism ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN CYCLOPHILIN-A; NEW-WORLD PRIMATES; OWL MONKEY CELLS; RETROVIRAL RESTRICTION; SIMIAN IMMUNODEFICIENCY; TRIM5-ALPHA DETERMINES; POSTENTRY RESTRICTION; CRYSTAL-STRUCTURE; HOST RESTRICTION AB In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5 alpha with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Sch Med,Dept Pathol,Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Sch Med,Dept Pathol,Div AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Yuan/B-4098-2013 FU NHLBI NIH HHS [HL 54785]; NIAID NIH HHS [AI 28691, AI 063987, AI 45405] NR 54 TC 60 Z9 64 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 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 2006 VL 351 IS 2 BP 404 EP 419 DI 10.1016/j.virol.2006.03.023 PG 16 WC Virology SC Virology GA 072CF UT WOS:000239649500015 PM 16650449 ER PT J AU Sarr, MG Warshaw, AL AF Sarr, Michael G. Warshaw, Andrew L. TI Ethical misconduct in publishing: the editors' perspective SO WORLD JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT International Surgical Week Conference CY AUG 21-25, 2005 CL Durban, SOUTH AFRICA ID JOURNAL-EDITORS; STATEMENT C1 Mayo Clin Coll Med, Gastroenterol Res Unit AL2 435, Rochester, MN 55905 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Sarr, MG (reprint author), Mayo Clin Coll Med, Gastroenterol Res Unit AL2 435, 200 1st St SW, Rochester, MN 55905 USA. EM sarr.michael@mayo.edu NR 7 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD AUG PY 2006 VL 30 IS 8 BP 1374 EP 1376 DI 10.1007/s00268-005-0646-0 PG 3 WC Surgery SC Surgery GA 071VF UT WOS:000239631300005 PM 16773251 ER PT J AU Vogel, M Lichterfeld, M Kaufmann, DE Mui, SK Altfeld, M Voigt, E Ahlenstiel, G Kupfer, B Walker, B Spengler, U Rockstroh, JK AF Vogel, M. Lichterfeld, M. Kaufmann, D. E. Mui, S. K. Altfeld, M. Voigt, E. Ahlenstiel, G. Kupfer, B. Walker, B. Spengler, U. Rockstroh, J. K. TI Structured treatment interruptions following immediate initiation of HAART in eight patients with acute HIV-1 seroconversion SO EUROPEAN JOURNAL OF MEDICAL RESEARCH LA English DT Article; Proceedings Paper CT 9th European AIDS Conference CY OCT 25-29, 2003 CL Warsaw, POLAND DE HIV-1; primary HIV-1 infection; HAART; investigational therapies; structured treatment interruption ID T-CELL RESPONSES; VIRAL CONTROL; INFECTION; CD4(+); NONPROGRESSORS; PROLIFERATION; REPLICATION; PATTERNS; VIREMIA; GENE AB Background: The immunological and clinical benefits of structured treatment interruptions (STIs) during primary HIV-1 infection remain largely unclear. Patients and Methods: Eight patients identified during primary HIV-1 infection were immediately treated with HAART and underwent subsequent STIs after reaching complete viral suppression of HIV-RNA in peripheral plasma. HAART was re-initiated if either HlV-1 RNA >5000 copies/ml, CD4-cells <200 cells/mu l or symptomatic HIV-1 disease was observed. Results: After treatment discontinuation, four of eight patients were able to persistently control HIV-1 viremia below 5000 copies/ml until the last time point of follow-up (median 3 years). CD4-cell counts were within the interquartile range of untreated individuals compared to historical reference data from the MACS cohort. In the remaining study subjects persistent virological control was not reached despite repeated STIs. Moreover, compared to the MACS cohort repetitive virological failures during STIs appeared to induce an accelerated decline of CD4-cells. Conclusion: Spontaneous HIV-1 control after treated primary HIV-1 infection was possible in four out of eight individuals, however, if STIs after treated primary infection ameliorate the overall HIV-1 disease progression remains unknown. In the absence of viral control, repetitive viral exposure during STIs might be associated with accelerated decline of CD4-cell counts. C1 Univ Bonn, Immunol Ambulanz Med Klin & Poliklin 1, Dept Internal Med 1, D-53127 Bonn, Germany. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Univ Bonn, Inst Med Microbiol & Immunol, D-5300 Bonn, Germany. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Rockstroh, JK (reprint author), Univ Bonn, Immunol Ambulanz Med Klin & Poliklin 1, Dept Internal Med 1, Sigmund Freud Str 25, D-53127 Bonn, Germany. EM juergen.rockstroh@ukb.uni-bonn.de OI Ahlenstiel, Golo/0000-0003-0026-1457 FU NCRR NIH HHS [5-M01-RR-00052]; NIAID NIH HHS [U01-AI-37613, U01-AI-35039, U01-AI-35040, U01-AI-35041, U01-AI-35042, U01-AI-35043, U01-AI-37984] NR 23 TC 1 Z9 2 U1 0 U2 4 PU I HOLZAPFEL VERLAG GMBH PI MUNICH PA RAUCHSTR 8, D-81679 MUNICH, GERMANY SN 0949-2321 J9 EUR J MED RES JI Eur. J. Med. Res. PD JUL 31 PY 2006 VL 11 IS 7 BP 273 EP 278 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 075XT UT WOS:000239921600002 PM 16899420 ER PT J AU Swarztrauber, K Graf, E Cheng, E AF Swarztrauber, Kari Graf, Eric Cheng, Eric TI The quality of care delivered to Parkinson's disease patients in the US Pacific Northwest Veterans Health System SO BMC NEUROLOGY LA English DT Article ID NURSING-HOME PLACEMENT; DEPRESSION; FALLS AB Background: Parkinson's disease (PD) is the second most common chronic neurological disorder of the elderly. Despite the fact that a comprehensive review of general health care in the United States showed that the quality of care delivered to patients usually falls below professional standards, there is limited data on the quality of care for patients with PD. Methods: Using the administrative database, the Pacific Northwest Veterans Health Administration (VHA) Data Warehouse, a population of PD patients with encounters from 10/1/98-12/31/04 were identified. A random sample of 350 patient charts underwent further review for diagnostic evaluation. All patients whose records revealed a physician diagnosis of definite or possible Idiopathic Parkinson's (IPD) disease (n=150) were included in a medical chart review to evaluate adherence to five evidence-based quality of care indicators. Results: For those care indicators with good inter-rater reliability, 16.6% of care received by PD patients was adherent for annual depression screening, 23.4% of care was adherent for annual fall screening and, 67.3% of care was adherent for management of urinary incontinence. Patients receiving specialty care were more likely to be adherent with fall screening than those not receiving specialty care OR=2.3, 95% CI=1.2-4.2, but less likely to be adherent with management of urinary incontinence, OR=0.3, 95% CI=0.1-0.8. Patients receiving care outside the VA system were more likely to be adherent with depression screening OR=2.4, 95% CI=>1.0-5.5 and fall screening OR=2.2, 95% CI=1.1-4.4. Conclusion: We found very low rates of adherence for annual screening for depression and falls for PD patients but reasonable adherence rates for management of urinary incontinence. Interestingly, receiving concurrent specialty care did not necessarily result in higher adherence for all care indicators suggesting some coordination and role responsibility confusion. The increased adherence in PD patients receiving care outside the VA system suggests that patients with outside care may demand better care within the VA system. C1 Providence Hlth Syst, Newberg, OR 97132 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. VA Greater Los Angeles Healthcare Syst, Parkinsons Dis Res Educ & Clin Ctr, Los Angeles, CA USA. RP Swarztrauber, K (reprint author), Providence Hlth Syst, Newberg, OR 97132 USA. EM swarztra@stanfordalumni.org; grafe@ohsu.edu; eric.cheng@med.va.gov NR 19 TC 3 Z9 4 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD JUL 28 PY 2006 VL 6 AR 26 DI 10.1186/1471-2377/6/26 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 074GA UT WOS:000239799500001 PM 16875503 ER PT J AU Dykxhoorn, DM Lieberman, J AF Dykxhoorn, Derek M. Lieberman, Judy TI Knocking down disease with siRNAs SO CELL LA English DT Editorial Material ID SMALL INTERFERING RNA; FAS PROTECTS MICE; IN-VIVO; GENE; INHIBITION; EXPRESSION; MICRORNAS C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NIAID NIH HHS [U19 AI056900] NR 23 TC 135 Z9 142 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 28 PY 2006 VL 126 IS 2 BP 231 EP 235 DI 10.1016/j.cell.2006.07.007 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 070VD UT WOS:000239552600005 PM 16873051 ER PT J AU Wu, YQ Borde, M Heissmeyer, V Feuerer, M Lapan, AD Stroud, JC Bates, DL Guo, L Han, AD Ziegler, SF Mathis, D Benoist, C Chen, L Rao, A AF Wu, Yongqing Borde, Madhuri Heissmeyer, Vigo Feuerer, Markus Lapan, Ariya D. Stroud, James C. Bates, Darren L. Guo, Liang Han, Aidong Ziegler, Steven F. Mathis, Diane Benoist, Christophe Chen, Lin Rao, Anjana TI FOXP3 controls regulatory T cell function through cooperation with NFAT SO CELL LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; NUCLEAR FACTOR; KAPPA-B; FORKHEAD-DOMAIN; GENE-EXPRESSION; DNA; SCURFIN; ANTIGEN; CALCINEURIN; MECHANISMS AB Antigen stimulation of immune cells activates the transcription factor NFAT, a key regulator of T cell activation and anergy. NFAT forms cooperative complexes with the AP-1 family of transcription factors and regulates T cell activation-associated genes. Here we show that regulatory T cell (Treg) function is mediated by an analogous cooperative complex of NFAT with the forkhead transcription factor FOXP3, a lineage specification factor for Tregs. The crystal structure of an NFAT:FOXP2:DNA complex reveals an extensive protein-protein interaction interface between NFAT and FOXP2. Structure-guided mutations of FOXP3, predicted to progressively disrupt its interaction with NFAT, interfere in a graded manner with the ability of FOXP3 to repress expression of the cytokine IL2, upregulate expression of the Treg markers CTLA4 and CD25, and confer suppressor function in a murine model of autoimmune diabetes. Thus by switching transcriptional partners, NFAT converts the acute T cell activation program into the suppressor program of Tregs. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Brigham & Womens Hosp,Sect Immunol & Immunogenet, Boston, MA 02115 USA. Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Univ Washington, Benaroya Res Inst Virginia Mason, Seattle, WA 98195 USA. RP Chen, L (reprint author), Univ So Calif, 1050 Childs Way, Los Angeles, CA 90089 USA. EM linchen@usc.edu; arao@cbr.med.harvard.edu RI Chen, Lin/A-3392-2008; Stroud, James/B-3230-2012 OI Stroud, James/0000-0003-0850-4812 FU NIGMS NIH HHS [R01 GM077320, T32 GM008759] NR 51 TC 610 Z9 648 U1 5 U2 27 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUL 28 PY 2006 VL 126 IS 2 BP 375 EP 387 DI 10.1016/j.cell.2006.05.042 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 070VD UT WOS:000239552600022 PM 16873067 ER PT J AU Gooz, M Gooz, P Luttrell, LM Raymond, JR AF Gooz, Monika Gooz, Pal Luttrell, Louis M. Raymond, John R. TI 5-HT2A receptor induces ERK phosphorylation and proliferation through ADAM-17 tumor necrosis factor-alpha-converting enzyme (TACE) activation and heparin-bound epidermal growth factor-like growth factor (HB-EGF) shedding in mesangial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; DIPHTHERIA-TOXIN RECEPTOR; METALLOPROTEASE-DISINTEGRINS; LYSOPHOSPHATIDIC ACID; CARDIAC-HYPERTROPHY; TNF-ALPHA; BINDING; TRANSACTIVATION; EXPRESSION; CLEAVAGE AB In this study, we present multiple lines of evidence to support a critical role for heparin-boundEGF( epidermal growth factor)like growth factor (HB-EGF) and tumor necrosis factor-alpha-converting enzyme (TACE) (ADAM17) in the transactivation of EGF receptor (EGFR), ERK phosphorylation, and cellular proliferation induced by the 5-HT2A receptor in renal mesangial cells. 5-hydroxy-tryptamine (5-HT) resulted in rapid activation of TACE, HB-EGF shedding, EGFR activation, ERK phosphorylation, and longer term increases in DNA content in mesangial cells. ERK phosphorylation was attenuated by 1) neutralizing EGFR antibodies and the EGFR kinase inhibitor, AG1478, 2) neutralizing HB-EGF, but not amphiregulin, antibodies, heparin, or CM197, and 3) pharmacological inhibitors of matrix-degrading metalloproteinases or TACE small interfering RNA. Exogenously administered HB-EGF stimulated ERK phosphorylation. Additionally, TACE was co-immunoprecipitated with HB-EGF. Small interfering RNA against TACE also blocked 5-HT-induced increases in ERK phosphorylation, HB-EGF shedding, and DNA content. In aggregate, this work supports a pathway map that can be depicted as follows: 5-HT -> 5-HT2A receptor -> TACE -> HB-EGF shedding -> EGFR -> ERK -> increased DNA content. To our knowledge, this is the first time that TACE has been implicated in 5-HT-induced EGFR transactivation or in proliferation induced by a G protein-coupled receptor in native cells in culture. C1 Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Div Rheumatol, Charleston, SC 29425 USA. Med Univ S Carolina, Div Endocrinol, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29425 USA. RP Gooz, M (reprint author), Med Univ S Carolina, Div Nephrol, CSB 829,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM beckm@musc.edu FU NCRR NIH HHS [P20 RR016434]; NIDDK NIH HHS [DK070054-01, R01 DK55524]; NIGMS NIH HHS [R01 GM-63909] NR 50 TC 64 Z9 64 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 28 PY 2006 VL 281 IS 30 BP 21004 EP 21012 DI 10.1074/jbc.M512096200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 065VF UT WOS:000239187300037 PM 16737974 ER PT J AU Galande, AK Hilderbrand, SA Weissleder, R Tung, CH AF Galande, Amit K. Hilderbrand, Scott A. Weissleder, Ralph Tung, Ching-Hsuan TI Enzyme-targeted fluorescent imaging probes on a multiple antigenic peptide core SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CATHEPSIN-S; DESIGN; EXPRESSION; PROTEASES; CANCER; TUMORS AB Peptide dendrimers have a variety of applications in biology such as the vehicles for drug and gene delivery, molecular inhibitors, protein mimics, and synthetic vaccines. The multiple antigenic peptide (MAP) system is a well-known example of a discrete, dendrimeric scaffold. We explored a novel application of the MAP-based scaffold by designing molecular probes that fluoresce only after enzymatic treatment. The probes, which were synthesized on solid support, incorporate a cathepsin S dipeptide substrate (Leu-Arg), and a poly(ethylene glycol) (PEG) chain in their dendritic arms. The fluorescence emission of the near-infrared fluorochromes attached to the N-termini of the dendritic arms was quenched. Mechanistic studies revealed formation of H-type dye aggregates within the tetravalent MAP system. By varying the length of the PEG chain, three probes were synthesized, CyPEG-1, CyPEG-2, and CyPEG-3 with 4, 8, and 12 ethylene oxide units, respectively. CyPEG-2 showed optimum aqueous solubility and quenching efficiency for imaging applications. Upon proteolytic activation with cathepsin S (EC 3.4.22.27), CyPEG-2 showed greater than 70-fold increase and more than 95% recovery in fluorescence emission. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01 CA99385, R21 CA114149, T32-CA79443] NR 23 TC 45 Z9 46 U1 1 U2 11 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 JUL 27 PY 2006 VL 49 IS 15 BP 4715 EP 4720 DI 10.1021/jm051001a PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 065EF UT WOS:000239141500031 PM 16854078 ER PT J AU Wykrzykowska, JJ Iliopoulos, O Gonzalez, RG Chan-Smutko, G Louis, DN Stone, JR Harris, NL AF Wykrzykowska, Joanna J. Iliopoulos, Othon Gilberto Gonzalez, R. Chan-Smutko, Gayun Louis, David N. Stone, James R. Harris, Nancy Lee TI Case 23-2006: A 36-year-old man with numbness in the right hand and hypertension - VHL disease with R167Q mutation (type 2), associated with adrenal pheochromocytoma, brain-stem and spinal cord hemangioblastomas, liver hemangiomas, renal cysts, a pancreatic endocrine tumor, and catecholamine-induced myocardial toxicity SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HIPPEL-LINDAU-DISEASE; ENDOTHELIAL GROWTH-FACTOR; GERMLINE MUTATIONS; SUPPRESSOR GENE; NEOPLASIA; INHIBITION; PREVALENCE; MOSAICISM; CARCINOMA; DIAGNOSIS C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Wykrzykowska, JJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 29 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 27 PY 2006 VL 355 IS 4 BP 394 EP 402 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 067DT UT WOS:000239282600009 ER PT J AU Ito, H Takeuchi, Y Shaffer, J Sykes, M AF Ito, Hiroshi Takeuchi, Yasuo Shaffer, Juanita Sykes, Megan TI Anti-CD40L monoclonal antibodies can replace antiCD4 monoclonal antibodies for the nonmyeloablative induction of mixed xenogeneic chimerism SO TRANSPLANTATION LA English DT Article DE xenotransplantation; tolerance; costimulation; chimerism; bone marrow ID NONLETHAL PREPARATIVE REGIMEN; BONE-MARROW TRANSPLANTATION; DONOR-SPECIFIC TRANSFUSION; T-CELL TOLERANCE; COSTIMULATORY BLOCKADE; CONDITIONING REGIMEN; CD40-CD40 LIGAND; CD4(+) CELLS; DELETION; SURVIVAL AB Background. We have previously demonstrated that xenogeneic bone marrow engraftment and donor-specific tolerance can be induced in mice receiving anti-CD4, -CD8, -Thy-1.2, and -NK1.1 monoclonal antibodies (mAbs) on Days -6 and -1, 3 Gy total body irradiation (TBI), and 7 Gy thymic irradiation on Day 0, followed by injection of T-cell depleted (TCD) rat bone marrow cells. We have recently demonstrated that anti-CD40L mAb treatment is sufficient to completely overcome CD4 cell-mediated resistance to allogeneic marrow engraftment and rapidly induce CD4 cell tolerance in an allogeneic combination. Methods. We investigated the ability of anti-CD40L mAb to promote mixed xenogeneic chimerism and donor-specific tolerance in B6 mice receiving anti-CD8, -Thy1.2 and -NK1.1 mAbs and 3 Gy TBI followed by TCD bone marrow transplantation (BMT) from F344 rats. Results. Administration of anti-CD4 mAb in this model could be completely replaced by one injection of anti-CD40L mAb. Evidence for deletional tolerance was obtained in mixed chimeras prepared with this anti-CD40L-based regimen. However, anti-NK1.1 and anti-Thy1.2 mAb could not be replaced by anti-CD40L mAb. Conclusions. These results demonstrate that anti-CD40L in combination with xenogeneic BMT can tolerize preexisting peripheral and intrathymic CD4 cells to xenoantigens. However, anti-CD40L does not prevent NK cell and/or gamma delta cell-mediated rejection of xenogencic bone marrow. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [P01HL18646] NR 30 TC 8 Z9 8 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 JUL 27 PY 2006 VL 82 IS 2 BP 251 EP 257 DI 10.1097/01.tp.0000226147.69877.6f PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 069JG UT WOS:000239441600018 PM 16858289 ER PT J AU El Essawy, B Otu, HH Choy, B Zheng, XX Libermann, TA Strom, TB AF El Essawy, Basset Otu, Hasan H. Choy, Bob Zheng, Xin Xiao Libermann, Towia A. Strom, Terry B. TI Proteomic analysis of the allograft response SO TRANSPLANTATION LA English DT Article DE proteomics; rejection; tolerance ID REJECTING RENAL-ALLOGRAFTS; SELDI-TOF MS; GENE-EXPRESSION; ACTIVATION TRANSCRIPTS; NONINVASIVE DIAGNOSIS; MESSENGER-RNA; KIDNEY; RECIPIENTS; TOLERANCE; BIOPSIES AB Background. As transcriptional profiling techniques appear to provide a useful means to evaluate the allograft response, we have now initiated an attempt to use proteomics to examine the allograft response. Methods. To this end, we have evaluated the use of Protein Chip technology, coupled with bioinformatics analysis towards discovery of allograft response biomarkers in a mouse skin transplant model. To compare samples obtained from acutely rejecting allograft recipients at days 7, 9, and 2 1, we treated one group with a potent antirejection regimen. Mean survival time in the fully MHC-mismatched skin graft model using this protocol is more than 100 days. We also studied recipients of nontreated syngenetic grafts. We applied Protein Chip technology toward discovery of allograft response markers in this model. Results. At days 7 and 9, before the clinical appearance of rejection at day 10, several protein biomarker candidates were detected, based on their molecular mass that clearly differentiated between rejection and the nonrejection groups. Conclusions. Protein profiling of serum as a means to characterize the allografts response of a given host deserves further testing in clinical studies. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02215 USA. RP Strom, TB (reprint author), Harvard Univ, Inst Med, Transplant Res Ctr BIDMC, Room 1026,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM tstrom@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179; Otu, Hasan/0000-0002-9253-8152 NR 31 TC 10 Z9 10 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 JUL 27 PY 2006 VL 82 IS 2 BP 267 EP 274 DI 10.1097/01.tp.0000226254.89987.ec PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 069JG UT WOS:000239441600020 PM 16858291 ER PT J AU Murakami, M Ito, H Harada, E Enoki, T Sykes, M Hamano, K AF Murakami, Masanori Ito, Hiroshi Harada, Eijiro Enoki, Tadahiko Sykes, Megan Hamano, Kimikazu TI Long-term survival of xenogeneic heart grafts achieved by costimulatory blockade and transient mixed chimerism SO TRANSPLANTATION LA English DT Article DE xenotransplantation; heart transplantation; tolerance; costimulation; chimerism; bone marrow ID NONLETHAL PREPARATIVE REGIMEN; CARDIAC XENOGRAFT SURVIVAL; RAT ISLET XENOGRAFTS; REGULATORY T-CELLS; ALLOGRAFT-REJECTION; TRANSPLANTATION TOLERANCE; MONOCLONAL-ANTIBODIES; CD40; INDUCTION; MICE AB Background. Xenotransplantation holds great promise in clinical medicine, but is limited by the vigorous rejection response elicited against solid organs transplanted across species barriers. In this study, we investigated the role of anti-CD40L monoclonal antibody (mAb) in inducing xenogeneic mixed chimerism and donor-specific heart transplantation tolerance. Methods. One day before heart transplantation, mice were injected intraperitoneally with anti-mouse CD8/NK1.1/Thy1.2 mAbs. On day 0, the mice received 3 Gy total body irradiation (TBI), an intravenous injection of unseparated bone marrow (BM) harvested from F344 rats, and an intraperitoneal injection of hamster antimouse CD40L mAb, MRI. Heart grafts from F344 rats were heterotopically transplanted into the abdomen of B6 mouse recipients. Using flow cytometric analysis of peripheral white blood cells, we assessed donor hematopoiesis at various times after bone marrow transplantation (BMT). Results. Chimerism subsided gradually and disappeared completely 18 weeks after BMT. The cardiac graft survived permanently, even after the mixed chimerism disappeared. To determine if the mice acquired donor-specific tolerance, second rat heart grafts were transplanted 120 days after the first heart transplantation. The second transplanted hearts were also accepted over 60 days. Histological analysis revealed no remarkable vasculopathy in the coronary vessels at any stage. Conclusions. These findings clearly show that costimulatory blockade plays an important role in inducing xenochimerism, and that transient mixed chimerism can induce permanent acceptance of rat to mouse cardiac xenografts. Transplantation of xenogeneic bone marrow cells under costimulatory blockade at the time of heart transplantation may induce transplantation tolerance. C1 Yamaguchi Univ, Grad Sch Med, Dept Surg & Clin Sci, Ube, Yamaguchi 7558505, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA USA. RP Ito, H (reprint author), Yamaguchi Univ, Grad Sch Med, Dept Surg & Clin Sci, 1-1-1 Minami Kogushi, Ube, Yamaguchi 7558505, Japan. EM hito@yamaguchi-u.ac.jp NR 40 TC 10 Z9 11 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 JUL 27 PY 2006 VL 82 IS 2 BP 275 EP 281 DI 10.1097/01.tp.0000226221.53161.10 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 069JG UT WOS:000239441600021 PM 16858292 ER PT J AU Jeffery, IB Higgins, DG Culhane, AC AF Jeffery, Ian B. Higgins, Desmond G. Culhane, Aedin C. TI Comparison and evaluation of methods for generating differentially expressed gene lists from microarray data SO BMC BIOINFORMATICS LA English DT Article ID CLASSIFICATION; CANCER; PREDICTION; SURVIVAL; TUMOR AB Background: Numerous feature selection methods have been applied to the identification of differentially expressed genes in microarray data. These include simple fold change, classical t-statistic and moderated t-statistics. Even though these methods return gene lists that are often dissimilar, few direct comparisons of these exist. We present an empirical study in which we compare some of the most commonly used feature selection methods. We apply these to 9 publicly available datasets, and compare, both the gene lists produced and how these perform in class prediction of test datasets. Results: In this study, we compared the efficiency of the feature selection methods; significance analysis of microarrays (SAM), analysis of variance (ANOVA), empirical bayes t-statistic, template matching, maxT, between group analysis (BGA), Area under the receiver operating characteristic (ROC) curve, the Welch t-statistic, fold change, rank products, and sets of randomly selected genes. In each case these methods were applied to 9 different binary ( two class) microarray datasets. Firstly we found little agreement in gene lists produced by the different methods. Only 8 to 21% of genes were in common across all 10 feature selection methods. Secondly, we evaluated the class prediction efficiency of each gene list in training and test cross-validation using four supervised classifiers. Conclusion: We report that the choice of feature selection method, the number of genes in the genelist, the number of cases (samples) and the noise in the dataset, substantially influence classification success. Recommendations are made for choice of feature selection. Area under a ROC curve performed well with datasets that had low levels of noise and large sample size. Rank products performs well when datasets had low numbers of samples or high levels of noise. The Empirical bayes t-statistic performed well across a range of sample sizes. C1 Natl Univ Ireland Univ Coll Dublin, Conway Inst, Dublin 4, Ireland. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Jeffery, IB (reprint author), Natl Univ Ireland Univ Coll Dublin, Conway Inst, Dublin 4, Ireland. EM Ian.Jeffery@ucd.ie; Des.Higgins@ucd.ie; aedin@jimmy.harvard.edu RI Higgins, des/J-6314-2012; Jeffery, Ian/I-4010-2013; OI Higgins, Des/0000-0002-3952-3285; Jeffery, Ian/0000-0001-9183-7292 NR 39 TC 189 Z9 201 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 26 PY 2006 VL 7 AR 359 DI 10.1186/1471-2105-7-359 PG 16 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 074FS UT WOS:000239798700002 PM 16872483 ER PT J AU Menn, B Garcia-Verdugo, JM Yaschine, C Gonzalez-Perez, O Rowitch, D Alvarez-Buylla, A AF Menn, Benedicte Garcia-Verdugo, Jose Manuel Yaschine, Cynthia Gonzalez-Perez, Oscar Rowitch, David Alvarez-Buylla, Arturo TI Origin of oligodendrocytes in the subventricular zone of the adult brain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adult oligodendrogenesis; CNS stem cells; oligodendrocyte progenitors; SVZ astrocyte; myelin repair; Olig2 ID NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; ELECTRON-MICROSCOPIC ANALYSIS; FIBROBLAST-GROWTH-FACTOR; PDGF ALPHA-RECEPTOR; RADIAL GLIAL-CELLS; PROGENITOR CELLS; MAMMALIAN BRAIN; NEURONAL MIGRATION; SPINAL-CORD AB Glial fibrillary acidic protein (GFAP)-positive astrocytes (type B cells) in the subventricular zone (SVZ) generate large numbers of new neurons in the adult brain. SVZ stem cells can also generate oligodendrocytes in vitro, but it is not known whether these adult primary progenitors generate oligodendrocytes in vivo. Myelin repair and oligodendrocyte formation in the adult brain is instead associated with glial-restricted progenitors cells, known as oligodendrocyte progenitor cells (OPCs). Here we show that type B cells also generate a small number of nonmyelinating NG2-positive OPCs and mature myelinating oligodendrocytes. Some type B cells and a small subpopulation of actively dividing type C (transit-amplifying) cells expressed oligodendrocyte lineage transcription factor 2 (Olig2), suggesting that oligodendrocyte differentiation in the SVZ begins early in the lineage. Olig2-positive, polysialylated neural cell adhesion molecule-positive, PDGF receptor alpha-positive, and beta-tubulin-negative cells originating in the SVZ migrated into corpus callosum, striatum, and fimbria fornix to differentiate into the NG2-positive nonmyelinating and mature myelinating oligodendrocytes. Furthermore, primary clonal cultures of type B cells gave rise to oligodendrocytes alone or oligodendrocytes and neurons. Importantly, the number of oligodendrocytes derived from type B cells in vivo increased fourfold after a demyelinating lesion in corpus callosum, indicating that SVZ astrocytes participate in myelin repair in the adult brain. Our work identifies SVZ type B cells as progenitors of oligodendrocytes in normal and injured adult brain. C1 Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dev & Stem Cell Biol Program, San Francisco, CA 94143 USA. Univ Valencia, Valencia 46010, Spain. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Alvarez-Buylla, A (reprint author), Univ Calif San Francisco, Dept Neurosurg, Box 0525, San Francisco, CA 94143 USA. EM abuylla@stemcell.ucsf.edu RI Gonzalez-Perez, Oscar/B-3680-2008; OI Gonzalez-Perez, Oscar/0000-0002-6527-485X; Garcia-Verdugo, Jose Manuel/0000-0001-9872-6499 FU NICHD NIH HHS [HD 32116] NR 85 TC 487 Z9 505 U1 2 U2 22 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 JUL 26 PY 2006 VL 26 IS 30 BP 7907 EP 7918 DI 10.1523/JNEUROSCI.1299-06.2006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 068GP UT WOS:000239361200015 PM 16870736 ER PT J AU Garcia-Osta, A Tsokas, P Pollonini, G Landau, EM Blitzer, R Alberini, CM AF Garcia-Osta, Ana Tsokas, Panayiotis Pollonini, Gabriella Landau, Emmanuel M. Blitzer, Robert Alberini, Cristina M. TI MuSK expressed in the brain mediates cholinergic responses, synaptic plasticity, and memory formation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE MuSK; brain; long-term plasticity; memory; oscillatory response; C/EBP ID RECEPTOR TYROSINE KINASE; LONG-TERM POTENTIATION; HIPPOCAMPAL THETA-RHYTHM; ELEMENT-BINDING PROTEIN; MUSCLE-SPECIFIC KINASE; NEUROMUSCULAR-JUNCTION FORMATION; IN-VIVO; SIGNALING PATHWAY; MYASTHENIA-GRAVIS; RAT HIPPOCAMPUS AB Muscle-specific tyrosine kinase receptor (MuSK) has been believed to be mainly expressed and functional in muscle, in which it mediates the formation of neuromuscular junctions. Here we show that MuSK is expressed in the brain, particularly in neurons, as well as in non-neuronal tissues. We also provide evidence that MuSK expression in the hippocampus is required for memory consolidation, because temporally restricted knockdown after training impairs memory retention. Hippocampal disruption of MuSK also prevents the learning-dependent induction of both cAMP response element binding protein (CREB) phosphorylation and CCAAT enhancer binding protein beta(C/EBP beta) expression, suggesting that the role of MuSK during memory consolidation critically involves the CREB-C/EBP pathway. Furthermore, we found that MuSK also plays an important role in mediating hippocampal oscillatory activity in the theta frequency as well as in the induction and maintenance of long-term potentiation, two synaptic responses that correlate with memory formation. We conclude that MuSK plays an important role in brain functions, including memory formation. Therefore, its expression and role are broader than what was believed previously. C1 Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Pharmacol, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. RP Alberini, CM (reprint author), Mt Sinai Sch Med, Dept Neurosci, Box 1065, New York, NY 10029 USA. EM Cristina.Alberini@mssm.edu OI Garcia-Osta, Ana/0000-0001-6326-9064 FU NIMH NIH HHS [MH65635] NR 74 TC 47 Z9 48 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 26 PY 2006 VL 26 IS 30 BP 7919 EP 7932 DI 10.1523/JNEUROSCI.1674-06.2006 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 068GP UT WOS:000239361200016 PM 16870737 ER PT J AU Morrow, DA de Lemos, JA Sabatine, MS Wiviott, SD Blazing, MA Shui, A Rifai, N Califf, RM Braunwald, E AF Morrow, David A. de Lemos, James A. Sabatine, Marc S. Wiviott, Stephen D. Blazing, Michael A. Shui, Amy Rifai, Nader Califf, Robert M. Braunwald, Eugene TI Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial SO CIRCULATION LA English DT Article DE coronary disease; prognosis; myocardial infarction; inflammation; C-reactive protein ID DENSITY-LIPOPROTEIN CHOLESTEROL; STATIN THERAPY; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; ARTERY-DISEASE; RISK-FACTORS; INFLAMMATION; MARKERS; ATHEROSCLEROSIS; PRAVASTATIN AB Background - Elevated levels of high-sensitivity C-reactive protein (hsCRP) are associated with higher risk of adverse outcomes in patients at risk for or with established coronary artery disease. Retrospective analyses suggest that this risk may be modified with statin therapy. However, a role for hsCRP in monitoring the success of therapy remains uncertain. Methods and Results - We measured the serum concentration of hsCRP at 30 days (n = 3813) and 4 months in patients with non-ST-elevation or ST-elevation acute coronary syndrome randomly assigned to an early intensive versus delayed conservative simvastatin strategy in the Aggrastat-to-Zocor Trial. Patients with hsCRP > 3 mg/L at 30 days had significantly higher 2-year mortality rates than those with hsCRP 1 to 3 mg/L or hsCRP < 1 mg/L ( 6.1% versus 3.7% versus 1.6%, P < 0.0001). Results were similar with hsCRP measured at 4 months. After adjusting for age, gender, diabetes, smoking, cardiovascular history, index event, lipid levels, and randomly assigned treatment, patients with hsCRP > 3 mg/L were at more than 3-fold higher risk of death (HR, 3.7; 95% CI, 1.9 to 7.2) compared with those with hsCRP < 1 mg/ L. "Average" levels of hsCRP ( 1 to 3 mg/ L) were also associated with increased risk compared with those with hsCRP < 1 mg/ L ( HR, 2.3; 95% CI, 1.2 to 4.6). Patients allocated to early intensive statin therapy were more likely to achieve hsCRP levels < 1 mg/L at 30 days (P = 0.028) and 4 months ( P < 0.0001). Conclusions - Achieved levels of hsCRP at 30 days and 4 months after acute coronary syndrome are independently associated with long-term survival. Patients treated with more aggressive statin therapy are more likely to achieve lower levels of hsCRP. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75230 USA. Duke Univ, Clin Res Inst, Durham, NC USA. Childrens Hosp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org FU NHLBI NIH HHS [U01 HL083-1341] NR 26 TC 180 Z9 201 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 25 PY 2006 VL 114 IS 4 BP 281 EP 288 DI 10.1161/CIRCULATIONAHA.106.628909 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 066NS UT WOS:000239237200008 PM 16847150 ER PT J AU Pujol, N Link, EM Liu, LX Kurz, CL Alloing, G Tan, MW Ray, KP Solari, R Johnson, CD Ewbank, JJ AF Pujol, Nathalie Link, Elizabeth M. Liu, Leo X. Kurz, C. Leopold Alloing, Genevieve Tan, Man-Wah Ray, Keith P. Solari, Roberto Johnson, Carl D. Ewbank, Jonathan J. TI A reverse genetic analysis of components of the toll signaling pathway in Caenorhabditis elegans (vol 11, pg 809, 2001) SO CURRENT BIOLOGY LA English DT Correction C1 Univ Mediterranee, CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille, France. Univ Mediterranee, CNRS, INSERM, Lab Genet & Physiol Dev, F-13288 Marseille, France. NemaPharm Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Glaxo Wellcome Res & Dev Ltd, Stevenage SG1 2NY, Herts, England. RP Ewbank, JJ (reprint author), Univ Mediterranee, CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille, France. EM ewbank@cjml.univ-mrs.fr RI Ewbank, Jonathan/G-4948-2010; Kurz, Cyril/L-7615-2016 OI Ewbank, Jonathan/0000-0002-1257-6862; NR 1 TC 0 Z9 0 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 25 PY 2006 VL 16 IS 14 BP 1477 EP 1477 DI 10.1016/j.cub.2006.07.019 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 067TE UT WOS:000239324700032 ER PT J AU Pitteloud, N Meysing, A Quinton, R Acierno, JS Dwyer, AA Plummer, L Fliers, E Boepple, P Hayes, F Seminara, S Hughes, VA Ma, J Bouloux, P Mohammadi, M Crowley, WF AF Pitteloud, Nelly Meysing, Astrid Quinton, Richard Acierno, James S., Jr. Dwyer, Andrew A. Plummer, Lacey Fliers, Eric Boepple, Paul Hayes, Frances Seminara, Stephanie Hughes, Viriginia A. Ma, Jinghong Bouloux, Pierre Mohammadi, Moosa Crowley, William F., Jr. TI Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE FGFR1 mutation; Kallmann syndrome; pubertal development; idiopathic hypogonadotropic hypogonadism ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; LUTEINIZING-HORMONE; FGF RECEPTOR; GENE; DEFICIENCY; HETEROGENEITY; EXPRESSION; MOLECULES; MECHANISM AB Background: Kallmann's syndrome (KS) is a clinically and genetically heterogeneous disorder consisting of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Mutations in KALI causing the X-linked form of KS have been identified in 10% of all KS patients and consistently result in a severe reproductive phenotype. KALI gene encodes for anosmin-1, a key protein involved in olfactory and GnRH neuronal migration through a putative interaction with FGFRI. Heterozygous mutations in the FGFRI gene accompanied by a high frequency of cleft palate and other facial dysmorphisms were recently identified in 8% of a large KS cohort, yet the reproductive phenotype of KS patients harboring FGFRI mutations has not been described. Results: One hundred and fifty probands with KS (130 males and 20 females) were studied to determine the frequency and distribution of FGFRI mutations and their detailed reproductive phenotypes. Fifteen heterozygous mutations in unrelated probands were identified. Twelve missense mutations (p.R78C, p.V102I, p.D224H, p.G237D, p.R254Q, p.V273M, p.E274G, p.Y339C, p.S346C, p.I538V, p.G703S and p.G703R) were distributed among the first, second and third immunoglobulin-like domains (D1-D3), as well as the tyrosine kinase domain (TKD). The mutations Y339C and S346C are located in exon 8B and code for the isoform FGFRIc. Additionally, two nonsense mutations (p.T585X and p.R622X) were documented in the TKD of the protein. A wide spectrum of reproductive function was observed among KS probands including: (1) a severe phenotype demonstrated by microphallus, cryptorchidism, no pubertal development, undetectable serum gonadotropins and low serum testosterone (T) and inhibin 13; (2) partial pubertal development; (3) the fertile eunuch variant of IHH with normal testicular size and active spermatogenesis with a reversal of HH after T therapy. In addition, we found an even wider spectrum of reproductive function within pedigrees carrying an FGFRI mutation ranging from IHH to delayed puberty to normal reproductive function (anosmia only or asymptomatic carriers). These observations strongly suggest a role for other genes that modify the phenotype of FGFRI mutations. Conclusion: KS patients and family members carrying an FGFR1 mutation present a broad spectrum of pubertal development in contrast to the almost uniform severe clinical phenotype described in KS subjects with a KALI mutation. Additionally, this report implicates the isoform FGFRIc in the pathogenesis of KS. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. UCL Royal Free & Univ Coll, Sch Med, Ctr Neuroendocrinol, London NW3 2PF, England. Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, NL-1105 AZ Amsterdam, Netherlands. NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Bartlett Hall Extens 5,55 Fruit St, Boston, MA 02114 USA. EM npitteloud@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Mohammadi, Moosa/0000-0003-2434-9437 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [R01 HD015788, R01HD15788, U54 HD028138, U54 HD029164]; NIDCR NIH HHS [R01 DE013686, 2R01 DE13686-06]; NIDDK NIH HHS [DK03892] NR 33 TC 90 Z9 95 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUL 25 PY 2006 VL 254 BP 60 EP 69 DI 10.1016/j.mce.2006.04.021 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 071QO UT WOS:000239616900009 PM 16764984 ER PT J AU Pallais, JC Bo-Abbas, Y Pitteloud, N Crowley, WF Seminara, SB AF Pallais, J. Carl Bo-Abbas, Yousef Pitteloud, Nelly Crowley, William F., Jr. Seminara, Stephanie B. TI Neuroendocrine, gonadal, placental, and obstetric phenotypes in patients with IHH and mutations in the G-protein coupled receptor, GPR54 SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE GPR54; metastin; kisspeptin; hypogonadotropic hypogonadism; pituitary; placenta ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; METASTASIS SUPPRESSOR GENE; HORMONE-RELEASING ACTIVITY; KISS-1 MESSENGER-RNA; GONADOTROPIN-SECRETION; REPRODUCTIVE AXIS; PEPTIDE; KISSPEPTIN; ACTIVATION; EXPRESSION AB The G protein coupled receptor, GPR54, is a key regulator of puberty and reproductive function. Despite its prismatic role, few patients with mutations in GPR54 and the phenotype of hypogonadotropic hypogonadism have been described. This report explores the neuroendocrine, gonadal, placental and obstetric phenotypes of patients with idiopathic hypogonadotropic hypogonadism (11411) carrying missense (L148S), nonsense (R331X), and nonstop (X399R) mutations in GPR54. A male patient harboring the mutations R331X and X399R demonstrated (1) increased sensitivity to exogenous pulsatile GnRH compared to a cohort of IHH patients undergoing similar therapy and (2) steady increases in testicular volume, spermatogenesis, and fertility while on long-term GnRH therapy. A female patient homozygous for the L148S mutation had (1) intact responses to exogenous GnRH and gonadotropins, (2) multiple conceptions, (3) two uncomplicated pregnancies of healthy children, suggesting grossly intact placental function, (4) spontaneous initiation of uterine contractions, and (5) lactation for several months post-partum. Taken together, these observations help to tease apart the neuroendocrine and gonadal phenotypes of patients bearing mutations in GPR54. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Reprod Endocrine Sci Ctr, Massachusetts Gen Hosp, Boston, MA 02114 USA. Kuwait Univ, Fac Med, Al Jabriyah 13110, Kuwait. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Bartlett Hall Extens 5,Fruit St, Boston, MA 02114 USA. EM sseminara@partners.org RI PITTELOUD, Nelly/K-2709-2014 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [R01 HD015788, R01 HD043341, U54 HD028138, U54 HD029164] NR 33 TC 52 Z9 55 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUL 25 PY 2006 VL 254 BP 70 EP 77 DI 10.1016/j.mce.2006.04.019 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 071QO UT WOS:000239616900010 PM 16757106 ER PT J AU Tschanz, JT Welsh-Bohmer, KA Lyketsos, CG Corcoran, C Green, RC Hayden, K Norton, MC Zandi, PP Toone, L West, NA Breitner, JCS AF Tschanz, J. T. Welsh-Bohmer, K. A. Lyketsos, C. G. Corcoran, C. Green, R. C. Hayden, K. Norton, M. C. Zandi, P. P. Toone, L. West, N. A. Breitner, J. C. S. CA Cache County Investigators TI Conversion to dementia from mild cognitive disorder - The Cache County Study SO NEUROLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the International-Neuropsychological-Society CY FEB 05-08, 2003 CL HONOLULU, HI SP Int Neuropsychol Soc ID ALZHEIMERS-DISEASE; ELDERLY POPULATION; NO DEMENTIA; IMPAIRMENT; PREVALENCE; DECLINE; QUESTIONNAIRE; PREDICTOR; EPSILON-4; CRITERIA AB Objective: To examine 3-year rates of conversion to dementia, and risk factors for such conversion, in a population-based sample with diverse types of cognitive impairment. Methods: All elderly (aged 65 or older) residents of Cache County, UT, were invited to undergo two waves of dementia screening and assessment. Three-year follow- up data were available for 120 participants who had some form of mild cognitive impairment at baseline. Of these, 51 had been classified at baseline with prodromal Alzheimer disease (proAD), and 69 with other cognitive syndromes (CS). Results: Three-year rates of conversion to dementia were 46% among those with cognitive impairment at baseline. By comparison, 3.3% without impairment converted to dementia in the interval. Among converters, AD was the most common type of dementia. In individuals with at least one APOE epsilon 4 allele, those with proAD or CS exhibited a 22- to 25-fold higher risk of dementia than cognitively unimpaired individuals (vs 5- to 10-fold higher risk in those without e4). Conclusions: Individuals with all types of mild cognitive impairment have an elevated risk of dementia over 3 years, more so in those with an APOE e4 allele. These results suggest value in dementia surveillance for broad groups of cognitively impaired individuals beyond any specific category, and utility of APOE genotyping as a prognostic method. C1 Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC USA. Johns Hopkins Univ, Div Geriatr Psychiat & Neuropsychiat, Dept Psychiat & Behav Sci, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Dept Mental Hlth, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Med Genet, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Tschanz, JT (reprint author), Utah State Univ, Dept Psychol, 4440 Old Main Hill, Logan, UT 84322 USA. EM joannt@cc.usu.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [R01-AG11380, R01-AG21136] NR 36 TC 73 Z9 77 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 25 PY 2006 VL 67 IS 2 BP 229 EP 234 DI 10.1212/01.wnl.0000224748.48011.84 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 066NW UT WOS:000239237600009 PM 16864813 ER PT J AU Szotek, PP Pieretti-Vanmarcke, R Masiakos, PT Dinulescut, DM Connolly, D Foster, R Dombkowski, D Preffer, F MacLaughlin, DT Donahoe, PK AF Szotek, Paul P. Pieretti-Vanmarcke, Rafael Masiakos, Peter T. Dinulescut, Daniela M. Connolly, Denise Foster, Rosemary Dombkowski, David Preffer, Frederic MacLaughlin, David T. Donahoe, Patricia K. TI Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer stem cells; breast cancer-resistance protein 1 ID DRUG EFFLUX CAPACITY; MULTIDRUG-RESISTANCE; IN-VIVO; GROWTH; EXPRESSION; PACLITAXEL; ASSAY; HETEROGENEITY; STATISTICS; SURVIVAL AB The recent identification of "side population" (SP) cells in a number of unrelated human cancers and their normal tissue sources has renewed interest in the hypothesis that cancers may arise from somatic stem/progenitor cells. The high incidence of recurrence attributable to multidrug resistance and the multiple histologic phenotypes indicative of multipotency suggests a stem cell-like etiology of ovarian cancer. Here we identify and characterize SP cells from two distinct genetically engineered mouse ovarian cancer cell lines. Differential efflux of the DNA-binding dye Hoechst 33342 from these cell lines defined a human breast cancer-resistance protein 1-expressing, verapamil-sensitive SP of candidate cancer stem cells. In vivo, mouse SP cells formed measurable tumors sooner than non-SP (NSP) cells when equal numbers were injected into the dorsal fat pad of nude mice. The presence of Mullerian Inhibiting Substance (MIS) signaling pathway transduction molecules in both SP and NSP mouse cells led us to investigate the efficacy of MIS against these populations in comparison with traditional chemotherapies. MIS inhibited the proliferation of both SP and NSP cells, whereas the lipophilic chemotherapeutic agent doxorubicin more significantly inhibited the NSP cells. Finally, we identified breast cancer-resistance protein 1-expressing verapamil-sensitive SPs in three of four human ovarian cancer cell lines and four of six patient primary ascites cells. In the future, individualized therapy must incorporate analysis of the stem cell-like subpopulation of ovarian cancer cells when designing therapeutic strategies for ovarian cancer patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Flow Cytometry Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Eugene Braunwald Res Ctr,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Hematol Oncol, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Pediat Surg Res Labs, 185 Cambridge St, Boston, MA 02114 USA. EM donahoe.patricia@mgh.harvard.edu FU NCI NIH HHS [1P50CA105009, 5T32CA071345-10, CA17393, P50 CA083638, P50 CA105009, R01 CA017393, T32 CA071345, U01 CA084242]; NICHD NIH HHS [HD32112, R01 HD032112] NR 42 TC 467 Z9 511 U1 3 U2 20 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 25 PY 2006 VL 103 IS 30 BP 11154 EP 11159 DI 10.1073/pnas.0603672103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 068DZ UT WOS:000239353900011 PM 16849428 ER PT J AU Hudert, CA Weylandt, KH Lu, Y Wang, JD Hong, S Dignass, A Serhan, CN Kang, JX AF Hudert, Christian A. Weylandt, Karsten H. Lu, Yan Wang, Jingdong Hong, Song Dignass, Axel Serhan, Charles N. Kang, Jing X. TI Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE inflammation; inflammatory bowel disease; lipid mediators; resolvins; protectins ID INFLAMMATORY-BOWEL-DISEASE; FATTY-ACIDS; NECROSIS-FACTOR; RESOLVIN E1; FISH-OIL; DOCOSATRIENES; RECEPTOR; EXPRESSION; INDUCTION; CYTOKINES AB Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are the precursors of potent lipid mediators and play an important role in regulation of inflammation. Generally, n-6 PUFA promote inflammation whereas n-3 PUFA have anti inflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived proinflammatory eicosanoids. Newly discovered resolvins and protectins are potent antiinflammatory-lipid mediators derived directly from n-3 PUFA with distinct pathways of action. However, the role of the n-3 PUFA tissue status in the formation of these antiinflammatory mediators has not been addressed. Here we show that an increased n-3 PUFA tissue status in transgenic mice that endogenously biosynthesize n-3 PUFA from n-6 PUFA leads to significant formation of anti inflammatory resolvins and effective reduction in inflammation and tissue injury in colitis. The endogenous increase in n-3 PUFA and related products did not decrease n-6 PUFA-derived lipid mediators such as leukotriene B4 and prostaglandin E2. The observed inflammation protection might result from decreased NF-kappa B activity and expression of TNF alpha, inducible NO synthase, and IL-1 beta, with enhanced muco-protection probably because of the higher expression of trefoil factor 3, Toll-interacting protein, and zonula occludens-1. These results thus establish the fat-1 transgenic mouse as a new experimental model for the study of n-3 PUFA-derived lipid mediators. They add insight into the molecular mechanisms of inflammation protection afforded by n-3 PUFA through formation of resolvins and protectins other than inhibition of n-6 PUFA-derived eicosanoid formation. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Med Berlin, Charite, Dept Gastroenterol, D-13353 Berlin, Germany. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, 149 13th St,Room 4433, Charlestown, MA 02129 USA. EM jxkang@partners.org FU NIDCR NIH HHS [P50 DE016191, P50-DE016191]; NIDDK NIH HHS [P30 DK043351, DK43351, P30 DK040561, P30 DK040561-11] NR 42 TC 241 Z9 248 U1 1 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 JUL 25 PY 2006 VL 103 IS 30 BP 11276 EP 11281 DI 10.1073/pnas/0601280103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 068DZ UT WOS:000239353900032 PM 16847262 ER PT J AU Dittman, JS Kaplan, JM AF Dittman, Jeremy S. Kaplan, Joshua M. TI Factors regulating the abundance and localization of synaptobrevin in the plasma membrane SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AP180; endocytosis; pHluorin; synaptic vesicle ID SYNAPTIC VESICLE ENDOCYTOSIS; CAENORHABDITIS-ELEGANS; NERVE-TERMINALS; C-ELEGANS; ACTIVE ZONES; TARGETING SIGNAL; EXOCYTOSIS; PROTEINS; FUSION; COMPLEX AB After synaptic vesicle fusion, vesicle proteins must be segregated from plasma membrane proteins and recycled to maintain a functional vesicle pool. We monitored the distribution of synaptobrevin, a vesicle protein required for exocytosis, in Caenorhabditis elegans motor neurons by using a pH-sensitive synaptobrevin GFP fusion protein, synaptopHluorin. We estimated that 30% of synaptobrevin was present in the plasma membrane. By using a panel of endocytosis and exocytosis mutants, we found that the majority of surface synaptobrevin derives from fusion of synaptic vesicles and that, in steady state, synaptobrevin equilibrates throughout the axon. The surface synaptobrevin was enriched near active zones, and its spatial extent was regulated by the clathrin adaptin AP180. These results suggest that there is a plasma membrane reservoir of synaptobrevin that is supplied by the synaptic vesicle cycle and available for retrieval throughout the axon. The size of the reservoir is set by the relative rates of exo- and endocytosis. 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 OI Dittman, Jeremy S./0000-0002-3850-9078 FU NIGMS NIH HHS [R01 GM054728, GM54728] NR 69 TC 77 Z9 92 U1 1 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 JUL 25 PY 2006 VL 103 IS 30 BP 11399 EP 11404 DI 10.1073/pnas.0600784103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 068DZ UT WOS:000239353900053 PM 16844789 ER PT J AU Cursiefen, C Chen, L Saint-Geniez, M Hamrah, P Jin, Y Rashid, S Pytowski, B Persaud, K Wu, Y Streilein, JW Dana, R AF Cursiefen, Claus Chen, Lu Saint-Geniez, Magali Hamrah, Pedram Jin, Yiping Rashid, Saadia Pytowski, Bronislaw Persaud, Kris Wu, Yan Streilein, J. Wayne Dana, Reza TI Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULARIZED HUMAN CORNEAS; MOUSE CORNEA; FACTOR-C; IN-VIVO; LYMPHANGIOGENESIS; ANGIOGENESIS; NEOVASCULARIZATION; MODEL; METASTASIS AB Transparency of the cornea, the window of the eye, is a prerequisite for vision. Angiogenesis into the normally avascular cornea is incompatible with good vision and, therefore, the cornea is one of the few tissues in the human body where avascularity is actively maintained. Here, we provide evidence for a critical mechanism contributing to corneal avascularity. VEGF receptor 3, normally present on lymphatic and proliferating blood vascular endothelium, is strongly constitutively expressed by corneal epithelium and is mechanistically responsible for suppressing inflammatory corneal angiogenesis. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Ophthalmol, D-91054 Erlangen, Germany. ImClone Syst Inc, New York, NY 10014 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu FU NEI NIH HHS [R01 EY012963, R01 EY010765, EY10765, EY12963] NR 30 TC 138 Z9 144 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 JUL 25 PY 2006 VL 103 IS 30 BP 11405 EP 11410 DI 10.1073/pnas.050112103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 068DZ UT WOS:000239353900054 PM 16849433 ER PT J AU Tamimi, RM Hankinson, SE Chen, WY Rosner, B Colditz, GA AF Tamimi, Rulla M. Hankinson, Susan E. Chen, Wendy Y. Rosner, Bernard Colditz, Graham A. TI Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HORMONE-REPLACEMENT THERAPY; ENDOGENOUS SEX-HORMONES; ANDROGEN REPLACEMENT; PLUS PROGESTIN; AROMATASE; PROLIFERATION; SURVEILLANCE; EXPRESSION; REANALYSIS; MENOPAUSE AB Background: The role of androgens in breast cancer etiology has been unclear. Epidemiologic studies suggest that endogenous testosterone levels are positively associated with breast cancer risk in postmenopausal women. Given the increasing trend in the use of hormone therapies containing androgens, we evaluated the relation between the use of estrogen and testosterone therapies and breast cancer. Methods: We conducted a prospective cohort study in the Nurses' Health Study from 1978 to 2002 to assess the risk of breast cancer associated with different types of postmenopausal hormone (PMH) formulations containing testosterone. During 24 years of follow-up (1359323 person-years), 4610 incident cases of invasive breast cancer were identified among postmenopausal women. Information on menopausal status, PMH use, and breast cancer diagnosis was updated every 2 years through questionnaires. Results: Among women with a natural menopause, the risk of breast cancer was nearly 2.5- fold greater among current users of estrogen plus testosterone therapies (multivariate relative risk, 2.48; 95% confidence interval, 1.53- 4.04) than among never users of PMHs. This analysis showed that risk of breast cancer associated with current use of estrogen and testosteronetherapy was significantly greater compared with estrogen-only therapy (P for heterogeneity,.007) and marginally greater than estrogen and progesterone therapy (P for heterogeneity,.11). Women receiving PMHs with testosterone had a 17.2%( 95% confidence interval, 6.7%-28.7%) increased risk of breast cancer per year of use. Conclusion: Consistent with the elevation in risk for endogenous testosterone levels, women using estrogen and testosterone therapies have a significantly increased risk of invasive breast cancer. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. RP Tamimi, RM (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM rulla.tamimi@channing.harvard RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA087969, CA089393] NR 47 TC 76 Z9 77 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 24 PY 2006 VL 166 IS 14 BP 1483 EP 1489 DI 10.1001/archinte.166.14.1483 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 066DZ UT WOS:000239211200008 PM 16864758 ER PT J AU Ay, I Tuncer, M AF Ay, Ilknur Tuncer, Meral TI Both endothelium and afferent nerve endings play a role in acetylcholine-induced renal vasodilation SO LIFE SCIENCES LA English DT Article DE acetylcholine; CGRP; nitric oxide; protein kinase A; vasodilation; renal ID GENE-RELATED PEPTIDE; ARTERIAL SMOOTH-MUSCLE; PERFUSED RAT-KIDNEY; NITRIC-OXIDE; HYPERPOLARIZING FACTOR; SENSORY NERVES; RELAXATION; PROSTACYCLIN; RESISTANCE; MECHANISM AB We investigated the nature and signaling pathways of endothelium- and sensory-nerve ending-derived substances involved in acetylcholine-induced vasodilation in rat isolated perfused kidney. Endothelial denudation by Triton X-100 (0.2%, 0.1 ml) or depletion of afferent nerve endings by capsaicin (10(-6) mol/l) attenuated acetylcholine-induced vasodilation. When these two. agents were administered together, the response to acetylcholine was completely inhibited. CGRP1 receptor blocker CGRP 8-37 (10(-7) mol/l) and adenosine A(2) receptor antagonist ZM 241 385 (10(-7) mol/l) inhibited acetylcholine-induced dilation. When indomethacin (10(-5) mol/l), a cyclooxygenase inhibitor, L-NOARG (10(-4) mol/l), a nitric oxide (NO) synthase inhibitor, and potassium chloride (30 mmol/l), to test EDHF response, were perfused simultaneously, the inhibition was greater than that was observed with each agent alone. Guanylate cyclase inhibitor ODQ (10(-5) mol/l) or protein kinase A inhibitor KT 5720 (5 x 10(-7) mol/l) inhibited acetylcholine-induced dilation. Gap junction uncoupler 18 alpha-glycyrrhetinic acid (10(-4) mol/l) caused an uncontrollable increase in basal perfusion pressure making it impossible to test against acetylcholine-induced dilation. Our data suggest that NO, prostanoids, EDHF, and CGRP released from vascular endothelium and afferent nerve endings participate in acetylcholine-induced vasodilation and their signal transduction molecules include protein kinase A and guanylate cyclase. (c) 2006 Elsevier Inc. All rights reserved. C1 Hacettepe Univ, Fac Med, Dept Pharmacol, TR-06100 Ankara, Turkey. RP Ay, I (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuromuscular Res Lab, Charlestown, MA 02129 USA. EM iay@partners.org NR 28 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 24 PY 2006 VL 79 IS 9 BP 877 EP 882 DI 10.1016/j.lfs.2006.03.004 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 066WN UT WOS:000239261200009 PM 16616212 ER PT J AU You, JW Chen, TC Mujat, M Park, BH de Boer, JF AF You, Jang-Woo Chen, Teresa C. Mujat, Mircea Park, B. Hyle de Boer, Johannes F. TI Pulsed illumination spectral-domain optical coherence tomography for human retinal imaging SO OPTICS EXPRESS LA English DT Article ID NERVE-FIBER LAYER; HIGH-SPEED; ULTRAHIGH-RESOLUTION; PHOTODYNAMIC THERAPY; MACULAR DEGENERATION; MOTION ARTIFACTS; SWEPT-SOURCE; THICKNESS; GLAUCOMA; IMAGES AB We present pulsed illumination spectral-domain optical coherence tomography ( SD-OCT) for in vivo human retinal imaging. We analyze the signal-to-noise ( SNR) for continuous wave ( CW) and pulsed illumination SD-OCT. The lateral beam scan motion is responsible for a SNR drop due to lateral scanning induced interference fringe washout. Pulsed illumination can reduce the SNR drop by shorter sample illumination time during the integration time of a camera. First, we demonstrate the SNR benefit of pulsed illumination over CW as function of lateral scan speed for a paper sample. Finally, we show better SNR in retinal images of a normal subject with pulsed illumination SD-OCT over CW at high lateral scanning speed. (c) 2006 Optical Society of America. C1 Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP You, JW (reprint author), Korea Adv Inst Sci & Technol, Dept Mech Engn, 373-1 Kusong Dong, Taejon 305701, South Korea. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 34 TC 14 Z9 14 U1 0 U2 2 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 JUL 24 PY 2006 VL 14 IS 15 BP 6739 EP 6748 DI 10.1364/OE.14.006739 PG 10 WC Optics SC Optics GA 067ZW UT WOS:000239342300018 PM 19516855 ER PT J AU Ghosh-Choudhury, N Singha, PK Woodruff, K St Clair, P Bsoul, S Werner, SL Choudhury, GG AF Ghosh-Choudhury, Nandini Singha, Prajjal K. Woodruff, Kathleen St Clair, Patricia Bsoul, Sameer Werner, Sherry L. Choudhury, Goutam Ghosh TI Concerted action of Smad and CREB-binding protein regulates bone morphogenetic protein-2-stimulated osteoblastic colony-stimulating factor-1 expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSTEOCLAST DIFFERENTIATION FACTOR; GROWTH-FACTOR-BETA; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSCRIPTIONAL REGULATION; SIGNAL-TRANSDUCTION; HISTONE ACETYLTRANSFERASES; FAMILY-MEMBERS; CELL-FORMATION; STROMAL CELLS; OP/OP MICE AB Bone remodeling depends upon proper osteoblast and osteoclast function. Bone morphogenetic protein-2 (BMP-2) stimulates differentiation of osteoblasts from pluripotent precursors. Osteoclast formation depends on the concerted action of osteoblast-derived receptor activator of NF-kappa B ligand and colony-stimulating factor-1 (CSF-1). BMP-2 stimulates receptor activator of NF-kappa B ligand expression. However, the effect of BMP-2 on CSF-1 expression has not been studied. We investigated the role of BMP-2 in CSF-1 expression in osteogenic C2C12 cells. Incubation of C2C12 cells with BMP-2 supported osteoclastogenesis of spleen cells with a concomitant increase in expression of CSF-1 mRNA and protein. To determine the mechanism, we identified a BMP-responsive element between -627 bp and -509 bp in the CSF-1 promoter. DNase I footprint analysis revealed the presence of consensus Smad binding motif in this region. Electrophoretic mobility shift assay showed BMP-2-stimulated binding of proteins to this motif. Mutation of core sequence as well as its 5'- and 3'-flanking sequences abolished the DNA-protein interaction resulting in inhibition of CSF-1 transcription. Supershift analysis detects the presence of Smads 1, 5, and 4 and the transcriptional coactivator CREB-binding protein in the BMP-responsive element-protein complex. In addition, Smads 1 and 5 alone or in combination with Smad 4 increased CSF-1 transcription. Furthermore, CREB-binding protein markedly increased transcription of CSF-1. These data represent the first evidence that BMP-2 increases the osteoclas-togenic CSF-1 expression by a transcriptional mechanism using the canonical Smad pathway and provide a mechanism for BMP-2-induced osteoclast differentiation. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhury@uthscsa.edu FU NIAMS NIH HHS [R01-AR52425, R01 AR042306]; NIDDK NIH HHS [R01 DK 50190, DK 55815, P50 DK061597] NR 69 TC 30 Z9 35 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 21 PY 2006 VL 281 IS 29 BP 20160 EP 20170 DI 10.1074/jbc.M511071200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 063RV UT WOS:000239038200040 PM 16707491 ER PT J AU Martinez-Hackert, E Anikeeva, N Kalams, SA Walker, BD Hendrickson, WA Sykulev, Y AF Martinez-Hackert, Erik Anikeeva, Nadia Kalams, Spyros A. Walker, Bruce D. Hendrickson, Wayne A. Sykulev, Yuri TI Structural basis for degenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL-RECEPTOR; CRYSTAL-STRUCTURES; BINDING-SITE; POSITIVE SELECTION; CROSS-REACTIVITY; VIRAL PEPTIDES; MATRIX PROTEIN; MHC COMPLEXES; TCR BINDING; ANTIGEN AB It is well established that even small changes in amino acid side chains of antigenic peptide bound to major histocompatibility complex (MHC) protein may completely abrogate recognition of the peptide-MHC (pMHC) complex by the T cell receptor (TCR). Often, however, several nonconservative substitutions in the peptide antigen are accommodated and do not impair its recognition by TCR. For example, a preponderance of natural sequence variants of the human immunodeficiency virus p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes, which implies that interactions with SL9 variants are degenerate both with respect to the class I MHCmolecule and with respect to TCR. Here we study the molecular basis for this degenerate recognition of SL9 variants. We show that several SL9 variants bind comparably well to soluble HLA-A2 and to a particular soluble TCR and that these variants are active in the cognate cytotoxicity assay. Natural SL9 variation is restricted by its context in the HIV p17 matrix protein. High resolution crystal structures of seven selected SL9 variants bound to HLA-A2 all have remarkably similar peptide conformations and side-chain dispositions outside sites of substitution. This preservation of the peptide conformation despite epitope variations suggests a mechanism for the observed degeneracy in pMHC recognition by TCR and may contribute to the persistence of SL9-mediated immune responses in chronically infected individuals. C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Immunol & Microbiol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Philadelphia, PA 19107 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Vanderbilt Univ, Med Ctr, Div Infect Dis, Nashville, TN 37232 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. RP Sykulev, Y (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Immunol & Microbiol, BLSB 650, Philadelphia, PA 19107 USA. EM ysykulev@lac.jci.tju.edu OI Martinez-Hackert, Erik/0000-0002-6182-7023 FU NIAID NIH HHS [AI43254, AI58755, AI39966] NR 50 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 21 PY 2006 VL 281 IS 29 BP 20205 EP 20212 DI 10.1074/jbc.M601934200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 063RV UT WOS:000239038200045 PM 16702212 ER PT J AU Cao, Y Espinola, JA Fossale, E Massey, AC Cuervo, AM MacDonald, ME Cotman, SL AF Cao, Yi Espinola, Janice A. Fossale, Elisa Massey, Ashish C. Cuervo, Ana Maria MacDonald, Marcy E. Cotman, Susan L. TI Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL ATP SYNTHASE; BATTEN-DISEASE; SUBUNIT-C; SACCHAROMYCES-CEREVISIAE; ALZHEIMERS-DISEASE; CARDIAC MYOCYTES; CELL-DEATH; STORAGE; AUTOPHAGOCYTOSIS; VACUOLES AB Juvenile neuronal ceroid lipofuscinosis is caused by mutation of a novel, endosomal/lysosomal membrane protein encoded by CLN3. The observation that the mitochondrial ATPase subunit c protein accumulates in this disease suggests that autophagy, a pathway that regulates mitochondrial turnover, may be disrupted. To test this hypothesis, we examined the autophagic pathway in Cln3(Delta ex7/8) knock-in mice and CbCln3(Delta ex7/8) cerebellar cells, accurate genetic models of juvenile neuronal ceroid lipofuscinosis. In homozygous knock-in mice, we found that the autophagy marker LC3-II was increased, and mammalian target of rapamycin was down-regulated. Moreover, isolated autophagic vacuoles and lysosomes from homozygous knock-in mice were less mature in their ultrastructural morphology than the wild-type organelles, and subunit c accumulated in autophagic vacuoles. Intriguingly, we also observed subunit c accumulation in autophagic vacuoles in normal aging mice. Upon further investigation of the autophagic pathway in homozygous knock-in cerebellar cells, we found that LC3-positive vesicles were altered and overlap of endocytic and lysosomal dyes was reduced when autophagy was stimulated, compared with wildtype cells. Surprisingly, however, stimulation of autophagy did not significantly impact cell survival, but inhibition of autophagy led to cell death. Together these observations suggest that autophagy is disrupted in juvenile neuronal ceroid lipofuscinosis, likely at the level of autophagic vacuolar maturation, and that activation of autophagy may be a prosurvival feedback response in the disease process. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. RP Cotman, SL (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. EM cotman@helix.mgh.harvard.edu FU NIA NIH HHS [AG02194]; NINDS NIH HHS [NS33648, R01 NS033648] NR 45 TC 137 Z9 140 U1 1 U2 4 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 JUL 21 PY 2006 VL 281 IS 29 BP 20483 EP 20493 DI 10.1074/jbc.M602180200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 063RV UT WOS:000239038200071 PM 16714284 ER PT J AU Grozinger, SO Rietzel, E Li, Q Bert, C Haberer, T Kraft, G AF Groezinger, Sven Oliver Rietzel, Eike Li, Qiang Bert, Christoph Haberer, Thomas Kraft, Gerhard TI Simulations to design an online motion compensation system for scanned particle beams SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID ORGAN MOTION; RESPIRATORY MOTION; CONFORMAL RADIOTHERAPY; TARGET VOLUME; SET-UP; TUMOR; TRACKING; THERAPY; DELIVERY; CANCER AB Respiration-induced target motion is a major problem in intensity-modulated radiation therapy. Beam segments are delivered serially to form the total dose distribution. In the presence of motion, the spatial relation between dose deposition from different segments will be lost. Usually, this results in over-and underdosage. Besides such interplay effects between target motion and dynamic beam delivery as known from photon therapy, changes in internal density have an impact on delivered dose for intensity-modulated charged particle therapy. In this study, we have analysed interplay effects between raster scanned carbon ion beams and target motion. Furthermore, the potential of an online motion strategy was assessed in several simulations. An extended version of the clinical treatment planning software was used to calculate dose distributions to moving targets with and without motion compensation. For motion compensation, each individual ion pencil beam tracked the planned target position in the lateral aswell as longitudinal direction. Target translations and rotations, including changes in internal density, were simulated. Target motion simulating breathing resulted in severe degradation of delivered dose distributions. For example, for motion amplitudes of +/- 15 mm, only 47% of the target volume received 80% of the planned dose. Unpredictability of resulting dose distributions was demonstrated by varying motion parameters. On the other hand, motion compensation allowed for dose distributions for moving targets comparable to those for static targets. Even limited compensation precision (standard deviation similar to 2 mm), introduced to simulate possible limitations of real-time target tracking, resulted in less than 3% loss in dose homogeneity. C1 GSI Darmstadt, D-64291 Darmstadt, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Peoples R China. RP Grozinger, SO (reprint author), GSI Darmstadt, D-64291 Darmstadt, Germany. EM svenoliver.groezinger@siemens.com RI Bert, Christoph/C-2585-2013 OI Bert, Christoph/0000-0002-8539-6600 NR 36 TC 30 Z9 31 U1 0 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 JUL 21 PY 2006 VL 51 IS 14 BP 3517 EP 3531 DI 10.1088/0031-9155/51/14/016 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 062LK UT WOS:000238945700017 PM 16825746 ER PT J AU Lau, NC Seto, AG Kim, J Kuramochi-Miyagawa, S Nakano, T Bartel, DP Kingston, RE AF Lau, Nelson C. Seto, Anita G. Kim, Jinkuk Kuramochi-Miyagawa, Satomi Nakano, Toru Bartel, David P. Kingston, Robert E. TI Characterization of the piRNA complex from rat testes SO SCIENCE LA English DT Article ID SMALL RNAS; DROSOPHILA; PIWI; GENE; DNA; SPERMATOGENESIS; HETEROCHROMATIN; MAINTENANCE; METHYLATION; TETRAHYMENA AB Small noncoding RNAs regulate processes essential for cell growth and development, including mRNA degradation, translational repression, and transcriptional gene silencing (TGS). During a search for candidate mammalian factors for TGS, we purified a complex that contains small RNAs and Riwi, the rat homolog to human Piwi. The RNAs, frequently 29 to 30 nucleotides in length, are called Piwi-interacting RNAs (piRNAs), 94% of which map to 100 defined (<= 101 kb) genomic regions. Within these regions, the piRNAs generally distribute across only one genomic strand or distribute on two strands but in a divergent, nonoverlapping manner. Preparations of piRNA complex ( piRC) contain rRecQ1, which is homologous to qde-3 from Neurospora, a gene implicated in silencing pathways. Piwi has been genetically linked to TGS in flies, and slicer activity cofractionates with the purified complex. These results are consistent with a gene-silencing role for piRC in mammals. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Osaka Univ, Microbial Dis Res Inst, Dept Mol Cell Biol, Suita, Osaka 5650871, Japan. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu NR 26 TC 495 Z9 542 U1 14 U2 69 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 21 PY 2006 VL 313 IS 5785 BP 363 EP 367 DI 10.1126/science.1130164 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 065IV UT WOS:000239154300048 PM 16778019 ER PT J AU Janne, PA AF Jaenne, Pasi A. TI Gefitinib for epidermal growth factor receptor mutant lung cancers: Searching for a weapon of mass destruction SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID TYROSINE KINASE DOMAIN; GENE COPY NUMBER; ACTIVATING MUTATIONS; SENSITIVITY; ADENOCARCINOMAS; RESPONSIVENESS; RESISTANCE; ERLOTINIB; SURVIVAL; THERAPY C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 22 TC 2 Z9 2 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 JUL 20 PY 2006 VL 24 IS 21 BP 3319 EP 3321 DI 10.1200/JCO.2006.06.6555 PG 3 WC Oncology SC Oncology GA 069BC UT WOS:000239418600002 PM 16785470 ER PT J AU Earle, CC AF Earle, Craig C. TI Do unto others ... SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CANCER C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 TC 4 Z9 5 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 20 PY 2006 VL 24 IS 21 BP 3331 EP 3332 DI 10.1200/JCO.2006.06.7561 PG 2 WC Oncology SC Oncology GA 069BC UT WOS:000239418600006 PM 16849746 ER PT J AU Goldberg, RM Sargent, DJ Morton, RF Fuchs, CS Ramanathan, RK Williamson, SK Findlay, BP Pitot, HC Alberts, S AF Goldberg, Richard M. Sargent, Daniel J. Morton, Roscoe F. Fuchs, Charles S. Ramanathan, Ramesh K. Williamson, Stephen K. Findlay, Brian P. Pitot, Henry C. Alberts, Steven TI Randomized controlled trial of reduced-dose bolus fluorouracil plus leucovorin and irinotecan or infused fluorouracil plus leucovorin and oxaliplatin in patients with previously untreated metastatic colorectal cancer: A North American intergroup trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID CLINICAL-TRIALS; SEQUENCE; DNA AB Purpose Previously, we reported results of Intergroup N9741, which compared standard bolus fluorouracil (FU), leucovorin, plus irinotecan (IFL) with infused FU, leucovorin, plus oxaliplatin (FOLFOX4) and irinotecan plus oxaliplatin in patients with untreated metastatic colorectal cancer. High rates of grade ! 3 toxicity on IFL (resulting in some deaths) led us to reduce the starting doses of both irinotecan and FU by 20% (rIFL). This article compares rIFL with FOLFOX4. Patients and Methods The primary comparison was time to progression, with secondary end points of response rate (RR), overall survival, and toxicity. Results Three hundred five patients were randomly assigned. The North Central Cancer Treatment Group Data Safety Monitoring Committee interrupted enrollment at a planned interim analysis when outcomes crossed predetermined stopping boundaries. The results were significantly superior for FOLFOX4 compared with rIFL for time to progression (9.7 v 5.5 months, respectively; P <.0001), RR (48% v 32%, respectively; P =.006), and overall survival (19.0 v 16.3 months, respectively; P =.026). Toxicity profiles were not significantly different between regimens for nausea, vomiting, diarrhea, febrile neutropenia, dehydration, or 60-day all-cause mortality. Sensory neuropathy and neutropenia were significantly more common with FOLFOX4. Approximately 75% of patients in both arms received second-line therapy; 58% of rIFL patients received oxaliplatin-based second-line therapy, and 55% of FOLFOX4 patients received irinotecan-based regimens as second-line therapy. Conclusion FOLFOX4 led to superior RR, time to progression, and overall survival compared with rIFL. The survival benefit for FOLFOX4 observed in the earlier stage of the study was preserved with equal use of either irinotecan or oxaliplatin as second-line therapy. C1 Univ N Carolina, Div Hematol & Oncol, Chapel Hill, NC 27514 USA. Mayo Clin, Div Biostat, Rochester, MN USA. Mayo Clin, Div Med Oncol, Rochester, MN USA. Iowa Oncol Res Assoc Community Clin Oncol Program, Des Moines, IA USA. Dana Farber Canc Ctr Inst, Dept Oncol, Boston, MA USA. Univ Pittsburgh, Inst Canc, Div Med Oncol, Pittsburgh, PA USA. Univ Kansas, Med Ctr, Div Hematol & Oncol, Kansas City, KS 66103 USA. Natl Canc Inst Canada, St Catharines, ON, Canada. RP Goldberg, RM (reprint author), Univ N Carolina, Div Hematol & Oncol, CB 7305,3009 Old Clin Bldg, Chapel Hill, NC 27514 USA. EM Goldberg@med.unc.edu RI Goldberg , Richard/M-1311-2013 FU NCI NIH HHS [CA21115, CA25224, CA32102, CA38926, CA77202] NR 20 TC 145 Z9 151 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 20 PY 2006 VL 24 IS 21 BP 3347 EP 3353 DI 10.1200/JCO.2006.06.1317 PG 7 WC Oncology SC Oncology GA 069BC UT WOS:000239418600009 PM 16849748 ER PT J AU Sweeney, CJ Roth, BJ Kabbinavar, FF Vaughn, DI Arning, M Curiel, RE Obasaju, CK Wang, Y Nicol, SJ Kaufman, DS AF Sweeney, Christopher J. Roth, Bruce J. Kabbinavar, Fairooz F. Vaughn, David I. Arning, Michael Curiel, Rafael E. Obasaju, Coleman K. Wang, Yanping Nicol, Steven J. Kaufman, Donald S. TI Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 20th Chemotherapy-Foundation Symposium CY NOV 12-15, 2003 CL New York, NY SP Chemotherapy Fdn ID COOPERATIVE-ONCOLOGY-GROUP; BLADDER-CANCER; REFRACTORY CARCINOMA; PROGNOSTIC-FACTORS; INTERFERON-ALPHA; TRIAL; CHEMOTHERAPY; PACLITAXEL; GEMCITABINE; CISPLATIN AB Purpose To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Patients and Methods Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m(2) intravenously on day 1 every 21 days, with vitamin B-12, folic acid, and dexamethasone prophylaxis. Results Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% Cl, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% Cl, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% Cl, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%, 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/ pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients). Conclusion Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hoosier Oncol Grp, Indianapolis, IN USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Penn, Philadelphia, PA 19104 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Kaufman, DS (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dskaufman@partners.org NR 34 TC 126 Z9 126 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 20 PY 2006 VL 24 IS 21 BP 3451 EP 3457 DI 10.1200/JCO.2005.03.6699 PG 7 WC Oncology SC Oncology GA 069BC UT WOS:000239418600024 PM 16849761 ER PT J AU Punglia, RS Weeks, JC Neville, BA Earle, CC AF Punglia, Rinaa S. Weeks, Jane C. Neville, Bridget A. Earle, Craig C. TI Radiation therapy after mastectomy between 1991 and 1999 in elderly women: Response to clinical trial information SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FEE-FOR-SERVICE; BREAST-CANCER; POSTMASTECTOMY RADIOTHERAPY; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; TREATMENT PATTERNS; COMORBIDITY INDEX; OLDER WOMEN; STAGE; HMO AB Purpose No systematic study has analyzed the changing patterns of use of postmastectomy radiation therapy (PMRT) during the period of information dissemination regarding the benefit of radiation therapy in this setting. We sought to study the receipt of PMRT in elderly women in this period, using a population-based cohort of women with breast cancer. Patients and Methods Using data from the linked Surveillance, Epidemiology, and End Results-Medicare database, we analyzed the use of radiation therapy between 1991 and 1999 in 19,699 women with stage I to III breast cancer who received mastectomy as definitive surgery. Multivariable logistic regression was used to investigate the association of diagnosis year and the use of PMRT, after controlling for clinical and sociodemographic factors. Results During the entire period studied, 2,160 (11.0%) patients treated with mastectomy received PMRT. The use of PMRT significantly increased in women diagnosed in 1996 (odds ratio [OR], 1.26; P =.04), 1997 (OR, 1.70; P <.0001), 1998 (OR, 1.57; P <.0001), and 1999 (OR, 1.77; P <.0001), relative to those diagnosed in 1991 after controlling for cancer, and sociodemographic and treatment characteristics. There were significant differences in the temporal trends of radiation use among different regions of the country (P <.0001), and between teaching versus nonteaching institutions (P =.04). Conclusion The use of PMRT in elderly women increased significantly during the period of data dissemination about its efficacy; however, the trends in adoption varied among different practice settings. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Div Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Punglia, RS (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Div Med Oncol, 454B S21-24,44 Binney St, Boston, MA 02115 USA. EM rpunglia@lroc.harvard.edu NR 26 TC 17 Z9 17 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 20 PY 2006 VL 24 IS 21 BP 3474 EP 3482 DI 10.1200/JCO.2006.05.7844 PG 9 WC Oncology SC Oncology GA 069BC UT WOS:000239418600027 PM 16849764 ER PT J AU Kesari, S Stiles, CD AF Kesari, Santosh Stiles, Charles D. TI The bad seed: PDGF receptors link adult neural progenitors to glioma stem cells SO NEURON LA English DT Editorial Material ID TUMORS; BRAIN; OLIG2 C1 Harvard Univ, Dana Farber Canc Ctr, Program Neuro Oncol, Boston, MA 02115 USA. RP Kesari, S (reprint author), Harvard Univ, Dana Farber Canc Ctr, Program Neuro Oncol, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 12 TC 22 Z9 23 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 JUL 20 PY 2006 VL 51 IS 2 BP 151 EP 153 DI 10.1016/j.neuron.2006.07.001 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 070PK UT WOS:000239535100002 PM 16846849 ER PT J AU Kirchhoff, BA Buckner, RL AF Kirchhoff, Brenda A. Buckner, Randy L. TI Functional-anatomic correlates of individual differences in memory SO NEURON LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; FREE-RECALL; LEARNING-STRATEGIES; REPORTED MEDIATORS; PREFRONTAL CORTEX; EPISODIC MEMORY; BRAIN ACTIVITY; LONG-TERM; ACTIVATION; RETRIEVAL AB Memory abilities differ greatly across individuals. To explore a source of these differences, we characterized the varied strategies people adopt during unconstrained encoding. Participants intentionally encoded object pairs during functional MRI. Principal components analysis applied to a strategy questionnaire revealed that participants variably used four main strategies to aid learning. Individuals' use of verbal elaboration and visual inspection strategies independently correlated with their memory performance. Verbal elaboration correlated with activity in a network of regions that included prefrontal regions associated with controlled verbal processing, while visual inspection correlated with activity in a network of regions that included an extrastriate region associated with object processing. Activity in regions associated with use of these, strategies was also correlated with memory performance. This study reveals functional-anatomic correlates of verbal and perceptual strategies that are variably used by individuals during encoding. These strategies engage distinct brain regions and may separately influence memory performance. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ct, Boston, MA 02129 USA. RP Kirchhoff, BA (reprint author), Washington Univ, Dept Psychol, Campus Box 1125,1 Brookings Dr, St Louis, MO 63130 USA. EM bkirchho@artsci.wustl.edu FU NIMH NIH HHS [MH57506] NR 56 TC 67 Z9 68 U1 3 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL 20 PY 2006 VL 51 IS 2 BP 263 EP 274 DI 10.1016/j.neuron.2006.06.006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 070PK UT WOS:000239535100013 PM 16846860 ER PT J AU Jagsi, R Guancial, EA Worobey, CC Henault, LE Chang, YC Starr, R Tarbell, NJ Hylek, EM AF Jagsi, Reshma Guancial, Elizabeth A. Worobey, Cynthia Cooper Henault, Lori E. Chang, Yuchiao Starr, Rebecca Tarbell, Nancy J. Hylek, Elaine M. TI The "gender gap" in authorship of Academic Medical Literature - A 35-year perspective SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONTROLLABLE LIFE-STYLE; SPECIALTY CHOICE; WOMEN PHYSICIANS; CAREER; STUDENTS; FACULTY; MEN; PUBLICATIONS; TRENDS; IMPACT AB Background: Participation of women in the medical profession has increased during the past four decades, but issues of concern persist regarding disparities between the sexes in academic medicine. Advancement is largely driven by peer-reviewed original research, so we sought to determine the representation of female physician-investigators among the authors of selected publications during the past 35 years. Methods: Original articles from six prominent medical journals - the New England Journal of Medicine (NEJM), the Journal of the American Medical Association (JAMA), the Annals of Internal Medicine (Ann Intern Med), the Annals of Surgery (Ann Surg), Obstetrics & Gynecology (Obstet Gynecol), and the Journal of Pediatrics (J Pediatr) - were categorized according to the sex of both the first and the senior (last listed) author. Sex was also determined for the authors of guest editorials in NEJM and JAMA. Data were collected for the years 1970, 1980, 1990, 2000, and 2004. The analysis was restricted to authors from U.S. institutions holding M.D. degrees. Results: The sex was determined for 98.5 percent of the 7249 U.S. authors of original research with M.D. degrees. The proportion of first authors who were women increased from 5.9 percent in 1970 to 29.3 percent in 2004 (P < 0.001), and the proportion of senior authors who were women increased from 3.7 percent to 19.3 percent (P < 0.001) during the same period. The proportion of authors who were women increased most sharply in Obstet Gynecol (from 6.7 percent of first authors and 6.8 percent of senior authors in 1970 to 40.7 percent of first authors and 28.0 percent of senior authors in 2004) and J Pediatr (from 15.0 percent of first authors and 4.3 percent of senior authors in 1970 to 38.9 percent of first authors and 38.0 percent of senior authors in 2004) and remained low in Ann Surg (from 2.3 percent of first authors and 0.7 percent of senior authors in 1970 to 16.7 percent of first authors and 6.7 percent of senior authors in 2004). In 2004, 11.4 percent of the authors of guest editorials in NEJM and 18.8 percent of the authors of guest editorials in JAMA were women. Conclusions: Over the past four decades, the proportion of women among both first and senior physician-authors of original research in the United States has significantly increased. Nevertheless, women still compose a minority of the authors of original research and guest editorials in the journals studied. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Off Womens Careers, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nephrol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. Boston Univ, Sch Med, Boston Med Ctr, Sect Gen Internal Med,Res Unit, Boston, MA 02118 USA. RP Jagsi, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Off Womens Careers, Bulfinch 370,55 Fruit St, Boston, MA 02114 USA. EM reshma_jagsi@post.harvard.edu OI Jagsi, Reshma/0000-0001-6562-1228 NR 36 TC 191 Z9 194 U1 1 U2 23 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 20 PY 2006 VL 355 IS 3 BP 281 EP 287 DI 10.1056/NEJMsa053910 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 064NY UT WOS:000239097600009 PM 16855268 ER PT J AU O'Neill, GN Gonzalez, RG Cros, DP Ackerman, RH Brown, RH Stemmer-Rachamimov, A Harris, NL Venna, N AF O'Neill, G. N. Gonzalez, R. Gilberto Cros, Didier P. Ackerman, Robert H. Brown, Robert H., Jr. Stemmer-Rachamimov, Anat Harris, Nancy Lee Venna, Nagagopal TI A man with a rapidly progressive gait disorder - Amyotrophic lateral sclerosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MOTOR-NEURON DISEASE; TRANSCRANIAL MAGNETIC STIMULATION; CEREBROSPINAL-FLUID; EL-ESCORIAL; TUNING FORK; TAU-PROTEIN; CRITERIA; ALS C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP O'Neill, GN (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 28 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 JUL 20 PY 2006 VL 355 IS 3 BP 296 EP 304 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 064NY UT WOS:000239097600013 PM 16855271 ER PT J AU Stremlau, M Song, BW Javanbakht, H Perron, M Sodroski, J AF Stremlau, Matthew Song, Byeongwoon Javanbakht, Hassan Perron, Michel Sodroski, Joseph TI Cyclophilin A: An auxiliary but not necessary cofactor for TRIM5 alpha restriction of HIV-1 SO VIROLOGY LA English DT Article DE cyclophilin; cyclosporine; immunophilin; rapamycin; retrovirus; TRIM5; restriction factor; human immunodeficiency virus ID IMMUNODEFICIENCY-VIRUS TYPE-1; RETROVIRUS RESTRICTION; SIMIAN IMMUNODEFICIENCY; MONKEY TRIM5-ALPHA; HUMAN-CELLS; OLD-WORLD; POSTENTRY RESTRICTION; REVERSE TRANSCRIPTION; B30.2(SPRY) DOMAIN; CYCLOSPORINE-A AB Cyclophilin A (Cyp A) binds the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein and contributes to the early events in virus replication in some cells. The retroviral restriction factor TRIM5 alpha can inhibit the early, post-entry phase of infection by associating with the incoming viral capsid. Cyp A has been proposed to prevent restriction factor binding in human cells, thus enhancing HIV-1 infectivity, and to potentiate restriction of HIV-1 in monkey cells. Here we show that the positive effects of Cyp A-CA binding on HIV-1 infectivity do not depend on human TRIM5 alpha. Disruption of Cyp A binding to CA partially relieved the block to HIV-1 infection imposed by several TRIM5 alpha variants, but Cyp A-CA binding was not absolutely required for TRIM5 alpha antiviral activity. Inhibition of Cyp A function by cyclosporine significantly decreased the efficiency of TRIM5 alpha-mediated restriction only when the restricted virus capsid interacted with Cyp A. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Div AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI063987, AI60354] NR 54 TC 68 Z9 70 U1 0 U2 5 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 JUL 20 PY 2006 VL 351 IS 1 BP 112 EP 120 DI 10.1016/j.virol.2006.03.015 PG 9 WC Virology SC Virology GA 067RI UT WOS:000239319900011 PM 16643975 ER PT J AU Montet, X Weissleder, R Josephson, L AF Montet, Xavier Weissleder, Ralph Josephson, Lee TI Imaging pancreatic cancer with a peptide-nanoparticle conjugate targeted to normal pancreas SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PROSTATE-CANCER; BOMBESIN ANALOG; EXOCRINE PANCREAS; IN-VIVO; RECEPTORS; VISUALIZATION; BINDING; TUMOR; BIODISTRIBUTION; INTERNALIZATION AB Designing molecules that bind to targets that become upregulated or overexpressed as normal cells become cancerous is an important strategy for both therapeutic and diagnostic drug design. We hypothesized that pancreatic ductal adenocarcinoma (PDAC) might be imaged with the inverse strategy, that is by the design of a nanoparticle-conjugate targeted to bombesin (BN) receptors present on normal acinar cells of the pancreas. Using the fluorescein hapten visualization method to assess the presence of bombesin ( BN) receptors, we first demonstrated BN receptors in the normal mouse and human pancreas, but then the lack of BN binding receptors in 13 out of 13 specimens of PDAC. The BN peptide-nanoparticle conjugate, BN-CLIO(Cy5.5), was synthesized and accumulated in the mouse pancreas in receptor dependent fashion, but not in a receptor dependent fashion in other tissues, based on tissue fluorescence measurements. The BN-CLIO(Cy5.5) nanoparticle decreased the T2 of normal pancreas and enhanced the ability to visualize tumor in a model of pancreatic cancer by MRI. The use of BN-CLIO(Cy5.5) nanoparticle as a normal tissue-targeted, T2-reducing contrast agent offers a promising approach to imaging PDAC. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. EM ljosephson@partners.org FU NCI NIH HHS [R24 CA92782]; NIBIB NIH HHS [R01 EB00662]; PHS HHS [P01 117969, P50 86355] NR 34 TC 88 Z9 93 U1 2 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL 19 PY 2006 VL 17 IS 4 BP 905 EP 911 DI 10.1021/bc060035 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 064WJ UT WOS:000239120500007 PM 16848396 ER PT J AU Kurth, T Gaziano, JM Cook, NR Logroscino, G Diener, HC Buring, JE AF Kurth, Tobias Gaziano, J. Michael Cook, Nancy R. Logroscino, Giancarlo Diener, Hans-Christoph Buring, Julie E. TI Migraine and risk of cardiovascular disease in women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; LOW-DOSE ASPIRIN; PRIMARY PREVENTION; VASCULAR EVENTS; HEADACHE; STROKE; AURA; PREVALENCE; ANGINA; HEALTH AB Context Migraine with aura has been associated with an adverse cardiovascular risk profile and prothrombotic factors that, along with migraine-specific physiology, may increase the risk of vascular events. Although migraine with aura has been associated with increased risk of ischemic stroke, an association with cardiovascular disease (CVD) and, specifically, coronary events remains unclear. Objective To evaluate the association between migraine with and without aura and subsequent risk of overall and specific CVD. Design, Setting, and Participants Prospective cohort study of 27 840 US women aged 45 years or older who were participating in the Women's Health Study, were free of CVD and angina at study entry (1992-1995), and who had information on self-reported migraine and aura status, and lipid measurements. This report is based on follow-up data through March 31, 2004. Main Outcome Measures The primary outcome measure was the combined end point of major CVD (first instance of nonfatal ischemic stroke, nonfatal myocardial infarction, or death due to ischemic CVD); other measures were first ischemic stroke, myocardial infarction, coronary revascularization, angina, and death due to ischemic CVD. Results At baseline, 5125 women (18.4%) reported any history of migraine; of the 3610 with active migraine (migraine in the prior year), 1434 (39.7%) indicated aura symptoms. During a mean of 10 years of follow-up, 580 major CVD events occurred. Compared with women with no migraine history, women who reported active migraine with aura had multivariable-adjusted hazard ratios of 2.15 (95% confidence interval [CI], 1.58-2.92; P<.001) for major CVD, 1.91 (95% CI, 1.17-3.10; P=.01) for ischemic stroke, 2.08 (95% CI, 1.30-3.31; P=.002) for myocardial infarction, 1.74 (95% CI, 1.23-2.46; P=.002) for coronary revascularization, 1.71 (95% CI, 1.16-2.53; P=.007) for angina, and 2.33 (95% CI, 1.21-4.51; P=.01) for ischemic CVD death. After adjusting for age, there were 18 additional major CVD events attributable to migraine with aura per 10 000 women per year. Women who reported active migraine without aura did not have increased risk of any vascular events or angina. Conclusions In this large, prospective cohort of women, active migraine with aura was associated with increased risk of major CVD, myocardial infarction, ischemic stroke, and death due to ischemic CVD, as well as with coronary revascularization and angina. Active migraine without aura was not associated with increased risk of any CVD event. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Univ Duisburg Essen, Dept Neurol, Essen, Germany. RP Kurth, T (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, 900 Commonwealth Ave, Boston, MA 02215 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012; LOGROSCINO, GIANCARLO/K-5148-2016 OI Kurth, Tobias/0000-0001-7169-2620; LOGROSCINO, GIANCARLO/0000-0003-0423-3242 FU NCI NIH HHS [CA-47988]; NHLBI NIH HHS [HL-43851] NR 41 TC 296 Z9 301 U1 0 U2 11 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 JUL 19 PY 2006 VL 296 IS 3 BP 283 EP 291 DI 10.1001/jama.296.3.283 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 064LA UT WOS:000239089900020 PM 16849661 ER PT J AU Fu, YC Luo, LH Luo, NL Garvey, WT AF Fu, Yuchang Luo, Liehong Luo, Nanlan Garvey, W. Timothy TI Proinflammatory cytokine production and insulin sensitivity regulated by overexpression of resistin in 3T3-L1 adipocytes SO NUTRITION & METABOLISM LA English DT Article ID ADIPOSE-TISSUE; GENE-EXPRESSION; PPAR-GAMMA; IN-VIVO; DIFFERENTIATION; GLUCOSE; OBESITY; ADIPOGENESIS; ADIPONECTIN; METABOLISM AB Resistin is secreted from adipocytes, and high circulating levels have been associated with obesity and insulin resistance. To investigate whether resistin could exert autocrine effects in adipocytes, we expressed resistin gene in 3T3-L1 fibroblasts using a lentiviral vector, and selected several stably-transduced cell lines under blasticidin selection. We observed that 3T3-L1 adipocytes expressing resistin have a decreased gene expression for related transcriptional factors (CCAAT/enhancer binding protein alpha(C/EBP alpha), peroxisome proliferator-activated receptor gamma (PPAR gamma), and adipocyte lipid binding protein (ALBP/aP2) which is one of target genes for the PPAR. during adipocyte differentiation,. Overexpression of resistin increased the levels of three proinflammatory cytokines, tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), which play important roles for insulin resistance, glucose and lipid metabolisms during adipogenesis. Furthermore, overexpressing resistin in adipocytes inhibits glucose transport 4 (GLUT4) activity and its gene expression, reducing insulin's ability for glucose uptake by 30 %. In conclusion, resistin overexpression in stably transduced 3T3-L1 cells resulted in: 1) Attenuation of programmed gene expression responsible for adipogenesis; 2) Increase in expression of proinflammatory cytokines; 3) Decrease in insulin responsiveness of the glucose transport system. These data suggest a new role for resistin as an autocrine/paracrine factor affecting inflammation and insulin sensitivity in adipose tissue. C1 Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Fu, YC (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. EM yfu@uab.edu; lhluo@uab.edu; nluo@uab.edu; garveyt@uab.edu FU NHLBI NIH HHS [P01 HL055782]; NIDDK NIH HHS [P30 DK056336, R01 DK038765] NR 27 TC 29 Z9 34 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-7075 J9 NUTR METAB JI Nutr. Metab. PD JUL 19 PY 2006 VL 3 AR 28 DI 10.1186/1743-7075-3-28 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 074JR UT WOS:000239809000001 PM 16854242 ER PT J AU Berkowitz, RI Fujioka, K Daniels, SR Hoppin, AG Owen, S Perry, AC Sothern, MS Renz, CL Pirner, MA Walch, JK Jasinsky, O Hewkin, AC Blakesley, VA AF Berkowitz, Robert I. Fujioka, Ken Daniels, Stephen R. Hoppin, Alison G. Owen, Stanford Perry, Arlette C. Sothern, Melinda S. Renz, Cheryl L. Pirner, Mark A. Walch, Julia K. Jasinsky, Olga Hewkin, Ann C. Blakesley, Vicky A. CA Sibutramine Adolescent Study Grp TI Effects of sibutramine treatment in obese adolescents - A randomized trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; WEIGHT-LOSS; FOLLOW-UP; CHILDHOOD OBESITY; US CHILDREN; LIFE-STYLE; OVERWEIGHT; REDUCTION; MORTALITY; MAINTENANCE AB Background: Increased prevalence of adolescent obesity requires effective treatment options beyond behavior therapy. Objective: To see whether sibutramine reduced weight more than placebo in obese adolescents who were receiving a behavior therapy program. Design: 12-month, 3:1 randomized, double-blind trial conducted from July 2000 to February 2002. Setting: 33 U.S. outpatient clinics. Participants: 498 participants 12 to 16 years of age with a body mass index (BMI) that was at least 2 units more than the U.S. weighted mean of the 95th percentile based on age and sex, to the upper limit of 44 kg/m(2). Interventions: Site-specific behavior therapy plus 10 mg of sibutramine or placebo. Blinded study medication dose was uptitrated to 15 mg or placebo at month 6 if initial BMI was not reduced by 10%. Measurements: Body mass index, waist circumference, body weight, fasting lipid and glycemic variables, safety, and tolerability. Results: Seventy-six percent of patients in the sibutramine group and 62% of patients in the placebo group completed the study. The estimated mean treatment group difference at month 12 (linear mixed-effects model) favored sibutramine for change from baseline in BMI (-2.9 kg/m(2) [95% Cl, -3.5 to -2.2 kg/m(2)]) and body weight (-8.4 kg [Cl, -9.7 to -7.2 kg]) (P < 0.001 for both). The sibutramine group had greater improvements in triglyceride levels, high-density lipoprotein cholesterol levels, insulin levels, and insulin sensitivity (P <= 0.001 for all). The rate of tachycardia was greater with sibutramine vs. placebo (12.5% vs. 6.2%; difference, 6.3 percentage points [Cl, 1.0 to 11.7 percentage points]) but did not lead to increased withdrawal (2.4% vs. 1.5%; difference, 0.9 percentage point [Cl, -1.7 to 3.5 percentage points]). Limitations: The 1-year study duration precluded assessment of long-term weight maintenance and putative health benefits and harms, and 24% and 38% of the sibutramine and placebo groups, respectively, did not complete follow-up. Conclusions: Sibutramine added to a behavior therapy program reduced BMI and body weight more than placebo and improved the profile of several metabolic risk factors in obese adolescents. C1 Childrens Hosp Philadelphia, Behav Hlth Unit, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Penn Scripps Clin, San Diego, CA USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Hlth Management, Gulfport, MS USA. Univ Miami, Sch Educ, Coral Gables, FL 33124 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. Pennington Biomed Res Ctr, New Orleans, LA USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Berkowitz, RI (reprint author), Childrens Hosp Philadelphia, Behav Hlth Unit, 3440 Market St,Suite 410, Philadelphia, PA 19104 USA. EM berkowitz@email.chop.edu NR 31 TC 128 Z9 130 U1 1 U2 6 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 JUL 18 PY 2006 VL 145 IS 2 BP 81 EP 90 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 063WU UT WOS:000239051400001 PM 16847290 ER PT J AU Mehta, RH Roe, MT Mulgund, J Ohman, EM Cannon, CP Gibler, WB Pollack, CV Smith, SC Ferguson, TB Peterson, ED AF Mehta, Rajendra H. Roe, Matthew T. Mulgund, Jyotsna Ohman, E. Magnus Cannon, Christopher P. Gibler, W. Brian Pollack, Charles V., Jr. Smith, Sidney C., Jr. Ferguson, T. Bruce Peterson, Eric D. TI Acute clopidogrel use and outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID UNSTABLE ANGINA; ASPIRIN; COMBINATION; GUIDELINES; MANAGEMENT; CRUSADE AB OBJECTIVES We sought to characterize patterns of clopidogrel use before coronary artery bypass grafting (CABG) and examine the drug's impact on risks for postoperative transfusions among patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). BACKGROUND Adherence in community practice to American College of Cardiology/American Heart Association guidelines for clopidogrel use among NSTE ACS patients has not been previously characterized. METHODS We evaluated 2,858 NSTE ACS patients undergoing CABG at 264 hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Initiative. We examined the patterns of acute clopidogrel therapy and its association with bleeding risks among those having "early" CABG <= 5 days and again among those having "late" surgery > 5 days after catheterization. RESULTS Within 24 h of admission, 852 patients (30%) received clopidogrel. In contrast to national guidelines, 87% of clopidogrel-treated patients underwent CABG <= 5 days after treatment. Among those receiving CABG within <= 5 days of last treatment, the use of clopidogrel was associated with a significant increase in blood transfusions (65.0% vs. 56.9%, adjusted odds ratio [OR] 1.36, 95% confidence interval [CI] 1.10 to 1.68) as well as the need for transfusion of >= 4 U of blood (27.7% vs. 18.4%, OR 1.70, 95% Cl 1.32 to 2.19). In contrast, acute clopidogrel therapy was not associated with higher bleeding risks if CABG was delayed > 5 days (adjusted OR 1.18, 95% Cl 0.54 to 2.58). CONCLUSIONS Despite guideline recommendations, the overwhelming majority of NSTE ACS patients treated with acute clopidogrel needing CABG have their surgery within <= 5 days of treatment. A failure to delay surgery is associated with increased blood transfusion requirements that must be weighed against the potential clinical and economic impacts of such delays. C1 Duke Clin Res Inst, Durham, NC 27715 USA. Div Cardiol, Durham, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. RP Mehta, RH (reprint author), Duke Clin Res Inst, Box 17969, Durham, NC 27715 USA. EM mehta007@dcri.duke.edu NR 12 TC 115 Z9 121 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 18 PY 2006 VL 48 IS 2 BP 281 EP 286 DI 10.1016/j.jacc.2006.04.029 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 064HO UT WOS:000239080000009 PM 16843176 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, Robert P. Braunwald, Eugene TI The year in non-ST-segment elevation acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID C-REACTIVE PROTEIN; INTENSIVE STATIN THERAPY; SYNDROME EVALUATION WISE; LOW-DENSITY-LIPOPROTEIN; MYOCARDIAL-INFARCTION; INFLAMMATORY BIOMARKERS; HEART-DISEASE; RECURRENT EVENTS; UNSTABLE ANGINA; RISK SCORE C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 110 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 18 PY 2006 VL 48 IS 2 BP 386 EP 395 DI 10.1016/j.acc.2006.05.040 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 064HO UT WOS:000239080000024 PM 16843191 ER PT J AU Leung, JW Leung, FW AF Leung, JW Leung, FW TI Papillotomy Performance Scoring Scale - a pilot validation study focused on the cut axis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SPHINCTEROTOMY; COMPLICATIONS AB Background No published Papillotomy Performance Scoring Scale exists. Aim To develop such a scale and to apply it to stratify the quality of performance of recorded papillotomies. Method Expert biliary endoscopists were polled regarding their opinion of a 'perfect' biliary papillotomy and experience with complications in relation to the cut axis. Based on these responses a scoring scale encompassing two components - wire alignment and cut orientation, was proposed. This scoring scale was presented to experienced and trainee endoscopists, who scored recording of five biliary papillotomies. The mean final combined score was used for stratification. Results The experts' opinion of a 'perfect' biliary papillotomy is one cut along the axis of the distal bile duct and papilla. Their reported experience with complications occurring outside of the perfect axis validated their consensus. Application of the scoring scale stratified recorded papillotomies based on the mean final combined scores. Conclusion These pilot data support the hypothesis that a scoring scale focused on the cut axis can be constructed based on expert opinion, experience and consensus. The possibility of stratification of mean final combined scores that are significantly different validates application of the scoring scale for assessment of papillotomy performance. C1 Sacramento VA Med Ctr, Sect Gastroenterol 111 GI, Mather, CA 95655 USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Vet Affairs No Calif Healthcare Syst, Res & Med Serv, Sacramento Vet Affairs Med Ctr, Sacramento, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Sepulveda, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Sepulveda, CA USA. RP Leung, JW (reprint author), Univ Calif Davis, Davis Sch Med, 10535 Hosp Way, Mather, CA 95655 USA. EM jwleung@ucdavis.edu NR 13 TC 3 Z9 3 U1 0 U2 0 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 JUL 15 PY 2006 VL 24 IS 2 BP 307 EP 312 DI 10.1111/j.1365-2036.2006.02978.x PG 6 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 057EQ UT WOS:000238579500012 PM 16842457 ER PT J AU Rajab, A Yoo, SY Abdulgalil, A Kathiri, S Ahmed, R Mochida, GH Bodell, A Barkovich, AJ Walsh, CA AF Rajab, Anna Yoo, Seung-Yun Abdulgalil, Aiman Kathiri, Salem Ahmed, Riaz Mochida, Ganeshwaran H. Bodell, Adria Barkovich, A. James Walsh, Christopher A. TI An autosomal recessive form of spastic cerebral palsy (CP) with microcephaly and mental retardation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE spastic diplegia; microcephaly; mental retardation; autosomal recessive inheritance ID PREVALENCE; CHILDREN AB Cerebral palsy (CP) is defined as any nonprogressive motor deficits resulting from cerebral abnormalities that occur in the prenatal or perinatal period. Symptoms become apparent during the first year of life. Genetic forms of CP account for about 2% in European populations but are thought to cause a substantial proportion in consanguineous families. We have identified a large consanguineous family from Oman with spastic diplegia, microcephaly, and mental retardation. Additional manifestations include hyperreflexia, clumsiness, unstable gait, drooling, and dysarthria. There was phenotypic variability among different individuals, but spastic diplegia, microcephaly, and mental retardation were three constant traits present in all affected individuals. (c) 2006 Wiley-Liss, Inc. C1 Minist Hlth, DGHA, Genet Unit, Muscat, Oman. Royal Hosp, Dept Pediat, Muscat, Oman. Rustag Reg Hosp, Pediat Unit, Rustaq, Oman. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Walsh, CA (reprint author), 77 Ave Louis Pasteur,NRB Room 266, Boston, MA 02115 USA. EM cwalsh@bidmc.harvard.edu FU Howard Hughes Medical Institute; NINDS NIH HHS [R01 NS035129, R37 NS035129-11, 2R37NS35129, R37 NS035129] NR 17 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUL 15 PY 2006 VL 140A IS 14 BP 1504 EP 1510 DI 10.1002/ajmg.a.31288 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 060KA UT WOS:000238799900003 PM 16761294 ER PT J AU Gao, BB Hansen, H Chen, HC Feener, EP AF Gao, Ben-Bo Hansen, Hans Chen, Hong-Chi Feener, Edward P. TI Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-beta and its binding to class IA PI3K in vascular smooth muscle cells SO BIOCHEMICAL JOURNAL LA English DT Article DE angiotensin (Ang); phosphoinositide 3-kinase (PI3K); platelet-derived growth factor receptor-beta (PDGFR-beta); receptor stimulation; tyrosine phosphorylation; vascular smooth muscle cell (VSMC) ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNALING CASCADES; DOWNSTREAM TARGET; GENE-EXPRESSION; ANG-II; TYPE-1; TRANSACTIVATION; KINASE; IDENTIFICATION AB PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85 alpha mutant lacking the p110-binding domain (Delta p85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (plasminogen activator inhibitor-1) mRNA expression. Using a GST (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src homology 2) domain as 'bait' followed by MS/MS (tandem MS), we identified a 70 kDa fragment of the p70 PDGFR-beta (platelet-derived growth factor receptor-beta) as a signalling adapter that is phosphorylated and recruits the p85 subunit of PI3K after Ang II stimulation of AT, (Ang 11 subtype 1) receptors on VSMCs. This fragment of the PDGFR-beta, which has a truncation of its extracellular domain, accounted for approx. 15% of the total PDGFR-detected in VSMCs with an antibody against its cytoplasmic domain. Stimulation of VSMCs with Ang 11 increased tyrosine-phosphorylation of p70 PDGFR-beta at Tyr(751) and Tyr(1021) and increased its binding to p85. PDGF also induced phosphorylation of p70 PDGFR-beta, a response inhibited by the PDGF tyrosine kinase selective inhibitor, AG1296. By contrast, Ang II-induced phosphorylation of the 70 kDa receptor was not affected by AG1296. Ang II-stimulated phosphorylation of the p70 PDGFR-beta was blocked by the AT, receptor antagonist, candesartan (CV 11974) and was partially inhibited by PP2 {4-amino-5(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]primidine}, an Src family kinase inhibitor. Our result suggests that the p70 PDGFR-beta functions as an adapter that recruits PI3K to the membrane upon AT(1) receptor stimulation. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Eisai Res Inst, Wilmington, MA 01887 USA. Tzu Chi Univ, Dept Life Sci, Hualien 97004, Taiwan. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK060165, DK60165, P30 DK036836, DK 36836] NR 27 TC 12 Z9 14 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 2006 VL 397 BP 337 EP 344 DI 10.1042/BJ20060095 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 064ZS UT WOS:000239129800012 PM 16569213 ER PT J AU Cheson, BD Greenberg, PL Bennett, JM Lowenberg, B Wijermans, PW Nimer, SD Pinto, A Beran, M de Witte, TM Stone, RM Mittelman, M Sanz, GF Gore, SD Schiffer, CA Kantarjian, H AF Cheson, Bruce D. Greenberg, Peter L. Bennett, John M. Lowenberg, Bob Wijermans, Pierre W. Nimer, Stephen D. Pinto, Antonio Beran, Miloslav de Witte, Theo M. Stone, Richard M. Mittelman, Moshe Sanz, Guillermo F. Gore, Steven D. Schiffer, Charles A. Kantarjian, Hagop TI Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia SO BLOOD LA English DT Article ID QUALITY-OF-LIFE; COLONY-STIMULATING FACTOR; LOW-RISK MYELODYSPLASIA; SYNDROME MDS; DARBEPOETIN ALPHA; CONTROLLED-TRIAL; ERYTHROPOIETIN; ANEMIA; MULTICENTER; AZACITIDINE AB The myelodysplastic syndromes (MDSs) are heterogeneous with respect to clinical characteristics, pathologic features, and cytogenetic abnormalities. This heterogeneity is a challenge for evaluating response to treatment. Therapeutic trials in MDS have used various criteria to assess results, making cross-study comparisons problematic. In 2000, an International Working Group (IWG) proposed standardized response criteria for evaluating clinically significant responses in MDS. These criteria included measures of alteration in the natural history of disease, hematologic improvement, cytogenetic response, and improvement in health-related quality of life. The relevance of the response criteria has now been validated prospectively in MIDS clinical trials, and they have gained acceptance in research studies and in clinical practice. Because limitations of the IWG criteria have surfaced, based on practical and reported experience, some modifications were warranted. In this report, we present recommendations for revisions of some of the initial criteria. C1 Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77230 USA. Georgetown Univ Hosp, Dept Hematol Oncol, Washington, DC 20007 USA. Stanford Univ, Ctr Canc, Stanford, CA 94305 USA. Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14627 USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Radboud Univ Nijmegen, Med Ctr, Dept Hematol, Nijmegen, Netherlands. Dana Farber Canc Inst, Boston, MA 02115 USA. Tel Aviv Univ, Sackler Sch Med, Dept Med, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. Hosp Univ Fe, Valencia, Spain. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Wayne State Univ, Karmanos Canc Ctr, Detroit, MI USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. RP Kantarjian, H (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd, Houston, TX 77230 USA. EM hkantarj@mdanderson.org RI Witte, T.J.M./L-4762-2015; OI SANZ, GUILLERMO/0000-0002-2767-8191 NR 42 TC 610 Z9 639 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2006 VL 108 IS 2 BP 419 EP 425 DI 10.1182/blood-2005-10-4149 PG 7 WC Hematology SC Hematology GA 064ZP UT WOS:000239129500012 PM 16609072 ER PT J AU Lan, P Tonomura, N Shimizu, A Wang, SM Yang, YG AF Lan, Ping Tonomura, Noriko Shimizu, Akira Wang, Shumei Yang, Yong-Guang TI Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34(+) cell transplantation SO BLOOD LA English DT Article ID CD4(+) T-CELLS; SCID-HU MOUSE; LYMPHOID-TISSUES; DENDRITIC CELLS; AUTOIMMUNITY; TOLERANCE; REJECTION; MODEL; HEMATOPOIESIS; ENGRAFTMENT AB Studies of the human immune system have been limited by the lack of an appropriate in vivo model. For this reason, efforts have been made to develop murine models with a functional human immune system. We report here that cotransplantation of human fetal thymus/liver tissues and CD34(+) hematopoietic stem/progenitor cells led to the development of sustained human hematopoiesis and a functional human immune system in immunodeficient NOD/SCID mice. The humanized mice showed systemic repopulation with a comprehensive array of human lymphohematopoietic cells, including T cells, B cells, and dendritic cells, and the formation of secondary lymphoid organs. Furthermore, these mice produce high levels of human IgM and IgG antibodies and mediate strong immune responses in vivo as demonstrated by skin xenograft rejection. Thus, the humanized NOD/SCID mice described in this paper provide a powerful model system to study human immune function. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Yang, YG (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu NR 29 TC 134 Z9 141 U1 2 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2006 VL 108 IS 2 BP 487 EP 492 DI 10.1182/blood-2005-11-4388 PG 6 WC Hematology SC Hematology GA 064ZP UT WOS:000239129500021 PM 16410443 ER PT J AU Cutler, C Miklos, D Kim, HT Treister, N Woo, SB Bienfang, D Klickstein, LB Levin, J Miller, K Reynolds, C Macdonell, R Pasek, M Lee, SJ Ho, V Soiffer, R Antin, JH Ritz, J Alyea, E AF Cutler, Corey Miklos, David Kim, Haesook T. Treister, Nathaniel Woo, Sook-Bin Bienfang, Don Klickstein, Lloyd B. Levin, Jesse Miller, Katherine Reynolds, Carol Macdonell, Rebecca Pasek, Mildred Lee, Stephanie J. Ho, Vincent Soiffer, Robert Antin, Joseph H. Ritz, Jerome Alyea, Edwin TI Rituximab for steroid-refractory chronic graft-versus-host disease SO BLOOD LA English DT Article; Proceedings Paper CT Joint Meeting of the American-Society-for-Blood-and-Marrow-Transplantation/Center-for-Interna tional-Blood-and-Marrow-Transplant-Research CY FEB 10-14, 2005 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; MONOCLONAL-ANTIBODY RITUXIMAB; RANDOMIZED CLINICAL-TRIAL; LYMPHOPROLIFERATIVE DISEASE; PREEMPTIVE THERAPY; B-CELLS; ANTI-CD20; CYCLOSPORINE; LYMPHOMA AB B cells may be implicated in the pathophysiology of chronic graft-versus-host disease (GVHD), as evidenced by antibody production against sex-mismatched, Y chromosome-encoded minor HLA antigens in association with chronic GVHD. We therefore designed a phase 1/2 study of anti-B-cell therapy with rituximab in steroid-refractory chronic GVHD. Twenty-one patients were treated with 38 cycles of rituximab. Rituximab was tolerated well, and toxicity was limited to infectious events. The clinical response rate was 70%, including 2 patients with complete responses. Responses were limited to patients with cutaneous and musculoskeletal manifestations of chronic GVHD and were durable through 1 year after therapy. The median dose of prednisone among treated subjects fell from 40 mg/day to 10 mg/day, 1 year after rituximab therapy (P < .001). A chronic GVHD symptom score improved in the majority of treated patients. Antibody titers against Y chromosome-encoded minor HLA antigens fell and remained low, whereas titers against infectious antigens (EBV, tetanus) remained stable or rose during the treatment period. We conclude that specific anti-B-cell therapy with rituximab may be beneficial for patients with steroid-refractory chronic GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00136396. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Rheumatol, Boston, MA 02115 USA. Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D1B30, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL070149] NR 40 TC 257 Z9 264 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2006 VL 108 IS 2 BP 756 EP 762 DI 10.1182/blood-2006-01-0233 PG 7 WC Hematology SC Hematology GA 064ZP UT WOS:000239129500057 PM 16551963 ER PT J AU Schwartz, GF Veronesi, U Clough, KB Dixon, JM Fentiman, IS Heywang-Koebrunner, SH Holland, R Hughes, KS Margolese, R Olivotto, IA Palazzo, JP Solin, LJ AF Schwartz, Gordon F. Veronesi, Umberto Clough, Krishna B. Dixon, J. Michael Fentiman, Ian S. Heywang-Koebrunner, Sylvia H. Holland, Roland Hughes, Kevin S. Margolese, Richard Olivotto, Ivo A. Palazzo, Juan P. Solin, Lawrence J. CA Consensus Conference Comm TI Proceedings of the Consensus Conference on Breast Conservation, April 28 to May 1, 2005, Milan, Italy SO CANCER LA English DT Article AB In a single generation the treatment of most women with early-stage breast cancer has changed dramatically. Clinical trials with more than 20 years of follow-up have documented that, for appropriately selected patients, breast conserving surgery followed by whole breast irradiation has an outcome equivalent to mastectomy. The appropriate selection of patients remains controversial. Questions remain regarding the role of new diagnostic imaging modalities, radiation therapy techniques, achieving optimal cosmesis, the choice and the timing of adjuvant chemotherapy, etc. 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, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Guys Hosp, Dept Surg Oncol, London SE1 9RT, England. Tech Univ Munich, 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. Jewish Gen Hosp, Dept Surg, Montreal, PQ, Canada. Univ British Columbia, Div Radiat Oncol, Victoria, BC, Canada. British Columbia Canc Agcy, Victoria, BC, Canada. Jefferson Med Coll, Dept Pathol, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Schwartz, GF (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA. EM gordon.schwartz@yahoo.com OI Hughes, Kevin/0000-0003-4084-6484 NR 2 TC 33 Z9 36 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 JUL 15 PY 2006 VL 107 IS 2 BP 242 EP 250 DI 10.1002/cncr.21988 PG 9 WC Oncology SC Oncology GA 062QO UT WOS:000238959800004 PM 16770785 ER PT J AU Kawakubo, H Brachtel, E Hayashida, T Yeo, G Kish, J Muzikansky, A Walden, PD Maheswaran, S AF Kawakubo, Hirofumi Brachtel, Elena Hayashida, Tetsu Yeo, Giminna Kish, Joshua Muzikansky, Alona Walden, Paul D. Maheswaran, Shyamala TI Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin D1 protein SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; MICRORNA TARGETS; CANCER; D1; AMPLIFICATION; BTG2; GROWTH; COMPONENT; IMMUNOHISTOCHEMISTRY; IDENTIFICATION AB The B-cell translocation gene-2 (BTG2) is present in the nuclei of epithelial cells in many tissues, including the mammary gland where its expression is regulated during glandular proliferation and differentiation in pregnancy. In immortalized mammary epithelial cells and breast cancer cells, BTG2 protein localized predominantly to the nucleus and cytoplasm, respectively. The highly conserved domains (BTG boxes A, B, and C) were required for regulating localization, suppression of cyclin D1 and growth inhibitory function of BTG2. Expression analysis of BTG2 protein in human breast carcinoma (n = 148) revealed the loss of nuclear expression in 46% of tumors, whereas it was readily detectable in the nuclei of adjacent normal glands. Loss of unclear BTG2 expression in estrogen receptor-alpha (ER alpha)-positive breast tumors correlated significantly with increased histologic grade and tumor size. Consistent with its ability to suppress cyclin D1 transcription, loss of nuclear BT62 expression in ER-positive breast carcinomas showed a significant correlation with cyclin D1 protein overexpression, suggesting that loss of BTG2 may be a factor involved in deregulating cyclin D1 expression in human breast cancer. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NYU, Med Ctr, Dept Urol, New York, NY 10016 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Dept Pathol, Jackson 904,55 Fruit St, Boston, MA 02114 USA. EM maheswaran@helix.mgh.harvard.edu FU NCI NIH HHS [CA84441, CA89138] NR 42 TC 48 Z9 50 U1 0 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 JUL 15 PY 2006 VL 66 IS 14 BP 7075 EP 7082 DI 10.1158/0008-5472.CAN-06-0379 PG 8 WC Oncology SC Oncology GA 064QE UT WOS:000239103400024 PM 16849553 ER PT J AU Zhang, Y Gurumurthy, CB Kim, J Bhat, I Gao, QS Dimri, G Lee, SW Band, H Band, V AF Zhang, Ying Gurumurthy, Channabasavaiah B. Kim, JunHyun Bhat, Ishfaq Gao, Qingshen Dimri, Goberdhan Lee, Sam W. Band, Hamid Band, Vimla TI The human orthologue of Drosophila ecdysoneless protein interacts with p53 and regulates its function SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; DEGRADATION; LIGASE; CANCER; CELLS; RETINOBLASTOMA; EXPRESSION; SENESCENT; ENCODES; PATHWAY AB Biochemical mechanisms that control the levels and function of key tumor suppressor proteins are of great interest as their alterations can lead to oncogenic transformation. Here, we identify, the human orthologue of Drosophila melanogaster ecdysoneless (hEcd) as a novel p53-interacting protein. Overexpression of hEcd increases the levels of p53 and enhances p53 target gene transcription whereas hEcd knockdown has the opposite effects on p53 levels and target acne expression. Furthermore, hEcd interacts with murine double minute-2 and stabilizes p53 by inhibiting murine double minute-2-mediated degradation of p53. Thus, hEcd protein represents a novel regulator of p53 stability and function. Our studies also represent the first demonstration of a biochemical function for hEcd protein and raise the possibility that altered hEcd levels and/or function may contribute to oncogenesis. C1 Evanston NW Healthcare Res Inst, Div Canc Biol, Evanston, IL 60201 USA. Evanston NW Healthcare Res Inst, Dept Med, Div Mol Oncol, Evanston, IL 60201 USA. Northwestern Univ, Feinberg Sch Med, Evanston, IL USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Band, V (reprint author), Evanston NW Healthcare Res Inst, Div Canc Biol, 1001 Univ Pl, Evanston, IL 60201 USA. EM v-band@northwestern.edu FU NCI NIH HHS [R01 CA095221-02, R01 CA095221-05, CA 99900, CA94143, R01 CA096986-03, R01 CA096986-05, R01 CA096986-02, CA81076, CA 87986, R01 CA095221-04, R01 CA095221-03, R01 CA096986-04, R01 CA095221-01A1, CA99163, R01 CA096986-01A1, CA 76118, CA96844] NR 35 TC 17 Z9 18 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 JUL 15 PY 2006 VL 66 IS 14 BP 7167 EP 7175 DI 10.1158/0008-5472.CAN-06-0722 PG 9 WC Oncology SC Oncology GA 064QE UT WOS:000239103400035 PM 16849563 ER PT J AU Choi, Y Weissleder, R Tung, CH AF Choi, Yongdoo Weissleder, Ralph Tung, Ching-Hsuan TI Selective antitumor effect of novel protease-mediated photodynamic agent SO CANCER RESEARCH LA English DT Article ID CATHEPSIN-B; CANCER; TUMOR; ANGIOGENESIS; CONJUGATE; THERAPY; MATRIX; PROBES; ASSAY AB A new approach to selective photodynamic therapy (PDT) was developed by designing chlorin e6 (Ce6)-containing macromolecules, which are sensitive to tumor-associated proteases. The agents are nontoxic in their native state but become fluorescent and produce singlet oxygen on protease conversion. Coupled with optimized delivery svstems, we show that (a) the agents efficiently accumulate in tumors due to the enhanced permeability and retention effect, (b) the agents are locally activated by proteases, (c) local drug concentration,, can be measured by quantitative fluorescence tomography, and (d) light-treated tumors show reduced growth. A single low dose of PDT (0.125 mg Ce6 equivalent/kg) was sufficient to suppress tumor growth by > 50%. Activatable singlet oxygen generation agents provide increased efficacy with reduced toxicity, and it could become a powerful PDT. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01 CA99385] NR 22 TC 110 Z9 112 U1 5 U2 22 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 JUL 15 PY 2006 VL 66 IS 14 BP 7225 EP 7229 DI 10.1158/0008-5472.CAN-06-0448 PG 5 WC Oncology SC Oncology GA 064QE UT WOS:000239103400042 PM 16849570 ER PT J AU Bodner, RA Housman, DE Kazantsev, AG AF Bodner, Ruth A. Housman, David E. Kazantsev, Aleksey G. TI New directions for neurodegenerative disease therapy - Using chemical compounds to boost the formation of mutant protein inclusions SO CELL CYCLE LA English DT Article DE Huntington's disease; Parkinson's disease; neurodegenerative diseases; aggregation; inclusion body; misfolded protein ID NEURONAL INTRANUCLEAR INCLUSIONS; UBIQUITIN-PROTEASOME SYSTEM; HUNTINGTONS-DISEASE; ALPHA-SYNUCLEIN; AGGREGATION INHIBITORS; PARKINSONS-DISEASE; POLYGLUTAMINE AGGREGATION; MOLECULAR CHAPERONES; COMMON MECHANISM; BODY FORMATION AB Neurodegenerative diseases such as Huntington's, Parkinson's and Alzheimer's diseases are marked by neuronal accumulation of toxic misfolded protein. Developing therapies for these misfolding diseases requires finding chemical compounds that can either clear toxic misfolded protein, or can protect neurons from their impact. Such compounds could not only provide the starting points for potential drugs, but could also provide valuable research tools for untangling the complexities of the disease process. Until now, chemical screens for these diseases have focused on finding compounds that prevent aggregation of mutant protein. We recently published a compound, B2, which promotes the formation of large inclusions by mutant Huntingtin and alpha-synuclein, while rescuing some of the toxic effects of these proteins. As inclusions were long believed to be toxic to cells, this contradicts previous therapeutic approaches. At the same time, the results support growing evidence for the protective effects of inclusions. In this review, we discuss these results, and place them in the context of ongoing therapeutic discovery efforts for Huntington's disease and other neurodegenerative diseases. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Bodner, RA (reprint author), MIT, Ctr Canc Res, E18-505,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rbodner@mit.edu NR 43 TC 24 Z9 25 U1 1 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL 15 PY 2006 VL 5 IS 14 BP 1477 EP 1480 DI 10.4161/cc.5.14.2929 PG 4 WC Cell Biology SC Cell Biology GA 086UF UT WOS:000240697800001 PM 16861893 ER PT J AU Garland, LL Hidalgo, M Mendelson, DS Ryan, DP Arun, BK Lovalvo, JL Eiseman, IA Olson, SC Lenehan, PF Eder, JP AF Garland, Linda L. Hidalgo, Manuel Mendelson, David S. Ryan, David P. Arun, Banu K. Lovalvo, Jennifer L. Eiseman, Irene A. Olson, Stephen C. Lenehan, Peter F. Eder, Joseph P. TI A phase I clinical and pharmacokinetic study of oral CI-1033 in combination with docetaxel in patients with advanced solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; BREAST-CANCER; III TRIAL; RANDOMIZED-TRIAL; EXPRESSION; ERLOTINIB; CHEMOTHERAPY; GEFITINIB AB Purpose: CI-1033 is an orally available 4-anilinoquinazolone irreversible tyrosine kinase inhibitor of erbB-1, erbB-2, and erbB-4. We conducted a dose escalation study of CI-1033 with docetaxel to assess the safety profile and pharmacokinetics of the combination and to establish the maximum tolerated dose. Experimental Design: Twenty-six patients with advanced solid tumors were treated on four dosing cohorts starting at CI-1033 (50 mg/d) + clocetaxel (75 mg/m(2)). An intermittent dosing schedule avoided concurrent drug dosing. Results: CI-1033 alone was escalated from 50 to 75 mg/d (dose level 2), where diarrhea was dose limiting; a 38% incidence of cycle 1 febrile neutropenia prompted dose de-escalation of both CI-1033 and clocetaxel for dose level 3, where dose-limiting toxicities prompted further de-escalation of CI-1033 to 45 mg/d. Given equivalent safety profiles for dose level 1 [CI-1033 (50 mg/d) + docetaxel (75 mg/m(2))] and dose level 4 [CI-1033 (45 mg/d) + clocetaxel (60 mg/m(2))], the former was determined to be the recommended phase II dose, given greater dose intensity of both drugs. Antitumor activity was noted in three patients, including a complete response in a patient with cervix uteri cancer. Pharmacokinetic analysis showed a possible effect of clocetaxel on CI-1033 pharmacokinetics. Conclusions: It is feasible to combine the irreversible pan-erbB tyrosine kinase inhibitor CI-1033 with clocetaxel on an intermittent dosing schedule in advanced cancer patients. We established the maximum tolerated dose and recommended phase II dose for the combination. Further investigation of this combination should include a rigorous analysis of the effect of clocetaxel on CI-1033 pharmacokinetics. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Arizona, Arizona Canc Ctr, Scottsdale, AZ USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Pfizer Global Res & Dev, Ann Arbor, MI USA. RP Garland, LL (reprint author), Univ Arizona, Arizona Canc Ctr, 1515 N Campbell Ave,Ste 1969E, Tucson, AZ 85724 USA. EM lgarland@azcc.arizona.edu RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 NR 45 TC 18 Z9 20 U1 0 U2 0 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 JUL 15 PY 2006 VL 12 IS 14 BP 4274 EP 4282 DI 10.1158/1078-0432.CCR-05-2507 PN 1 PG 9 WC Oncology SC Oncology GA 068KR UT WOS:000239373200022 PM 16857802 ER PT J AU Kwak, EL Jankowski, J Thayer, SP Lauwers, GY Brannigan, BW Harris, PL Okimoto, RA Haserlat, SM Driscoll, DR Ferry, D Muir, B Settleman, J Fuchs, CS Kulke, MH Ryan, DP Clark, JW Sgroi, DC Haber, DA Bell, DW AF Kwak, Eunice L. Jankowski, Janusz Thayer, Sarah P. Lauwers, Gregory Y. Brannigan, Brian W. Harris, Patricia L. Okimoto, Ross A. Haserlat, Sara M. Driscoll, David R. Ferry, David Muir, Beth Settleman, Jeff Fuchs, Charles S. Kulke, Matthew H. Ryan, David P. Clark, Jeff W. Sgroi, Dennis C. Haber, Daniel A. Bell, Daphne W. TI Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; PHASE-II TRIAL; TYROSINE KINASE; SOMATIC MUTATIONS; GENE-MUTATIONS; GEFITINIB SENSITIVITY; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; EGFR MUTATIONS; ONCOLOGY-GROUP AB Purpose: Specific activating mutations within the epidermal growth factor receptor (EGFR) identify a subset of non - small cell lung cancers with dramatic sensitivity to the specific tyrosine kinase inhibitors (TKI), gefitinib and erlotinib. Despite the abundant expression of EGFR protein in a broad range of epithelial cancers, EGFR mutations have not been reported in a substantial fraction of other cancers. Given recent reports of TKI-responsive cases of esophageal and pancreatic cancer, this study was designed to determine the prevalence of EGFR mutations in these gastrointestinal cancers. Experimental Design: We sequenced exons 18 to 21 of EGFR from 21 cases of Barrett's esophagus, 5 cases of high-grade esophageal dysplasia, 17 cases of esophageal adenocarcinoma, and 55 cases of pancreatic adenocarcinoma. Subsets of esophageal (n = 7) and pancreatic cancer cases (n = 5) were obtained from patients who were subsequently treated with gefitinib or erlotinib-capecitabine, respectively. Results: Mutations of EGFR were identified in two esophageal cancers (11.7%), three cases of Barrett's esophagus (14.2%), and two pancreatic cancers (3.6%). The mutations consisted of the recurrent missense L858R and in-frame deletion del E746-A750, previously characterized as activating EGFR mutations in non-small cell lung cancer. We also identified the TKI drug resistance - associated EGFR T790M mutation in an untreated case of Barrett's esophagus and the corresponding adenocarcinoma. Conclusion: The presence of activating mutations within EGFR in both esophageal and pancreatic adenocarcinomas defines a previously unrecognized subset of gastrointestinal tumors in which EGFR signaling may play an important biological role. EGFR mutations in premalignant lesions of Barrett's esophagus also point to these as an early event in transformation of the esophageal epithelium. The role of genotype - directed TKI therapy should be tested in prospective clinical trials. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charleston, SC USA. Univ Oxford, Dept Clin Pharmacol, Oxford, England. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Royal Hosp Wolverhampton, Ctr Oncol, Wolverhampton, W Midlands, England. RP Bell, DW (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY7,149 13th St, Charlestown, MA 02129 USA. EM bell@helix.mgh.harvard.edu RI Jankowski, Janusz/H-2706-2012; Mendez, Pedro /J-8955-2016 OI Jankowski, Janusz/0000-0003-2130-9181; Mendez, Pedro /0000-0001-6713-7907 FU NCI NIH HHS [R01 CA11530, R01 CA115830]; NIDDK NIH HHS [K08 DK071329]; PHS HHS [P01 95281] NR 51 TC 111 Z9 119 U1 2 U2 6 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 JUL 15 PY 2006 VL 12 IS 14 BP 4283 EP 4287 DI 10.1158/1078-0432.CCR-06-0189 PN 1 PG 5 WC Oncology SC Oncology GA 068KR UT WOS:000239373200023 PM 16857803 ER PT J AU Lynch, TJ Adjei, AA Bunn, PA Eisen, TG Engelman, J Goss, GD Haber, DA Heymach, JV Janne, PA Johnson, BE Johnson, DH Lilenbaum, RC Meyerson, M Sandler, AB Sequist, LV Settleman, J Wong, KK Hart, CS AF Lynch, Thomas J. Adjei, Alex A. Bunn, Paul A., Jr. Eisen, Tim G. Engelman, Jeffrey Goss, Glenwood D. Haber, Daniel A. Heymach, John V. Jaenne, Pasi A. Johnson, Bruce E. Johnson, David H. Lilenbaum, Rogerio C. Meyerson, Matthew Sandler, Alan B. Sequist, Lecia V. Settleman, Jeffrey Wong, Kwok-Kin Hart, Carol S. TI Summary statement: Novel agents in the treatment of lung cancer: Advances in epidermal growth factor receptor-targeted agents SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Lowe Ctr Thorac Oncol, Dana Farber Canc Inst, Boston, MA USA. Mayo Clin Rochester, Rochester, MN USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Royal Marsden Hosp, Surrey, England. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Mt Sinai Canc Ctr, Miami Beach, FL USA. InforMEDical, Narberth, PA USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 210, Boston, MA 02114 USA. EM tlynch@partners.org RI Johnson, David/A-7437-2009; Meyerson, Matthew/E-7123-2012; OI wong, kwok kin/0000-0001-6323-235X NR 2 TC 29 Z9 31 U1 0 U2 0 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 JUL 15 PY 2006 VL 12 IS 14 SU S BP 4365S EP 4371S DI 10.1158/1078-0432.CCR-06-1005 PN 2 PG 7 WC Oncology SC Oncology GA 069HU UT WOS:000239437800001 PM 16857812 ER PT J AU Engelman, JA Cantley, LC AF Engelman, Jeffrey A. Cantley, Lewis C. TI The role of the ErbB family members in non-small cell lung cancers sensitive to epidermal growth factor receptor kinase inhibitors SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 3rd Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 23-24, 2005 CL Cambridge, MA ID TYROSINE KINASE; EGF RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; GEFITINIB SENSITIVITY; SIGNAL-TRANSDUCTION; GENE-MUTATIONS; TUMOR-CELLS; SURVIVAL; ERLOTINIB; THERAPY AB Inhibitors targeting the epidermal growth factor receptor (EGFR) are effective in a subset of non-small cell lung cancers, Such cancers often harbor EGFR mutations and/or amplification. These cancers require EGFR activity for the maintenance of critical intracellular survival and growth. signaling pathways. Evidence is now accruing that EGFR works in concert with other ErbB family members, particularly HER2 and Erb3, to activate these signaling pathways in a subset of lung cancers. These findings have important implications regarding the biology of these cancers and may lead to improved methods for identifying tumors that are responsive to EGFR kinase inhibitors and alternative therapies to treat cancers driven by ErbB signaling. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Signal Transduct, Boston, MA 02215 USA. RP Engelman, JA (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, New Res Bldg,77 Ave Louis Pasteur,Room 1052, Boston, MA 02115 USA. EM jengelman@partners.org RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 38 TC 45 Z9 46 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2006 VL 12 IS 14 SU S BP 4372S EP 4376S DI 10.1158/1078-0432.CCR-06-0795 PN 2 PG 5 WC Oncology SC Oncology GA 069HU UT WOS:000239437800002 PM 16857813 ER PT J AU Thomas, RK Weir, B Meyerson, M AF Thomas, Roman K. Weir, Barbara Meyerson, Matthew TI Genomic approaches to lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 3rd Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 23-24, 2005 CL Cambridge, MA ID GROWTH-FACTOR-RECEPTOR; GASTROINTESTINAL STROMAL TUMORS; NUCLEOTIDE POLYMORPHISM ARRAYS; ABL TYROSINE KINASE; GENE-EXPRESSION ANALYSIS; CHRONIC MYELOID-LEUKEMIA; HIGH-RESOLUTION ANALYSIS; OF-FUNCTION MUTATIONS; SMALL-CELL; COPY-NUMBER AB The last decade has seen remarkable success in clinical targeting of activated oncogenes in cancer. We have applied gene expression profiling, high-density single-nucleotide polymorphism arrays, and systematic resequencing of genes to identify novel oncogenes and signaling pathways in lung cancer that might represent therapeutic targets. Systematic resequencing of tyrosine kinase genes' has led to the discovery of somatic mutations in the epidermal growth factor receptor (EGFR) gene in lung adenocarcinomas. These mutations range in frequency from 10% in Caucasian to 40% in East Asian patients. Lung cancer - derived EGFR mutations are oncogenic and are tightly associated with clinical response to the EGFR kinase inhibitors erlotinib and gefitinib. Furthermore, gene expression profiling has been shown to classify patients according to their clinical outcome, indicating that the application of this technique may help in guiding patient selection for therapy in the futures. Finally, genome-wide analyses of copy number gains and losses were successfully applied to detect gene amplifications and deletions. Taken together, the application of genomics technologies has led to important discoveries with clinical implications in lung cancer that might help to improve clinical care for patients suffering from this highly fatal tumor. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. RP Meyerson, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M446, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 73 TC 25 Z9 26 U1 0 U2 0 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 JUL 15 PY 2006 VL 12 IS 14 BP 4384S EP 4391S DI 10.1158/1078-0432.CCR-06-0098 PG 8 WC Oncology SC Oncology GA 069HU UT WOS:000239437800004 PM 16857815 ER PT J AU Sharma, SV Fischbach, MA Haber, DA Settleman, J AF Sharma, Sreenath V. Fischbach, Michael A. Haber, Daniel A. Settleman, Jeffrey TI "Oncogenic shock": Explaining oncogene addiction through differential signal attenuation SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 3rd Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 23-24, 2005 CL Cambridge, MA ID MULTISTAGE CARCINOGENESIS; CELL CIRCUITRY; APOPTOSIS; PHOSPHORYLATION; PHOSPHATASE; DISORDERS; THERAPY; CANCER; KINASE; ERK AB "Oncogene addiction" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. We propose that "addiction" may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapopotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call "oncogenic shock," prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death. This mechanism may contribute to the rapid and dramatic clinical responses observed in some cancer patients treated with selective tyrosine kinase inhibitors and could yield additional drug targets that determine the balance of signaling outputs from activated oncoproteins. C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 14 TC 50 Z9 52 U1 1 U2 3 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 JUL 15 PY 2006 VL 12 IS 14 SU S BP 4392S EP 4395S DI 10.1158/1078-0432.CCR-06-0096 PN 2 PG 4 WC Oncology SC Oncology GA 069HU UT WOS:000239437800005 PM 16857816 ER PT J AU Dutt, A Wong, KK AF Dutt, Amit Wong, Kwok-Kin TI Mouse models of lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 3rd Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 23-24, 2005 CL Cambridge, MA ID EPIDERMAL-GROWTH-FACTOR; LARGE T-ANTIGEN; RECEPTOR TYROSINE KINASE; LI-FRAUMENI-SYNDROME; CIS-ACTING ELEMENTS; K-RAS ONCOGENE; TRANSGENIC MICE; PULMONARY ADENOCARCINOMAS; CONDITIONAL EXPRESSION; TARGETED EXPRESSION AB Human lung cancer is responsible for similar to 30% of all cancer deaths worldwide with >160,000 deaths in the United States alone annually. Recent advances in the identification of novel mutations relevant to lung cancer from a myriad of genomic studies might translate into meaningful diagnostic and therapeutic progress. Towards this end, a genetic model animal system that can validate the oncogenic roles of these mutations in vivo would facilitate the understanding of the pathogenesis of lung cancer as well as provide ideal preclinical models for targeted therapy testing. The mouse is a promising model system, as complex human genetic traits causal to lung cancer, from inherited polymorphisms to somatic mutations, can be recapitulated in its genome via genetic manipulation. We present here a brief overview of the existing mouse models of lung cancers and the challenges and opportunities for building the next generation of lung cancer mouse models. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, 44 Binney St,D810, Boston, MA 02115 USA. EM Kwong1@partners.org RI Dutt, Amit/I-1911-2013; OI Dutt, Amit/0000-0002-1119-4774; wong, kwok kin/0000-0001-6323-235X FU NIA NIH HHS [K08AG 2400401] NR 50 TC 16 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2006 VL 12 IS 14 SU S BP 4396S EP 4402S DI 10.1158/1078-0432.CCR-06-0414 PN 2 PG 7 WC Oncology SC Oncology GA 069HU UT WOS:000239437800006 PM 16857817 ER PT J AU Sequist, LV Joshi, VA Janne, PA Bell, DW Fidias, P Lindeman, NI Louis, DN Lee, JC Mark, EJ Longtine, J Verlander, P Kucherlapati, R Meyerson, M Haber, DA Johnson, BE Lynch, TJ AF Sequist, Lecia V. Joshi, Victoria A. Jaenne, Pasi A. Bell, Daphne W. Fidias, Pahos Lindeman, Neal I. Louis, David N. Lee, Jeffrey C. Mark, Eugene J. Longtine, Janina Verlander, Peter Kucherlapati, Raju Meyerson, Matthew Haber, Daniel A. Johnson, Bruce E. Lynch, Thomas J. TI Epidermal growth factor receptor mutation testing in the care of lung cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 3rd Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 23-24, 2005 CL Cambridge, MA ID PHASE-III TRIAL; EGFR MUTATIONS; GEFITINIB SENSITIVITY; ACTIVATING MUTATIONS; TYROSINE KINASE; GENE-MUTATIONS; HIGH-FREQUENCY; NEVER-SMOKERS; CELL; ERLOTINIB AB As the literature about epidermal growth factor receptor (EGFR) mutations grows and screening for mutations becomes increasingly integrated into clinical care, it is important to examine how best to do somatic mutational analyses and how best to use the test results in clinical decision making. We began offering mutation screening by comprehensive direct sequence analysis of exons 18 to 24 of the tyrosine kinase domain of EGFR in August 2004 as part of clinical cancer care and protocol therapy at our institutions, All identified potential mutations are confirmed with three to five independent PCRs of the original genomic DNA sample and, if not previously noted in the literature, are compared with the patient's germ-line DNA to ensure the finding is somatic. We form analyzed the first 100 patients to undergo EGFR sequence analysis and found that testing was feasible and significantly affected the treatment of patients with non-small cell lung cancer (NSCLC). Patients harboring EGFR mutations were significantly more likely to receive recommendations for therapy with EGFR tyrosine kinase inhibitors (i.e., gefitinib or erlotinib) than patients without mutations. However, negative EGFR test results did not prevent physicians from administering these agents to selected patients. Ideally, a standardized technique for mutation testing could be developed, with demonstrated reproducibility and validity. Clinical trials incorporating molecular diagnostics are ongoing to assess the efficacy of EGFR tyrosine kinase inhibitors a first-line therapy for metastatic NSCLC and as adjuvant therapy for early-stage resected NSCLC. It is likely that mutation testing and other molecular analyses will be most useful in these two clinical situations. C1 Massachusetts Gen Hosp, Ctr Canc, Yawkey Ctr Outpatient Care, 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, Partners HealthCare Ctr Genet & Genom, Mol Med Lab, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Broad Inst, Boston, MA USA. Harvard Univ, Broad Inst, Boston, MA 02115 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey Ctr Outpatient Care, 32 Fruit St,7th Floor, Boston, MA 02114 USA. EM LVSequist@Partners.org RI Meyerson, Matthew/E-7123-2012 NR 32 TC 54 Z9 55 U1 0 U2 0 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 JUL 15 PY 2006 VL 12 IS 14 SU S BP 4403S EP 4408S DI 10.1158/1078-0432.CCR-06-0099 PN 2 PG 6 WC Oncology SC Oncology GA 069HU UT WOS:000239437800007 PM 16857818 ER PT J AU Janne, PA Johnson, BE AF Jaenne, Pasi A. Johnson, Bruce E. TI Effect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 3rd Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 23-24, 2005 CL Cambridge, MA ID PARAFFIN-EMBEDDED TISSUE; GENE COPY NUMBER; ACTIVATING MUTATIONS; GEFITINIB SENSITIVITY; EGFR MUTATIONS; ERLOTINIB; ADENOCARCINOMAS; SURVIVAL; THERAPY; TRIAL AB Somatic mutations in the epidermal growth factor receptor (EGFR) have been identified in patients with advanced non - small cell lung cancer who achieve dramatic clinical and radiographic response to the EGFR tyrosine kinase inhibitors (TKI) gefitinib and erlotinib. These mutations in EGFR are found more frequently in patients with adenocarcinomas, nonsmokers, patients of Asian ethnicity, and in females; the same populations that are the most likely to have a clinical response when treated with EGFR TKIs. Retrospective studies comparing the outcomes of patients with and without EGFR mutations treated with EGFR TKIs show a significant clinical benefit of EGFR TKIs in patients with EGFR mutations. These findings suggest that for patients with advanced non - small cell lung cancer bearing EGFR mutations, treatment with an EGFR TKI should be incorporated as at least part of their initial therapy. These approaches are being studied in ongoing clinical trials and will spur the development of additional technology for EGFR mutation detection. C1 Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, D1234,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 39 TC 45 Z9 47 U1 1 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 JUL 15 PY 2006 VL 12 IS 14 SU S BP 4416S EP 4420S DI 10.1158/1078-0432.CCR-06-0555 PN 2 PG 5 WC Oncology SC Oncology GA 069HU UT WOS:000239437800009 PM 16857820 ER PT J AU Johnson, BE Janne, PA AF Johnson, Bruce E. Jaenne, Pasi A. TI Rationale for a phase II trial of pertuzumab, a HER-2 dimerization inhibitor, in patients with non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 3rd Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 23-24, 2005 CL Cambridge, MA ID GROWTH-FACTOR RECEPTOR; METASTATIC BREAST-CANCER; MONOCLONAL-ANTIBODY; GEFITINIB THERAPY; TRASTUZUMAB; ERLOTINIB; MUTATIONS; CARCINOMA; SURVIVAL; OVEREXPRESSION AB Background and Rationale: In non -small cell lung cancer, (NSCLC) HER-2-gene amplification and 3+ staining by immunohistochemistry are present in only 2% to 5% of the tumors. Therefore, relatively few patients with lung cancer are likely to benefit,from treatment-with trastuzumab, the humanized monoclonal antibody that is effective in the 20% of,patients with breast cancer and HER-2 gene amplification and/or 3+ staining by immunohistochemistry. Pertuzumab (rhuMAb 2C4), a humanized HER2 antibody, represents a new class. of, targeted therapeutics that inhibit, dimerization of HER2 with ligand-activated, EGFR (HER1), HER3, and HER-4. Pertuzumab can have antitumor activity-in patients with HER-2 present on the tumor without gene amplification or 3+ staining by immunohistochemistry. Preclinical xenograft studies have shown efficacy of pertuzumab in treating NSCLC. Therefore, a trial was undertaken for patients with relapsed NSCLC. Materials and Methods: Subjects with advanced or recurrent NSCLC treated previously, with chemotherapy were treated with pertuzumab (840 mg i.v. loading close,then 420 mg every 3,weeks). Mandatory fresh tumor biopsies before treatment were obtained for biomarker analysis including HER-2 phosohorylation Computed for tomography scans were obtained,every two cycles to assess tumor response. Tumor response (response evaluation criteria in solid, tumors criteria) was the primary end point. Results: As reported in a previous abstract, none of the 33 patients with NSCLC and evaluable disease had a response to the treatment. Conclusions: Pertuzumab has an appropriate rationale for therapeutic use in patients with NSCLC. A phase II trial in with patients NSCLC has completed enrollment,and the details of the trial will be presented in a future publication. This article will review-the preclinical rationale for undertaking a study of pertuzumab for patients with relapsed NSCLC. C1 Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. EM bejohnson@partners.org NR 30 TC 15 Z9 15 U1 4 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 JUL 15 PY 2006 VL 12 IS 14 SU S BP 4436S EP 4440S DI 10.1158/1078-0432.CCR-06-0629 PN 2 PG 5 WC Oncology SC Oncology GA 069HU UT WOS:000239437800013 PM 16857824 ER PT J AU Chiao, EY Giordano, TP Palefsky, JM Tyring, S El Serag, H AF Chiao, EY Giordano, TP Palefsky, JM Tyring, S El Serag, H TI Screening HIV-infected individuals for anal cancer precursor lesions: A systematic review SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID SQUAMOUS INTRAEPITHELIAL LESIONS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-PAPILLOMAVIRUS INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; POSITIVE MEN; CELL CARCINOMA; COST-EFFECTIVENESS; HIGH PREVALENCE; HOMOSEXUAL-MEN; RISK-FACTORS AB Individuals with human immunodeficiency virus ( HIV) infection are at increased risk for human papillomavirus-related squamous cell cancer of the anus. Screening HIV-infected patients for squamous cell cancer of the anus and human papillomavirus-related anal dysplasia may prevent excess morbidity and mortality. We have conducted a systematic review of the indirect evidence in the literature regarding the utility of anal Papanicolau ( Pap) smear screening of HIV-infected individuals in the highly active antiretroviral therapy era. Although there are no published studies evaluating the efficacy of anal Pap smear screening for preventing squamous cell cancer of the anus or anal intraepithelial neoplasia, we reviewed data regarding the burden of disease, anal Pap smear sensitivity and specificity, the prevalence of anal dysplasia, and 1 cost effectiveness study. The available evidence demonstrates that HIV-infected individuals have an increased risk for squamous cell cancer of the anus and anal intraepithelial neoplasia. This review identifies important areas for further study before routine anal Pap smear screening can be recommended. C1 Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Chiao, EY (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM echiao@bcm.tmc.edu FU NIMH NIH HHS [K23MH67505] NR 100 TC 153 Z9 158 U1 2 U2 7 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 JUL 15 PY 2006 VL 43 IS 2 BP 223 EP 233 DI 10.1086/505219 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 053WY UT WOS:000238338000016 PM 16779751 ER PT J AU Gori, F Friedman, LG Demay, MB AF Gori, Francesca Friedman, Lauren G. Demay, Marie B. TI Wdr5, a WD-40 protein, regulates osteoblast differentiation during embryonic bone development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Wdr5; BIG-3; endochondral bone formation; Wnt signaling; osteoblasts; differentiation; osteoprotegerin ID HORMONE-RELATED PEPTIDE; INDIAN-HEDGEHOG; CHONDROCYTE DIFFERENTIATION; PARATHYROID-HORMONE; IN-VITRO; GROWTH-PLATE; MORPHOGENETIC PROTEINS; PTH/PTHRP RECEPTOR; REPEAT PROTEIN; MICE AB Wdr5 accelerates osteoblast and chondrocyte differentiation in vitro, and is developmentally expressed in osteoblasts as well as in proliferating and hypertrophic chondrocytes. To investigate the role of Wdr5 during endochondral bone development, transgenic mice overexpressing Wdr5 under the control of the 2.3-kb fragment of the mouse alpha(1) I collagen promoter were generated. The transgene was specifically expressed in the osteoblasts of transgene positive mice and was absent in the growth plate. Histological analyses at embryonic day 14.5 demonstrated that the humeri of transgene positive embryos were longer than those isolated from wild-type littermates largely due to an expansion of the hypertrophic chondrocyte layer. Acceleration of osteoblast differentiation was observed with greater and more extensive expression of type I collagen and more extensive mineral deposition in the bone collar of transgene positive embryos. Acceleration of vascular invasion was also observed in transgene positive mice. Postnatal analyses of transgenic mice confirmed persistent acceleration of osteoblast differentiation. Targeted expression of Wdr5 to osteoblasts resulted in earlier activation of the canonical. Wnt signaling pathway in the bone collar as well as in primary calvarial osteoblast cultures. In addition, overexpression of Wdr5 increased the expression of OPG, a target of the canonical Wnt signaling pathway. Overall, our findings suggest that Wdr5 accelerates osteoblast differentiation in association with activation of the canonical Wnt pathway. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Demay, MB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK36597] NR 52 TC 21 Z9 23 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2006 VL 295 IS 2 BP 498 EP 506 DI 10.1016/j.ydbio.2006.02.031 PG 9 WC Developmental Biology SC Developmental Biology GA 064YX UT WOS:000239127700003 PM 16730692 ER PT J AU Ho, DM Chan, J Bayliss, P Whitman, M AF Ho, Diana M. Chan, Joanne Bayliss, Peter Whitman, Malcolm TI Inhibitor-resistant type I receptors reveal specific requirements for TGF-beta signaling in vivo SO DEVELOPMENTAL BIOLOGY LA English DT Article DE nodal; activin; TGF beta; Xenopus; zebrafish; ALK; mesoderm induction; left-right patterning ID GROWTH-FACTOR-BETA; VERTEBRATE DEVELOPMENT; BIOLOGICAL EVALUATION; TARAM-A; XENOPUS; ACTIVIN; SUPERFAMILY; ALK4; IDENTIFICATION; EMBRYOGENESIS AB Activin/nodal-like TGF-beta superfamily ligands signal through the type I receptors Alk4, Alk5, and Alk7, and are responsible for mediating a number of essential processes in development. SB-431542, a chemical inhibitor of activin/nodal signaling, acts by specifically interfering with type I receptors. Here, we use inhibitor-resistant mutant receptors to examine the efficacy and specificity of SB-431542 in Xenopus and zebrafish embryos. Treatment with SB-431542 eliminates Smad2 phosphorylation in vivo and generates a phenotype very similar to those observed in genetic mutants in the nodal signaling pathway. Inhibitor-resistant Alk4 efficiently rescues Smad2 signaling, developmental phenotype, and marker gene expression after inhibitor treatment. This system was used to examine type I receptor specificity for several activin/nodal ligands. We find that Alk4 can efficiently rescue signaling by a wide range of ligands, while Alk7 can only weakly rescue signaling by the same ligands. In whole embryos, nodal signaling during gastrulation can be rescued with Alk4, but not Alk7, while Alk5 can only mediate signaling by ligands expressed later in development. The combination of the ALK inhibitor SB-431542 with inhibitor-resistant ALKs provides a powerful set of tools for examining nodal/activin signaling during embryogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Whitman, M (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM mwhittman@hms.harvard.edu NR 43 TC 34 Z9 36 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2006 VL 295 IS 2 BP 730 EP 742 DI 10.1016/j.ydbio.2006.03.050 PG 13 WC Developmental Biology SC Developmental Biology GA 064YX UT WOS:000239127700022 PM 16684517 ER PT J AU Lin, LZ Bu, L Cai, CL Zhang, XX Evans, S AF Lin, Lizhu Bu, Lei Cai, Chen-Leng Zhang, Xiaoxue Evans, Sylvia TI Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Isl1; cardiac morphogenesis; smoothened; neuropilin2; outflow tract; aortic arch artery; anterior pole of the heart ID ANTERIOR HEART FIELD; DIGEORGE-SYNDROME; CARDIOVASCULAR DEVELOPMENT; PHARYNGEAL ARCH; MOUSE; SEMAPHORIN; TBX1; DIFFERENTIATION; GROWTH; ROLES AB The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in both foregut endoderm and cardiogenic mesoderm and is required for earliest stages of heart development. Here, we report that isl1 is also required upstream of Shh. We find that, in isl1 null mice, Sonic hedgehog (Shh) is downregulated in foregut endoderm. Shh signals through the unique activating receptor smoothened (Smo). To investigate the role of hedgehog signaling in the isl1 domain, we ablated smo utilizing isl1-cre. Isl1-cre;smo mutants exhibit cardiovascular defects similar to those observed in Shh null mice, defining a spatial requirement for hedgehog signaling within isl1 expression domains for aortic arch and outflow tract formation. Semaphorin signaling through neuropilin receptors npn1 and npn2 is required for aortic arch and outflow tract formation. We find that expression of npn2 is downregulated in is11-cre;smo mutants, suggestingan isl1/Shh/npn pathway required to affect morphogenesis at the anterior pole of the heart. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif San Diego, Skaggs Sch Pharm, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Cambridge, MA 02139 USA. RP Evans, S (reprint author), Univ Calif San Diego, Skaggs Sch Pharm, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM syevans@ucsd.edu RI Bu, Lei/F-4461-2011; Evans, Sylvia/G-1980-2015 FU NHLBI NIH HHS [R01 HL74066, R01 HL70867] NR 32 TC 59 Z9 67 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2006 VL 295 IS 2 BP 756 EP 763 DI 10.1016/j.ydbio.2006.03.053 PG 8 WC Developmental Biology SC Developmental Biology GA 064YX UT WOS:000239127700024 PM 16687132 ER PT J AU Hall, EJ Suit, HD AF Hall, Eric J. Suit, Herman D. TI Frank Ellis, OBE, MD, D.Sc. - Obituary SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Biographical-Item C1 Columbia Univ, Ctr Radiol Res, Med Ctr, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Hall, EJ (reprint author), Columbia Univ, Ctr Radiol Res, Med Ctr, P&S Room 11-230,630 W 168th St, New York, NY 10032 USA. EM ejhl@columbia.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2006 VL 65 IS 4 BP 963 EP 964 DI 10.1016/j.ijrobp.2006.03.043 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 061NH UT WOS:000238878800001 ER PT J AU Roach, M Hanks, G Thames, H Schellhammer, P Shipley, WU Sokol, GH Sandler, H AF Roach, Mack, III Hanks, Gerald Thames, Howard, Jr. Schellhammer, Paul Shipley, William U. Sokol, Gerald H. Sandler, Howard TI Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: Recommendations of the RTOG-ASTRO Phoenix Consensus Conference SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE biochemical recurrence; prostate cancer; radiotherapy; PSA failure ID EXTERNAL-BEAM RADIOTHERAPY; ADJUVANT ANDROGEN ABLATION; PHASE-III TRIAL; RADIATION-THERAPY; RADICAL PROSTATECTOMY; SEED IMPLANTATION; ANTIGEN BOUNCE; FREE SURVIVAL; PSA; BRACHYTHERAPY AB In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and backdating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined "at call" (not backdated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to "adequate follow-up." To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature. (c) 2006 Elsevier Inc. C1 Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Eastern Virginia Med Sch, Dept Urol, Norfolk, VA 23501 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Roach, M (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, 1600 Divisadero St,Suite H1031, San Francisco, CA 94143 USA. EM roach@radonc17.ucsf.edu NR 37 TC 1049 Z9 1063 U1 2 U2 30 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 JUL 15 PY 2006 VL 65 IS 4 BP 965 EP 974 DI 10.1016/j.ijrobp.2006.04.029 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 061NH UT WOS:000238878800002 PM 16798415 ER PT J AU Thames, HD Kuban, DA DeSilvio, ML Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL AF Thames, Howard D. Kuban, Deborah A. DeSilvio, Michelle L. Levy, Larry B. Horwitz, Eric M. Kupelian, Patrick A. Martinez, Alvaro A. Michalski, Jeff M. Pisansky, Thomas M. Sandler, Howard M. Shipley, William U. Zelefsky, Michael J. Zietman, Anthony L. TI Increasing external beam dose for T1-T2 prostate cancer: Effect on risk groups 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 prostate cancer; radiotherapy; risk groups; multi-institutional analysis; clinical disease-free survival ID III RANDOMIZED TRIAL; RADIATION-THERAPY; BIOCHEMICAL FAILURE; RADIOTHERAPY; CARCINOMA; DEFINITIONS; IRRADIATION; SURVIVAL; ERA AB Purpose: The aim of this study was to investigate effect of increasing dose on risk groups for clinical failure (CF: local failure or distant failure or hormone ablation or PSA >= 25 ng/ml) in patients with T1-T2 prostate cancer treated with external beam radiotherapy. Methods and Materials: Patients (n = 4,537) were partitioned into nonoverlapping dose ranges, each narrow enough that dose was not a predictor of CF, and risk groups for CF were determined using recursive partitioning analysis (RPA). The same technique was applied to the highest of these dose ranges (70-76 Gy, 1,136 patients) to compare risk groups for CF in this dose range with the conventional risk-group classification. Results: Cutpoints defining low-risk groups in each dose range shifted to higher initial PSA levels and Gleason scores with increasing dose. Risk groups for CF in the dose range 70-76 Gy were not consistent with conventional risk groups. Conclusions: The conventional classification of risk groups was derived in the early PSA era, when total doses < 70 Gy were common, and it is inconsistent with risk groups for patients treated to doses > 70 Gy. Risk-group classifications must be continuously re-examined whenever the trend is toward increasing total dose. (c) 2006 Elsevier Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Amer Coll Radiol, Philadelphia, PA USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. William Beaumont Hosp, Dept Radiat Oncol, Detroit, MI USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO 63110 USA. Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Thames, HD (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM hdt@odin.mdacc.tmc.edu NR 15 TC 18 Z9 19 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 JUL 15 PY 2006 VL 65 IS 4 BP 975 EP 981 DI 10.1016/j.ijrobp.2006.02.043 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 061NH UT WOS:000238878800003 PM 16750319 ER PT J AU Tishler, RB Posner, MR Norris, CM Mahadevan, A Sullivan, C Goguen, L Wirth, LJ Costello, R Case, M Stowell, S Sammartino, D Busse, PM Haddad, RI AF Tishler, Roy B. Posner, Marshall R. Norris, Charles M., Jr. Mahadevan, Anand Sullivan, Christopher Goguen, Laura Wirth, Lori J. Costello, Rosemary Case, MaryAnn Stowell, Sara Sammartino, Dan Busse, Paul M. Haddad, Robert I. TI Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol DE head-and-neck cancer; chemoradiation; concomitant boost radiation; docetaxel ID FLUOROURACIL INDUCTION CHEMOTHERAPY; STAGE OROPHARYNX CARCINOMA; ADVANCED LARYNGEAL-CANCER; PHASE-II TRIAL; RANDOMIZED-TRIAL; NEOADJUVANT CHEMOTHERAPY; ORGAN PRESERVATION; RADIOTHERAPY; PACLITAXEL; CISPLATIN AB Purpose: In a Phase I/II trial, we investigated concurrent weekly docetaxel and concomitant boost radiation in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) after induction chemotherapy. Patients and Methods: Patients presented with American Joint Committee on Cancer Stage III/IV and were treated initially with induction chemotherapy using cisplatinum/5-fluorouracil (PF), carboplatinum-5-FU, or docetaxel-PF. Patients then received docetaxel four times weekly with concomitant boost (CB) radiation (1.8 Gy once-daily X20, 1.8/1.5 Gy twice a day). Fifteen patients each received 20 mg/M-2 and 25 mg/M-2. Results: Thirty-one patients were enrolled and 30 were evaluable for response and toxicity. Median follow-up was 42 months (range, 27-63 months). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, and unknown primary 4. Eighty-seven percent of patients had N2/N3 disease; 60% had T3/T4 disease. Twenty percent of patients had a complete response (CR) to induction chemotherapy. After chemoradiotherapy, 21 of 30 patients had a CR, 2 had progressive disease, and 7 had partial response (PR). Nineteen of 26 patients presenting with neck disease had neck dissections, and 7 of 19 were positive. Ninety-three percent of all patients were rendered disease-free after all planned therapy. Treatment failed in 8 patients, and 7 have died of disease. An additional patient died with no evidence of disease. Twenty-one patients (70%) are currently alive with no evidence of disease. No acute dose-limiting toxicity was observed at either dose level. Conclusions: This intensive treatment regimen of concurrent docetaxellconcomitant boost radiation and surgery after induction chemotherapy in poor prognosis patients yields good local regional control and survival. Docetaxel/CB chemoradiotherapy represents an aggressive alternative regimen to platinum-based chemoradiotherapy or surgery in patients who have a poor response to induction chemotherapy. (c) 2006 Elsevier Inc. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Tishler, RB (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM roy_tishler@dfci.harvard.edu NR 40 TC 23 Z9 23 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 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2006 VL 65 IS 4 BP 1036 EP 1044 DI 10.1016/j.ijrobp.2006.02.010 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 061NH UT WOS:000238878800011 PM 16682134 ER PT J AU Connor, NP Cohen, SB Kammer, RE Sullivan, PA Brewer, KA Hong, TS Chappell, RJ Harari, PM AF Connor, Nadine P. Cohen, Stacy B. Kammer, Rachael E. Sullivan, Paula A. Brewer, Kathryn A. Hong, Theodore S. Chappell, Richard J. Harari, Paul M. TI Impact of conventional radiotherapy on health-related quality of life and critical functions of the head and neck SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE head-and-neck neoplasms radiotherapy; radiotherapy-adverse events; quality of life; salivation-radiation effects; deglutition-radiation effects ID LARYNGEAL-CANCER PATIENTS; EUROPEAN ORGANIZATION; RADIATION-THERAPY; WEIGHT-LOSS; CROSS-VALIDATION; XEROSTOMIA; QUESTIONNAIRE; PREDICTORS; PRESERVATION; CHEMOTHERAPY AB Purpose: Head-and-neck radiotherapy is associated with significant morbidities. Our purpose was to document impact of morbidities by use of multiple objective measures and health-related quality of life (HR-QOL). Methods and Materials: Ten head-and-neck cancer patients were evaluated before receiving conventional head-and-neck radiotherapy and at 1 month and 6 months after treatment. We evaluated weight, saliva production, diet, swallow function, auditory function, and HR-QOL. Results: After radiotherapy, weight was reduced in 89% of subjects. Salivary function was significantly reduced and did not resolve by 6 months. Diet impairment and abnormalities in swallowing function persisted at 6 months. Perception of physical functioning was reduced after treatment, and swallowing, coughing, and dry-mouth symptoms increased. Very few changes were observed in auditory function. Conclusions: Conventional head-and-neck radiotherapy is associated with substantial functional deficits and diminished HR-QOL. Deficits reported here can serve as a baseline for comparison with results derived from new radiotherapy-treatment techniques. (c) 2006 Elsevier Inc. C1 Univ Wisconsin, Sch Med, Dept Otolaryngol Head & Neck Surg, Madison, WI USA. Univ Wisconsin, Dept Commun Disorders, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Human Oncol, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Biostat & Med Informat, Madison, WI USA. RP Connor, NP (reprint author), Clin Sci Ctr K4-711,600 Highland Ave, Madison, WI 53792 USA. EM connor@surgery.wisc.edu FU NCI NIH HHS [P01 CA88960] NR 44 TC 40 Z9 42 U1 2 U2 8 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 JUL 15 PY 2006 VL 65 IS 4 BP 1051 EP 1062 DI 10.1016/j.ijrobp.2006.01.054 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 061NH UT WOS:000238878800013 PM 16682129 ER PT J AU Roof, KS Coen, J Lynch, TJ Wright, C Fidias, P Willett, CG Choi, NC AF Roof, Kevin S. Coen, John Lynch, Thomas J. Wright, Cameron Fidias, Panos Willett, Christopher G. Choi, Noah C. TI Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE esophageal cancer; paclitaxel; combined modality therapy ID PHASE-II TRIAL; COMBINED-MODALITY THERAPY; SQUAMOUS-CELL CARCINOMA; RANDOMIZED-TRIAL; CHEMOTHERAPY; SURGERY; TAXOL; CHEMORADIOTHERAPY; RADIOTHERAPY; CHEMORADIATION AB Purpose: Phase I-II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer. Patients and Methods: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994-2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. Results: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n = 81) or PFT-R (n = 83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%). Conclusions: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted. (c) 2006 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Roof, KS (reprint author), SE Radiat Oncol Grp, 200 Queens Rd,Suite 400, Charlotte, NC 28204 USA. EM kroof@sero.net NR 28 TC 24 Z9 27 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 JUL 15 PY 2006 VL 65 IS 4 BP 1120 EP 1128 DI 10.1016/j.ijrobp.2006.02.013 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 061NH UT WOS:000238878800021 PM 16730135 ER PT J AU Lim, M Bellon, JR Gelman, R Silver, B Recht, A Schnitt, SJ Harris, JR AF Lim, May Bellon, Jennifer R. Gelman, Rebecca Silver, Barbara Recht, Abram Schnitt, Stuart J. Harris, Jay R. TI A prospective study of conservative surgery without radiation therapy in select patients with stage I breast cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE breast; carcinoma; lumpectomy; radiation therapy ID 20-YEAR FOLLOW-UP; RANDOMIZED-TRIAL; POSTOPERATIVE RADIOTHERAPY; CONSERVING SURGERY; ADJUVANT CHEMOTHERAPY; TUBULAR CARCINOMA; SYSTEMIC THERAPY; TUMOR RECURRENCE; LOCAL RECURRENCE; MARGIN STATUS AB Purpose: The effectiveness of radiation therapy (RT) in reducing local recurrence after breast-conserving surgery (BCS) in unselected patients with early stage invasive breast cancer has been demonstrated in multiple randomized trials. Whether a subset of women can achieve local control without RT is unknown. In 1986, we initiated a prospective one-arm trial of BCS alone for highly selected breast-cancer patients. This report updates those results. Methods and Materials: Eighty-seven (of 90 planned) patients enrolled from 1986 until closure in 1992, when a predefined stopping boundary was crossed. Patients were required to have a unicentric, T1, pathologic nodenegative invasive ductal, mucinous, or tubular carcinoma without an extensive intraductal component or lymphatic-vessel invasion. Surgery included local excision with margins of at least 1 cut or a negative re-excision. No RT or systemic therapy was given. Results: Results are available on 81 patients (median follow-up, 86 months). Nineteen patients (23%) had local recurrence (LR) as a first site of failure (average annual LR: 3.5 per 100 patient-years of follow-up). Other sites of first failure included 1 ipsilateral axilla, 2 contralateral breast cancers, and 4 distant metastases. Six patients developed other (nonbreast) malignancies. Nine patients have died, 4 of metastatic breast cancer and 5 of unrelated causes. Conclusions: Even in this highly selected cohort, a substantial risk of local recurrence occurred after BCS alone with margins of 1.0 cut or more. These results suggest that with the possible exception of elderly women with comorbid conditions, radiation therapy after BCS remains standard treatment. (c) 2006 Elsevier Inc. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Biostat & Computat Bio, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. RP Bellon, JR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM jbellon@lroc.harvard.edu NR 35 TC 33 Z9 35 U1 1 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 JUL 15 PY 2006 VL 65 IS 4 BP 1149 EP 1154 DI 10.1016/j.ijrobp.2006.02.006 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 061NH UT WOS:000238878800024 PM 16750330 ER PT J AU Montoya, CJ Jie, HB Al-Harthi, L Mulder, C Patino, PJ Rugeles, MT Krieg, AM Landay, AL Wilson, SB AF Montoya, Carlos J. Jie, Hyun-Bae Al-Harthi, Lena Mulder, Candice Patino, Pablo J. Rugeles, Maria T. Krieg, Arthur M. Landay, Alan L. Wilson, S. Brian TI Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KILLER T-CELLS; IMMUNODEFICIENCY-VIRUS-INFECTION; INTERFERON-PRODUCING CELLS; INNATE IMMUNE-SYSTEM; TOLL-LIKE RECEPTORS; NATURAL-KILLER; CPG DNA; ADAPTIVE IMMUNITY; I INTERFERON; CYTOKINE SECRETION AB CD1d-restricted invariant NK T (iNKT) cells and dendritic cells (DCs) have been shown to play crucial roles in various types of immune responses, including TLR9-dependent antiviral responses initiated by plasmacytoid DCs (pDCs). However, the mechanism by which this occurs is enigmatic because TLRs are absent in iNKT cells and human pDCs do not express Md. To explore this process, pDCs were activated with CpG oligodeoxyribonucleotides, which stimulated the secretion of several cytokines such as type I and TNF-alpha. These cytokines and other soluble factors potently induced the expression of activation markers on iNKT cells, selectively enhanced double-negative iNKT cell survival, but did not induce their expansion or production of cytokines. Notably, pDC-derived factors licensed iNKT cells to respond to myeloid DCs: an important downstream cellular target of iNKT cell effector function and a critical contributor to the initiation of adaptive immune responses. This interaction supports the notion that iNKT cells can mediate cross-talk between DC subsets known to express mutually exclusive TLR and cytokine profiles. C1 Massachusetts Gen Hosp, Diabetes Res Unit, Cambridge, MA 02139 USA. Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. Univ Antioquia, Biogenesis Corp, Grp Immunovirol, Medellin, Colombia. Coley Pharmacol Grp, Wellesley, MA 02481 USA. RP Wilson, SB (reprint author), Massachusetts Gen Hosp, Diabetes Res Unit, 65 Landsdowne St,Room 528, Cambridge, MA 02139 USA. EM alanday@rush.edu; bwilson@rics.bwh.harvard FU NIAID NIH HHS [2R01 AI 45051, 5P01 AI 055793] NR 84 TC 54 Z9 56 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2006 VL 177 IS 2 BP 1028 EP 1039 PG 12 WC Immunology SC Immunology GA 062ED UT WOS:000238926500031 PM 16818759 ER PT J AU Margolin, DH Saunders, EH Bronfin, B de Rosa, N Axthelm, MK Goloubeva, OG Eapen, S Gelman, RS Letvin, NL AF Margolin, David H. Saunders, Erika H. Bronfin, Benjamin de Rosa, Nicole Axthelm, Michael K. Goloubeva, Olga G. Eapen, Sara Gelman, Rebecca S. Letvin, Norman L. TI Germinal center function in the spleen during simian HIV infection in rhesus monkeys SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODY-RESPONSES; HUMAN MONOCLONAL-ANTIBODIES; PRIMARY IMMUNE-RESPONSE; HIV-1/SIV CHIMERIC VIRUS; SOMATIC HYPERMUTATION; ENVELOPE GLYCOPROTEIN; IN-SITU; MOLECULAR CHARACTERIZATION; LINKED GLYCOSYLATION AB Infection with HIV-1, SIV, or simian HIV is associated with abnormalities in the number, size, and structure of germinal centers (GCs). To determine whether these histopathologic abnormalities are associated with abnormallities in Ab development, we analyzed nucleotide sequences of Igs from splenic GCs of simian HIV-infected macaques. Virus-specific GCs were identified in frozen splenic tissue sections by inverse immunohistochemistry using rHIV-1 gp120 as a probe. B cells from envelope-specific GCs were isolated from these sections using laser capture microdissection. Their Igs were amplified from cDNA using nested PCR, then cloned and sequenced. Nucleotide sequences were recovered from nine multimember clonal lineages. Within each lineage, sequences had similar V-D-J or V-J junctions but differed by somatic mutations distributed throughout the variable domain. The clones were highly mutated, similar to that previously reported for HIV-1-specific human IgG Abs. The average clone had 37 mutations in the V region, for a frequency of 0.11 mutations/base. The mutational pattern was strikingly nonrandom, with somatic mutations occurring preferentially at RGYW/WRCY hotspots. Transition mutations were favored over transversions, with C -> T and G -> A replacements together accounting for almost one-third of all mutations. Analysis of replacement and silent mutations in the framework and CDRs suggests that the Igs were subjected to affinity selection. These data demonstrate that the process of Ab maturation is not seriously disrupted in GCs during the early stages of immunodeficiency virus infection, and that Env-specific Igs developing in GCs are subject to extensive somatic mutation and profound selection pressures. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Viral Pathogenesis Div, Boston, MA 02215 USA. Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Viral Pathogenesis Div, RE-113,330 Brookline Av, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu FU NCI NIH HHS [CA 75922]; NCRR NIH HHS [RR 000163, RR 016025, RR 018107]; NIAID NIH HHS [AI 054292, AI 067854, AI 20729, AI 28691, AI 45370, AI 01587] NR 75 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2006 VL 177 IS 2 BP 1108 EP 1119 PG 12 WC Immunology SC Immunology GA 062ED UT WOS:000238926500040 PM 16818768 ER PT J AU Zhang, WT Mainero, C Kumar, A Wiggins, CJ Benner, T Purdon, PL Bolar, DS Kwong, KK Sorensen, AG AF Zhang, WT Mainero, C Kumar, A Wiggins, CJ Benner, T Purdon, PL Bolar, DS Kwong, KK Sorensen, AG TI Strategies for improving the detection of fMRI activation in trigeminal pathways with cardiac gating SO NEUROIMAGE LA English DT Article DE fMRI; trigeminal; brainstem; pons; thalamus; cardiac gating; dual-echo ID BRAIN-STEM ACTIVATION; CERVICAL SPINAL-CORD; STIMULATION; HUMANS; REDUCTION; PAINFUL; MOTION; NERVE AB Functional magnetic resonance imaging (fMRI) has become a powerful tool for studying the normal and diseased human brain. The application of fMRI in detecting neuronal signals in the trigeminal system, however, has been hindered by low detection sensitivity due to activation artifacts caused by cardiac pulse-induced brain and brainstem movement. A variety of cardiac gating techniques have been proposed to overcome this issue, typically by phase locking the sampling to a particular time point during each cardiac cycle. We sought to compare different cardiac gating strategies for trigeminal system fMRI. In the present study, we used tactile stimuli to elicit brainstem and thalamus activation and compared the fMRI results obtained without cardiac gating and with three different cardiac gating strategies: single-echo with TR of 3 or 9 heartbeats (HBs) and dual-echo T2*-mapping EPI (TR = 2 HBs, TE = 21/55 ms). The dual-echo T2* mapping and the single-echo with TR of 2 and 3 HBs cardiac-gated fMRI techniques both increased detection rate of fMRI activation in brainstem. Activation in the brainstem and the thalamus was best detected by cardiac-gated dual-echo EPI. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Zhang, WT (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,2301,13th St, Charlestown, MA 02129 USA. EM wtzhang@nmr.mgh.harvard.edu FU NCRR NIH HHS [M01-RR-01066, 5P41RR014075]; NIGMS NIH HHS [T32 GM007753]; NINDS NIH HHS [5P01 NS35611-07] NR 30 TC 19 Z9 19 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 15 PY 2006 VL 31 IS 4 BP 1506 EP 1512 DI 10.1016/j.neuroimage.2006.02.033 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 059AC UT WOS:000238704700010 PM 16624588 ER PT J AU Stevenson, K Ferer, M Bromhal, GS Gump, J Wilder, J Smith, DH AF Stevenson, K Ferer, M Bromhal, GS Gump, J Wilder, J Smith, DH TI 2-D network model simulations of miscible two-phase flow displacements in porous media: Effects of heterogeneity and viscosity SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE miscible drainage; heterogeneity; viscous fingering; pore-level modeling ID CAPILLARY TUBE NETWORKS; RESERVOIR PERFORMANCE; DRAINAGE AB There are long-standing uncertainties regarding the relative significance of the role of porous medium heterogeneities vs. the role of fluid properties in determining the efficiencies of various strategies for fluid injection into porous media. In this paper, we study both the role of heterogeneities and of viscosity ratio in determining the characteristics of miscible, two-phase flow in two-dimensional (2-D) porous media. Not surprisingly, we find that both are significant in determining the flow characteristics. For a variety of statistical distributions of pore-throat radii, we find that the coefficient of variation (the ratio of the standard deviation of the radii to their mean) is a reliable predictor of the injected fluid saturation as well as the width of the interfacial region. Consistent with earlier results, we find that viscosity ratio causes a crossover from fractal viscous fingering to standard compact flow at a characteristic crossover time which varies inversely with viscosity ratio. The studies in this paper show that the power law relating characteristic time to viscosity ratio does not depend upon the distribution of pore-throat radii or upon the connectivity (coordination number) of the medium each of which affects the porosity; this suggests that the power law may be entirely independent of the structure of the porous medium. This power law relationship leads to a robust dependence of the flow properties upon a particular ratio of the saturation to a given power of the viscosity ratio. This dependence is reminiscent of the empirical "quarter power mixing rule" in three dimensions. As such, this work provides a physical understanding of the origin and limitations of this empirical mixing rule. (c) 2006 Elsevier B.V. All rights reserved. C1 W Virginia Univ, Dept Phys, Morgantown, WV 26506 USA. US DOE, Natl Energy Technol Lab, Morgantown, WV 26507 USA. W Virginia Univ, Dept Stat, Morgantown, WV 26506 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. USN, Ctr Surface Warfare, Res & Technol Dept, Indian Head, MD 20640 USA. RP Ferer, M (reprint author), W Virginia Univ, Dept Phys, Morgantown, WV 26506 USA. EM mferer@wvu.edu NR 26 TC 17 Z9 18 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD JUL 15 PY 2006 VL 367 BP 7 EP 24 DI 10.1016/j.physa.2005.12.009 PG 18 WC Physics, Multidisciplinary SC Physics GA 052MB UT WOS:000238236700002 ER PT J AU Maron, R Levine, D Dobbs, TE Geisler, WM AF Maron, Rhodemarie Levine, Deborah Dobbs, Thomas E. Geisler, William M. TI Two cases of Pott disease associated with bilateral psoas abscesses - Case report SO SPINE LA English DT Article DE Pott disease; vertebral osteomyelitis; psoas abscess ID SPINAL TUBERCULOSIS; DEVELOPED COUNTRY; INFECTION; DIAGNOSIS; FEATURES; ADULTS AB Study Design. Two case reports and a literature review of spinal osteomyelitis with bilateral psoas abscesses secondary to Mycobacterium tuberculosis. Objective. Describe the presentation, diagnosis, treatment, and outcome of spinal tuberculosis (i.e., Pott disease). Summary of Background Data. Pott disease is a well-known condition in unindustrialized countries causing multiple spinal deformities in children. However, its association with bilateral psoas abscesses in adults with minimal risk factors is not commonly recognized in industrialized countries. Methods. There are 2 adult cases of Pott disease with psoas abscesses presented, and the relevant literature is reviewed. Plain spine radiographs, spine magnetic resonance imaging ( MRI), routine bacterial and acid-fast bacilli cultures of infected material, and other diagnostic testing for M. tuberculosis were performed. Results. Plain radiographs and MRI of the spine showed vertebral osteomyelitis with compression fractures, and MRI also revealed bilateral psoas abscesses. Acid-fast bacilli culture and other M. tuberculosis diagnostic testing of psoas abscess specimens confirmed the diagnosis of M. tuberculosis. Conclusion. Although spinal osteomyelitis with psoas abscess is classically associated with Staphylococcus aureus infection, Pott disease should be considered in this clinical setting, and risk factor assessment and testing for tuberculosis should be performed. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Deep S Ctr Effect, Birmingham, AL USA. RP Geisler, WM (reprint author), Univ Alabama, Dept Med, ZRB Room 242,703 19th St S, Birmingham, AL 35294 USA. EM wgeisler@uab.edu NR 20 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JUL 15 PY 2006 VL 31 IS 16 BP E561 EP E564 DI 10.1097/01.brs.0000225998.99872.7f PG 4 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 065YV UT WOS:000239197200031 PM 16845344 ER PT J AU Yu, LY Quinn, DA Garg, HG Hales, CA AF Yu, LY Quinn, DA Garg, HG Hales, CA TI Gene expression of cyclin-dependent kinase inhibitors and effect of heparin on their expression in mice with hypoxia-induced pulmonary hypertension SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE CDK inhibitor; gene array; pulmonary hypertension; hypoxia; mice; heparin ID SMOOTH-MUSCLE-CELLS; RETINOBLASTOMA PROTEIN; DOWN-REGULATION; CANCER CELLS; P27(KIP1); PROLIFERATION; ARREST; PROGRESSION; ACTIVATION; P21(CIP1) AB The balance between cell proliferation and cell quiescence is regulated delicately by a variety of mediators, in which cyclin-dependent kinases (CDK) and CDK inhibitors (CDKI) play a very important role. Heparin which inhibits pulmonary artery smooth muscle cell (PASMC) proliferation increases the levels of two CDK1s, p21 and p27, although only p27 is important in inhibition of PASMC growth in vitro and in vivo. In the present study we investigated the expression profile of all the cell cycle regulating genes, including all seven CDKIs (p21, p27, p57, p15, p16, p18, and p19), in the lungs of mice with hypoxia-induced pulmonary hypertension. A cell cycle pathway specific gene microarray was used to profile the 96 genes involved in cell cycle regulation. We also observed the effect of heparin on gene expression. We found that (a) hypoxic exposure for two weeks significantly inhibited p27 expression and stimulated p 18 activity, showing a 98% decrease in p27 and 81% increase in p18; (b) other CDKIs, p21, p57 p15, p16, and p19 were not affected significantly in response to hypoxia; (c) heparin treatment restored p27 expression, but did not influence p18; (d) ERK1/2 and p38 were mediators in heparin upregulation of p27. This study provides an expression profile of cell cycle regulating genes under hypoxia in mice with hypoxia-induced pulmonary hypertension and strengthens the previous finding that p27 is the only CDKI involved in heparin regulation of PASMC proliferation and hypoxia-induced pulmonary hypertension. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Pulm,Crit Care Unit, Boston, MA 02114 USA. RP Hales, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Pulm,Crit Care Unit, Boston, MA 02114 USA. EM chales@partners.org FU NHLBI NIH HHS [HL03920, HL39150] NR 36 TC 29 Z9 31 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 14 PY 2006 VL 345 IS 4 BP 1565 EP 1572 DI 10.1016/j.bbrc.2006.05.060 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 054VH UT WOS:000238406200038 PM 16729969 ER PT J AU Bandyopadhyay, S Lion, JM Mentaverri, R Ricupero, DA Kamel, S Romero, JR Chattopadhyay, N AF Bandyopadhyay, S Lion, JM Mentaverri, R Ricupero, DA Kamel, S Romero, JR Chattopadhyay, N TI Attenuation of osteoclastogenesis and osteoclast function by apigenin SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE flavonoids; bone resorption; osteoporosis; rheumatic arthritis; tumor necrosis factor; interferon gamma ID TUMOR-NECROSIS-FACTOR; MURINE BONE-MARROW; CELLS IN-VITRO; FACTOR-KAPPA-B; FACTOR-ALPHA; ESTROGEN DEFICIENCY; OSTEOBLASTIC CELLS; FACTOR-RECEPTOR; IFN-GAMMA; T-CELLS AB The physiological effects of the flavone, apigenin on bone cells were studied. We first show that apigenin inhibits tumor necrosis factor alpha (TNF alpha)- and interferon gamma (IFN gamma)-induced secretion of several osteoclastogenic cytokines from MC3T3-E1 mouse calvarial osteoblast cell line. Ligands of the TNT receptor family constitute the most potent osteoclastic cytokines. In MC3T3-E1 cells, apigenin dose-dependently (from 5 to 20 mu M) inhibits TNF alpha-induced production of the osteoclastogenic cytokines, IL-6 (interleukin-6), RANTES (regulated upon activation, normal T cell-expressed and -secreted), monocyte chemoattractant protein-1 (MCP-1) and MCP-3. In addition, apigenin inhibits IFN gamma-stimulated secretion of monokines, CXCL-9, and -10 in MC3T3-E1 cells. Next, we show that apigenin strongly inhibits differentiation of 3T3-L1 preadipocytes to adipocytes with attendant inhibition of adipocyte differentiation -induced IL-6, MCP-1, and leptin production. Inhibition of adipogenic differentiation by apigenin could be due to induction of osteogensis as it robustly upregulates mRNA levels of bone morphogenetic protein-6 (BMP-6). Finally, the presence of apigenin inhibited osteoclast differentiation from the RAW 264.7 cell line by reducing receptor activator of nuclear factor kappa ligand (RANKL)-induced expression of tartrate-resistant acid phosphatase (TRAP), RANK, and calcitonin receptor but not CCR1, resulting in the inhibition of multinucleated osteoclast formation. Similarly, apigenin inhibited expression of the osteoclast differentiation markers TRAP, RANK, and c-Fms in osteoclast precursor cells obtained from mouse bone marrow following treatment with RANKL and macrophage colony stimulating factor (MCSF). Furthermore, apigenin induced apoptosis of mature osteoclasts obtained from rabbit long bone and inhibited bone resorption. In all instances, a structurally related compound, flavone had no significant effect. These data suggest that apigenin has multiple effects on all three bone cells that could prevent bone loss in vivo. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Fac Pharm, Unite Etude Mecan Resorpt Osseuse, F-80037 Amiens, France. Fac Pharm, INSERM, F-80037 Amiens, France. RP Chattopadhyay, N (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM Naibedya@rics.bwh.harvard.edu OI Bandyopadhyay, Sanghamitra /0000-0002-1490-3599; Chattopadhyay, Naibedya/0000-0003-2473-0246 FU NIAMS NIH HHS [AR02215]; NIEHS NIH HHS [ES014462] NR 77 TC 37 Z9 42 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 14 PY 2006 VL 72 IS 2 BP 184 EP 197 DI 10.1016/j.bcp.2006.04.018 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 058YK UT WOS:000238700300007 PM 16750176 ER PT J AU Frezza, C Cipolat, S de Brito, OM Micaroni, M Beznoussenko, GV Rudka, T Bartoli, D Polishuck, RS Danial, NN De Strooper, B Scorrano, L AF Frezza, Christian Cipolat, Sara de Brito, Olga Martins Micaroni, Massimo Beznoussenko, Galina V. Rudka, Tomasz Bartoli, Davide Polishuck, Roman S. Danial, Nika N. De Strooper, Bart Scorrano, Luca TI OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion SO CELL LA English DT Article ID CYTOCHROME-C RELEASE; CELL-DEATH; INTERMEMBRANE SPACE; MAMMALIAN-CELLS; PROTEIN; FISSION; MITOFUSIN-1; FAMILY; BAX; FRAGMENTATION AB Mitochondria amplify activation of caspases during apoptosis by releasing cytochrome c and other cofactors. This is accompanied by fragmentation of the organelle and remodeling of the cristae. Here we provide evidence that Optic Atrophy 1 (OPA1), a profusion dynamin-related protein of the inner mitochondrial membrane mutated in dominant optic atrophy, protects from apoptosis by preventing cytochrome c release independently from mitochondrial fusion. OPA1 does not interfere with activation of the mitochondrial "gatekeepers" BAX and BAK, but it controls the shape of mitochondrial cristae, keeping their junctions; tight during apoptosis. Tightness of cristae junctions correlates with oligomerization of two forms of OPA1, a soluble, intermembrane space and an integral inner membrane one. The proapoptotic BCL-2 family member BID, which widens cristae junctions, also disrupts OPA1 oligomers. Thus, OPA1 has genetically and molecularly distinct functions in mitochondrial fusion and in cristae remodeling during apoptosis. C1 Venetian Inst Mol Med, Dulbecco Telethon Inst, Padua, Italy. Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Italy. Flanders Interuniv Inst Biotechnol, VIB4, Ctr Human Genet, Neuronal Cell Biol & Gene Transfer Lab, Louvain, Belgium. Katholieke Univ Leuven, Louvain, Belgium. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Scorrano, L (reprint author), Venetian Inst Mol Med, Dulbecco Telethon Inst, Padua, Italy. EM luca.scorrano@unipd.it RI Scorrano, Luca/A-6652-2008; Frezza, Christian/G-2174-2010; De Strooper, Bart/F-6507-2012; OI Scorrano, Luca/0000-0002-8515-8928; De Strooper, Bart/0000-0001-5455-5819; Frezza, Christian /0000-0002-3293-7397 FU Telethon [TCP02016] NR 47 TC 658 Z9 672 U1 5 U2 32 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 14 PY 2006 VL 126 IS 1 BP 177 EP 189 DI 10.1016/j.cell.2006.06.025 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 066JF UT WOS:000239224800025 PM 16839885 ER PT J AU Jafri, F El-Shewy, HM Lee, MH Kelly, M Luttrell, DK Luttrell, LM AF Jafri, Farahdiba El-Shewy, Hesham M. Lee, Mi-Hye Kelly, Margaret Luttrell, Deirdre K. Luttrell, Louis M. TI Constitutive ERK1/2 activation by a chimeric neurokinin 1 receptor-beta-arrestin1 fusion protein - Probing the composition and function of the G protein-coupled receptor "signalsome" SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ARRESTIN; MAP KINASE; REGULATED KINASES; VISUAL ARRESTIN; EGF RECEPTOR; CANCER-CELLS; SUBSTANCE-P; BETA-ARRESTIN-2; DESENSITIZATION; UBIQUITINATION AB The beta-arrestins, a small family of G protein-coupled receptor (GPCR)-binding proteins involved in receptor desensitization, have been shown to bind extracellular signal-regulated kinases 1 and 2 (ERK1/2) and function as scaffolds for GPCR-stimulated ERK1/2 activation. To better understand the mechanism of beta-arrestin-mediated ERK1/2 activation, we compared ERK1/2 activation by the wild-type neurokinin 1 (NK1) receptor with a chimeric NK1 receptor having beta-arrestin1 fused to the receptor C terminus (NK1- beta Arr1). The NK1 receptor couples to both Gs and G(q/11), resides on the plasma membrane, and mediates rapid ERK1/2 activation and nuclear translocation in response to neurokinin A. In contrast, NK1-beta Arr1 is a G protein-uncoupled "constitutively desensitized" receptor that resides almost entirely in an intracellular endosomal compartment. Despite its inability to respond to neurokinin A, we found that NK1-beta Arr1 expression caused robust constitutive activation of cytosolic ERK1/2 and that endogenous Raf, MEK1/2, and ERK1/2 coprecipitated in a complex with NK1-beta Arr1. While agonist- dependent ERK1/2 activation by the NK1 receptor was independent of protein kinase A(PKA) or PKC activity, NK1-beta Arr1-mediated ERK1/2 activation was completely inhibited when basal PKA and PKC activity were blocked. In addition, the rate of ERK1/ 2 dephosphorylation was slowed in NK1-beta Arr1-expressing cells, suggesting that beta-arrestin-bound ERK1/2 is protected from mitogen-activated protein kinase phosphatase activity. These data suggest that beta-arrestin binding to GPCRs nucleates the formation of a stable "signalsome" that functions as a passive scaffold for the ERK1/2 cascade while confining ERK1/2 activity to an extranuclear compartment. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 96 Jonathan Lucas St,816 CSB,POB 250624, Charleston, SC 29425 USA. EM luttrell@musc.edu FU NIDDK NIH HHS [DK55524] NR 50 TC 22 Z9 22 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 JUL 14 PY 2006 VL 281 IS 28 BP 19346 EP 19357 DI 10.1074/jbc.M512643200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061BU UT WOS:000238847000050 PM 16670094 ER PT J AU Sala-Valdes, M Ursa, A Charrin, S Rubinstein, E Hemler, ME Sanchez-Madrid, F Yanez-Mo, M AF Sala-Valdes, Monica Ursa, Angeles Charrin, Stephanie Rubinstein, Eric Hemler, Martin E. Sanchez-Madrid, Francisco Yanez-Mo, Maria TI EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATITIS-C VIRUS; INTERCELLULAR-ADHESION MOLECULE-3; ALPHA-3-BETA-1 INTEGRIN; T-LYMPHOCYTES; ERM PROTEINS; CD9-DEFICIENT MICE; PLASMA-MEMBRANE; GAMETE FUSION; MAJOR CD9; CD81 AB EWI-2 and EWI-F, two members of a novel subfamily of I-g proteins, are direct partners of tetraspanins CD9 (Tspan29) and CD81 (Tspan28). These EWI proteins contain a stretch of basic charged amino acids in their cytoplasmic domains that may act as binding sites for actin-linking ezrin-radixin-moesin (ERM) proteins. Confocal microscopy analysis revealed that EWI-2 and EWI-F colocalized with ERM proteins at microspikes and microvilli of adherent cells and at the cellular uropod in polarized migrating leukocytes. Immunoprecipitation studies showed the association of EWI-2 and EWI-F with ERM proteins in vivo. Moreover, pulldown experiments and protein-protein binding assays with glutathione S-transferase fusion proteins containing the cytoplasmic domains of EWI proteins corroborated the strong and direct interaction between ERMs and these proteins. The active role of ERMs was further confirmed by double transfections with the N-terminal domain of moesin, which acts as a dominant negative form of ERMs, and was able to delocalize EWIs from the uropod of polarized leukocytes. In addition, direct association of EWI partner CD81 C-terminal domain with ERMs was also demonstrated. Functionally, silencing of endogenous EWI-2 expression by short interfering RNA in lymphoid CEM cells augmented cell migration, cellular polarity, and increased phosphorylation of ERMs. Hence, EWI proteins, through their direct interaction with ERM proteins, act as linkers to connect tetraspanin-associated microdomains to actin cytoskeleton regulating cell motility and polarity. C1 UAM, Serv Inmunol, Hosp Univ Princesa, Madrid 28006, Spain. Hop Paul Brousse, INSERM, U602, F-94807 Villejuif, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yanez-Mo, M (reprint author), UAM, Serv Inmunol, Hosp Univ Princesa, Diego Leon 62, Madrid 28006, Spain. EM myanez.hlpr@salud.madrid.org RI Yanez-Mo, Maria/K-8577-2014; Sanchez-Madrid, Francisco/M-7889-2016; OI Yanez-Mo, Maria/0000-0001-7484-2866; Sanchez-Madrid, Francisco/0000-0001-5303-0762; Rubinstein, Eric/0000-0001-7623-9665 NR 57 TC 94 Z9 99 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 14 PY 2006 VL 281 IS 28 BP 19665 EP 19675 DI 10.1074/jbc.M602116200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061BU UT WOS:000238847000080 PM 16690612 ER PT J AU Kallianpur, AR Hulgan, T Canter, JA Ritchie, MD Haines, JL Robbins, GK Shafer, RW Clifford, DB Haas, DW AF Kallianpur, Asha R. Hulgan, Todd Canter, Jeffrey A. Ritchie, Marylyn D. Haines, Jonathan L. Robbins, Gregory K. Shafer, Robert W. Clifford, David B. Haas, David W. TI Hemochromatosis (HFE) gene mutations and peripheral neuropathy during antiretroviral therapy SO AIDS LA English DT Article DE drug toxicity; hemochromatosis mutations; HIV; iron deficiency; nucleoside reverse transcriptase inhibitors; peripheral neuropathy ID RESTLESS LEGS SYNDROME; REVERSE-TRANSCRIPTASE INHIBITORS; IMMUNODEFICIENCY-VIRUS-INFECTION; SEQUENTIAL 3-DRUG REGIMENS; HEREDITARY HEMOCHROMATOSIS; MITOCHONDRIAL TOXICITY; NUCLEOSIDE ANALOGS; HIV-1 INFECTION; INITIAL THERAPY; IRON-DEFICIENCY AB Objective: Peripheral neuropathy (PN) often complicates nucleoside reverse transcriptase inhibitor (NRTI) therapy of HIV infection and may involve mitochondrial dysfunction. Since iron deficiency is associated with some types of PN, and iron is essential for mitochondrial function, we tested the hypothesis that hemochromatosis (HFE) gene mutations influence susceptibility to NRT1-induced PN. Design: Case-control study involving multicenter, AIDS Clinical Trials Group (ACTG) protocol 384 and ACTG Human DNA Repository specimens. Methods: Study participants were randomized to receive three- or four-drug antiretroviral therapy with didanosine (ddl) plus stavudine (d4T) or zidovudine plus lamivudine, given with efavirenz, nelfinavir, or both, with up to three years of follow-up. PN was ascertained based on signs and symptoms. HFE C282Y and H63D genotypes were determined, and associations with PN were assessed using logistic regression. Results: Of 509 participants, 147 (29%) developed PN, 73% of whom had been randomized to receive ddl plus d4T. Among ddl/d4T-ever-treated individuals, HFE C282Y heterozygotes developed PN on ddl/d4T significantly less often than C282Y non-carriers, adjusting for age, CD4 lymphocyte count and viral load at baseline, and concomitant antiretroviral drugs [6% vs. 35%, respectively, in whites; adjusted odds ratio (OR), 0.17; 95% confidence interval (CI) 0.03-0.83; P = 0.021]. Regardless of race/ethnicity, ddl/d4T-associated PN was uncommon in C282Y heterozygotes [race-adjusted OR, 0.30; 95% CI 0.09-0.96); P = 0.0421. Conclusions: Iron-loading HFE mutations such as C282Y are associated with a decreased risk of PIN during antiretroviral therapy. This finding has potential implications for the prediction and prevention of NRT1-associated PN, particularly in populations at risk of iron deficiency. (c) 2006 Lippincott Williams & Wilkins. C1 Vanderbilt Univ, Sch Med, Div Gen Internal Med & Publ Hlth, Ctr Hlth Serv Res,GRECC,TVHS VA Med Ctr, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Ctr Hlth Serv Res, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. VA Tennessee Valley Healthcare Syst, GRECC, Nashville, TN USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Stanford Univ, Dept Med Infect Dis, Palo Alto, CA 94304 USA. Washington Univ, Sch Med, Dept Neurol & Neurol Surg, St Louis, MO 63110 USA. RP Kallianpur, AR (reprint author), Vanderbilt Univ, Sch Med, Div Gen Internal Med & Publ Hlth, Ctr Hlth Serv Res,GRECC,TVHS VA Med Ctr, Rm 4B109,1310 24th Ave S, Nashville, TN 37212 USA. EM asha.kallianpur@vanderbilt.edu RI Robbins, Gregory/F-7988-2011; Ritchie, Marylyn/C-1114-2012; Haines, Jonathan/C-3374-2012; Hulgan, Todd/B-3947-2014 OI Hulgan, Todd/0000-0002-3339-067X FU NCCIH NIH HHS [AT002508]; NCRR NIH HHS [RR000095]; NIAID NIH HHS [AI25903, AI38858, AI46339, AI54999]; NICHD NIH HHS [5K12HD43483]; NINDS NIH HHS [NS32228] NR 58 TC 31 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 13 PY 2006 VL 20 IS 11 BP 1503 EP 1513 DI 10.1097/01.aids.0000237366.56864.3c PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 076VE UT WOS:000239985400005 PM 16847405 ER PT J AU Silverberg, MJ Wegner, SA Milazzo, MJ McKaig, RG Williams, CF Agan, BK Armstrong, AW Gange, SJ Hawkes, C O'Connell, RJ Ahuja, SK Dolan, MJ AF Silverberg, Michael J. Wegner, Scott A. Milazzo, Mark J. McKaig, Rosemary G. Williams, Carolyn F. Agan, Brian K. Armstrong, Adam W. Gange, Stephen J. Hawkes, Clifton O'Connell, Robert J. Ahuja, Sunil K. Dolan, Matthew J. CA Tri-Service AIDS Clinical TI Effectiveness of highly-active antiretroviral therapy by race/ethnicity SO AIDS LA English DT Article DE highly-active antiretroviral therapy; survival; AIDS; race/ethnicity; HIV seroconversion; effectiveness ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; POPULATION EFFECTIVENESS; AFRICAN-AMERICANS; AIDS PROGRESSION; GENE VARIANTS; HIV DISEASE; DRUG-USE; CCR5; RACE AB Objective: To determine the effectiveness of HAART by race/ethnicity. Design: Prospective multicenter cohort study. Methods: We studied 991 African-Americans and 911 European-Americans enrolled in the United States Military's Tri-Service AIDS Clinical Consortium Natural History Study who had dates of HIV seroconversion known within 5 years and followed between 1990 and 2002. We determined the rate of disease progression to AIDS and death for subjects in this cohort. Multivariable models evaluated race, pre-HAART (1990-1995) and HAART (1996-2002) eras, age, gender and military service. Results: In the pre-HAART era, African-Americans had a statistically nonsignificant trend towards better outcomes: the relative hazards (RH) of AIDS and death for African-Americans compared to European-Americans were 0.85 [95% confidence interval (CI), 0.68-1.051 and 0.77 (95% CI, 0.55-1.08), respectively. In the HAART era, outcomes were similar by race: 1.17 (95% CI, 0.86-1.61) for AIDS and 1.11 (95% CI, 0.81-1.53) for death with overlapping Kaplan-Meier curves. Relative to the pre-HAART era, the adjusted RH of AIDS in the HAART era was 0.41 (95% CI, 0.31-0.54) and 0.30 (95% CI, 0.22-0.40) for African-American and European-American participants, respectively. Analogous RH for death were 0.55 (95% CI, 0.38-0.80) and 0.38 (95% CI, 0.27-0.54). The precipitous declines in AIDS and death in the HAART era were not statistically different by race. Conclusions: In a large multi-racial cohort with equal access to health care, HIV treatment outcomes by race/ethnicity were similar. (c) 2006 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. TACC, NHS, Rockville, MD USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Retrovirol, Washington, DC 20307 USA. NIAID, Epidemiol Branch, Div AIDS, NIH,DHHS, Bethesda, MD 20892 USA. Wilford Hall USAF Med Ctr, Dept Infect Dis, Lackland AFB, TX 78236 USA. USN, Med Ctr, Portsmouth, VA USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. S Texas Vet Hlth Care Syst, Vet Adm Res Ctr Aids & HIV 1 Infect, San Antonio, TX USA. Univ Texas Hlth Ctr, Dept Med, San Antonio, TX USA. Def Inst Med Operat, Brooks AFB, TX USA. RP Dolan, MJ (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Matthew.Dolan@brooks.af.mil OI Gange, Stephen/0000-0001-7842-512X; Agan, Brian/0000-0002-5114-1669 FU NIAID NIH HHS [U01-AI-42590] NR 37 TC 35 Z9 36 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 13 PY 2006 VL 20 IS 11 BP 1531 EP 1538 DI 10.1097/01.aids.0000237369.41617.0f PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 076VE UT WOS:000239985400008 PM 16847408 ER PT J AU Alter, G Suscovich, TJ Kleyman, M Teigen, N Streeck, H Zaman, MT Meier, A Altfeld, M AF Alter, Galit Suscovich, Todd J. Kleyman, Marianna Teigen, Nickolas Streeck, Hendrik Zaman, M. Tauheed Meier, Angela Altfeld, Marcus TI Low perforin and elevated SHIP-1 expression is associated with functional anergy of natural killer cells in chronic HIV-1 infection SO AIDS LA English DT Article ID T-CELLS; INTERFERON-GAMMA; NK CELLS; SUBSET; CYTOTOXICITY; INDIVIDUALS; RECOVERY AB Natural killer (NK) cells are critical for the first-line defense in infection. Treated viremic HIV-1 infection is associated with the expansion of an anergic subset of CD3-CD56-CD16+ NK cells unable to respond to stimulation with MHC-devoid target cells or with mitogens. These CD3-CD56-CD16+ NK cells expressed SHIP-1 and had significantly reduced perforin levels. This observation suggests a mechanism for the reduced functional activity of CD3-CD56-CD16+ NK cells in chronic HIV-1 infection. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02114 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. EM maltfeld@partners.org NR 16 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 13 PY 2006 VL 20 IS 11 BP 1549 EP 1551 DI 10.1097/01.aids.0000237371.31315.48 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 076VE UT WOS:000239985400010 PM 16847410 ER PT J AU Hochberg, LR Serruya, MD Friehs, GM Mukand, JA Saleh, M Caplan, AH Branner, A Chen, D Penn, RD Donoghue, JP AF Hochberg, Leigh R. Serruya, Mijail D. Friehs, Gerhard M. Mukand, Jon A. Saleh, Maryam Caplan, Abraham H. Branner, Almut Chen, David Penn, Richard D. Donoghue, John P. TI Neuronal ensemble control of prosthetic devices by a human with tetraplegia SO NATURE LA English DT Article ID SPINAL-CORD-INJURY; BRAIN-COMPUTER INTERFACE; PRIMARY MOTOR CORTEX; CORTICAL ACTIVITY; ELECTRODE ARRAY; MOVEMENT SIGNAL; DIRECTION; PATTERNS; SYSTEM; DISCHARGE AB Neuromotor prostheses ( NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis. C1 Brown Univ, Dept Neurosci, Providence, RI 02912 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02114 USA. Brown Univ, Brain Sci Program, Providence, RI 02912 USA. Brown Univ, Dept Engn, Providence, RI 02912 USA. Vet Hlth Adm, Dept Vet Affairs, Rehabil Res & Dev Serv, Ctr Restorat & Regenerat Med, Providence, RI 02908 USA. Brown Univ, Dept Clin Neurosci Neurosurg, Providence, RI 02905 USA. Rhode Isl Hosp, Dept Neurosurg, Providence, RI 02905 USA. Brown Univ, Dept Rehabil Med, Providence, RI 02903 USA. Sargent Rehabil Ctr, Warwick, RI 02818 USA. Cyberkinet Neurotechnol Syst Inc, Foxboro, MA 02035 USA. Cyberkinet Neurotechnol Syst Inc, Salt Lake City, UT 84108 USA. Rehabil Inst Chicago, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. Univ Chicago Hosp, Dept Neurosurg, Chicago, IL 60637 USA. RP Donoghue, JP (reprint author), Brown Univ, Dept Neurosci, POB 1953, Providence, RI 02912 USA. EM john_donoghue@brown.edu RI Gabriel, Gemma/D-7901-2014; Franco-Hurtado, Fernando/E-5599-2017; OI Gabriel, Gemma/0000-0003-2140-6299; Franco-Hurtado, Fernando/0000-0001-5775-0150; Hochberg, Leigh/0000-0003-0261-2273 NR 44 TC 1443 Z9 1502 U1 71 U2 384 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 13 PY 2006 VL 442 IS 7099 BP 164 EP 171 DI 10.1038/nature04970 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 062XJ UT WOS:000238979700039 PM 16838014 ER PT J AU Barrett-Connor, E Mosca, L Collins, P Geiger, MJ Grady, D Kornitzer, M McNabb, MA Wenger, NK AF Barrett-Connor, E Mosca, L Collins, P Geiger, MJ Grady, D Kornitzer, M McNabb, MA Wenger, NK CA RUTH Trial Investigators TI Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ESTROGEN-REPLACEMENT THERAPY; RANDOMIZED CLINICAL-TRIAL; VERTEBRAL FRACTURE RISK; CORONARY-HEART-DISEASE; MULTIPLE OUTCOMES; PLUS PROGESTIN; TAMOXIFEN; REDUCTION; STROKE; OSTEOPOROSIS AB BACKGROUND: The effect of raloxifene, a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer is not established. METHODS: We randomly assigned 10,101 postmenopausal women (mean age, 67.5 years) with CHD or multiple risk factors for CHD to 60 mg of raloxifene daily or placebo and followed them for a median of 5.6 years. The two primary outcomes were coronary events (i.e., death from coronary causes, myocardial infarction, or hospitalization for an acute coronary syndrome) and invasive breast cancer.) RESULTS: As compared with placebo, raloxifene had no significant effect on the risk of primary coronary events (533 vs. 553 events; hazard ratio, 0.95; 95 percent confidence interval, 0.84 to 1.07), and it reduced the risk of invasive breast cancer (40 vs. 70 events; hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for one year); the benefit was primarily due to a reduced risk of estrogen-receptor-positive invasive breast cancers. There was no significant difference in the rates of death from any cause or total stroke according to group assignment, but raloxifene was associated with an increased risk of fatal stroke (59 vs. 39 events; hazard ratio, 1.49; 95 percent confidence interval, 1.00 to 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous thromboembolism (103 vs. 71 events; hazard ratio, 1.44; 95 percent confidence interval, 1.06 to 1.95; absolute risk increase, 1.2 per 1000 woman-years). Raloxifene reduced the risk of clinical vertebral fractures (64 vs. 97 events; hazard ratio, 0.65; 95 percent confidence interval, 0.47 to 0.89; absolute risk reduction, 1.3 per 1000). CONCLUSIONS: Raloxifene did not significantly affect the risk of CHD. The benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke. C1 Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Royal Brompton Hosp, Dept Cardiac Med, London, England. Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England. Lilly Res Labs, Indianapolis, IN USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Free Univ Brussels, Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Brussels, Belgium. Emory Univ, Sch Med, Atlanta, GA USA. RP Barrett-Connor, E (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM ebarrettconnor@ucsd.edu RI Boehm, Bernhard/F-8750-2015 NR 31 TC 540 Z9 561 U1 3 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 13 PY 2006 VL 355 IS 2 BP 125 EP 137 DI 10.1056/NEJMoa062462 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 062UP UT WOS:000238970600004 PM 16837676 ER PT J AU Lee, DS Pencina, MJ Benjamin, EJ Wang, TJ Levy, D O'Donnell, CJ Nam, B Larson, MG D'Agostino, RB Vasan, RS AF Lee, DS Pencina, MJ Benjamin, EJ Wang, TJ Levy, D O'Donnell, CJ Nam, B Larson, MG D'Agostino, RB Vasan, RS TI Association of parental heart failure with risk of heart failure in offspring SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LEFT-VENTRICULAR MASS; FAMILIAL DILATED CARDIOMYOPATHY; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; FRAMINGHAM; GENE; HISTORY; POLYMORPHISM; HYPERTROPHY AB BACKGROUND: The association between heart failure in parents and the prevalence of left ventricular systolic dysfunction and the risk of heart failure in their offspring has not been investigated in a community-based setting. METHODS: We examined the cross-sectional association of heart failure in parents with the prevalence of left ventricular systolic dysfunction, as well as left ventricular mass, internal dimensions, and wall thickness, in 1497 participants of the Framingham Offspring Study (mean age, 57 years; 819 women) who underwent routine echocardiography. We also investigated prospectively whether heart failure in parents increased the risk of heart failure in 2214 offspring (mean age, 44 years; 1150 women). RESULTS: As compared with the 1039 participants whose parents did not have heart failure, the 458 participants in the cross-sectional cohort who had at least one parent with heart failure were more likely to have increased left ventricular mass (17.0 percent vs. 26.9 percent), left ventricular internal dimensions (18.6 percent vs. 23.4 percent), and left ventricular systolic dysfunction (3.1 percent vs. 5.7 percent); the multivariable-adjusted odds ratios were 1.35 (95 percent confidence interval, 0.99 to 1.84), 1.29 (95 percent confidence interval, 0.96 to 1.72), and 2.37 (95 percent confidence interval, 1.22 to 4.61), respectively. In the longitudinal cohort, heart failure developed in 90 offspring during follow-up (mean length of follow-up, 20 years). The age- and sex-adjusted 10-year incidence rates of heart failure were 2.72 percent among offspring with a parent with heart failure, as compared with 1.62 percent among those without a parent with heart failure. This increase in risk persisted after multivariable adjustment (hazard ratio, 1.70; 95 percent confidence interval, 1.11 to 2.60). CONCLUSIONS: Heart failure in parents is associated with an increased prevalence of left ventricular systolic dysfunction cross-sectionally and an elevated risk of heart failure longitudinally. Our data emphasize the contribution of familial factors to the heart-failure burden in the community. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Lee, Douglas/J-4315-2014; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K24HL04334, K23 HL074077, N01-HC-25195, U01 HL 66582] NR 34 TC 78 Z9 80 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 13 PY 2006 VL 355 IS 2 BP 138 EP 147 DI 10.1056/NEJMoa052948 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 062UP UT WOS:000238970600005 PM 16837677 ER PT J AU Barker, FG Rabinov, JD Eskandar, E AF Barker, FG Rabinov, JD Eskandar, E TI Case 21-2006: A 61-year-old man with left-sided facial pain - Left trigeminal neuralgia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MICROVASCULAR DECOMPRESSION; MANAGEMENT C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. NR 16 TC 6 Z9 6 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 JUL 13 PY 2006 VL 355 IS 2 BP 183 EP 188 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 062UP UT WOS:000238970600012 ER PT J AU Blumenthal, D AF Blumenthal, D TI Employer-sponsored insurance - Riding the health care tiger SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DISEASE MANAGEMENT; SAVINGS ACCOUNTS; QUALITY; PLAN C1 Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. NR 31 TC 18 Z9 18 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 JUL 13 PY 2006 VL 355 IS 2 BP 195 EP 202 DI 10.1056/NEJMhpr060704 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 062UP UT WOS:000238970600015 PM 16837686 ER PT J AU Ton-Nu, TT Levine, RA Handschumacher, MD Dorer, DJ Yosefy, C Fan, DL Hua, LQ Jiang, L Hung, J AF Ton-Nu, Thanh-Thao Levine, Robert A. Handschumacher, Mark D. Dorer, David J. Yosefy, Chaim Fan, Dali Hua, Lanqi Jiang, Leng Hung, Judy TI Geometric determinants of functional tricuspid regurgitation - Insights from 3-dimensional echocardiography SO CIRCULATION LA English DT Article DE tricuspid annulus; echocardiography; regurgitation ID ISCHEMIC MITRAL REGURGITATION; ARTERY SYSTOLIC PRESSURE; VALVE REPAIR; DIMENSIONAL ECHOCARDIOGRAPHY; DOPPLER-ECHOCARDIOGRAPHY; DILATED CARDIOMYOPATHY; RING SELECTION; FLOW; ANNULOPLASTY; REPLACEMENT AB Background - Tricuspid regurgitation (TR) is an important predictor of morbidity and mortality in heart failure. We aimed to examine the 3D geometry of the tricuspid valve annulus (TVA) in patients with functional TR, comparing them with patients with normal tricuspid valve function and relating annular geometric changes to functional TR. Methods and Results - TVA shape was examined by real-time 3D echocardiography in 75 patients: 35 with functional TR and 40 with normal tricuspid valve function (referent group). The 3D shape of the TVA was reconstructed from rotated 2D planes, and the annular plane was computed by least-squares fitting. Annular area and mediolateral, anteroposterior, and high (superior)- low (inferior) distances were calculated. TR was assessed by vena contracta width. The normal TVA has a bimodal pattern (high-low distance = 7.23 +/- 1.05 mm). High points were located anteroposteriorly, and low points were located mediolaterally. With moderate or greater TR (vena contracta width 5.80 +/- 2.62 mm), the TVA became dilated (17.24 +/- 4.75 versus 9.83 +/- 2.18 cm(2), P < 0.0001, TR versus referent), more planar with decreased high-low distance (4.14 +/- 1.05 mm), and more circular with decreased ratio of mediolateral/anteroposterior (1.11 +/- 0.09 versus 1.32 +/- 0.09, P < 0.0001, TR versus referent). Conclusions - The normal TVA has a bimodal shape with distinct high points located anteroposteriorly and low points located mediolaterally. With functional TR, the annulus becomes larger, more planar, and circular. These changes in annular shape with TR have potentially important mechanistic and therapeutic implications for tricuspid valve repair. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Baystate Med Ctr, Springfield, MA USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. EM Jhung@partners.org FU NHLBI NIH HHS [K23HL004504, R01 HL072265] NR 43 TC 107 Z9 111 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 11 PY 2006 VL 114 IS 2 BP 143 EP 149 DI 10.1161/CIRCULATIONAHA.106.611889 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 062IF UT WOS:000238937100009 PM 16818811 ER PT J AU Hong, CC Peterson, QP Hong, JY Peterson, RT AF Hong, Charles C. Peterson, Quinn P. Hong, Ji-Young Peterson, Randall T. TI Artery/vein specification is governed by opposing phosphatidylinositol-3 kinase and MAP kinase/ERK signaling SO CURRENT BIOLOGY LA English DT Article ID EMBRYONIC VASCULAR DEVELOPMENT; PHOSPHOINOSITIDE 3-KINASE; ZEBRAFISH; GRIDLOCK; PATHWAY; DIFFERENTIATION; EMBRYOGENESIS; ACTIVATION AB Angioblasts are multipotent progenitor cells that give rise to arteries or veins [1]. Genetic disruption of the gridlock gene perturbs the artery/vein balance, resulting in generation of insufficient numbers of arterial cells [2]. However, within angioblasts the precise biochemical signals that determine the artery/vein cell-fate decision are poorly understood. We have identified by chemical screening two classes of compounds that compensate for a mutation in the gridlock gene [3]. Both target the VEGF signaling pathway and reveal two downstream branches emanating from the VEGF receptor with opposing effects on arterial specification. We show that activation of ERK (p42/44 MAP kinase) is a specific marker of early arterial progenitors and is among the earliest known determinants of arterial specification. In embryos, cells fated to contribute to arteries express high levels of activated ERK, whereas cells fated to contribute to veins do not. Inhibiting the phosphatidylinositol-3 kinase (PI3K) branch with GS4898 or known PI3K inhibitors, or by expression of a dominant-negative form of AKT promotes arterial specification. Conversely, inhibition of the ERK branch blocks arterial specification, and expression of constitutively active AKT promotes venous specification. In summary, chemical genetic analysis has uncovered unanticipated opposing roles of PI3K and ERK in artery/vein specification. C1 Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM peterson@cvrc.mgh.harvard.edu RI Hong, Charles/C-9989-2010 FU NHLBI NIH HHS [HL079267, K08 HL081535, R01 HL079267] NR 26 TC 106 Z9 111 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 11 PY 2006 VL 16 IS 13 BP 1366 EP 1372 DI 10.1016/j.cub.2006.05.046 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 064YY UT WOS:000239127800033 PM 16824925 ER PT J AU Traynor, BJ Bruijn, L Conwit, R Beal, F O'Neill, G Fagan, C Cudkowicz, ME AF Traynor, B. J. Bruijn, L. Conwit, R. Beal, F. O'Neill, G. Fagan, C. Cudkowicz, M. E. TI Neuroprotective agents for clinical trials in ALS - A systematic assessment SO NEUROLOGY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MOUSE MODEL; PLACEBO-CONTROLLED TRIAL; MOTOR-NEURON DISEASE; GROWTH-FACTOR-I; PROLONGS SURVIVAL; SPINAL-CORD; VITAMIN-E; CEREBROSPINAL-FLUID; EXTEND SURVIVAL AB Background: Riluzole is currently the only Food and Drug Administration-approved treatment for ALS, but its effect on survival is modest. Objective: To identify potential neuroprotective agents for testing in phase III clinical trials and to outline which data need to be collected for each drug. Methods: The authors identified 113 compounds by inviting input from academic clinicians and researchers and via literature review to identify agents that have been tested in ALS animal models and in patients with ALS. The list was initially narrowed to 24 agents based on an evaluation of scientific rationale, toxicity, and efficacy in previous animal and human studies. These 24 drugs underwent more detailed pharmacologic evaluation. Results: Twenty drugs were selected as suitable for further development as treatments for patients with ALS. Talampanel and tamoxifen have completed early phase II trials and have demonstrated preliminary efficacy. Other agents (ceftriaxone, minocycline, ONO-2506, and IGF-1 polypeptide) are already in phase III trials involving large numbers of patients with ALS. Remaining agents (AEOL 10150, arimoclomol, celastrol, coenzyme Q10, copaxone, IGF-1 viral delivery, memantine, NAALADase inhibitors, nimesulide, scriptaid, sodium phenylbutyrate, thalidomide, trehalose) require additional preclinical animal data, human toxicity and pharmacokinetic data including CNS penetration prior to proceeding to large scale phase III human testing. Further development of riluzole analogues should be considered. Conclusions: Several potential neuroprotective compounds, representing a wide range of mechanisms, are available and merit further investigation in ALS. C1 Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Trials Unit, Boston, MA 02114 USA. ALS Assoc, Palm Harbor, FL USA. NINDS, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Neurol, New York, NY 10021 USA. Biogen Idec Inc, Cambridge, MA USA. Univ Georgia, Coll Pharm, Augusta, GA USA. Med Coll Georgia, Augusta, GA 30912 USA. RP Traynor, BJ (reprint author), NIMH, Bldg 35,Room 1A110,35 Convent Dr, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov RI Traynor, Bryan/G-5690-2010 NR 85 TC 126 Z9 140 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 11 PY 2006 VL 67 IS 1 BP 20 EP 27 DI 10.1212/01.wnl.0000223353.34006.54 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 062IB UT WOS:000238936700008 PM 16832072 ER PT J AU Religa, D Strozyk, D Cherny, RA Volitakis, I Haroutunian, V Winblad, B Naslund, J Bush, AI AF Religa, D. Strozyk, D. Cherny, R. A. Volitakis, I. Haroutunian, V. Winblad, B. Naslund, J. Bush, A. I. TI Elevated cortical zinc in Alzheimer disease SO NEUROLOGY LA English DT Article ID NEUTRON-ACTIVATION ANALYSIS; AMYLOID PRECURSOR PROTEIN; CYTOCHROME-C-OXIDASE; APP TRANSGENIC MICE; A-BETA; SENILE PLAQUES; TRACE-ELEMENTS; COPPER LEVELS; REGIONAL-DISTRIBUTION; HIPPOCAMPAL-NEURONS AB Objective: To determine whether changes in brain biometals in Alzheimer disease (AD) and in normal brain tissue are tandemly associated with amyloid beta- peptide (A beta) burden and dementia severity. Methods: The authors measured zinc, copper, iron, manganese, and aluminum and A beta levels in postmortem neocortical tissue from patients with AD (n = 10), normal age-matched control subjects (n = 14), patients with schizophrenia (n = 26), and patients with schizophrenia with amyloid (n = 8). Severity of cognitive impairment was assessed with the Clinical Dementia Rating Scale (CDR). Results: There was a significant, more than twofold, increase of tissue zinc in the AD-affected cortex compared with the other groups. Zinc levels increased with tissue amyloid levels. Zinc levels were significantly elevated in the most severely demented cases (CDR 4 to 5) and in cases that had an amyloid burden greater than 8 plaques/mm(2). Levels of other metals did not differ between groups. Conclusions: Brain zinc accumulation is a prominent feature of advanced Alzheimer disease (AD) and is biochemically linked to brain amyloid beta-peptide accumulation and dementia severity in AD. C1 Mental Hlth Res Inst, Oxidat Biol Lab, Parkville, Vic 3052, Australia. Karolinska Inst, Neurotec, Expt Genet, Stockholm, Sweden. Polish Acad Sci, Med Res Ctr, PL-00901 Warsaw, Poland. Albert Einstein Coll Med, Kennedy Ctr, Dept Neurol, Bronx, NY 10467 USA. Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Lab Oxidat Biol, Charlestown, MA USA. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RP Bush, AI (reprint author), Mental Hlth Res Inst, Oxidat Biol Lab, 155 Oak St, Parkville, Vic 3052, Australia. EM abush@mhri.edu.au RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [AG05138, AG02219, R01AG12686]; NIMH NIH HHS [MH45212] NR 76 TC 146 Z9 152 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 11 PY 2006 VL 67 IS 1 BP 69 EP 75 DI 10.1212/01.wnl.0000223644.08653.b5 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 062IB UT WOS:000238936700016 PM 16832080 ER PT J AU Chen, YW Gurol, ME Rosand, J Viswanathan, A Rakich, SM Groover, TR Greenberg, SM Smith, EE AF Chen, Y. W. Gurol, M. E. Rosand, J. Viswanathan, A. Rakich, S. M. Groover, T. R. Greenberg, S. M. Smith, E. E. TI Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy SO NEUROLOGY LA English DT Article ID AUSTRIAN STROKE PREVENTION; LOBAR INTRACEREBRAL HEMORRHAGE; CARDIOVASCULAR HEALTH; CAROTID ATHEROSCLEROSIS; COGNITIVE DECLINE; MRI; PROTEIN; VALIDATION; DISEASE; VOLUME AB Objective: To determine the rate of progression of white matter lesions and hemorrhages in a cohort with cerebral amyloid angiopathy (CAA). Methods: The authors analyzed data from 26 patients with possible (3) or probable (23) CAA, diagnosed by the Boston Criteria. Brain maps of white matter hyperintensities, normalized to head size (nWMH), were created by blinded computer-assisted segmentation of MRI images obtained at baseline and after a median follow-up interval of 1.1 year. Results: There was a substantial nWMH volume increase over the interscan interval (median 0.5 mL/year, interquartile range 0.1 to 2.8, p < 0.001). The median yearly increase, expressed as a percentage of the baseline WMH volume, was 18%. The characteristic most strongly associated with nWMH volume increase was the baseline nWMH volume (r = 0.57, p = 0.002). The volume of nWMH progression was also associated with history of cognitive impairment (median 5.0 mL/year in cognitively impaired subjects vs 0.3 mL/year in cognitively unimpaired, p = 0.02) but not age or hypertension. This association remained present in an analysis stratified by baseline WMH volume. New hemorrhages, including asymptomatic microbleeds, were seen in 46% of subjects. The number of new MRI hemorrhages correlated strongly with baseline nWMH (r = 0.53, p = 0.005) but not with nWMH progression (r = 0.22, p = 0.28). Conclusions: There is a progressive increase in white matter lesions in subjects with cerebral amyloid angiopathy. The association of white matter lesions with incident lobar hemorrhages suggests that white matter damage may reflect a progressive microangiopathy due to cerebral amyloid angiopathy. C1 Massachusetts Gen Hosp, Ctr Human Genet REs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Il Shin Hosp, Dept Neurol, Taipei, Taiwan. Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Ctr Human Genet REs, VBK 725,55 Fruit St, Boston, MA 02114 USA. EM eesmith@partners.org RI Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Smith, Eric/0000-0003-3956-1668 FU NIA NIH HHS [R01 AG026484]; NINDS NIH HHS [K23 NS-046327, K23 NS046327] NR 31 TC 99 Z9 100 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 11 PY 2006 VL 67 IS 1 BP 83 EP 87 DI 10.1212/01.wnl.0000223613.57229.24 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 062IB UT WOS:000238936700018 PM 16832082 ER PT J AU Bibbins-Domingo, K Chertow, GM Fried, LF Odden, MC Newman, AB Kritchevsky, SB Harris, TB Satterfield, S Cummings, SR Shlipak, MG AF Bibbins-Domingo, Kirsten Chertow, Glenn M. Fried, Linda F. Odden, Michelle C. Newman, Anne B. Kritchevsky, Stephen B. Harris, Tamara B. Satterfield, Suzanne Cummings, Steven R. Shlipak, Michael G. TI Renal function and heart failure risk in older black and white individuals - The health, aging, and body composition study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; FACTOR INTERVENTION TRIAL; CYSTATIN-C CONCENTRATION; CHRONIC KIDNEY-DISEASE; RACIAL-DIFFERENCES; UNITED-STATES; ATHEROSCLEROSIS RISK; EXPLANATORY FACTORS; AFRICAN-AMERICANS; ATTRIBUTABLE RISK AB Background: Chronic kidney disease is a risk factor for heart failure, an association that may be particularly important in blacks who are disproportionately affected by both processes. Our objective was to determine whether the association of chronic kidney disease with incident heart failure differs between blacks and whites. Methods: The study population comprised participants in the Health, Aging, and Body Composition Study without a diagnosis of heart failure (1124 black and 1676 white community-dwelling older persons). The main predictors were quintiles of cystatin C and creatinine concentrations and estimated glomerular filtration rate. The main outcome measure was incident heart failure. Results: Over a mean 5.7 years, 200 participants developed heart failure. High concentrations of cystatin C and low estimated glomerular filtration rate were each associated with heart failure, but the magnitude was greater for blacks than for whites (cystatin C concentration: adjusted hazard ratio for quintile 5 [>= 1.18 mg/dL] vs quintile 1 [< 0.84 mg/dL] was 3.0 [95% confidence interval 1.4-6.5] in blacks and 1.4 [95% confidence interval, 0.8-2.5] in whites; estimated glomerular filtration rate: adjusted hazard ratio for quintile 5 (< 59.2 mL/min) vs quintile 1 (> 86.7 mL/min) was 2.7 [95% confidence interval, 1.4-4.9] in blacks and 1.8 [95% confidence interval, 0.9-3.6] in whites). For cystatin C, this association was observed at more modest decrements in kidney function among blacks as well. The population attributable risk of heart failure was 47% for blacks with moderate or high concentrations of cystatin C (>= 0.94 mg/dL) (56% prevalence) but only 5% among whites (64% prevalence). Conclusion: The association of kidney dysfunction with heart failure appears stronger in blacks than for whites, particularly when cystatin C is used to measure kidney function. C1 Univ Calif San Francisco, Div Gen Internal Med, SFGH, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Univ Pittsburgh, Div Renal & Electrolyte, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15261 USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94115 USA. RP Bibbins-Domingo, K (reprint author), Univ Calif San Francisco, Div Gen Internal Med, SFGH, Box 1364, San Francisco, CA 94143 USA. EM bbinsk@medicine.ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-95095, N01-HL073208-01]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIDDK NIH HHS [R01 DK 06648] NR 34 TC 32 Z9 34 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 10 PY 2006 VL 166 IS 13 BP 1396 EP 1402 DI 10.1001/archinte.166.13.1396 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 062AK UT WOS:000238916500009 PM 16832005 ER PT J AU Maynard, C Lowy, E Rumsfeld, J Sales, AE Sun, HL Kopjar, B Fleming, B Jesse, RL Rusch, R Fihn, SD AF Maynard, Charles Lowy, Elliott Rumsfeld, John Sales, Ann E. Sun, Haili Kopjar, Branko Fleming, Barbara Jesse, Robert L. Rusch, Roxane Fihn, Stephan D. TI The prevalence and outcomes of in-hospital acute myocardial infarction in the department of veterans affairs health system SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MEDICAL-CENTERS; MORTALITY; CARE; PROJECT; US AB Background: Most studies of the epidemiology and treatment of acute myocardial infarction (AMI) have focused on patients who experienced onset of their symptoms in the community and then presented to the hospital. There are, however, patients whose symptoms of AMI begin after hospitalization for other medical conditions. The purposes of this study were to determine the prevalence of in-hospital AMI in the Veterans Health Administration (VHA) and to compare baseline characteristics, treatments, and outcomes according to whether individuals presented with AMI or had an in-hospital AMI. Methods: This was a retrospective cohort study of 7054 veterans who were hospitalized for AMI in 127 VHA medical centers between July 2003 and August 2004. The main outcome measure was 30-day mortality. Key covariates included age, body mass index, admission systolic blood pressure, heart rate, previous use of lipid-lowering drugs, elevated admission troponin value, prolonged and/or atypical chest pain on admission, and ST-segment elevation on the initial electrocardiogram. Results: There were 792 patients (11.2%) who had AMI while hospitalized for other medical conditions. These patients differed substantially from those who presented to the hospital with AMI. The odds of 30-day mortality were greater in the in-hospital group (odds ratio, 3.6; 95% confidence interval, 3.1-4.3; P < .001) and remained higher after statistical adjustment (odds ratio, 2.0; 95% confidence interval, 1.7-2.4; P < .001). Conclusion: Although most attention has been paid to patients with AMI admitted via the community emergency medical system or through the emergency department, AMI occurring during hospitalization for other medical problems is an important clinical problem. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. VA Eastern Colorado Hlth Care Syst, Dept Cardiol, Denver, CO USA. US Dept Vet Affairs, Off Qual & Performance, Washington, DC USA. Hunter Holmes McGuire Vet Affairs Med Ctr, Dept Cardiol, Richmond, VA USA. RP Maynard, C (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Mail Code 152,1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM cmaynard@u.washington.edu RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015; OI Maynard, Charles/0000-0002-1644-7814; Sales, Anne/0000-0001-9360-3334 NR 21 TC 27 Z9 27 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 10 PY 2006 VL 166 IS 13 BP 1410 EP 1416 DI 10.1001/archinte.166.13.1410 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 062AK UT WOS:000238916500011 PM 16832007 ER PT J AU Sorensen, AG AF Sorensen, A. Gregory TI Magnetic resonance as a cancer imaging biomarker SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID APPARENT DIFFUSION-COEFFICIENT; HIGH-RESOLUTION MEASUREMENT; PROTON MR SPECTROSCOPY; CEREBRAL BLOOD-VOLUME; TRACER BOLUS PASSAGES; HIGH-GRADE GLIOMAS; IN-VIVO; TUMOR ANGIOGENESIS; BRAIN-TUMORS; SOLITARY METASTASES AB Cancer is a diverse disease with many manifestations. Magnetic resonance (MR) has a wide range of sensitivities, and therefore has often been used to study cancer in humans in numerous different ways, most typically with MR spectroscopy and MR imaging. This article is not an exhaustive catalog of the use of MR in cancer, but will briefly highlight some of the many promising MR methods that have been developed, proposed, or used to focus on the problem of detecting and characterizing cancer, its treatments, and adverse effects. C1 Massachusetts Gen Hosp, Dept Radiol, Athinouia A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA USA. MIT, Boston, MA USA. RP Sorensen, AG (reprint author), Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu NR 57 TC 40 Z9 43 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 JUL 10 PY 2006 VL 24 IS 20 BP 3274 EP 3281 DI 10.1200/JCO.2006.06.6597 PG 8 WC Oncology SC Oncology GA 064HV UT WOS:000239080700007 PM 16829651 ER PT J AU Papay, R Gaivin, R Jha, A McCune, DF McGrath, JC Rodrigo, MC Simpson, PC Doze, VA Perez, DM AF Papay, R Gaivin, R Jha, A McCune, DF McGrath, JC Rodrigo, MC Simpson, PC Doze, VA Perez, DM TI Localization of the mouse alpha(1A)-adrenergic receptor (AR) in the brain: alpha(1A)AR is expressed in neurons, GABAergic interneurons, and NG2 oligodendrocyte progenitors SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE adrenergic receptor; in situ; localization; brain; transgenic ID IN-SITU HYBRIDIZATION; GLUTAMIC-ACID DECARBOXYLASE; ARTERIAL BLOOD-PRESSURE; MULTIPLE SYSTEM ATROPHY; CENTRAL-NERVOUS-SYSTEM; RAT SPINAL-CORD; ALPHA(1B)-ADRENERGIC RECEPTOR; ALPHA-1-ADRENERGIC RECEPTORS; SUBCELLULAR-LOCALIZATION; ALPHA-ADRENOCEPTORS AB alpha(1)-Adrenergic receptors (ARs) are not well defined in the central nervous system. The particular cell types and areas that express these receptors are uncertain because of the lack of high avidity antibodies and selective ligands. We have developed transgenic mice that either systemically overexpress the human alpha(1A)-AR subtype fused with the enhanced green fluorescent protein (EGFP) or express the EGFP protein alone under the control of the mouse alpha(1A)-AR promoter. We confirm our transgenic model against the alpha(1A)-AR knockout mouse, which expresses the LacZ gene in place of the coding region for the alpha(1A)-AR. By using these models, we have now determined cellular localization of the alpha(1A)-AR in the brain, at the protein level. The alpha(1A)-AR or the EGFP protein is expressed prominently in neuronal cells in the cerebral cortex, hippocampus, hypothalamus, midbrain, pontine olivary nuclei, trigeminal nuclei, cerebellum, and spinal cord. The types of neurons were diverse, and the alpha(1A)-AR colocalized with markers for glutamic acid decarboxylase (GAD), gamma-aminobutyric acid (GABA), and N-methyl-D-aspartate (NMDA) receptors. Recordings from alpha(1A)-AR EGFP-expressing cells in the stratum oriens of the hippocampal CA1 region confirmed that these cells were interneurons. We could not detect expression of the alpha(1A)-AR in mature astrocytes, oligodendrocytes, or cerebral blood vessels, but we could detect the alpha(1A)-AR in oligodendrocyte progenitors. We conclude that the alpha(1A)-AR is abundant in the brain, expressed in various types of neurons, and may regulate the function of oligodendrocyte progenitors, interneurons, GABA, and NMDA receptor containing neurons. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Cardiol NB50, Cleveland, OH 44195 USA. Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58201 USA. Univ Glasgow, Inst Biomed & Life Sci, Div Neurosci & Biomed Syst, Autonom Physiol Unit, Glasgow, Lanark, Scotland. San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, CVRI, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Perez, DM (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Cardiol NB50, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM perezd@ccf.org RI McGrath, John/G-6485-2012 OI McGrath, John/0000-0002-5276-0381 FU NCRR NIH HHS [5P20RR017699]; NHLBI NIH HHS [HL31113, R01 HL031113, R01HL61438]; PHS HHS [T32] NR 74 TC 52 Z9 53 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 10 PY 2006 VL 497 IS 2 BP 209 EP 222 DI 10.1002/cne.20992 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 050EC UT WOS:000238069300005 PM 16705673 ER PT J AU Kalita, MK Ramasamy, G Duraisamy, S Chauhan, VS Gupta, D AF Kalita, Mridul K. Ramasamy, Gowthaman Duraisamy, Sekhar Chauhan, Virander S. Gupta, Dinesh TI ProtRepeatsDB: a database of amino acid repeats in genomes SO BMC BIOINFORMATICS LA English DT Article ID HUMAN ANDROGEN RECEPTOR; MYCOBACTERIUM-TUBERCULOSIS; PLASMODIUM-FALCIPARUM; PROTEIN REPEATS; TETRATRICOPEPTIDE REPEATS; STATISTICAL SIGNIFICANCE; TRINUCLEOTIDE REPEATS; GENETIC-MARKERS; PRION PROTEINS; RICH REGIONS AB Background: Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB http://bioinfo.icgeb.res.in/repeats/ is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats. Description: ProtRepeatsDB (v1.2) consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeats; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology ( GO) annotation IDs and regular expressions (REGEXP) describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences. Conclusion: ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific repeat markers, interspecies variations and polymorphism. C1 Int Ctr Genet Engn & Biotechnol, Malaria Grp, Struct & Computat Biol Grp, New Delhi 110067, India. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gupta, D (reprint author), Int Ctr Genet Engn & Biotechnol, Malaria Grp, Struct & Computat Biol Grp, Aruna Asaf Ali Marg, New Delhi 110067, India. EM mridulkk@icgeb.res.in; gowtham@icgeb.res.in; sekhar_duraisamy@dfci.harvard.edu; virander@icgeb.res.in; dinesh@icgeb.res.in RI Gupta, Dinesh/C-1079-2009 OI Gupta, Dinesh/0000-0002-7548-8835 NR 48 TC 19 Z9 19 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 7 PY 2006 VL 7 AR 336 DI 10.1186/1471-2105-7-336 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 073JR UT WOS:000239739500001 PM 16827924 ER PT J AU Morissette, MR Cook, SA Foo, S McKoy, G Ashida, N Novikov, M Scherrer-Crosbie, M Li, L Matsui, T Brooks, G Rosenzweig, A AF Morissette, Michael R. Cook, Stuart A. Foo, ShiYin McKoy, Godfrina Ashida, Noboru Novikov, Mikhail Scherrer-Crosbie, Marielle Li, ng Li Matsui, Takashi Brooks, Gavin Rosenzweig, Anthony TI Myostatin regulates cardiomyocyte growth through modulation of Akt signaling SO CIRCULATION RESEARCH LA English DT Article DE myostatin; Akt; p38; hypertrophy ID BETA SUPERFAMILY MEMBER; ACTIVATED PROTEIN-KINASES; SKELETAL-MUSCLE MASS; CARDIAC-HYPERTROPHY; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; TRANSGENIC MICE; HEART; PATHWAY; GENE AB Myostatin is a highly conserved, potent negative regulator of skeletal muscle hypertrophy in many species, from rodents to humans, although its mechanisms of action are incompletely understood. Transcript profiling of hearts from a genetic model of cardiac hypertrophy revealed dramatic upregulation of myostatin, not previously recognized to play a role in the heart. Here we show that myostatin abrogates the cardiomyocyte growth response to phenylephrine in vitro through inhibition of p38 and the serine - threonine kinase Akt, a critical determinant of cell size in many species from drosophila to mammals. Evaluation of male myostatin-null mice revealed that their cardiomyocytes and hearts overall were slightly smaller at baseline than littermate controls but exhibited more exuberant growth in response to chronic phenylephrine infusion. The increased cardiac growth in myostatin-null mice corresponded with increased p38 phosphorylation and Akt activation in vivo after phenylephrine treatment. Together, these data demonstrate that myostatin is dynamically regulated in the heart and acts more broadly than previously appreciated to regulate growth of multiple types of striated muscle. C1 Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Hammersmith Hosp, MRC, Ctr Clin Sci, London, England. Univ Reading, Cardiovasc Res Grp, Sch Pharm, Reading, Berks, England. RP Rosenzweig, A (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiol, 330 Brookline Ave,RW 456, Boston, MA 02215 USA. EM arosenzw@bidmc.harvard.edu RI Cook, Stuart/G-9567-2011 FU NHLBI NIH HHS [HL-04250, K08 HL004250, T32 HL007208, R01 HL061557, 5T32HL07208-25, HL-59521, HL-61557, R01 HL059521]; NIA NIH HHS [K01 AG026337, K01 AG026337-01A1]; Wellcome Trust NR 40 TC 101 Z9 103 U1 0 U2 1 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 JUL 7 PY 2006 VL 99 IS 1 BP 15 EP 24 DI 10.1161/01.RES.0000231290.45676.d4 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 060ZA UT WOS:000238839800006 PM 16763166 ER PT J AU Wegener, E Oeckinghaus, A Papadopoulou, N Lavitas, L Schmidt-Supprian, M Ferch, U Mak, TW Ruland, J Heissmeyer, V Krappmann, D AF Wegener, Elmar Oeckinghaus, Andrea Papadopoulou, Nikoletta Lavitas, Liron Schmidt-Supprian, Marc Ferch, Uta Mak, Tak W. Ruland, Juergen Heissmeyer, Vigo Krappmann, Daniel TI Essential role for I kappa B kinase beta in remodeling Carma1-Bcl10-Malt1 complexes upon T cell activation SO MOLECULAR CELL LA English DT Article ID ANTIGEN RECEPTOR; C-THETA; IMMUNOLOGICAL SYNAPSE; LYMPHOCYTE-ACTIVATION; SIGNALING PATHWAY; PKC-THETA; CARMA1; PROTEIN; BCL10; REQUIREMENT AB T cell receptor (TCR) signaling to IKB kinase (IKK)/NFKB is controlled by PKC theta-dependent activation of the Carma1, Bcl10, and Malt1 (CBM) complex. Antigen-induced phosphorylation of BcI10 has been reported, but its physiological function is unknown. Here we show that the putative downstream kinase IKK beta is required for initial CBM complex formation. Further, upon engagement of IKK beta/Malt1/Bcl10 with Carma1, IKK beta phosphorylates Bcl10 in the C terminus and thereby interferes with Bcl10/Malt1 association and Bcl10-mediated IKK gamma ubiquitination. Mutation of the IKK beta phosphorylation sites on Bcl10 enhances expression of NF-kappa B target genes IL-2 and TNF alpha after activation of primary T cells. Thus, our data provide evidence that IKK beta serves a dual role upstream of its classical substrates, the I kappa B proteins. While being essential for triggering initial CBM complex formation, IKK beta-dependent phosphorylation of Bcl10 exhibits a negative regulatory role in T cell activation. C1 Max Delbruck Ctr Mol Med, D-13095 Berlin, Germany. Free Univ Berlin, Dept Biol Chem & Pharm, D-14195 Berlin, Germany. GSF Natl Res Ctr Environm & Hlth, Inst Mol Immunol, D-81377 Munich, Germany. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. Tech Univ Munich, Dept Med 3, Klinikum Rechts Isar, D-81675 Munich, Germany. Univ Toronto, Dept Med Biophys & Immunol, Adv Med Discovery Inst, Toronto, ON M5G 2C1, Canada. RP Krappmann, D (reprint author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13095 Berlin, Germany. EM daniel.krappmann@gsf.de RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 NR 36 TC 83 Z9 85 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL 7 PY 2006 VL 23 IS 1 BP 13 EP 23 DI 10.1016/j.molcel.2006.05.027 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 066FS UT WOS:000239215700002 PM 16818229 ER PT J AU Chowdhury, D Beresford, PJ Zhu, PC Zhang, D Sung, JS Demple, B Perrino, FW Lieberman, J AF Chowdhury, Dipanjan Beresford, Paul J. Zhu, Pengcheng Zhang, Dong Sung, Jung-Suk Demple, Bruce Perrino, Fred W. Lieberman, Judy TI The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death SO MOLECULAR CELL LA English DT Article ID NUCLEOSIDE DIPHOSPHATE KINASE; ASSEMBLY PROTEIN SET; SUPPRESSOR NM23-H1; REPAIR NUCLEASE; APOPTOSIS; EXCISION; TARGET; DAMAGE; FRAGMENTATION; ENDONUCLEASE AB Granzyme A (GzmA) activates a caspase-independent cell death pathway with morphological features of apoptosis. Single-stranded DNA damage is initiated when the endonuclease NM23-H1 becomes activated to nick DNA after granzyme A cleaves its inhibitor, SET. SET and NM23-H1 reside in an endoplasmic reticulum-associated complex (the SET complex) that translocates to the nucleus in response to superoxide generation by granzyme A. We now find the 3'-to-5' exonuclease TREX1, but not its close homolog TREX2, in the SET complex. TREX1 binds to SET and colocalizes and translocates with the SET complex. NM23-H1 and TREX1 work in concert to degrade DNA. Silencing NM23-H1 or TREX1 inhibits DNA damage and death of cells treated with perforin (PFN) and granzyme A, but not of cells treated with perforin and granzyme B (GzmB). After granzyme A activates NM23-H1 to make single-stranded nicks, TREX1 removes nucleotides from the nicked 3' end to reduce the possibility of repair by rejoining the nicked ends. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pediat, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pediat, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NCI NIH HHS [CA71993]; NIAID NIH HHS [AI45587]; NIGMS NIH HHS [GM069962, GM40000] NR 37 TC 134 Z9 146 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL 7 PY 2006 VL 23 IS 1 BP 133 EP 142 DI 10.1016/j.molcel.2006.06.005 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 066FS UT WOS:000239215700012 PM 16818237 ER PT J AU Bortfeld, T AF Bortfeld, Thomas TI IMRT: a review and preview SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Review ID INTENSITY-MODULATED RADIOTHERAPY; DYNAMIC MULTILEAF COLLIMATION; RADIATION-THERAPY; CONFORMAL RADIOTHERAPY; ROTATION THERAPY; DOSE DISTRIBUTIONS; X-RAYS; OPTIMIZATION; CONSTRAINTS; FIELDS AB The very first cornerstone paper on intensity-modulated radiation therapy (IMRT) was published in Physics in Medicine and Biology, and many seminal IMRT works have since appeared in this journal. Today IMRT is a widely used clinical treatment modality in many countries. This contribution to the 50th anniversary issue reviews the physical, mathematical, and technological milestones that have facilitated the clinical implementation and success of IMRT. In particular, the basic concepts and developments of both IMRT treatment planning ('inverse planning') and the delivery of cone-beam IMRT with a multileaf collimator from a fixed number of static beam directions are discussed. An outlook into the future of IMRT concludes the paper. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. NR 68 TC 144 Z9 151 U1 4 U2 17 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 JUL 7 PY 2006 VL 51 IS 13 BP R363 EP R379 DI 10.1088/0031-9155/51/13/R21 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 062LI UT WOS:000238945500022 PM 16790913 ER PT J AU Yoshida, S Kono, K Lowery, DM Bartolini, S Yaffe, MB Ohya, Y Pellman, D AF Yoshida, S Kono, K Lowery, DM Bartolini, S Yaffe, MB Ohya, Y Pellman, D TI Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis SO SCIENCE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; FISSION YEAST; CELL-WALL; BUDDING YEAST; PHOSPHORYLATION; PLK1; IDENTIFICATION; ACTOMYOSIN; SUBSTRATE; DIVISION AB The links between the cell cycle machinery and the cytoskeletal proteins controlling cytokinesis are poorly understood. The small guanine nucleotide triphosphate (GTP)-binding protein RhoA stimulates type II myosin contractility and formin-dependent assembly of the cytokinetic actin contractile ring. We found that budding yeast Polo-like kinase Cdc5 controls the targeting and activation of Rho1 ( RhoA) at the division site via Rho1 guanine nucleotide exchange factors. This role of Cdc5 (Polo-like kinase) in regulating Rho1 is likely to be relevant to cytokinesis and asymmetric cell division in other organisms. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Chiba 2778562, Japan. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu RI Yoshida, Satoshi/C-5016-2011 NR 28 TC 99 Z9 99 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 7 PY 2006 VL 313 IS 5783 BP 108 EP 111 DI 10.1126/science.1126747 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 061DA UT WOS:000238850200043 PM 16763112 ER PT J AU Wright, AA Katz, IT AF Wright, Alexi A. Katz, Ingrid T. TI Roe versus reality - Abortion and women's health SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Wright, AA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 14 Z9 14 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 JUL 6 PY 2006 VL 355 IS 1 BP 1 EP + DI 10.1056/NEJMp068083 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 060DT UT WOS:000238783200001 PM 16822990 ER PT J AU Miller, AJ Mihm, MC AF Miller, Arlo J. Mihm, Martin C., Jr. TI Mechanisms of disease - Melanoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID MICROPHTHALMIA TRANSCRIPTION FACTOR; CUTANEOUS MALIGNANT-MELANOMA; TUMOR-SUPPRESSOR GENE; CELL-CYCLE ARREST; BETA-CATENIN; BRAF MUTATIONS; INTEGRIN ALPHA(V)BETA(3); MELANOCORTIN-1 RECEPTOR; ULTRAVIOLET-RADIATION; METASTATIC MELANOMA C1 Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mihm, MC (reprint author), Massachusetts Gen Hosp, Dept Dermatopathol, 55 Fruit St,Warren 827, Boston, MA 02114 USA. FU NIGMS NIH HHS [T32 GM007753, T32-GM07753] NR 107 TC 658 Z9 681 U1 5 U2 84 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 6 PY 2006 VL 355 IS 1 BP 51 EP 65 DI 10.1056/NEJMra052166 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 060DT UT WOS:000238783200007 PM 16822996 ER PT J AU Blumenthal, D AF Blumenthal, David TI Employer-sponsored health insurance in the United States - Origins and implications SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CARE; QUALITY C1 Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. NR 35 TC 51 Z9 51 U1 3 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 6 PY 2006 VL 355 IS 1 BP 82 EP 88 DI 10.1056/NEJMhpr060703 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 060DT UT WOS:000238783200014 PM 16823002 ER PT J AU Jorenby, DE Hays, JT Rigotti, NA Azoulay, S Watsky, EJ Williams, KE Billing, CB Gong, J Reeves, KR AF Jorenby, DE Hays, JT Rigotti, NA Azoulay, S Watsky, EJ Williams, KE Billing, CB Gong, J Reeves, KR CA Varenicline Phase 3 Study Grp TI Efficacy of varenicline, an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUESTIONNAIRE; TOLERANCE; SMOKERS; PATCH AB Context Varenicline, a partial agonist at the alpha 4 beta 2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine. Objective To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR). Design, Setting, and Participants A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study. Intervention Varenicline titrated to 1 mg twice daily (n= 344) or bupropion SR titrated to 150 mg twice daily (n= 342) or placebo (n= 341) for 12 weeks, plus weekly brief smoking cessation counseling. Main Outcome Measures Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52). Results During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group(odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P=.003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P=.004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%). Conclusions Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR. C1 Univ Wisconsin, Sch Med & Publ Hlth, Ctr Tobacco Res & Intervent, Madison, WI 53711 USA. Mayo Clin Coll Med, Div Gen Internal Med, Rochester, MN USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Pfizer Global Res & Dev, Groton, CT USA. RP Jorenby, DE (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Ctr Tobacco Res & Intervent, Suite 200,1930 Monroe St, Madison, WI 53711 USA. EM dej@ctri.medicine.wisc.edu NR 21 TC 799 Z9 830 U1 7 U2 49 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 JUL 5 PY 2006 VL 296 IS 1 BP 56 EP 63 DI 10.1001/jama.296.1.56 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 058RU UT WOS:000238683100022 PM 16820547 ER PT J AU Jha, AK AF Jha, AK TI Measuring hospital quality - What physicians do? How patients fare? Or both? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; SECULAR TRENDS; UNITED-STATES; US HOSPITALS; CARE; MORTALITY; DISEASE; ADULTS C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, VA Boston Healthcare Syst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, VA Boston Healthcare Syst, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu NR 20 TC 27 Z9 28 U1 0 U2 4 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 JUL 5 PY 2006 VL 296 IS 1 BP 95 EP 97 DI 10.1001/jama.296.1.95 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 058RU UT WOS:000238683100028 PM 16820553 ER PT J AU Chen, WY Manson, JE AF Chen, Wendy Y. Manson, Joann E. TI Premature ovarian failure in cancer survivors: New insights, looming concerns SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CORONARY-HEART-DISEASE; BREAST-CANCER; POSTMENOPAUSAL WOMEN; HORMONE-THERAPY; EARLY MENOPAUSE; FRACTURE RISK; BONE MASS; EARLY AGE; OOPHORECTOMY; HYSTERECTOMY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA 02215 USA. RP Manson, JE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, 900 Comonwealth Ave E, Boston, MA 02215 USA. EM jmanson@rics.bwh.harvard.edu NR 26 TC 5 Z9 6 U1 0 U2 0 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 JUL 5 PY 2006 VL 98 IS 13 BP 880 EP 881 DI 10.1093/jnci/djj276 PG 2 WC Oncology SC Oncology GA 060QX UT WOS:000238817800001 PM 16818846 ER PT J AU Abramson, N Costantino, JR Garber, JE Berliner, N Wickerham, DL Wolmark, N AF Abramson, Neil Costantino, Joseph R. Garber, Judy E. Berliner, Nancy Wickerham, D. Lawrence Wolmark, Norman TI Effect of Factor v Leiden and prothrombin G20210 -> A mutations on thromboembolic risk in the national surgical adjuvant breast and bowel project breast cancer prevention trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT San Antonio Breast Care Symposium CY 2002 CL San Antonio, TX ID ACTIVATED PROTEIN-C; VENOUS THROMBOSIS; RESISTANCE; TAMOXIFEN; HYPERCOAGULABILITY; THROMBOPHILIA; THERAPY; DISEASE; WOMEN AB Background: In the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Project (BCPT), tamoxifen use was associated with an increased relative risk for venous thromboembolic events, including deep vein thrombosis and pulmonary emboli, compared with placebo. However, the involvement of hypercoagulability factors in this association is unclear. Methods: To examine possible associations among the risk of venous thromboembolic events, tamoxifen use, and Factor V Leiden (FVL) and prothrombin G20210 -> A (PT20210) mutations, which are involved in promoting blood coagulation, we used a nested, matched, case-control (1: 4) design and compared women in the BCPT who had experienced venous thromboembolic events (n = 76) with women who did not (n = 295). FVL and PT20210 mutations were detected in genomic DNA that was isolated from blood samples collected at trial enrollment. Results: Venous thromboembolic events occurred in 28 women (deep vein thrombosis in 22 and pulmonary emboli in six) who were taking placebo and in 53 women (deep vein thrombosis in 35 and pulmonary emboli in 18) who were taking tamoxifen (relative risk = 1.90, 95% confidence interval = 1.18 to 3.12). Excessive risk for venous thromboembolic events was observed only in the first 36 months of therapy. There were no differences in age, smoking, and race between the groups, but women with venous thromboembolic events had a higher body mass index than women without (mean standard deviation, 30 kg/m(2) +/- 7.7 versus 27.1 +/- 5.6; P <.001). FVL and/or PT20210 mutations were found in nine women (four on tamoxifen and five on placebo) with venous thromboembolic events and in 20 control subjects (nine on tamoxifen and 11 on placebo). No associations were found between risk of venous thromboembolic events and mutation status in either treatment group. Conclusions: Venous thromboembolic disease in the BCPT women is associated with tamoxifen use and body mass index, but not with FVL and PT20210 mutations. Screening women at risk for breast cancer for FVL and/or PT20210 appears to offer no benefit in determining the risk of tamoxifen-associated thromboembolic events. C1 Univ Florida, Baptist Canc Inst, Jacksonville, FL 32207 USA. Operat Ctr, Natl Surg Adjuvant Breast & Bowel Project Operat, Pittsburgh, PA USA. Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, New Haven, CT USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Abramson, N (reprint author), Univ Florida, Baptist Canc Inst, 3rd Floor,1235 San Marco Blvd, Jacksonville, FL 32207 USA. EM abrm1h@bellsouth.net FU NCI NIH HHS [U10-CA-37377, U10CA-12027, U10- CA-69974, U10CA-69651] NR 26 TC 32 Z9 35 U1 0 U2 1 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 JUL 5 PY 2006 VL 98 IS 13 BP 904 EP 910 DI 10.1093/jnci/djj262 PG 7 WC Oncology SC Oncology GA 060QX UT WOS:000238817800008 PM 16818854 ER PT J AU Massol, RH Boll, W Griffin, AM Kirchhausen, T AF Massol, Ramiro H. Boll, Werner Griffin, April M. Kirchhausen, Tomas TI A burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hsc70; endocytosis; lipids ID MEDIATED ENDOCYTOSIS; DYNAMIN INTERACTIONS; MOLECULAR CHAPERONE; SYNAPTOJANIN; DOMAIN; ENDOPHILIN; HSC70; PROTEIN; DISSOCIATION; MACHINERY AB Clathrin-coated pits assemble on a membrane and pinch off as coated vesicles. The released vesicles then rapidly lose their clathrin coats in a process mediated by the ATPase Hsc70, recruited by auxilin, a J-domain-containing cofactor. How is the uncoating process regulated? We find that during coat assembly small and variable amounts of auxilin are recruited transiently but that a much larger burst of association occurs after the peak of dynamin signal, during the transition between membrane constriction and vesicle budding. We show that the auxilin burst depends on domains of the protein likely to interact with lipid head groups. We conclude that the timing of auxilin recruitment determines the onset of uncoating. We propose that, when a diffusion barrier is established at the constricting neck of a fully formed coated pit and immediately after vesicle budding, accumulation of a specific lipid can recruit sufficient auxilin molecules to trigger uncoating. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU NIGMS NIH HHS [R01 GM075252, R01 GM075252-01] NR 36 TC 84 Z9 85 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 2006 VL 103 IS 27 BP 10265 EP 10270 DI 10.1073/pnas.0603369103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 064DM UT WOS:000239069400022 PM 16798879 ER PT J AU Swirski, FK Pittet, MJ Kircher, MF Aikawa, E Jaffer, FA Libby, P Weissleder, R AF Swirski, Filip K. Pittet, Mikael J. Kircher, Moritz F. Aikawa, Elena Jaffer, Farouc A. Libby, Peter Weissleder, Ralph TI Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atherosclerosis; imaging; leukocyte ID RECEPTOR-DEFICIENT MICE; ATHEROSCLEROSIS IN-VIVO; NECROSIS-FACTOR-ALPHA; APOLIPOPROTEIN-E; LDL RECEPTOR; REDUCES ATHEROSCLEROSIS; LESION FORMATION; INFLAMMATION; RECRUITMENT; PLAQUES AB Monocytes participate importantly in the pathogenesis of atherosclerosis, but their spatial and temporal recruitment from circulation remains uncertain. This study tests the hypothesis that monocyte accumulation in atheroma correlates with the extent of disease by using a sensitive and simple quantitative assay that allows tracking of highly enriched populations of blood monocytes. A two-step isolation method yielded viable and functionally intact highly enriched peripheral blood monocyte populations (> 90%). Recipient mice received syngeneic monocytes labeled in two ways: by transgenically expressing EGFP or with a radioactive tracer [In-111]oxine. After 5 days, more labeled cells accumulated in the aorta, principally the aortic root and ascending aorta, of 10-wk-old ApoE(-/-) compared with 10-wk-old C57BL/6 mice (223 +/- 3 vs. 87 +/- 22 cells per aorta). Considerably more monocytes accumulated in 20-wk-old ApoE(-/-) mice on either chow (314 +/- 41 cells) or high-cholesterol diet (395 +/- 53 cells). Fifty-week-old ApoE(-/-) mice accumulated even more monocytes in the aortic root, ascending aorta, and thoracic aorta after both chow (503 +/- 67 cells) or high-cholesterol diet (648 81 cells). Labeled monocyte content in the aorta consistently correlated with lesion surface area. These data indicate that monocytes accumulate continuously during atheroma formation, accumulation increases in proportion to lesion size, and recruitment is augmented with hypercholesterolemia. These results provide insights into mechanisms of atherogenesis and have implications for the duration of therapies directed at leukocyte recruitment. C1 Harvard Univ, Ctr Mol Imaging Res, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Ctr Mol Imaging Res, Sch Med, Massachusetts Gen Hosp, 13th St,Bldg 149,Room 5403,CNY 149, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NCI NIH HHS [R24 CA092782, R24 CA92782]; NHLBI NIH HHS [U01 HL080731] NR 33 TC 181 Z9 182 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 2006 VL 103 IS 27 BP 10340 EP 10345 DI 10.1073/pnas.0604260103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 064DM UT WOS:000239069400035 PM 16801531 ER PT J AU Moy, TI Ball, AR Anklesaria, Z Casadei, G Lewis, K Ausubel, FM AF Moy, Terence I. Ball, Anthony R. Anklesaria, Zafia Casadei, Gabriele Lewis, Kim Ausubel, Frederick M. TI Identification of novel antimicrobials using a live-animal infection model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antibiotic resistance chemical genetics; Enterococcus faecalis; antiinfectives ID ANTIBACTERIAL DRUG DISCOVERY; RESISTANT ENTEROCOCCUS-FAECALIS; NEMATODE CAENORHABDITIS-ELEGANS; INNATE IMMUNITY; VIRULENCE; HOST; CYTOTOXICITY; FAECIUM; MAP AB The alarming increase of antibiotic-resistant bacterial pathogens points to the need for novel therapeutic approaches to combat infection. To discover novel antimicrobials, we devised a screen to identify compounds that promoted the survival of the model laboratory nematode Caenorhabditis elegans infected with the human opportunistic pathogen Enterococcus faecalis. E. faecalis colonizes the nematode intestinal tract, forming a persistent lethal infection. Infected nematodes were rescued by antibiotic treatment in a dose-dependent manner, and antibiotic treatment markedly reduced the number of bacteria colonizing the nematode intestine. To facilitate high throughput screening of compound libraries, we adapted a previously developed agar-based C. elegans-E. faecalis infection assay so that it could be carried out in liquid medium in standard 96-well microtiter plates. We used this simple infection system to screen 6,000 synthetic compounds and 1,136 natural product extracts. We identified 16 compounds and 9 extracts that promoted nematode survival. Some of the compounds and extracts inhibited E. faecalis growth in vitro, but, in contrast to traditional antibiotics, the in vivo effective dose of many of these compounds was significantly lower than the minimum inhibitory concentration needed to prevent the growth of E. faecalis in vitro. Moreover, many of the compounds and extracts had little or no affect on in vitro bacterial growth. Our findings indicate that the whole-animal G elegans screen identifies not only traditional antibiotics, but also compounds that target bacterial virulence or stimulate host defense. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Northeastern Univ, Dept Biol, Boston, MA 02115 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU NIAID NIH HHS [R21 AI059483] NR 39 TC 146 Z9 162 U1 3 U2 21 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 2006 VL 103 IS 27 BP 10414 EP 10419 DI 10.1073/pnas.0604055103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 064DM UT WOS:000239069400048 PM 16801562 ER PT J AU Knight, CL Fihn, SD AF Knight, Christopher L. Fihn, Stephan D. TI Update in general internal medicine SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CONTROLLED-TRIALS; METAANALYSIS; PREVENTION; THERAPY; DISEASE; HEALTH; RISK C1 Univ Washington, Med Ctr, Seattle, WA 98105 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Knight, CL (reprint author), Univ Washington, Med Ctr, 4245 Roosevelt Way NE,Campus Box 354 760, Seattle, WA 98105 USA. EM clknight@u.washington.edu NR 16 TC 4 Z9 4 U1 1 U2 1 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 JUL 4 PY 2006 VL 145 IS 1 BP 52 EP 61 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 062IS UT WOS:000238938400007 PM 16818929 ER PT J AU Graybill, C van Hoek, AN Desai, D Carruthers, AM Carruthers, A AF Graybill, C van Hoek, AN Desai, D Carruthers, AM Carruthers, A TI Ultrastructure of human erythrocyte GLUT1 SO BIOCHEMISTRY LA English DT Article ID TRANSPORTER OLIGOMERIC STRUCTURE; SIZE-EXCLUSION CHROMATOGRAPHY; GLUCOSE-TRANSPORTER; SUGAR TRANSPORTER; LACTOSE PERMEASE; ESCHERICHIA-COLI; GLYCEROL-3-PHOSPHATE TRANSPORTER; LIGAND-BINDING; CYTOCHALASIN-B; RAPID METHOD AB This study was undertaken to examine GLUT1 quaternary structure. Independent but complementary methodologies were used to investigate the influence of membrane-solubilizing detergents on GLUT1/lipid/detergent micelle hydrodynamic radii. Hydrodynamic size analysis and electron microscopy of GLUT1/lipid/detergent micelles and freeze-fracture electron microscopy of GLUT1 proteoliposomes support the hypothesis that the glucose transporter is a multimeric (probably tetrameric) complex of GLUT1 proteins. GLUT1 forms a multimeric complex in octyl glucoside that dissociates upon addition of reductant. Some detergents (e. g., CHAPS and dodecyl maltoside) promote the dissociation of GLUT1 oligomers into smaller aggregation states (dimers or monomers). These complexes do not reassemble as larger oligomers when dissociating detergents are subsequently replaced with nondissociating detergents such as octyl glucoside or cholic acid. When dissociating detergents are replaced with lipids, the resulting proteoliposomes catalyze protein-mediated sugar transport, and the subsequent addition of solubilizing, nondissociating detergents generates higher (tetrameric) GLUT1 aggregation states. These findings suggest that some detergents stabilize while others destabilize GLUT1 quaternary structure. GLUT1 does not appear to exchange rapidly between protein/lipid/detergent micelles but is able to self-associate in the plane of the lipid bilayer. C1 Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01606 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Carruthers, A (reprint author), Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, 364 Plantat St, Worcester, MA 01606 USA. EM anthony.carruthers@umassmed.edu FU NIDDK NIH HHS [DK 36081, DK 44888] NR 39 TC 15 Z9 15 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 4 PY 2006 VL 45 IS 26 BP 8096 EP 8107 DI 10.1021/bi060398x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 056XP UT WOS:000238558700016 PM 16800634 ER PT J AU Wexler, DJ AF Wexler, DJ TI Low risk of depression in diabetes? Would that it were so SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material ID QUALITY-OF-LIFE C1 Massachusetts Gen Hosp, Dept Endocrinol, Boston, MA 02114 USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, Dept Endocrinol, 55 Fruit St, Boston, MA 02114 USA. EM dwexler@partners.org NR 7 TC 2 Z9 2 U1 0 U2 0 PU CMA MEDIA INC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUL 4 PY 2006 VL 175 IS 1 BP 47 EP 48 DI 10.1503/cmaj.060612 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 055YV UT WOS:000238488200018 PM 16818908 ER PT J AU Deguchi, J Aikawa, M Tung, CH Aikawa, E Kim, DE Ntziachristos, V Weissleder, R Libby, P AF Deguchi, J Aikawa, M Tung, CH Aikawa, E Kim, DE Ntziachristos, V Weissleder, R Libby, P TI Inflammation in atherosclerosis - Visualizing matrix metalloproteinase action in macrophages in vivo SO CIRCULATION LA English DT Article DE atherosclerosis; imaging; inflammation; macrophages; metalloproteinases ID CORONARY-ARTERY-DISEASE; INCREASES COLLAGEN CONTENT; MATRIX-METALLOPROTEINASE-9 GENE; CARDIOVASCULAR-DISEASE; PLAQUES; INHIBITOR; RUPTURE; STABILIZATION; MECHANISMS; EXPRESSION AB Background - Matrix metalloproteinases (MMPs) in inflamed atherosclerotic plaques may contribute to extracellular matrix remodeling and the onset of acute thrombotic complications. Methods and Results - To test the hypothesis that optical molecular imaging with the use of an activatable near-infrared fluorescence (NIRF) probe can detect enzymatic action of MMP in atherosclerotic plaques, we used a NIRF substrate for gelatinases (MMP-2/gelatinase-A and MMP-9/gelatinase-B) in apolipoprotein E-deficient (apoE(-/-)) mice that consumed a high-cholesterol diet for 12 weeks and age-matched apoE(+/+) mice as control. The aortas of apoE(-/-) mice at 24 hours after probe yielded intense NIRF signals, as detected by NIRF reflectance ex vivo, compared with negligible signals in aortas of apoE(+/+) mice with/without probe administration or atherosclerotic apoE(-/-) aortas without probe. Gelatinase inhibitor treatment abolished NIRF signals in apoE(-/-) mouse aortas ex vivo. Sites of gelatinase activity visualized by NIRF colocalized with macrophage accumulation, immunoreactive MMP-2 and MMP-9, and gelatinolytic activity detected by in situ zymography. Furthermore, fluorescence molecular tomography indicated in vivo that atherosclerotic aortas of apoE(-/-) mice produced NIRF signals for gelatinase action, whereas aortas of apoE(-/-) mice injected with the probe or apoE(-/-) aortas with no probe exhibited negligible NIRF signals. Conclusions - These results suggest the feasibility of noninvasively imaging the enzymatic action of MMPs in vivo, an approach that may gauge inflammatory foci in atherosclerosis, assess cardiovascular risk, and evaluate the effects of therapeutic interventions. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Aikawa, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 77 Ave Louis Pasteur,NRB 741, Boston, MA 02115 USA. EM maikawa@rics.bwh.harvard.edu; plibby@rics.bwh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R24-CA92782]; NHLBI NIH HHS [HL-56985, HL-66086, HL-80472, U01-HL080731] NR 50 TC 248 Z9 264 U1 2 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 4 PY 2006 VL 114 IS 1 BP 55 EP 62 DI 10.1161/CIRCULATIONAHA.106.619056 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058TV UT WOS:000238688400014 PM 16801460 ER PT J AU Ikonomidis, JS Jones, JA Barbour, JR Stroud, RE Clark, LL Kaplan, BS Zeeshan, A Bavaria, JE Gorman, JH Spinale, FG Gorman, RC AF Ikonomidis, JS Jones, JA Barbour, JR Stroud, RE Clark, LL Kaplan, BS Zeeshan, A Bavaria, JE Gorman, JH Spinale, FG Gorman, RC TI Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with Marfan syndrome SO CIRCULATION LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc DE aneurysm; aorta; Marfan; MMP; TIMP ID INTEGRIN ALPHA(V) SUBUNIT; FIBRILLIN-1; ACTIVATION; BINDING; CELLS; LOCALIZATION; ADHESION; MICE AB Background-Marfan syndrome (MFS) is known to cause ascending thoracic aortic aneurysms (ATAAs). Transforming growth factor beta (TGF-beta) has recently been implicated in this process. Imbalances between the matrix metalloproteinases ( MMPs) and their endogenous inhibitors (TIMPs) have also been shown to contribute to aneurysm formation. Whether and to what degree MMP, TIMP, and TGF-beta signaling profiles are altered in ATAAs in MFS compared with non-MFS patients remains unknown. Methods and Results-ATAA samples taken during aortic replacement from age-matched MFS (n = 9) and non-MFS (n = 18) patients were assessed for representative subtypes of all MMP classes, all 4 known TIMPs, and type 2 TGF-beta receptors (TGFBR2). Results were expressed as a percentage (mean +/- SEM) of reference control samples (100%; n = 18) obtained from patients without ATAA. In MFS, decreased MMP-2 ( 76 +/- 7; P < 0.05 versus control), increased MMP-12 (161 +/- 27% versus control; P < 0.05), and increased MT1-MMP 248 +/- 64% versus 91 +/- 21 non-MFS and control; P < 0.05) were observed. TIMP-3 (74 +/- 23%) was reduced compared with control values (P < 0.05) and TIMP-2 was elevated (128 +/- 31%) compared with non-MFS ( 3 +/- 19%; P < 0.05). In non-MFS samples, MMP-1 ( 70 +/- 16%), MMP-3 ( 7 +/- 18%), MMP-8 (75 +/- 11%), MMP-9 ( 69 +/- 14%), and MMP-12 (85 +/- 15%) were decreased compared with control (P < 0.05). TIMPs 1 to 3 were reduced in non-MFS compared with control values (P < 0.05). TGFBR2 were increased in MFS ( 193 +/- 32%) compared with non-MFS (95 +/- 16%) and controls (P < 0.05). Conclusions-A unique MMP and TIMP portfolio was observed in ATAAs from MFS compared with non-MFS patients. In addition, MFS samples showed evidence of increased TGF-beta signaling. These differences suggest disparate mechanisms of extracellular matrix remodeling between these 2 groups of patients. C1 Med Univ S Carolina, Div Cardiothorac Surg, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Univ Penn, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Ralph H Johnson Vet Affairs Med Ctr, Suite 409 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM ikonomij@musc.edu FU NHLBI NIH HHS [R01 HL 059165-07, R01 HL075488-01] NR 32 TC 42 Z9 42 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 4 PY 2006 VL 114 SU 1 BP I365 EP I370 DI 10.1161/CIRCULATIONAHA.105.000810 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058TT UT WOS:000238688200059 PM 16820601 ER PT J AU Kuwahara, E Otsuji, Y Iguro, Y Ueno, T Zhu, F Mizukami, N Kubota, K Nakashiki, K Yuasa, T Yu, B Uemura, T Takasaki, K Miyata, M Hamasaki, S Kisanuki, A Levine, RA Sakata, R Tei, C AF Kuwahara, E Otsuji, Y Iguro, Y Ueno, T Zhu, F Mizukami, N Kubota, K Nakashiki, K Yuasa, T Yu, B Uemura, T Takasaki, K Miyata, M Hamasaki, S Kisanuki, A Levine, RA Sakata, R Tei, C TI Mechanism of Recurrent/Persistent Ischemic/Functional mitral regurgitation in the chronic phase after surgical annuloplasty - Importance of augmented posterior leaflet tethering SO CIRCULATION LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc DE coronary disease; mitral valve; valvuloplasty ID LEFT-VENTRICULAR DYSFUNCTION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; PAPILLARY-MUSCLE; REPAIR; MOTION; CARDIOMYOPATHY; DETERMINANTS; INSIGHTS AB Background - Surgical annuloplasty can potentially hoist the posterior annulus anteriorly, exaggerate posterior leaflet (PML) tethering, and lead to recurrent ischemic/functional mitral regurgitation (MR). Characteristics of leaflet configurations in late postoperative MR were investigated. Methods and Results - In 30 patients with surgical annuloplasty for ischemic MR and 20 controls, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, posterior and apical displacement of the coaptation and the MR grade were measured by echocardiography before, early after, and late after surgery. Early after surgery, grade of MR and AML tethering generally decreased (P < 0.01), whereas PML tethering significantly worsened (P < 0.01). Nine of the 30 patients showed recurrent/ persistent MR late after surgery. Compared with patients without late MR, those with the MR showed similar reduction in the annular area, significant re- increase in posterior displacement of the coaptation, and progressive worsening in PML tethering (P < 0.05) late after surgery in comparison to the early phase. Both preoperative MR and late postoperative MR were significantly correlated with all tethering variables in univariate analysis. Although apical displacement of the coaptation was the primary determinant of preoperative MR (r(2) = 0.60, P < 0.0001), increased PML tethering was the primary determinant of late MR (r(2) = 0.75, P < 0.0001). Conclusions - Whereas both leaflets tethering is related to preoperative ischemic MR, both leaflets tethering but with predominant contribution from augmented and progressive PML tethering is related to recurrent/ persistent ischemic/ functional MR late after surgical annuloplasty. C1 Kagoshima Univ, Dept Cardiovasc Med, Kagoshima 8908520, Japan. Kagoshima Univ, Dept Clin Lab, Kagoshima 8908520, Japan. Kagoshima Univ, Dept Cardiovasc Surg, Kagoshima 8908520, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Otsuji, Y (reprint author), Kagoshima Univ, Dept Cardiovasc Med, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. EM yutaka@m.kufm.kagoshima-u.ac.jp NR 25 TC 50 Z9 51 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 JUL 4 PY 2006 VL 114 SU 1 BP I529 EP I534 DI 10.1161/CIRCULATIONAHA.105.000729 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058TT UT WOS:000238688200086 PM 16820632 ER PT J AU Messas, E Yosefy, C Chaput, M Guerrero, JL Sullivan, S Menasche, P Carpentier, A Desnos, M Hagege, AA Vlahakes, GJ Levine, RA AF Messas, E Yosefy, C Chaput, M Guerrero, JL Sullivan, S Menasche, P Carpentier, A Desnos, M Hagege, AA Vlahakes, GJ Levine, RA TI Chordal cutting does not adversely affect left ventricle contractile function SO CIRCULATION LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc DE chordae; echocardiography; mitral valve; regurgitation ID ISCHEMIC MITRAL REGURGITATION; LEAFLET 2ND-ORDER CHORDAE; MECHANISM; ECHOCARDIOGRAPHY; ANNULOPLASTY; APPARATUS AB Background - Severing a limited number of second-order chordae to the anterior leaflet can improve ischemic mitral regurgitation (MR). Some concerns have been raised regarding possible influence on regional and global left ventricle (LV) function. We evaluated changes in cardiac function in 5 normal sheep with cutting of pre-instrumented chords in the beating heart to maintain constant load. Methods and Results - Under cardiopulmonary bypass, wires were placed around the 2 central basal chordae and brought outside the heart, which was restarted. Hemodynamic and imaging data were collected before and after chordal cutting by radiofrequency ablation using those wires. Segmental contractility was assessed invasively using sonomicrometers and noninvasively using Doppler tissue velocity and strain rate (with strain rate viewed as less load- dependent than ejection fraction) at 6 sites: base, mid- ventricle, and apex along the anteroseptal and posterolateral walls. We found no changes from before to after chordal cutting in LV end-diastolic volume (47.2 +/- 3.3 after cutting versus 48.4 +/- 4.6 mL before cutting, P = 0.66), end-systolic volume (21.5 +/- 1.2 versus 22.3 +/- 2.8 mL, P = 0.68), ejection fraction (54.2 +/- 1.8 versus 54.2 +/- 2.7%, P = 0.96), systolic ventricular elastance (7.28 +/- 1.68 versus 7.66 +/- 2.11 mm Hg/mL, P = 0.64), preload-recruitable stroke work (46.6 +/- 7.7 versus 50.2 +/- 10.7 mm Hg, P = 0.76), and LVdP/dt (1480 +/- 238 versus 1392 +/- 250 mm Hg/s, P = 0.45). Doppler tissue velocities and longitudinal strain rates surrounding the papillary muscles were unchanged, as were sonomicrometer longitudinal and mediolateral absolute strains. No wall motion abnormalities were visible around the papillary muscles, and no MR developed. Conclusion - We find no evidence for acutely decreased global or segmental LV contractility with chordal cutting. This absence of adverse effects is consistent with long-term clinical experience with cutting these chords in valve repair. C1 Univ Paris 05, Fac Med, INSERM U633, APHP,Dept Cardiol, Paris, France. Hop Europeen Georges Pompidou, Dept Cardiovasc Surg, Paris, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02115 USA. RP Messas, E (reprint author), Hop Broussais, INSERM U633, Hop Europeen Georges Pompidou, Dept Cardiol, 6 Rue Didot, F-75014 Paris, France. EM emmanuel.messas@free.fr NR 25 TC 12 Z9 12 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 JUL 4 PY 2006 VL 114 SU 1 BP I524 EP I528 DI 10.1161/CIRCULATIONAHA.105.000612 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058TT UT WOS:000238688200085 PM 16820631 ER PT J AU Mukherjee, R Apple, KA Squires, CE Kaplan, BS McLean, JE Saunders, SM Stroud, RE Spinale, FG AF Mukherjee, R Apple, KA Squires, CE Kaplan, BS McLean, JE Saunders, SM Stroud, RE Spinale, FG TI Protein kinase C isoform activation and endothelin-1 mediated defects in myocyte contractility after cardioplegic arrest and reperfusion SO CIRCULATION LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc DE active relaxation; cardioplegia; endothelin; kinases; myocyte contractility ID CARDIOPULMONARY BYPASS; POSTOPERATIVE RECOVERY; VENTRICULAR MYOCYTES; HEART-FAILURE; CIRCULATION; CHANNELS AB Background-Endothelin-1 (ET-1) is released after hyperkalemic cardioplegic arrest (CA) and reperfusion and may contribute to contractile dysfunction. ET-1 receptor transduction causes activation of protein kinase C (PKC) isoforms, which can cause differential intracellular events. The goal of this study was to determine which PKC isoforms contribute to myocyte contractile dysfunction with ET-1 and CA. Methods and Results-Percent shortening (PERSHORT) and the time to 50% relaxation (T50) were measured in porcine (n = 22) left ventricular myocytes, randomized (minimum: 30 cells/group) to normothermia: (cell media for 2 hours/37 degrees C), and CA: (2 hours/4 degrees C, 24 mEq K+ solution followed by reperfusion in cell media), ET-1/CA: (100 pM ET-1 during CA). Studies were performed in the presence and absence of PKC inhibitors (500nM) against the classical (Beta-I, Beta-II, Gamma) and novel (Epsilon, Eta) isoforms (myocytes from a minimum of 3 pigs per inhibitor). CA reduced PERSHORT by approximate to 35% from normothermia (P < 0.05), which was further reduced with ET-1. PKC-Beta-II or PKC-Gamma inhibition increased PERSHORT from ET-1/CA as well as CA only (P < 0.05). CA prolonged T50 by approximate to 19% from normothermia (P < 0.05) and was further prolonged with ET-1. Inhibition of the classical PKC isoforms reduced T50 from ET-1/CA (P < 0.05). Inhibition of novel PKC isoforms did not yield similar effects on either PERSHORT or T50 with ET-1/CA. Conclusions-Inhibition of the classical PKC isoforms relieved the negative inotropic and lusitropic effects of ET-1 after CA. These findings provide mechanistic support for developing targeted inhibitory strategies with respect to ET-1 signaling and myocyte contractile dysfunction with cardioplegic arrest and reperfusion. C1 Med Univ S Carolina, Div Cardiothorac Surg Res, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Mukherjee, R (reprint author), Med Univ S Carolina, Div Cardiothorac Surg Res, 770 MUSC Complex,Suite 625, Charleston, SC 29425 USA. EM mukherr@musc.edu FU NHLBI NIH HHS [HL-97012, HL-66029, HL-45024]; PHS HHS [P01-48788] NR 23 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 4 PY 2006 VL 114 SU 1 BP I308 EP I313 DI 10.1161/CIRCULATIONAHA.105.001388 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058TT UT WOS:000238688200050 PM 16820591 ER PT J AU Ramlawi, B Feng, J Mieno, S Szabo, C Zsengeller, Z Clements, R Sodha, N Boodhwani, M Bianchi, C Sellke, FW AF Ramlawi, B Feng, J Mieno, S Szabo, C Zsengeller, Z Clements, R Sodha, N Boodhwani, M Bianchi, C Sellke, FW TI Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass SO CIRCULATION LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc DE apoptosis; blood cardioplegia; extracorporeal circulation; ischemia reperfusion; myocardial protection; signal transduction ID VASCULAR ENDOTHELIAL DYSFUNCTION; CELL-DEATH; MYOCARDIAL-ISCHEMIA; REPERFUSION INJURY; CARDIAC MYOCYTES; ARREST; PATHWAY; SURVIVAL; DISEASE; SURGERY AB Background-Cardioplegic arrest ( CA) using cold blood cardioplegia (CBC) has been reported to reduce ischemia-reperfusion (IR)-induced myocardial injury via apoptosis. We studied key apoptotic mediators via the caspase-dependent and intrinsic pathways as well as poly( ADP)-ribosylating protein ( PARP) activity in myocardial and peripheral tissues after CA and cardiopulmonary bypass (CBP). Methods and Results-Right atrial (RA) and skeletal muscle(SM) was harvested from cardiac surgical patients with similar baseline characteristics (N = 6) before and after CPB and CBC. Total and modified caspase-3, Bcl-2, Bad, apoptosis-inducing factor (AIF), and PARP were quantified by immunoblotting. Terminal caspase-3 activity was assessed and immunohistochemistry was performed for PARP and AIF. TUNEL staining was used for identification of apoptotic cells. Microarray gene expression analysis was performed using Affymetrix U95 GeneChip. In RA tissue, CA with CBC significantly increased phosphorylation of Bcl-2 (Ser(70)), Bad (Ser(112)) (2.63 +/- 0.4 and 1.77 +/- 0.3- fold respectively; P < 0.05), and cleavage of the downstream caspase 3 (1.45 +/- 0.1-fold; P < 0.05). There was no significant change in total protein levels. Also, there was an increase in mature AIF (57 kDa) levels (1.22 +/- 0.01-fold; P < 0.05) and a trend toward nuclear translocation on histological staining. Caspase 3 activity was increased 1.5 +/- 0.14-fold (P < 0.05). The number of apoptotic cells in atrial tissue increased after compared with before CPB/CA using TUNEL staining (1.55 +/- 0.66 versus 0.325 +/- 0.05%, respectively; P = 0.03). In contrast, SM samples did not show any of the changes observed in RA tissue after CPB. Conclusion-Despite optimal current surgical myocardial protection, we found that CA with CBC induced both programmed cell death and survival signaling in myocardial tissue. C1 BIDMC, Div Cardiothorac Surg, LMOB, Boston, MA 02215 USA. BIDMC, Div Cardiothorac Surg, Boston, MA 02215 USA. BIDMC, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Semmelweis Univ, Med Sch, Dept Human Physiol & Expt Res, Budapest, Hungary. Univ Med & Dent New Jersey, Dept Surg, Newark, NJ USA. Harvard Univ, Childrens Hosp, Sch Med, Perlmutter Lab, Boston, MA USA. RP Sellke, FW (reprint author), BIDMC, Div Cardiothorac Surg, LMOB, 2A,110 Francis St, Boston, MA 02215 USA. EM fsellke@caregroup.harvard.edu OI Feng, Jun/0000-0003-4762-7532 FU NHLBI NIH HHS [HL-69024, HL04095-06, HL-46716] NR 26 TC 13 Z9 13 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 4 PY 2006 VL 114 SU 1 BP I257 EP I263 DI 10.1161/CIRCULATIONAHA.105.000828 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058TT UT WOS:000238688200042 PM 16820582 ER PT J AU Trimarchi, S Nienaber, CA Rampoldi, V Myrmel, T Suzuki, T Bossone, E Tolva, V Deeb, MG Upchurch, GR Cooper, JV Fang, JM Isselbacher, EM Sundt, TM Eagle, KA AF Trimarchi, S Nienaber, CA Rampoldi, V Myrmel, T Suzuki, T Bossone, E Tolva, V Deeb, MG Upchurch, GR Cooper, JV Fang, JM Isselbacher, EM Sundt, TM Eagle, KA CA IRAD Investigators TI Role and results of surgery in acute type B aortic dissection - Insights from the International Registry of Acute Aortic Dissection (IRAD) SO CIRCULATION LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc DE aorta; aortic diseases; disease management; treatment outcome ID ANEURYSMS; THERAPY; MANAGEMENT; DIAGNOSIS AB Background-The clinical profiles and outcomes of patients treated surgically for acute type B aortic dissection (ABAD) are often reported for those in small series or for those cared for at a single institution over a long time period, during which a continuous evolution in techniques has occurred. Accordingly, we sought to evaluate the clinical features and surgical results of patients enrolled in the International Registry of Acute Aortic Dissection by identifying primary factors that influenced surgical outcome and estimating average surgical mortality for ABAD in the current era. Methods and Results-A comprehensive analysis of 290 clinical variables and their relation to surgical outcomes for 82 patients who required surgery for ABAD (from a population of 1256 patients; mean +/- SD age, 60.6 +/- 15.0 years; 82.9% male) and who were enrolled in the International Registry of Acute Aortic Dissection was performed. The overall in-hospital mortality was 29.3%. Factors associated with increased surgical mortality based on univariate analysis were preoperative coma or altered consciousness, partial thrombosis of the false lumen, evidence of periaortic hematoma on diagnostic imaging, descending aortic diameter > 6 cm, right ventricle dysfunction at surgery, and shorter time from the onset of symptoms to surgery. Factors associated with favorable outcomes included radiating pain, normotension at surgery (systolic blood pressure 100 to 149 mm Hg), and reduced hypothermic circulatory arrest time. The 2 independent predictors of surgical mortality were age > 70 years (odds ratio, 4.32; 95% confidence interval, 1.30 to 14.34) and preoperative shock/hypotension (odds ratio, 6.05; 95% confidence interval, 1.12 to 32.49). Conclusions-The present study provides insights into current-day clinical profiles and surgical outcomes of ABAD. Knowledge about different preoperative clinical conditions may help surgeons in making treatment decisions among these high-risk patients. C1 Policlin San Donato, Cardiovasc Ctr E Malan, I-20097 San Donato Milanese, Italy. Univ Rostock, D-2500 Rostock 1, Germany. Univ Tromso Hosp, N-9012 Tromso, Norway. Univ Tokyo, Tokyo, Japan. CNR, Lecce, Italy. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. RP Trimarchi, S (reprint author), Policlin San Donato, Cardiovasc Ctr E Malan, Via Morandi 30, I-20097 San Donato Milanese, Italy. EM satrimarchi@yahoo.it RI Trimarchi, Santi/J-7361-2016; OI Trimarchi, Santi/0000-0001-5996-3264; tolva, valerio/0000-0002-4642-0727 NR 26 TC 67 Z9 79 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 4 PY 2006 VL 114 SU 1 BP I357 EP I364 DI 10.1161/CIRCULATIONAHA.105.000620 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058TT UT WOS:000238688200058 PM 16820600 ER PT J AU Scirica, BM Sabatine, MS Morrow, DA Gibson, CM Murphy, SA Wiviott, SD Giugliano, RP McCabe, CH Cannon, CP Braunwald, E AF Scirica, BM Sabatine, MS Morrow, DA Gibson, CM Murphy, SA Wiviott, SD Giugliano, RP McCabe, CH Cannon, CP Braunwald, E TI The role of clopidogrel in early and sustained arterial patency after fibrinolysis for ST-segment elevation myocardial infarction - The ECG CLARITY-TIMI 28 study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TIMI 14 TRIAL; SUCCESSFUL REPERFUSION; THROMBOLYSIS; RESOLUTION; THERAPY; EXTENT; PREDICTOR; DEVIATION; INSIGHTS; ASPIRIN AB OBJECTIVES This study was designed to determine the relationship between clopidogrel and early ST-segment resolution (STRes) and the interaction of the two with clinical outcomes after fibrinolysis. BACKGROUND ST-segment resolution is an early noninvasive marker of coronary reperfusion. METHODS The CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28) trial randomized 3,491 patients with ST-segment elevation myocardial infarction (STEMI) undergoing fibrinolysis to clopidogrel versus placebo. ST-segment resolution was defined as complete (> 70%), partial (30% to 70%), or none (< 30%). RESULTS Electrocardiograms were valid for interpretation in 2,431 patients at 90 min and 2,087 at 180 min. There was no difference in the rate of complete STRes between the clopidogrel and placebo groups at 90 min (38.4% vs. 36.6% at 90 min). When patients were stratified by STRes category, treatment with clopidogrel resulted in greater benefit among those with evidence of early STRes, with greater odds of an open artery at late angiography in patients with partial (odds ratio [OR] 1.4, p = 0.04) or complete (OR 2.0, p < 0.001) STRes, but no improvement in those with no STRes at 90 min (OR 0.89, p = 0.48) (p for interaction = 0.003). Clopidogrel was also associated with a significant reduction in the odds of an in-hospital death or myocardial infarction in patients who achieved partial (OR 0.30, p = 0.003) or complete STRes at 90 min (OR 0.49, p = 0.056), whereas clinical benefit was not apparent in patients who had no STRes (OR 0.98, p = 0.95) (p for interaction = 0.027). By 30 days, the clinical benefit of clopidogrel was predominately seen in patients with complete STRes. CONCLUSIONS Clopidogrel appears to improve late coronary patency and clinical outcomes by preventing reocclusion of open arteries rather than by facilitating early reperfusion. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM bscirica@partners.org NR 21 TC 43 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 4 PY 2006 VL 48 IS 1 BP 37 EP 42 DI 10.1016/j.jacc.2006.02.052 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 059FH UT WOS:000238718200006 PM 16814646 ER PT J AU Kawasaki, M Bouma, BE Bressner, J Houser, SL Nadkarni, SK MacNeill, BD Jang, IK Fujiwara, H Tearney, GJ AF Kawasaki, M Bouma, BE Bressner, J Houser, SL Nadkarni, SK MacNeill, BD Jang, IK Fujiwara, H Tearney, GJ TI Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID STENT NEOINTIMAL HYPERPLASIA; ATHEROSCLEROTIC PLAQUE; IN-VITRO; ARTERIES; CLASSIFICATION; VALIDATION; GEOMETRY; BIOPSY; IMPACT AB OBJECTIVES The purpose of the present study was to validate the diagnostic accuracy of optical coherence tomography (OCT), integrated backscatter intravascular ultrasound (IB-IVUS), and conventional intravascular ultrasound (C-IVUS) for tissue characterization of coronary plaques and to evaluate the advantages and limitations of each of these modalities. BACKGROUND The diagnostic accuracy of OCT for characterizing tissue types is well established. However, comparisons among OCT, C-IVUS, and IB-IVUS have not been done. METHODS We examined 128 coronary arterial sites (42 coronary arteries) from 17 cadavers; IVUS and OCT images were acquired on the same slice as histology. Ultrasound signals were obtained using an IVUS system with a 40-MHz catheter and digitized at 1 GHz with 8-bit resolution. The IB values of the ultrasound signals were calculated with a fast Fourier transform. RESULTS Using histological images as a gold standard, the sensitivity of OCT for characterizing calcification, fibrosis, and lipid pool was 100%, 98%, and 95%, respectively. The specificity of OCT was 100%, 94%, and 98%, respectively (Cohen's K = 0.92). The sensitivity of IB-IVUS was 100%, 94%, and 84%, respectively. The specificity of IB-IVUS was 99%, 84%, and 97%, respectively (Cohen's K = 0.80). The sensitivity of C-IVUS was 100%, 93%, and 67%, respectively. The specificity of C-IVUS was 99%, 61%, and 95%, respectively (Cohen's K = 0.59). CONCLUSIONS Within the penetration depth of OCT, OCT has a best potential for tissue characterization of coronary plaques. Integrated backscatter IVUS has a better potential for characterizing fibrous lesions and lipid pools than C-IVUS. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Gifu Univ, Grad Sch Med, Gifu, Japan. RP Kawasaki, M (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 40 Blossom St, Boston, MA 02114 USA. EM masanori@ya2.so-net.ne.jp NR 31 TC 112 Z9 117 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 4 PY 2006 VL 48 IS 1 BP 81 EP 88 DI 10.1016/j.jacc.2006.02.062 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 059FH UT WOS:000238718200012 PM 16814652 ER PT J AU Ellinor, PT Sasse-Klaassen, S Probst, S Gerull, B Shin, JT Toeppel, A Heuser, A Michely, B Yoerger, DM Song, BS Pilz, B Krings, G Coplin, B Lange, PE Dec, GW Hennies, HC Thierfelder, L MacRae, CA AF Ellinor, PT Sasse-Klaassen, S Probst, S Gerull, B Shin, JT Toeppel, A Heuser, A Michely, B Yoerger, DM Song, BS Pilz, B Krings, G Coplin, B Lange, PE Dec, GW Hennies, HC Thierfelder, L MacRae, CA TI A novel locus for dilated cardiomyopathy, diffuse myocardial fibrosis, and sudden death on chromosome 10q25-26 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-FAILURE; MUTATIONS; DISEASE; GENE; PROTEIN; ORGANIZATION; DEFICIENT; DYSPLASIA; RELATIVES; FAMILY AB OBJECTIVES We sought to identify the genetic locus for an inherited form of dilated cardiomyopathy (DCM) that is characterized by diffuse myocardial fibrosis and sudden death. BACKGROUND Genetic studies have mapped multiple loci for DCM, which is a major cause of nonischemic heart failure; however, the genes responsible for the majority of cases have yet to be identified. METHODS Sixty-six family members were evaluated by 12-lead electrocardiogram (ECG), echocardiogram, and laboratory studies. Individuals with echocardiographically documented DCM were defined as affected. Subjects were considered unaffected if they were older than 20 years of age, had a normal ECG and echocardiogram, no personal history of heart failure, and had no affected offspring. Genotyping was performed using polymorphic markers. RESULTS Genome-wide linkage analysis identified a novel locus for this inherited phenotype on chromosome 10q25.3-q26.13. Peak two-point logarithm of the odds scores > 3.0 were obtained independently with each family using the markers D10S1773 and D10S1483, respectively. Haplotype analyses defined a critical interval of 14.0 centiMorgans between D10S1237 and D10S1723, corresponding to a physical distance of 9.5 megabases. Multipoint linkage analyses confirmed this interval and generated a peak logarithm of the odds score of 8.2 indicating odds of > 100,000,000:1 in favor of this interval as the location of the gene defect responsible for DCM in these families. CONCLUSIONS We have mapped a novel locus for cardiomyopathy, diffuse myocardial fibrosis, and sudden death to chromosome 10q25-q26. The identification of the causative gene in this interval will be an important step in understanding the fundamental mechanisms of heart failure and sudden death. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Max Delbruck Ctr Mol Med, Berlin, Germany. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Humboldt Univ, Franz Volhard Clin, HELIOS Clin GmbH, Charite, Berlin, Germany. Humboldt Univ, Pediat Clin, Div Cardiol, Charite, Berlin, Germany. Albany Associates Cardiol, Albany, NY USA. German Heart Inst, Dept Congenital Heart Dis, Berlin, Germany. Cologne Ctr Genom, Cologne, Germany. RP MacRae, CA (reprint author), Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. EM lthier@mdc-berlin.de; cmacrae@partners.org OI Heuser, Arnd/0000-0002-3334-960X FU NHLBI NIH HHS [HL71632, HL75431, R01 HL075431] NR 35 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 4 PY 2006 VL 48 IS 1 BP 106 EP 111 DI 10.1016/j.jacc.2006.01.079 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 059FH UT WOS:000238718200016 PM 16814656 ER PT J AU Joner, M Finn, AV Farb, A Mont, EK Kolodgie, FD Ladich, E Kutys, R Skorija, K Gold, HK Virmani, R AF Joner, M Finn, AV Farb, A Mont, EK Kolodgie, FD Ladich, E Kutys, R Skorija, K Gold, HK Virmani, R TI Pathology of drug-eluting stents in humans - Delayed healing and late thrombotic risk SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID CORONARY-ARTERY; INTRAVASCULAR ULTRASOUND; POOLED ANALYSIS; MODERN-ERA; SIROLIMUS; PACLITAXEL; IMPLANTATION; PREDICTORS; RAPAMYCIN; DELIVERY AB OBJECTIVES This study examined human drug-eluting stents (DES) to determine the long-term effects of these stents on coronary arterial healing and identified mechanisms underlying late stent thrombosis (LST). BACKGROUND Although DES reduce the need for repeat revascularization compared with bare-metal stents (BMS), data suggest the window of thrombotic risk for Cypher (Cordis Corp., Miami Lakes, Florida) and Taxus (Boston Scientific Corp., Natick, Massachusetts) DES extends far beyond that for BMS. METHODS From a registry of 40 autopsies of DES (68 stents), 23 DES cases of > 30 days duration were compared with 25 matched autopsies of BMS implantation. Late stent thrombosis was defined as an acute thrombus within a stent > 30 days old. RESULTS Of 23 patients with DES > 30 days old, 14 had evidence of LST. Cypher and Taxus DES showed greater delayed heating characterized by persistent fibrin deposition (fibrin score 2.3 +/- 1.1 vs. 0.9 +/- 0.8, p = 0.0001) and poorer endothelialization (55.8 +/- 26.5%) compared with BMS (89.8 +/- 20.9, p = 0.0001); Moreover, DES with LST showed more delayed healing compared with patent DES. In 5 of 14 patients suffering LST, antiplatelet therapy had been withdrawn. Additional procedural and pathologic risk factors for LST were: 1) local hypersensitivity reaction; 2) ostial and/or bifurcation stenting; 3) malapposition/incomplete apposition; 4) restenosis; and 5) strut penetration into a necrotic core. CONCLUSIONS The Cypher and Taxus DES result in delayed arterial healing when compared with BMS of similar implant duration. The cause of DES LST is multifactorial with delayed healing in combination with other clinical and procedural risk factors playing a role. C1 Int Registry Pathol, CV Path, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Dept Internal Med, Cardiac Unit, Boston, MA 02114 USA. Miami Dade Cty Med Examiner Dept, Miami, FL USA. US FDA, Int Cardiol Devices Branch, Rockville, MD 20857 USA. RP Virmani, R (reprint author), Int Registry Pathol, CV Path, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 39 TC 1513 Z9 1623 U1 21 U2 145 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 4 PY 2006 VL 48 IS 1 BP 193 EP 202 DI 10.1016/j.jacc.2006.03.042 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 059FH UT WOS:000238718200027 PM 16814667 ER PT J AU Houston, TK Wall, T Allison, JJ Palonen, K Willett, LL Keife, CI Massie, FS Benton, EC Heudebert, GR AF Houston, Thomas K. Wall, Terry Allison, Jeroan J. Palonen, Katri Willett, Lisa L. Keife, Catarina I. Massie, F. Stanford Benton, E. Cason Heudebert, Gustavo R. TI Implementing achievable benchmarks in preventive health: A controlled trial in residency education SO ACADEMIC MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; MEDICAL-RECORD AUDIT; QUALITY IMPROVEMENT; PRACTICE GUIDELINES; GENERAL-PRACTICE; CHART AUDITS; CARE; PERFORMANCE; FEEDBACK; CALL AB Purpose To evaluate the Preventive Health Achievable Benchmarks Curriculum, a multifaceted improvement intervention that included an objective, practice-based performance evaluation of internal medicine and pediatric residents' delivery of preventive services. Method The authors conducted a nonranclonnized experiment of intervention versus control group residents with baseline and follow-up of performance audited for 2001-2004. All 130 internal medicine and 78 pediatric residents at two continuity clinics at the University of Alabama School of Medicine, Birmingham, participated. Performance of preventive care was assessed by structured chart review. The multifaceted feedback curriculum included individualized performance feedback, academic detailing by faculty, and collective didactic sessions. The main outcome was difference in receipt of preventive care for patients seen by intervention and control residents, comparing baseline and follow-up. Results Charts were reviewed for 3,958 patients Receipt of preventive care increased for patients of intervention residents, but not for patients of control residents. For the intervention group, significant increases occurred for five of six indicators in internal medicine: smoking screening, quit smoking advice, colon cancer screening, pneumonia vaccine, and lipid screening; and four of six in pediatrics: parental quit smoking advice, car seats, car restraints, and eye alignment (P < .05 for all). For control residents, no consistent improvements were seen. There was greater improvement for intervention than for control residents for four of six indicators in internal medicine, and two of six in pediatrics. Conclusions Using a multifaceted feedback curriculum, the authors taught residents about the care they provide and improved documented patient care. C1 Univ Alabama, Sch Med, Div Gen Internal Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. Univ Alabama, Sch Med, Ctr Outcomes & Effectiveness Res, Birmingham, AL 35233 USA. Univ Alabama, Sch Med, Div Gen Pediat, Birmingham, AL 35294 USA. RP Houston, TK (reprint author), Univ Alabama, Sch Med, Div Gen Internal Med, 1530 3rd Ave S,FOT 720, Birmingham, AL 35294 USA. EM thouston@uab.edu RI Houston, Thomas/F-2469-2013; OI Allison, Jeroan/0000-0003-4472-2112 NR 37 TC 11 Z9 12 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2006 VL 81 IS 7 BP 608 EP 616 DI 10.1097/01.ACM.0000232410.97399.8f PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 061UU UT WOS:000238899100004 PM 16799281 ER PT J AU Weissmann, PF Branch, WT Gracey, CF Haidet, P Frankel, RM AF Weissmann, Peter F. Branch, William T. Gracey, Catherine F. Haidet, Paul Frankel, Richard M. TI Role modeling humanistic behaviour: Learning bedside manner from the experts SO ACADEMIC MEDICINE LA English DT Article ID COMMUNICATION-SKILLS; PATIENT SATISFACTION; ATTENDING-PHYSICIAN; HIDDEN CURRICULUM; MEDICAL-EDUCATION; HUMAN DIMENSIONS; CARE; STUDENTS; RESIDENTS; SETTINGS AB Purpose Humanistic care is regarded as important by patients and professional accrediting agencies, but little is known about how attitudes and behaviors in this domain are taught in clinical settings. To answer this question, the authors studied how excellent clinical teachers impart the behaviors and attitudes consistent with humanistic care to their learners. Method Using an observational, qualitative methodology, the authors studied 12 clinical faculty identified by the medical residents enrolled from 2003 to 2004 as excellent teachers of humanistic care on the inpatient medical services at four medical universities in the United States (University of Minnesota Medical School, Emory University, University of Rochester School of Medicine, and Baylor College of Medicine). Observations were conducted by the authors using standardized field notes. After each encounter, the authors debriefed patients, learners (residents and medical students), and the teaching physicians in semistructured interviews. Results Clinical teachers taught primarily by role modeling. Although they were highly aware of their significance as role models, they did not typically address the human dimensions of care overtly. Despite the common themes of role modeling identified, each clinical teacher exhibited unique teaching strategies. These clinical teachers identified self-reflection as the primary method by which they developed and refined their teaching strategies. Conclusions Role modeling is the primary method by which excellent clinical teachers try to teach medical residents humanistic aspects of medical care. Although clinical teachers develop unique teaching styles and strategies, common themes are shared and could be used for the future development of clinical faculty. C1 Univ Minnesota, Dept Med, Hennepin Cty Med Ctr, Sch Med, Minneapolis, MN 55415 USA. Emory Univ, Sch Med, Div Gen Internal Med, Atlanta, GA USA. Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Indiana Univ, Sch Med, Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Richard L Roudebush Vet Affairs Med Ctr, Ctr Implementing Evidence Based Practice, Indianapolis, IN 46202 USA. RP Weissmann, PF (reprint author), Univ Minnesota, Dept Med, Hennepin Cty Med Ctr, Sch Med, 701 Pk Ave S, Minneapolis, MN 55415 USA. EM weiss017@umn.edu NR 43 TC 67 Z9 68 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2006 VL 81 IS 7 BP 661 EP 667 DI 10.1097/01.ACM.0000232423.81299.fe PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 061UU UT WOS:000238899100012 PM 16799294 ER PT J AU Swick, S Hall, S Beresin, E AF Swick, Susan Hall, Sarah Beresin, Eugene TI Assessing the ACGME competencies in psychiatry training programs SO ACADEMIC PSYCHIATRY LA English DT Article ID STRUCTURED CLINICAL EXAMINATION; EMERGENCY-MEDICINE RESIDENTS; STANDARDIZED PATIENTS; INTERPERSONAL SKILLS; GENERAL COMPETENCES; 360-DEGREE FEEDBACK; CORE COMPETENCES; GLOBAL RATINGS; RELIABILITY; PERFORMANCE AB In 2000, the Accreditation Council of Graduate Medical Education (ACGME) laid out a definition of competence that included six specific areas of focus: patient care (including clinical reasoning), medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism, and systems-based practice. The ACGME's intention was to mandate increasingly reliable and valid assessment measures to be used by all training programs over the next decade, with the goal of providing "more credible, accurate, reliable and useful educational outcome data." In this article, the authors will review definitions of competency according to the new ACGME standards and examine the assessment tools currently available, including global evaluations, 360-degree evaluations, checklists, standardized examinations and direct observations. The authors will provide an overview of critical considerations in different assessment methods, including timing, psychometric properties, benchmarks, and feedback. Finally, the authors will discuss the relevant literature concerning the strengths and weaknesses of these various assessment tools. Throughout, the authors will comment on the applicability of the literature on assessment to the field of psychiatry and consider directions for competency assessment within and beyond psychiatric training. Following the paper is an annotated bibliography of the literature for those wishing to explore this topic more deeply and a list of web-based resources that may be used by those wishing to access available instruments. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Child & Adolescent Psychiat Residency Training Pr, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. RP Swick, S (reprint author), Massachusetts Gen Hosp, Dept Child Psychiat, YAW-6-6A,55 Fruit St, Boston, MA 02114 USA. NR 39 TC 42 Z9 43 U1 1 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JUL-AUG PY 2006 VL 30 IS 4 BP 330 EP 351 DI 10.1176/appi.ap.30.4.330 PG 22 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 072QK UT WOS:000239687900015 PM 16908614 ER PT J AU Woolf, CJ AF Woolf, Clifford J. TI Identifying and validating novel analgesic drug targets SO ACTA PHARMACOLOGICA SINICA LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD JUL PY 2006 VL 27 SU 1 BP 5 EP 5 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 071HI UT WOS:000239590000029 ER PT J AU Tache, Y AF Tache, Yvette TI New CRF antagonists: A new approach to IBS SO ACTA PHARMACOLOGICA SINICA LA English DT Meeting Abstract DE CRF; CRFl receptor; gut function; visceral pain C1 Univ Calif Los Angeles, Digest Dis Res Ctr, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Div Digest Dis, 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 BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD JUL PY 2006 VL 27 SU 1 BP 6 EP 6 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 071HI UT WOS:000239590000037 ER PT J AU Lerwill, MF AF Lerwill, Melinda F. TI The evolution of lobular neoplasia SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Article DE lobular neoplasia; atypical lobular hyperplasia; lobular carcinoma in situ; invasive lobular carcinoma; E-cadherin; 16q ID CARCINOMA-IN-SITU; E-CADHERIN GENE; BREAST-CANCER RISK; TERM FOLLOW-UP; FEMALE BREAST; INTRAEPITHELIAL NEOPLASIA; PROSPECTIVE NATIONWIDE; PROTEIN EXPRESSION; CATENIN EXPRESSION; TUMOR-METASTASIS AB Lobular neoplasia of the breast, encompassing both atypical lobular hyperplasia and lobular carcinoma in situ, remains a poorly understood entity. Often misconceived of as simply a risk factor for subsequent carcinoma, lobular neoplasia likely constitutes both a generalized risk factor and a direct precursor to invasive disease. Recent molecular studies, particularly those examining alterations in the E-cadherin gene, provide compelling evidence to support a role for lobular neoplasia as a direct precursor to invasive lobular carcinoma. These molecular studies also provide early insights into the biologic relationship of atypical lobular hyperplasia and lobular carcinoma in situ. The ability to stratify lobular neoplasia into high-risk and low-risk categories based on molecular attributes is on the horizon. With this ability will come an evolution in our thinking, diagnosis, and management of this enigmatic disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Lerwill, MF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. EM mlerwill@partners.org NR 66 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD JUL PY 2006 VL 13 IS 4 BP 157 EP 165 DI 10.1097/00125480-200607000-00002 PG 9 WC Pathology SC Pathology GA 069KE UT WOS:000239444000002 PM 16858149 ER PT J AU Safren, SA Kumarasamy, N Hosseinipour, M Harwood, MM Hoffman, I McCauley, M Jumbe, A Nyirenda, C Mimiaga, MJ Solomon, S Celentano, D Mayer, KH AF Safren, Steven A. Kumarasamy, N. Hosseinipour, Mina Harwood, Meaghan M. Hoffman, Irving McCauley, Marybeth Jumbe, Allan Nyirenda, Christina Mimiaga, Matthew J. Solomon, Suniti Celentano, David Mayer, Kenneth H. TI Perceptions about the acceptability of assessments of HIV medication adherence in Lilongwe, Malawi and Chennai, India SO AIDS AND BEHAVIOR LA English DT Article DE antiretroviral therapy; adherence; developing countries; qualitative research ID ANTIRETROVIRAL THERAPY; INCREASE ADHERENCE; SELF-REPORT; MONITORING/; POPULATION AB Little research exists on acceptability issues related to assessments of adherence to ART in resource-poor settings. To help prepare for two large-scale, multisite ART intervention trials, this qualitative study of individuals in Chennai, India (49 men, 11 women; 33 taking ART, 27 not) and Lilongwe, Malawi (5 men, 5 women, all taking ART) examined potential limitations of different types of adherence assessments: an adherence questionnaire, a pill diary, a pillbox, an electronic pill cap, and a medication punch card. Many participants reported that the various assessments would be acceptable. Potential limitations included issues surrounding literacy, the desire to appease one's medical provider, privacy and stigma, and "cheating." These potential limitations are similar to the limitations of these assessments in Western settings. However, the data highlight the need to consider individual patient level concerns when assessing ART adherence in different cultural settings. Innovative ways of monitoring adherence while maintaining standardization across sites are required in multisite trials. C1 Fenway Community Hlth, Res & Evaluat Dept, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. YRG Care, Ctr AIDS Res & Educ, Madras, Tamil Nadu, India. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. Family Hlth Int, Arlington, VA USA. Kamuzu Cent Hosp, Malawi Minist Hlth, Lilongwe, Malawi. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Brown Univ, Miriam Hosp, Providence, RI 02912 USA. RP Safren, SA (reprint author), Fenway Community Hlth, Res Dept, 7 Haviland St, Boston, MA 02215 USA. EM ssafren@fenwayhealth.org FU FIC NIH HHS [TW00237]; NIAID NIH HHS [U01 AI48040-03] NR 21 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD JUL PY 2006 VL 10 IS 4 BP 443 EP 450 DI 10.1007/s10461-006-9094-6 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 070TP UT WOS:000239547600015 PM 16604297 ER PT J AU Becker, HC Myrick, H Veatch, LM AF Becker, HC Myrick, H Veatch, LM TI Pregabalin is effective against behavioral and electrographic seizures during alcohol withdrawal SO ALCOHOL AND ALCOHOLISM LA English DT Article ID PLACEBO-CONTROLLED TRIAL; GENERALIZED ANXIETY DISORDER; ETHANOL WITHDRAWAL; DOUBLE-BLIND; POSTHERPETIC NEURALGIA; NONCONVULSIVE SEIZURES; ADJUNCTIVE THERAPY; DOSE-RESPONSE; GABAPENTIN; CALCIUM AB Aims: Pregabalin has been shown to possess anticonvulsant, analgesic, and anxiolytic properties in a variety of testing situations. This study was designed to evaluate the ability of pregabalin to exert its anticonvulsant effects against behavioral and electrographic measures of CNS hyperexcitability associated with alcohol withdrawal in a mouse model of ethanol dependence. Methods: Adult mice were chronically exposed to ethanol and, upon withdrawal, were tested for behavioral signs of seizure activity (handling-induced convulsions) or abnormalities in spontaneous EEG activity recorded from cortical and subcortical sites. Results: Pregabalin (50-200 mg/kg) administered 1 and 4 h into withdrawal dose dependently reduced severity of handling-induced convulsions in comparison to vehicle-treated mice. Similarly, pregabalin reduced the frequency in which EEG activity was interrupted by trains of high-voltage synchronous activity in a dose-related fashion. Finally, pregabalin treatment of repeated withdrawals was effective in blocking the development of withdrawal sensitization observed in vehicle-treated mice. Conclusions: Collectively, these results suggest that pregabalin may be an effective therapeutic agent for medical management of alcohol detoxification. C1 Inst Psychiat, Ctr Drug & Alcohol Programs, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Vet Affairs, Charleston, SC USA. RP Becker, HC (reprint author), Inst Psychiat, Ctr Drug & Alcohol Programs, Charleston Alcohol Res Ctr, 67 President St, Charleston, SC 29425 USA. EM beckerh@musc.edu FU NIAAA NIH HHS [P50-AA10761] NR 57 TC 17 Z9 20 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JUL-AUG PY 2006 VL 41 IS 4 BP 399 EP 406 DI 10.1093/alcalc/ag1029 PG 8 WC Substance Abuse SC Substance Abuse GA 059VC UT WOS:000238759300009 PM 16636010 ER PT J AU Alhomsi, K Laposata, M AF Alhomsi, K Laposata, M TI Fatty acid ethyl ester effects on interleukin-2 production, cyclic AMP synthesis, and calcium influx in human mononuclear cells SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE white blood cells; mononuclear cells; fatty acid ethyl esters; ethyl oleate; interleukin-2; calcium; adenosine cyclic monophosphate; alcohol; ethanol; immunity ID WHITE BLOOD-CELLS; ETHANOL; ALCOHOL; PROLIFERATION; METABOLITES; SUPPRESSES; ACTIVATION; THYMOCYTES; INCREASE; DAMAGE AB Background: Fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites, are produced by the esterification of fatty acids and ethanol. Plasma and serum FAEE correlate linearly with blood ethanol levels and are present in organs most commonly damaged by ethanol abuse. Our previous studies have shown that there is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. Objectives: We studied the effects of FAEE on selected early events of mononuclear cell activation that follow stimulation with phytohemagglutinin (PHA). Fatty acid ethyl esters induced changes in cytosolic free calcium ([Ca2+]) levels, the production and secretion of interleukin-2 (IL-2) by the cells, and intracellular cAMP concentrations. Methods: A mononuclear fraction of human white blood cells (WBC) was incubated with physiologic doses of FAEE. For experiments involving IL-2 production and calcium influx, PHA-stimulated cells were incubated with 10, 25, 50, or 100 mu M ethyl oleate, a representative FAEE species, for 60 minutes. Interleukin-2 was measured by enzyme immunometeric assay and maximum levels of Ca2+ were monitored by spectrofluorimetry. In other experiments, mononuclear cells were incubated with 10, 25, and 50 mu M ethyl oleate for 0.08 to 120 minutes, and then the concentration of cAMP was determined by a cAMP competitive enzyme immunoassay system. Results: Fatty acid ethyl esters inhibited the PHA-induced IL-2 production and secretion in activated human mononuclear cells. Fatty acid ethyl esters also inhibited PHA-induced [Ca2+] influx into cells in a dose-dependent fashion. There was a rapid increase in the intracellular cAMP concentration of mononuclear cells induced by FAEE, with FAEE dose dependence. The cAMP concentration decreased as the incubation time with FAEE was increased. Conclusions: Fatty acid ethyl esters inhibited PHA-stimulated IL-2 production and Ca2+ influx into human mononuclear cells and elevated intracellular cAMP concentration. These changes in mononuclear cell signaling may be associated with the immunosuppression associated with alcohol abuse. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northeastern Univ, Dept Biomed Sci, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Room 235,55 Fruit St, Boston, MA 02114 USA. EM mlaposata@partners.org NR 23 TC 4 Z9 4 U1 1 U2 1 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 JUL PY 2006 VL 30 IS 7 BP 1121 EP 1125 DI 10.1111/j.1530-0277.2006.000129.x PG 5 WC Substance Abuse SC Substance Abuse GA 052SB UT WOS:000238253100004 PM 16792558 ER PT J AU Best, CA Sarkola, T Eriksson, CJP Cluette-Brown, JE Laposata, M AF Best, CA Sarkola, T Eriksson, CJP Cluette-Brown, JE Laposata, M TI Increased plasma fatty acid ethyl ester levels following inhibition of oxidative metabolism of ethanol by 4-methylpyrazole treatment in human subjects SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; alcoholic pancreatitis; ethanol; fatty acid ethyl esters; 4-methylpyrazole ID CHRONIC-PANCREATITIS; NONOXIDATIVE METABOLITES; ALCOHOL; ENZYMES; MARKERS; POLYMORPHISMS; ACETALDEHYDE; FOMEPIZOLE; CIRRHOSIS; INJURY AB Background: Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative metabolites of ethanol, mediate ethanol-induced organ damage. A direct association between pancreas-specific toxicity and increased levels of FAEE following inhibition of the oxidative metabolism of ethanol by 4-methylpyrazole (4-MP) has previously been shown in studies with rats. Methods: We obtained plasma samples from 32 healthy human volunteers who drank ethanol following 4-MP or placebo ingestion to determine whether in vivo inhibition of oxidative metabolism of ethanol causes a shift to nonoxidative metabolism of ethanol and the subsequent production of increased levels of FAEE. Plasma FAEE were isolated by solid-phase extraction and quantified by gas chromatography-mass spectrometry (GC-MS). Results: Plasma FAEE levels in subjects receiving 4-MP treatment before ethanol consumption were elevated compared with plasma FAEE concentrations taken from control subjects who received a placebo before ethanol ingestion. Increased FAEE levels in the 4-MP treatment group occurred after peak blood ethanol, and peak FAEE levels were achieved. There was a correlation between the blood ethanol and the plasma FAEE levels, and the correlation persisted in the presence or absence of 4-MP. The peak FAEE values were greater in men than in women, with or without 4-MP treatment. Conclusions: Our results indicate that the in vivo inhibition of the oxidative metabolism of ethanol using 4-MP results in an increased circulating concentration of FAEE, products of the nonoxidative metabolism of ethanol. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northeastern Univ, Dept Biomed Sci, Boston, MA 02115 USA. Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, 55 Fruit St,Gray 235, Boston, MA 02114 USA. EM mlaposata@partners.org NR 30 TC 6 Z9 6 U1 0 U2 3 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 JUL PY 2006 VL 30 IS 7 BP 1126 EP 1131 DI 10.1111/j.1530-0277.2006.00138.x PG 6 WC Substance Abuse SC Substance Abuse GA 052SB UT WOS:000238253100005 PM 16792559 ER PT J AU Shaib, YH Davila, JA El-Serag, B AF Shaib, Y. H. Davila, J. A. El-Serag, B. TI The epidemiology of pancreatic cancer in the United States: changes below the surface SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SURVIVAL; PANCREATICODUODENECTOMY; STATISTICS; CARCINOMA; AMERICANS; WHITES AB Background Pancreatic cancer is the fourth leading cause of cancer death in the United States. Aim To examine temporal changes in the incidence and survival of patients with pancreatic adenocarcinoma. Methods Using data from nine registries of the Surveillance, Epidemiology and End Results programme, age-adjusted incidence rates per 100 000 and survival rates were calculated for pancreatic cancer between 1977 and 2001. Results We identified 58 655 cases of pancreatic cancer. The age-adjusted incidence rate remained stable during the study period (11.3 in 1977-1981 and 10.9 in 1997-2001). Overall, men were 30% more affected than women (age-adjusted incidence rate of 13.0 in men and 9.8 in women). The age-adjusted incidence rates were almost 50% higher among Blacks (16.4) than Whites (10.8) and people of other races (9.8). Over time the proportions of patients with localized disease decreased from 12.3% to 7.4% and those with regional disease increased from 18.6% to 25.8%, while metastatic disease remained stable (52.5% vs. 49.8%). The 1-year relative survival increased from 15.2% in 1977-1981 to 21.6% in 1997-2001. Conclusions The incidence of pancreatic cancer is stable. A shift from localized to regional disease was observed over time. The overall survival remains poor despite important improvements among patients with early stage disease. C1 Michael E Debakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Michael E Debakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Shaib, YH (reprint author), Michael E Debakey Vet Affairs Med Ctr, Sect Hlth Serv Res, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM yshaib@bcm.tmc.edu RI qiao, zhixin/I-3408-2012 NR 18 TC 86 Z9 95 U1 0 U2 0 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 JUL 1 PY 2006 VL 24 IS 1 BP 87 EP 94 DI 10.1111/j.1365-2036.2006.02961.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 053LH UT WOS:000238306100008 PM 16803606 ER PT J AU Mitchell, SL Kiely, DK Jones, RN Prigerson, H Volicer, L Teno, JM AF Mitchell, Susan L. Kiely, Dan K. Jones, Richard N. Prigerson, Holly Volicer, Ladislav Teno, Joan M. TI Advanced dementia research in the nursing home: The CASCADE study SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE dementia; palliative care; nursing home; methodology ID OF-LIFE CARE; END-STAGE DEMENTIA; ADVANCED COGNITIVE IMPAIRMENT; OLDER PERSONS; RESIDENTS; SCALE; CAREGIVER; HEALTH; POPULATION; VALIDATION AB Despite the growing number of persons with advanced dementia, and the need to improve their end-of-life care, few studies have addressed this important topic. The objectives of this report are to present the methodology established in the CASCADE (Choices, Attitudes, and Strategies for Care of Advanced Dementia at the End-of-Life) study, and to describe how challenges specific to this research were met. The CASCADE study is an ongoing, federally funded, 5-year prospective cohort study of nursing [nursing home (NH)] residents with advanced dementia and their health care proxies (HCPs) initiated in February 2003. Subjects were recruited from 15 facilities around Boston. The recruitment and data collection protocols are described. The demographic features, ownership, staffing, and quality of care of participant facilities are presented and compared to NHs nationwide. To date, 189 resident/HCP dyads have been enrolled. Baseline data are presented, demonstrating the success of the protocol in recruiting and repeatedly assessing NH residents with advanced dementia and their HCPs. Factors challenging and enabling implementation of the protocol are described. The CASCADE experience establishes the feasibility of conducting rigorous, multisite dementia NH research, and the described methodology serves as a detailed reference for subsequent CASCADE publications as results from the study emerge. C1 Hebrew Senior Life Inst Aging Res, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Ctr Psychosocial Oncol & Palliat Care Res, Boston, MA 02115 USA. Univ S Florida, Sch Aging Studies, Tampa, FL USA. Brown Univ, Sch Med, Ctr Gerontol & Hlth Care Res, Dept Community Hlth, Providence, RI 02912 USA. RP Mitchell, SL (reprint author), Hebrew Senior Life, Dept Med, 1200 Ctr St, Boston, MA 02131 USA. EM smitchell@hrca.harvard.edu RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU NIA NIH HHS [R01 AG024091-01, K24 AG033640, P50 AG005134, P50 AG05134, R01 AG024091] NR 51 TC 58 Z9 58 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JUL-SEP PY 2006 VL 20 IS 3 BP 166 EP 175 DI 10.1097/00002093-200607000-00008 PG 10 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 080AB UT WOS:000240217900008 PM 16917187 ER PT J AU Kiely, DK Volicer, L Teno, J Jones, RN Prigerson, HG Mitchell, SL AF Kiely, Dan K. Volicer, Ladislav Teno, Joan Jones, Richard N. Prigerson, Holly G. Mitchell, Susan L. TI The validity and reliability of scales for the evaluation of end-of-life care in advanced dementia SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE dementia; nursing homes; palliative care; end-of-life; health care proxy ID NURSING-HOME; QUALITY AB The lack of valid and reliable instruments designed to measure the experiences of older persons with advanced dementia and those of their health care proxies has limited palliative care research for this condition. This study evaluated the reliability and validity of 3 End-of-Life in Dementia (EOLD) scales that measure the following outcomes: (1) satisfaction with the terminal care (SWC-EOLD), (2) symptom management (SM-EOLD), and (3) comfort during the last 7 days of life (CAD-EOLD). Data were derived from interviews with the health care proxies (SWC-EOLD) and primary care nurses (SM-EOLD, CAD-EOLD) for 189 nursing home residents with advanced dementia living in 15 Boston-area facilities. The scales demonstrated satisfactory to good reliability: SM-EOLD (alpha = 0.68), SWC-EOLD (alpha = 0.83), and CAD-EOLD (alpha = 0.82). The convergent validity of these scales, as measured against other established instruments assessing similar constructs, was good (correlation coefficients ranged from 0.50 to 0.81). The results of this study demonstrate that the 3 EOLD scales demonstrate "internal consistency" reliability and demonstrate convergent validity, and further establish their utility in palliative care dementia research. C1 Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Ctr Psychosocial Oncol & Palliat Care Res, Boston, MA 02115 USA. Univ S Florida, Sch Aging Studies, Tampa, FL USA. Brown Univ, Sch Med, Ctr Gerontol & Hlth Care Res, Dept Community Hlth, Providence, RI 02912 USA. RP Kiely, DK (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM kiely@mail.hrca.harvard.edu OI Jones, Richard/0000-0002-1049-218X FU NIA NIH HHS [K24 AG033640, P50 AG005134, P50 AG05134, R01 AG024091, R01 AG024091-01] NR 22 TC 46 Z9 46 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JUL-SEP PY 2006 VL 20 IS 3 BP 176 EP 181 DI 10.1097/00002093-200607000-00009 PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 080AB UT WOS:000240217900009 PM 16917188 ER PT J AU Cooper, CJ Murphy, TP Matsumoto, A Steffes, M Cohen, DJ Jaff, M Kuntz, R Jamerson, K Reid, D Rosenfield, K Rundback, J D'Agostino, R Henrich, W Dworkin, L AF Cooper, Christopher J. Murphy, Timothy P. Matsumoto, Alan Steffes, Michael Cohen, David J. Jaff, Michael Kuntz, Richard Jamerson, Kenneth Reid, Diane Rosenfield, Kenneth Rundback, John D'Agostino, Ralph Henrich, William Dworkin, Lance TI Stent revascularization for the prevention of cardiovascular and renal events among patients with renal artery stenosis and systolic hypertension: Rationale and design of the CORAL trial SO AMERICAN HEART JOURNAL LA English DT Article ID ATHEROSCLEROTIC RENOVASCULAR DISEASE; BODY-FLUID VOLUMES; RANDOMIZED-TRIAL; ANGIOTENSIN-II; BLOOD-PRESSURE; HEART-FAILURE; CARDIAC-CATHETERIZATION; MYOCARDIAL-INFARCTION; MORPHOLOGIC EVIDENCE; BALLOON ANGIOPLASTY AB Background Atherosclerotic renal artery stenosis is a problem with no consensus on diagnosis or therapy. The consequences of renal ischemia are neuroendocrine activation, hypertension, and renal insufficiency that can potentially result in acceleration of atherosclerosis, further renal dysfunction, myocardial infarction, heart failure, stroke, and death. Whether revascularization improves clinical outcomes when compared with optimum medical therapy is unknown. Methods CORAL is a randomized clinical trial contrasting optimum medical therapy alone to stenting with optimum medical therapy on a composite cardiovascular and renal end point: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine, and need for renal replacement therapy. The secondary end points evaluate the effectiveness of revascularization in important subgroups of patients and with respect to all-cause mortality, kidney function, renal artery potency, microvascular renal function, and blood pressure control. We will also correlate stenosis severity with longitudinal renal function and determine the value of stenting from the perspectives of quality of life and cost-effectiveness. The primary entry criteria are (1) an atherosclerotic renal stenosis of >= 60% with a 20 mm Hg systolic pressure gradient or >= 80% with no gradient necessary and (2) systolic hypertension of >= 155 mm Hg on >= 2 anti hypertensive medications. Randomization will occur in 1080 subjects. The study has 90% power to detect a 28% reduction in primary end point hazard rate. Conclusions CORAL represents a unique opportunity to determine the incremental value of stent revascularization, in addition to optimal medical therapy, for the treatment of atherosclerotic renal artery stenosis. C1 Med Univ Ohio, Dept Med, Toledo, OH 43614 USA. Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. Univ Virginia, Charlottesville, VA USA. Univ Minnesota, Minneapolis, MN USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NHLBI, Bethesda, MD 20892 USA. Holy Name Hosp, Teaneck, NJ USA. Boston Univ, Boston, MA 02215 USA. Univ Maryland, Baltimore, MD 21201 USA. RP Cooper, CJ (reprint author), Med Univ Ohio, Dept Med, 3000 Arlington Ave,Hosp Room 1192, Toledo, OH 43614 USA. EM ccooper@mco.edu RI Schulz, Sandra/F-6238-2012 FU NHLBI NIH HHS [HL071556] NR 70 TC 186 Z9 191 U1 0 U2 8 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 JUL PY 2006 VL 152 IS 1 BP 59 EP 66 DI 10.1016/j.ahj.2005.09.011 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 063ZY UT WOS:000239060200008 PM 16824832 ER PT J AU Janardhanan, R Kenchaiah, S Velazquez, EJ Park, Y McMurray, JJV Weaver, WD Finn, PV White, HD Marin-Neto, JA O'Connor, C Pfeffer, MA Califf, RM Solomon, SD AF Janardhanan, Rajesh Kenchaiah, Satish Velazquez, Eric J. Park, Yuhyun McMurray, John J. V. Weaver, W. Douglas Finn, Peter V. White, Harvey D. Marin-Neto, Jose A. O'Connor, Chris Pfeffer, Marc A. Califf, Robert M. Solomon, Scott D. CA VALIANT Invest TI Extent of coronary artery disease as a predictor of outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc ID RISK STRATIFICATION; NATIONAL-REGISTRY; PROGNOSIS; VALSARTAN; SCORE; MODEL AB Background Left ventricular systolic dysfunction (LVSD) and heart failure (HF) are powerful predictors of poor outcome after acute myocardial infarction (MI). It is not known, however, whether the extent of coronary artery disease (CAD) independently influences cardiovascular (CV) outcomes in these high-risk patients. Methods In the Valsortan in Acute Myocardial Infarction Study (VALIANT), 14703 patients were randomly assigned 191 to receive either captopril monotherapy, valsartan monotherapy, or a valsartan and captopril combination between 0.5 14 and 10 days after acute MI complicated by LVSD, HF, or both. Cox proportional hazards models were used to evaluate the 14 relation between the extent of CAD (the number of diseased vessels as assessed by angiography) and a range of CV outcomes and all-cause mortality. Results Coronary angiography data were available on 5742 (40%) of the 14703 randomized patients. Single-vessel disease was reported in 1955 patients (34%), 2-vessel disease in 1598 (28%), and 3-vessel disease in 2189 (38%). For all CV outcomes, the risk increased with the severity of CAD (P for trend <.002). A comparison of single-, 2-, and 3-vessel disease showed that, after adjusting for all known covariates, including revascularization and ejection fraction, 2-vessel disease was associated with a 40% increased hazard (P =.008) and 3-vessel disease was associated with an 85% increased hazard (P <.001) for all-cause mortality. The fully adjusted hazard ratios for death and other CV outcomes increased significantly with increasing extent of CAD. Conclusions increasing extent of CAD, as detected by angiography, is a significant and independent risk factor for adverse CV outcomes after MI complicated by HF, LVSD, or both. The observed risk was apparent even after excluding patients who had undergone revascularization. C1 Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. Duke Univ, Duke Clin Res Inst, Div Cardiol, Durham, NC 27706 USA. Dana Farber Canc Inst, Dept Stat, Boston, MA 02115 USA. Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. Henry Ford Hosp, Div Cardiol, Detroit, MI 48202 USA. Auckland City Hosp, Div Cardiol, Auckland, New Zealand. Univ Sao Paulo, Div Cardiol, BR-05508 Sao Paulo, Brazil. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Solomon, Scott/I-5789-2013; Kenchaiah, Satish/A-1519-2016; OI mcmurray, john/0000-0002-6317-3975 NR 15 TC 9 Z9 10 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 JUL PY 2006 VL 152 IS 1 BP 183 EP 189 DI 10.1016/j.ahj.2005.11.013 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 063ZY UT WOS:000239060200031 PM 16824854 ER PT J AU Lieber, CS Weiss, DG Morgan, TR Paronetto, F AF Lieber, CS Weiss, DG Morgan, TR Paronetto, F TI Aspartate aminotransferase to platelet ratio index in patients with alcoholic liver fibrosis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHRONIC HEPATITIS-C; BIOPSY; CIRRHOSIS; POLYENYLPHOSPHATIDYLCHOLINE; VARIABILITY; FIBROTEST; DIAGNOSIS; DISEASE; TESTS; APRI AB OBJECTIVE: Aspartate aminotransferase (AST) to platelet ratio index (APRI) has been proposed as an easily determined and accurate noninvasive marker of liver fibrosis in chronic hepatitis C. To validate APRI in hepatitis C and to determine its usefulness in other liver diseases, we evaluated APRI in patients with liver fibrosis due to excessive alcohol consumption with or without viral hepatitis C. METHODS: A total of 1,308 subjects from two VA cooperative studies of alcoholic liver disease were evaluated. Liver biopsy was available from 781 noncirrhotic patients while a history of decompensation was present in 527. Alcohol intake was determined by self-report. Hepatitis C was confirmed by PCR. RESULTS: Ninety-eight percent were men with a mean age of 51.5 yr. Alcohol intake averaged 19 drinks/day for 20.6 yr. One hundred thirty-three (10.2%) were hepatitis C positive. In the HCV-positive subgroup, APRI had a sensitivity of 35.6% and a specificity of 29.7% for significant fibrosis. Of 64 patients classified as significant fibrosis, 21 (32.8%) were incorrectly classified. In the 507 HCV negative patients with biopsy confirmed fibrosis, the sensitivity of APRI for significant fibrosis was 13.2% and the specificity was 77.6%. Twenty percent were classified incorrectly. CONCLUSION: APRI has low sensitivity and specificity for the diagnosis of significant fibrosis in patients with alcoholic liver disease, including patients who have hepatitis C. Given the frequent history of alcohol use in patients with hepatitis C, APRI may be of limited usefulness in the diagnosis of fibrosis in many patients. C1 James J Peters VA Med Ctr, Alcohol Dependency Treatment Practice, Bronx, NY 10468 USA. James J Peters VA Med Ctr, Ctr Alcohol Res & Treatment, Sect Liver Dis & Nutr, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Vet Affaird Maryland Hlth Care Syst, Perry Point, MD USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. Univ Calif Irvine, Sch Med, Div Gastroenterol, Irvine, CA 92717 USA. RP Lieber, CS (reprint author), James J Peters VA Med Ctr, Alcohol Dependency Treatment Practice, 151-2,130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA014326] NR 21 TC 54 Z9 56 U1 0 U2 2 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 JUL PY 2006 VL 101 IS 7 BP 1500 EP 1508 DI 10.1111/j.1572-0241.2006.00610.x PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 058GU UT WOS:000238654300016 PM 16863553 ER PT J AU Monto, A Kakar, S Dove, LM Bostrom, A Miller, EL Wright, TL AF Monto, A Kakar, S Dove, LM Bostrom, A Miller, EL Wright, TL TI Contributions to hepatic fibrosis in HIV-HCV coinfected and HCV monoinfected patients SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CO-INFECTED PATIENTS; LIVER FIBROSIS; ANTIRETROVIRAL THERAPY; PROGRESSION; IMPACT; STEATOSIS; CIRRHOSIS; ALCOHOL; DISEASE AB OBJECTIVES: The aim of this study was to further explore the severity of liver disease and its predictors in a cohort of hepatitis C virus (HCV) infected patients, some of whom were coinfected with the human immunodeficiency virus (HIV). METHODS: This is a retrospective, cross-sectional study of patients undergoing liver biopsy to stage HCV disease prior to consideration of anti-HCV therapy. RESULTS: A total of 92 HIV-HCV coinfected and 372 HCV monoinfected patients were included. As might be expected, coinfected patients differed from monoinfected patients in a number of ways, including having lower body mass index (BMI), and lower alcohol intake. Liver disease was very similar between the two groups, with mean fibrosis score of 1.45 u for coinfected and 1.53 u for monoinfected (p = NS). Histological inflammation score dominated multivariate models of fibrosis when it was included in them. When only clinical predictors were used in multivariate models, BMI and type 2 diabetes had independent associations in monoinfected patients, whereas low CD4 count, current or nadir, was the only variable with an independent association in coinfected patients. CONCLUSIONS: Coinfected patients do not have uniformly worse liver disease than monoinfected patients. Immune compromise plays an important role in liver disease in coinfected patients, and the role of other clinical factors in liver disease may differ between these two groups, as well. C1 San Francisco Vet Affairs Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, Gastroenterol Sect, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Monto, A (reprint author), San Francisco Vet Affairs Med Ctr, Dept Pathol, 4150 Clement St,111B, San Francisco, CA 94121 USA. FU NIDA NIH HHS [DA-13737] NR 21 TC 21 Z9 21 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 JUL PY 2006 VL 101 IS 7 BP 1509 EP 1515 DI 10.1111/j.1572-0241.2006.00613.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 058GU UT WOS:000238654300017 PM 16863554 ER PT J AU Reddy, D Siegel, CA Sands, BE Kane, S AF Reddy, D Siegel, CA Sands, BE Kane, S TI Possible association between isotretinoin and inflammatory bowel disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACNE AB OBJECTIVES: The Physician's Desk Reference lists inflammatory bowel disease (IBD) as a possible adverse event associated with the use of isotretinoin, a popular acne prescription medication. Our aim was to perform a systematic examination of reports of IBD associated with isotretinoin use. METHODS: All reports filed with the Food and Drug Administration (FDA) via the MedWatch system were requested and reviewed. Strength of causality was determined using the Naranjo adverse drug reaction (ADR) probability scale. RESULTS: All of the adverse reports filed with the FDA between 1997 and 2002 were accessed and reviewed. Eighty-five cases of IBD associated with isotretinoin use were reported. According to the Naranjo ADR probability scale, 4 cases (5%) scored in the "highly probable" range for isotretinoin as the cause of IBD, 58 cases (68%) were "probable," 23 cases (27%) were "possible," and no cases were "doubtful." CONCLUSIONS: In a subgroup of patients, isotretinoin might serve as a trigger for IBD. C1 Univ Chicago, Dept Med, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Siegel, CA (reprint author), Dartmouth Coll, Hitchcock Med Ctr, 1 Med Ctr Dr, Lebanon, NH 03756 USA. NR 19 TC 60 Z9 61 U1 0 U2 3 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 JUL PY 2006 VL 101 IS 7 BP 1569 EP 1573 DI 10.1111/j.1572-0241.2006.00632.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 058GU UT WOS:000238654300025 PM 16863562 ER PT J AU Saxena, R de Bakker, PIW Singer, K Mootha, V Burtt, N Hirschhorn, JN Gaudet, D Isomaa, B Daly, MJ Groop, L Ardlie, KG Altshuler, D AF Saxena, Richa de Bakker, Paul I. W. Singer, Karyn Mootha, Vamsi Burtt, Noel Hirschhorn, Joel N. Gaudet, Daniel Isomaa, Bo Daly, Mark J. Groop, Leif Ardlie, Kristin G. Altshuler, David TI Comprehensive association testing of common mitochondrial DNA variation in metabolic disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID INSULIN-RESISTANCE; PARKINSONS-DISEASE; FRIEDREICHS-ATAXIA; SKELETAL-MUSCLE; POLYMORPHISMS; LONGEVITY; POPULATION; VARIANT; HUMANS; RISK AB Many lines of evidence implicate mitochondria in phenotypic variation: ( a) rare mutations in mitochondrial proteins cause metabolic, neurological, and muscular disorders; ( b) alterations in oxidative phosphorylation are characteristic of type 2 diabetes, Parkinson disease, Huntington disease, and other diseases; and ( c) common missense variants in the mitochondrial genome ( mtDNA) have been implicated as having been subject to natural selection for adaptation to cold climates and contributing to "energy deficiency" diseases today. To test the hypothesis that common mtDNA variation influences human physiology and disease, we identified all 144 variants with frequency > 1% in Europeans from > 900 publicly available European mtDNA sequences and selected 64 tagging single-nucleotide polymorphisms that efficiently capture all common variation ( except the hypervariable D-loop). Next, we evaluated the complete set of common mtDNA variants for association with type 2 diabetes in a sample of 3,304 diabetics and 3,304 matched nondiabetic individuals. Association of mtDNA variants with other metabolic traits ( body mass index, measures of insulin secretion and action, blood pressure, and cholesterol) was also tested in subsets of this sample. We did not find a significant association of common mtDNA variants with these metabolic phenotypes. Moreover, we failed to identify any physiological effect of alleles that were previously proposed to have been adaptive for energy metabolism in human evolution. More generally, this comprehensive association-testing framework can readily be applied to other diseases for which mitochondrial dysfunction has been implicated. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA USA. Univ Montreal, Chicoutimi Hosp, Community Genom Ctr, Montreal, PQ, Canada. Folkhalsan Res Ctr, Folkhalsan Genet Inst, Helsinki, Finland. Malmska Municipal Hlth Ctr & Hosp, Pietarsaari, Finland. Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. RP Altshuler, D (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Sinches Res Bldg,175 Cambridge St,CPZN-6818, Boston, MA 02114 USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858 NR 59 TC 116 Z9 122 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 2006 VL 79 IS 1 BP 54 EP 61 DI 10.1086/504926 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 053YD UT WOS:000238341200006 PM 16773565 ER PT J AU Thamer, M Zhang, Y Kaufman, J Stefanik, K Cotter, DJ AF Thamer, Mae Zhang, Yi Kaufman, James Stefanik, Kevin Cotter, Dennis J. TI Factors influencing route of administration for epoetin treatment among hemodialysis patients in the United States SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE anemia management; pharmacotherapy; route of administration; erythropoietin; clinical guidelines; practice pattern variation; cost savings; cost ID STAGE RENAL-DISEASE; PATIENTS RECEIVING HEMODIALYSIS; INTRAVENOUS EPOETIN; ANEMIA MANAGEMENT; DIALYSIS OUTCOMES; PRACTICE PATTERNS; HEALTH-CARE; ERYTHROPOIETIN; IMPROVEMENT; INDICATORS AB Background Published clinical guidelines advocate subcutaneous (SC) administration for epoetin therapy, although this is practiced among only 7% of all hemodialysis patients. Despite this disparity, few studies have examined factors associated with route of epoetin administration in hemodialysis patients. Methods: Data from the Centers for Medicare & Medicaid Services End-Stage Renal Disease Clinical Performance Measures Project were used to identify 13,854 patients receiving hemodialysis in 3,069 dialysis facilities from October to December in 1999 and 2000. Unadjusted associations were examined by using t-test and chi-square test. Adjusted associations were estimated by using generalized estimating equations to control for clustering of patients within the same dialysis facility. Results: In the United States, use of the SC route of epoetin administration varies widely across the country. After adjusting for patient sociodemographics and comorbidities, the greatest rates of SC therapy are found in the Midwest and West, in providers not affiliated with chains, and in hospital-based and not-for-profit freestanding units. Previous exposure to SC administration (as a predialysis or peritoneal dialysis patient) predicted subsequent SC use, for-profit and large chains were significantly less likely to use SC administration, and increased use of injectable drugs overall (to maximize income) was associated with less SC use. Conclusion: In addition to regional variation in SC use, study findings indicate that physician decision making for epoetin administration route is influenced primarily by type of ownership and financial incentives. Adherence to published clinical guidelines was not a consistent predictor of SC use. Given the similar effectiveness, but significantly decreased dose associated with SC epoetin, these findings suggest an enormous opportunity for cost savings for the Medicare program. C1 Med Technol & Practice Patterns Inst, Bethesda, MD 20814 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Cotter, DJ (reprint author), Med Technol & Practice Patterns Inst, 4733 Bethesda Ave,Ste 510, Bethesda, MD 20814 USA. EM dcott@mtppi.org FU NIDDK NIH HHS [R01-DK066011-01A2] NR 48 TC 11 Z9 11 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2006 VL 48 IS 1 BP 77 EP 87 DI 10.1053/j.ajkd.2006.03.040 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 060UD UT WOS:000238826200009 PM 16797389 ER PT J AU Painter, P Johansen, KL AF Painter, Patricia Johansen, Kirsten L. TI Improving physical functioning: Time to be a part of routine care SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID EXERCISE CAPACITY; HEMODIALYSIS; DIALYSIS; MORTALITY; SURVIVAL; ASSOCIATION; PATIENT; PROGRAM; HEALTH C1 Univ Minnesota, Dept Internal Med, Div Renal Dis & Hypertens, Minneapolis, MN 55455 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. RP Painter, P (reprint author), Univ Minnesota, Dept Internal Med, Div Renal Dis & Hypertens, Minneapolis, MN 55455 USA. NR 26 TC 33 Z9 34 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2006 VL 48 IS 1 BP 167 EP 170 DI 10.1053/j.ajkd.2006.05.004 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 060UD UT WOS:000238826200021 PM 16797401 ER PT J AU Delea, TE Karnon, J Smith, RE Johnston, SRD Brandman, J Sung, JCY Goss, PE AF Delea, Thomas E. Karnon, Jonathan Smith, Robert E. Johnston, Stephen R. D. Brandman, Jane Sung, Jennifer C. Y. Goss, Paul E. TI Cost-effectiveness of extended adjuvant letrozole therapy after 5 years of adjuvant tamoxifen therapy in postmenopausal women with early-stage breast cancer SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article; Proceedings Paper CT 27th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX ID ISOLATED LOCOREGIONAL RECURRENCE; RANDOMIZED-TRIAL; AMERICAN-SOCIETY; HORMONAL-THERAPY; LOCAL RECURRENCE; UPDATED FINDINGS; ELDERLY-WOMEN; HIP FRACTURE; PHASE-III; FOLLOW-UP AB Objective: To estimate the cost-effectiveness of extended adjuvant letrozole in postmenopausal women with early breast cancer and estrogen or progesterone receptor-positive tumors who had completed 5 years of adjuvant tamoxifen. Study Design: Cost-effectiveness analysis using a Markov model. Methods: Using a Markov model, we estimated the incremental cost per quality-adjusted life-year (QALY) gained with extended adjuvant letrozole vs no extended adjuvant therapy. Probabilities of breast cancer recurrence or new contralateral tumor adverse effects and death were estimated using data from the MA.17 study and other secondary sources. Costs (in 2004 US dollars) and quality-of-life effects (utilities) of breast cancer events and adverse effects were derived from the literature. Results: In base-case analyses, extended adjuvant letrozole vs no extended adjuvant therapy results in an expected gain of 0.34 QALYs per patient (13.62 vs 13.28 QALYs), at an additional lifetime cost of $9699 per patient ($55 254 vs $45 555). The incremental cost per QALY gained with letrozole is $28 728. Cost-effectiveness is sensitive to the assumed reduction in risk of breast cancer events with letrozole but is insensitive to the risks, costs, and quality-of-life effects of osteoporosis and hip fracture. Cost-effectiveness is less than $100 000 per QALY for node-positive patients younger than 81 years and for node-negative patients younger than 73 years. Conclusion: For postmenopausal women with early breast cancer who have completed 5 years of adjuvant tamoxifen, the cost-effectiveness of extended adjuvant letrozole is within the range of other generally accepted medical interventions in the United States. C1 Policy Analysis Inc, MSIA, Brookline, MA 02245 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Sheffield, Sch Hlth & Related Res, Sheffield, S Yorkshire, England. Royal Marsden Hosp, Dept Med, London SW3 6JJ, England. S Carolina Oncol Assoc, Columbia, SC USA. Novartis Pharmaceut, Florham Pk, NJ USA. Novartis Pharmaceut, E Hanover, NJ USA. RP Delea, TE (reprint author), Policy Analysis Inc, MSIA, 4 Davis Court, Brookline, MA 02245 USA. EM tdelea@pai2.com NR 56 TC 28 Z9 28 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2006 VL 12 IS 7 BP 374 EP 386 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 063WR UT WOS:000239051100004 PM 16834524 ER PT J AU Menon, V Rumsfeld, JS Roe, MT Cohen, MG Peterson, ED Brindis, RG Chen, AY Pollack, CV Smith, SC Gibler, WB Ohman, EM AF Menon, Venu Rumsfeld, John S. Roe, Matthew T. Cohen, Mauricio G. Peterson, Eric D. Brindis, Ralph G. Chen, Anita Y. Pollack, Charles V., Jr. Smith, Sidney C., Jr. Gibler, W. Brian Ohman, E. Magnus TI Regional outcomes after admission for high-risk non ST-segment elevation acute coronary syndromes SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE acute coronary syndromes; non-ST elevation myocardial infarction; outcomes; regional variation ID ACUTE MYOCARDIAL-INFARCTION; COOPERATIVE CARDIOVASCULAR PROJECT; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; MEDICARE BENEFICIARIES; THROMBOLYTIC THERAPY; AMERICAN-COLLEGE; UNSTABLE ANGINA; CARE; MANAGEMENT AB PURPOSE: An analysis of reginal variation across the United States in the treatment and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) has not been previously performed. SUBJECTS AND METHODS: We assessed contemporary practice and outcomes in 56,466 high-risk patients with NSTE ACS (positive cardiac markers and/or ischemic ST-segment changes) admitted to 310 hospitals across four defined regions in the United States from January 1, 2001, to September 30, 2003. Patient clinical characteristics, acute (< 24 hours) and discharge medications, in-hospital procedures, and in-hospital case-fatality rates were evaluated. RESULTS: Statistically significant but clinically small differences in baseline characteristics including age, gender, rates of diabetes, hypertension, and smoking, as well as medical treatment, including a greater than 5% variation in acute use of beta-blockers, clopidogrel, and statins use, were noted across regions. Adjusted rates of revascularization were similar across regions. Overall in-hospital case- fatality rate was 4.1%, with the highest rates in the Midwest (4.6%) and the lowest in the Northeast (3.5%). Adjusted odds ratios (OR) (95% confidence interval [CI] for death were significantly higher in the Midwest (OR 1.42, CI 1.19-1.70), West (OR 1.40 CI 1.05-1.87), and South (OR 1.33, CI 1.08-1.62), compared with the Northeast. CONCLUSIONS: Management of high-risk patients with NSTE ACS is relatively uniform across the United States. However, in-hospital case- fatality rates vary significantly by region, and the differences are not explained by adjustment for standard clinical variables. (c) 2006 Elsevier Inc. All rights reserved. C1 Cleveland Clin Fdn, Dept Cardiol, Cleveland, OH 44195 USA. Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. Duke Univ, Med Ctr, Div Cardiol, Durham, NC USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Univ N Carolina, Sch Med, Div Cardiol, Chapel Hill, NC USA. Oakland Kaiser Permanente Hosp, San Francisco, CA USA. Univ Penn, Sch Med & Dent, Dept Emergency Med, Philadelphia, PA 19104 USA. Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH USA. RP Menon, V (reprint author), Cleveland Clin Fdn, Dept Cardiol, 9500 Euclid Ave,F-15, Cleveland, OH 44195 USA. EM menonv@ccf.org OI Cohen, Mauricio/0000-0003-2038-6070 NR 17 TC 8 Z9 8 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2006 VL 119 IS 7 BP 584 EP 590 DI 10.1016/j.amjmed.2006.01.018 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 060XP UT WOS:000238835500010 PM 16828630 ER PT J AU Gulati, A Sullivan, R Buring, JE Sullivan, DA Dana, R Schaumberg, DA AF Gulati, Abha Sullivan, Rose Buring, Julie E. Sullivan, David A. Dana, Reza Schaumberg, Debra A. TI Validation and repeatability of a short questionnaire for dry eye syndrome SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; OPTOMETRIC PRACTICES; SYMPTOMS; SIGNS; ASSOCIATION; POPULATION; EPIDEMIOLOGY; PREVALENCE; ASPIRIN; HEALTH AB PURPOSE: To clinically validate and ascertain the re peatability of a short questionnaire for dry eye syndrome (DES), consisting of two questions pertaining to symptoms (dryness and irritation) and one question regarding previous history of clinically diagnosed DES. DESIGN: Clinical validation study with repeated assessments. METHODS: A short questionnaire for DES was administered to participants of two large cohort studies, the Women's Health Study (WHS) and the Physicians' Health Study (PHS). A supplementary questionnaire comprising 16 questions pertaining to symptoms was mailed to a subset of 450 WHS and 240 PHS participants, selected so that a third of these subjects had DES based on their response to the short questionnaire. Repeatability of the dryness and irritation symptom questions was ascertained using intraclass correlation coefficient (ICC). Standardized ophthalmologic examination was performed on 53 subjects. Sensitivity and specificity of the short questionnaire was determined using a combination of clinical tests to define clinical DES. RESULTS: An ICC of 0.75 for dryness and 0.65 for irritation was found between subsequent measurements. Participants' responses to the dryness and irritation questions were highly correlated (r = 0.75) with a score derived from responses to the longer 16-symptom questionnaire. The short questionnaire for DES had a sensitivity of 77% and specificity of 83% when cutoff point for clinical DES was Schirmer 1 value :5 10 mm or tear breakup time < 10 seconds. CONCLUSION: The short questionnaire for DES is a sensitive and repeatable tool that is easy to administer in large epidemiologic research studies as well as clinical research. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Schepens Eye Res Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm, Boston, MA 02215 USA. RP Schaumberg, DA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM dschaumberg@rics.bwh.harvard.edu FU NCI NIH HHS [CA47988, CA40360]; NHLBI NIH HHS [HL43851] NR 27 TC 43 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2006 VL 142 IS 1 BP 125 EP 131 DI 10.1016/j.ajo.2006.02.038 PG 7 WC Ophthalmology SC Ophthalmology GA 064HF UT WOS:000239079100017 PM 16815260 ER PT J AU Brodsky, JR Smith, TW Litofsky, S Lee, DJ AF Brodsky, Jacob R. Smith, Thomas W. Litofsky, Scott Lee, Daniel J. TI Lipoma of the cerebellopontine angle SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID NONACOUSTIC TUMORS; ACOUSTIC NERVE; INNER-EAR; MR AB Lipomas of the cerebellopontine angle (CPA) are unusual tumors that typically present with hearing loss, tinnitus, dizziness, and occasionally facial neuropathies. We describe the case of a healthy 42-year-old woman who presented with left-sided hearing loss and facial synkinesis. T1-weighted magnetic resonance imaging revealed an enhancing lesion of the left CPA with no signal on fat suppression sequences. Despite conservative therapy, the patient developed progressive hemifacial spasm, and a suboccipital craniotomy approach was used to debulk the tumor, which encased cranial nerves V, VII, VIII, IX, X, and XI. Surgical histopathology demonstrated mature adipocytes, consistent with lipoma. Two years after surgery, the patient remains free of facial nerve symptoms. Cerebellopontine angle lipomas are rare lesions of the skull base and are reliably diagnosed with T1-weighted and fat suppression magnetic resonance sequences, which we recommend in the routine radiologic workup of CPA tumors. Accurate preoperative diagnosis is crucial because most CPA lipomas should be managed conservatively. Partial surgical resection is indicated only to alleviate intractable cranial neuropathies or relieve brainstem compression. (C) 2006 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Sch Med, Dept Otolaryngol, Worcester, MA USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. Univ Missouri, Sch Med, Div Neurol Surg, Columbiaville, MI USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Lee, DJ (reprint author), UMass Mem Med Ctr, Dept Otolaryngol, 55 Lake Ave N, Worcester, MA 01655 USA. EM djlee@massmed.org OI Litofsky, N. Scott/0000-0001-6373-7462 NR 17 TC 13 Z9 14 U1 0 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JUL-AUG PY 2006 VL 27 IS 4 BP 271 EP 274 DI 10.1016/j.amjoto.2005.11.002 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 062ZH UT WOS:000238985000012 PM 16798407 ER PT J AU Schnapp, LM Donohoe, S Chen, JZ Sunde, DA Kelly, PM Ruzinski, J Martin, T Goodlett, DR AF Schnapp, LM Donohoe, S Chen, JZ Sunde, DA Kelly, PM Ruzinski, J Martin, T Goodlett, DR TI Mining the acute respiratory distress syndrome proteome: Identification of the insulin-like growth factor (IGF)/IGF-binding protein-3 pathway in acute lung injury SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BRONCHOALVEOLAR LAVAGE FLUID; IDIOPATHIC PULMONARY-FIBROSIS; TANDEM MASS-SPECTROMETRY; III PROCOLLAGEN PEPTIDE; IGF BINDING PROTEIN-3; FACTOR-I; FIBROBLAST PROLIFERATION; NEUTROPHIL APOPTOSIS; STATISTICAL-MODEL; CELL APOPTOSIS AB To obtain a more complete protein profile of the airspace milieu in acute respiratory distress syndrome (ARDS) and to identify new mediators, we analyzed bronchoalveolar lavage fluid (BALF) by shotgun proteomics. Using BALF from three patients, we identified a total of 870 different proteins, a nearly 10-fold increase from previous reports. Among the proteins identified were known markers of lung injury, such as surfactant, proteases, and serum proteins. We also identified several biologically interesting proteins not previously identified in patients with ARDS, including insulin-like growth factor-binding protein-3 (IGFBP-3). Because of the known role of IGFBP-3 in regulating cell survival, we measured IGFBP-3 levels by enzyme-linked imnumosorbent assay in ARDS BALF. Normal controls had low levels of IGFBP-3, whereas patients with early ARDS had a significant increase in IGFBP-3. The IGF pathway, acting through the type 1 IGF-receptor, repressed apoptosis of lung fibroblasts but not lung epithelial cells. Furthermore, depletion of IGF in ARDS BALF led to enhanced fibroblast apoptosis. Our data suggest that the IGFBP-3/IGF pathway is involved in the pathogenesis of lung injury, illustrating the power of shotgun proteomics to catalog proteins present in complex biological fluids, such as BALF, from which hypotheses can be developed and tested. C1 Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. Inst Syst Biol, Seattle, WA USA. Univ Washington, Dept Med Chem, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA USA. RP Schnapp, LM (reprint author), Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, 325 9Th Ave, Seattle, WA 98104 USA. EM lschnapp@u.washington.edu FU NHLBI NIH HHS [N01HV28179, P50 HL073996, R01 HL073028, R01 HL73028, N01-HV-28179]; NIAID NIH HHS [1U54AI57141-01, U54 AI057141]; NIEHS NIH HHS [5P30ES007033-10, P30 ES007033] NR 51 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2006 VL 169 IS 1 BP 86 EP 95 DI 10.2353/ajpath.2006.050612 PG 10 WC Pathology SC Pathology GA 058KU UT WOS:000238664700008 PM 16816363 ER PT J AU Cattaruzza, F Cenac, N Barocelli, E Impicciatore, M Hyun, E Vergnolle, N Sternini, C AF Cattaruzza, F Cenac, N Barocelli, E Impicciatore, M Hyun, E Vergnolle, N Sternini, C TI Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; GENE-RELATED PEPTIDE; MAST-CELL TRYPTASE; NITRIC-OXIDE; MOLECULAR-CLONING; SUBSTANCE-P; NECROTIZING ENTEROCOLITIS; PARACELLULAR PERMEABILITY; NEUROGENIC MECHANISM; SUGGESTIVE EVIDENCE AB We hypothesized that proteinase-activated receptor-2 (PAR(2)) modulates intestinal injuries induced by ischemia/reperfusion. Ischemia (I hour) plus reperfusion (6 hours) significantly delayed gastrointestinal transit (GIT) compared with sham operation. Intraduodenal injection of PAR(2)-activating peptide SLIGRL-NH2 Significantly accelerated transit in ischemia/reperfusion but not in sham-operated rats. GIT was significantly delayed in ischemia/reperfusion and sham-operated PAR(2)(-/-) mice compared with PAR(2)(+/+) SIJGRL-NH2 Significantly accelerated transit in ischemia/reperfusion in PAR2+/+ but not in PAR(2)(+/+) mice. Prevention of mast cell degranulation with cromolyn, ablation of visceral afferents; with capsaicin, and antagonism of calcitonin gene-related peptide (CGRP) and neurokinin-1 receptors with CGRP(8-37) and RP67580, respectively, abolished the SLIGRL-NH2-induced stimulatory effect on transit in ischemia/reperfusion. Tissue damage was significantly reduced by SLIGRL-NH2; this effect was not observed in cromolyn-, capsaicin-, or RP67580-treated rats but was detected following CGRP(8-37). lntestinal PARI mRNA levels were not affected by SLIGRL-NH2 in ischemia/reperfusion. We propose that PAR2 modulates GIT and tissue damage in intestinal ischemia/reperfusion by a mechanism dependent on mast cells and visceral afferents. PAR, effect on transit might be mediated by CGRP and substance P, whereas the effect on tissue damage appears to involve substance P but not CGRP. PAR, might he a signaling system in the neuroimmune communication in intestinal ischemia/reperfusion. C1 Vet Affairs Greater Los Angeles Hlth Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Div Digest Dis, Dept Med, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Div Digest Dis, Dept Neurobiol, David Geffen Sch Med, Los Angeles, CA USA. Univ Calgary, Dept Pharmacol & Therapeut, Calgary, AB, Canada. Univ Parma, Dept Pharmacol Biol & Appl Chem Sci, I-43100 Parma, Italy. RP Sternini, C (reprint author), Vet Affairs Greater Los Angeles Hlth Syst, 11301 Wilshire Blvd,CURE Bldg 115,Rm 224, Los Angeles, CA 90073 USA. EM csternin@ucla.edu RI Barocelli, Elisabetta/C-4509-2013 FU NCI NIH HHS [F32 CA090073]; NIDDK NIH HHS [DK 41301, DK 51455, DK 57037] NR 67 TC 39 Z9 42 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2006 VL 169 IS 1 BP 177 EP 188 DI 10.2353/ajpath.2006.051098 PG 12 WC Pathology SC Pathology GA 058KU UT WOS:000238664700016 PM 16816371 ER PT J AU Selim, AA Mahon, M Juppner, H Bringhurst, FR Divieti, P AF Selim, AA Mahon, M Juppner, H Bringhurst, FR Divieti, P TI Role of calcium channels in carboxyl-terminal parathyroid hormone receptor signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE calcium influx; osteocytes ID PEPTIDE RECEPTOR; CELLS; EXPRESSION; REGION; FRAGMENTS; METABOLISM; BINDING; MUSCLE AB Parathyroid hormone (PTH), an 84-amino acid polypeptide, is a major systemic regulator of calcium homeostasis that activates PTH/PTHrP receptors (PTH1Rs) on target cells. Carboxyl fragments of PTH (CPTH), secreted by the parathyroids or generated by PTH proteolysis in the liver, circulate in blood at concentrations much higher than intact PTH-(1-84) but cannot activate PTH1Rs. Receptors specific for CPTH fragments (CPTHRs), distinct from PTH1Rs, are expressed by bone cells, especially osteocytes. Activation of CPTHRs was previously reported to modify intracellular calcium within chondrocytes. To further investigate the mechanism of action of CPTHRs in osteocytes, cytosolic free calcium concentration ([Ca2+](i)) was measured in the PTH1R-null osteocytic cell line OC59, which expresses abundant CPTHRs but no PTH1Rs. [Ca2+](i) was assessed by single-cell ratiometric microfluorimetry in fura-2-loaded OC59 cells. A rapid and transient increase in [Ca2+](i) was observed in OC59 cells in response to the CPTH fragment hPTH-(53-84) (250 nM). No [Ca2+](i) signal was observed in COS-7 cells, in which CPTHR binding also cannot be detected. Neither hPTH-(1-34) nor a mutant CPTH analog, [Ala(55-57)]hPTH-(53-84), that does not to bind to CPTHRs, increased [Ca2+](i) in OC59 cells. The [Ca2+](i) response to hPTH-(53-84) required the presence of extracellular calcium and was blocked by inhibitors of voltage-dependent calcium channels (VDCCs), including nifedipine (100 nM), omega-agatoxin IVA (10 nM), and omega-conotoxin GVIA (100 nM). We conclude that activation of CPTHRs in OC59 osteocytic cells leads to a rapid increase in influx of extracellular calcium, most likely through the opening of VDCCs. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Divieti, P (reprint author), Massachusetts Gen Hosp, Endocrine Unit, W501, Boston, MA 02114 USA. EM divieti@helix.mgh.harvard.edu FU NIAMS NIH HHS [AR-47062]; NIDDK NIH HHS [DK-65032, DK-02889] NR 29 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 2006 VL 291 IS 1 BP C114 EP C121 DI 10.1152/ajpcell.00566.2005 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 053EI UT WOS:000238287500014 PM 16687470 ER PT J AU Aschenbach, WG Ho, RC Sakamoto, K Fujii, N Li, YF Kim, YB Hirshman, MF Goodyear, LJ AF Aschenbach, WG Ho, RC Sakamoto, K Fujii, N Li, YF Kim, YB Hirshman, MF Goodyear, LJ TI Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3 beta signaling pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin; Wnt; Akt; protein kinase C; glycogen-synthase kinase-3 beta ID GLYCOGEN-SYNTHASE KINASE-3-BETA; DIFFERENTIAL REGULATION; MYOTUBE HYPERTROPHY; KINASE 3-BETA; INSULIN; AKT; ACTIVATION; PHOSPHORYLATION; EXPRESSION; AXIN AB Regulation of Dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3 beta signaling pathway. Am J Physiol Endocrinol Metab 291: E152-E158, 2006. First published February 14, 2006; doi: 10.1152/ajpendo. 00180.2005.-beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3 beta (GSK-3 beta). In skeletal muscle, both insulin and exercise decrease GSK-3 beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin. Immunoblotting demonstrated that Dvl, Axin, GSK-3 beta, and beta-catenin proteins are expressed in rat red and white gastrocnemius muscles. Treadmill running exercise in vivo significantly decreased beta-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. beta-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r(2) = 0.84, P < 0.001). beta-Catenin dephosphorylation was accompanied by increases in GSK-3 beta Ser(9) phosphorylation and Dvl- GSK-3 beta association. In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl- GSK-3 beta interaction. In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3 beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Res Div,Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Res Div,Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [R01-AR-42238, F32-AR-049662]; NIDDK NIH HHS [R01-DK-68626, F32-DK-59769] NR 38 TC 18 Z9 20 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2006 VL 291 IS 1 BP E152 EP E158 DI 10.1152/ajpendo.00180.2005 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 057FJ UT WOS:000238581400017 PM 16478782 ER PT J AU Hataishi, R Rodrigues, AC Neilan, TG Morgan, JG Buys, E Shiva, S Tambouret, R Jassal, DS Raher, MJ Furutani, E Ichinose, F Gladwin, MT Rosenzweig, A Zapol, WM Picard, MH Bloch, KD Scherrer-Crosbie, M AF Hataishi, R Rodrigues, AC Neilan, TG Morgan, JG Buys, E Shiva, S Tambouret, R Jassal, DS Raher, MJ Furutani, E Ichinose, F Gladwin, MT Rosenzweig, A Zapol, WM Picard, MH Bloch, KD Scherrer-Crosbie, M TI Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial infarction; cardiac injury; murine model ID ISCHEMIA/REPERFUSION INJURY; EXTRACORPOREAL-CIRCULATION; NEUTROPHIL ADHESION; LEUKOCYTE ADHESION; SUPEROXIDE ANION; NADPH OXIDASE; NO; INHALATION; THERAPY; ENDOTHELIUM AB To learn whether nitric oxide ( NO) inhalation can decrease myocardial ischemia-reperfusion ( I/R) injury, we studied a murine model of myocardial infarction ( MI). Anesthetized mice underwent left anterior descending coronary artery ligation for 30, 60, or 120 min followed by reperfusion. Mice breathed NO beginning 20 min before reperfusion and continuing thereafter for 24 h. MI size and area at risk were measured, and left ventricular ( LV) function was evaluated using echocardiography and invasive hemodynamic measurements. Inhalation of 40 or 80 ppm, but not 20 ppm, NO decreased the ratio of MI size to area at risk. NO inhalation improved LV systolic function, as assessed by echocardiography 24 h after reperfusion, and systolic and diastolic function, as evaluated by hemodynamic measurements 72 h after reperfusion. Myocardial neutrophil infiltration was reduced in mice breathing NO, and neutrophil depletion prevented inhaled NO from reducing myocardial I/R injury. NO inhalation increased arterial nitrite levels but did not change myocardial cGMP levels. Breathing 40 or 80 ppm NO markedly and significantly decreased MI size and improved LV function after ischemia and reperfusion in mice. NO inhalation may represent a novel method to salvage myocardium at risk of I/R injury. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-42397, HL-70896, HL-57172] NR 49 TC 79 Z9 80 U1 0 U2 6 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 JUL PY 2006 VL 291 IS 1 BP H379 EP H384 DI 10.1152/ajpheart.01172.2005 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 052VR UT WOS:000238262500047 PM 16443673 ER PT J AU Milan, DJ Jones, IL Ellinor, PT MacRae, CA AF Milan, DJ Jones, IL Ellinor, PT MacRae, CA TI In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE repolarization; arrhythmia ID PROPRANOLOL; DISEASE; REPOLARIZATION; EXERCISE; HEART AB In the last decade the zebrafish has become a major model organism for the study of development and organogenesis. To maximize the experimental utility of this organism, it will be important to establish methods for adult phenotyping. We previously proposed that the embryonic zebrafish may be useful in high-throughput screening for drug-induced cardio-toxicity. We now describe a method for the reproducible recording of the adult zebrafish ECG and illustrate its application in the investigation of QT-prolonging drugs. Zebrafish ECGs were obtained by inserting two needle electrodes through the ventral epidermis. Fish were perfused orally, and motion artifacts were eliminated with a paralytic dose of mu-conotoxin GIIIB. Test compounds were delivered via the perfusion system. Without a means of hydration and oxygenation, the fish succumb rapidly. The use of a perfusion system allowed stable recording for > 6 h. Baseline conduction intervals were as follows: PR, 66 ms (SD 14); QRS, 34 ms (SD 11); QT, 242 ms (SD 54); and R-R, 398 ms (SD 77). The known QT-prolonging agents astemizole, haloperidol, pimozide, and terfenadine caused corrected QT increases of 18% (SD 9), 16% (SD 11), 17% (SD 9), and 11% (SD 6), respectively. The control drugs clonidine, penicillin and propranolol did not prolong the corrected QT interval. In conclusion, perfusion and muscular paralysis allows stable, low-noise recording of zebrafish ECGs. Agents known to cause QT prolongation in humans caused QT prolongation in fish in each case. The development of rigorous tools for the phenotyping of adult zebrafish will complement the high-throughput assays currently under development for embryonic and larval fish. C1 Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP MacRae, CA (reprint author), Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. EM cmacrae@partners.org FU NHLBI NIH HHS [HL-071632, HL-075431, HL-076361, K08 HL076361]; NIGMS NIH HHS [R21 GM075946] NR 19 TC 86 Z9 91 U1 3 U2 16 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 JUL PY 2006 VL 291 IS 1 BP H269 EP H273 DI 10.1152/ajpheart.00960.2005 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 052VR UT WOS:000238262500035 PM 16489111 ER PT J AU Russo, LM Mckee, M Brown, D AF Russo, Leileata M. McKee, Mary Brown, Dennis TI Methyl-beta-cyclodextrin induces vasopressin-independent apical accumulation of aquaporin-2 in the isolated, perfused rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE diabetes insipidus; collecting duct; endocytosis; immunocytochemistry; aquaporin recycling ID NEPHROGENIC DIABETES-INSIPIDUS; RENAL EPITHELIAL-CELLS; WATER CHANNEL; PLASMA-MEMBRANE; AQP2; PHOSPHORYLATION; ENDOCYTOSIS; EXPRESSION; TISSUE AB Vasopressin increases urine concentration by stimulating plasma membrane accumulation of aquaporin-2 (AQP2) in collecting duct principal cells, allowing bulk water flow across the collecting duct from lumen to interstitium down an osmotic gradient. Mutations in the vasopressin type 2 receptor (V2R) cause hereditary X-linked nephrogenic diabetes insipidus (NDI), a disease characterized by excessive urination and dehydration. Recently, we showed that inhibition of endocytosis by the cholesterol-depleting drug methyl-beta-cyclodextrin (m beta CD) induces plasma membrane accumulation of AQP2 in transfected renal epithelial cells overexpressing epitope-tagged AQP2. Here, we asked whether m beta CD could induce membrane accumulation of AQP2 in situ using the isolated, perfused kidney (IPK). By immunofluorescence and electron microscopy, we show that AQP2 was shifted from a predominantly intracellular localization to the apical membrane of principal cells following 1-h perfusion of Sprague-Dawley rat kidneys with 5 mM m beta CD. Quantification of staining revealed that the intensity of AQP2 was increased from 647 +/- 114 (control) to 1,968 +/- 299 units (m beta CD; P < 0.001), an effect similar to that seen after perfusion with 4 nM dDAVP (1,860 +/- 298, P < 0.001). Similar changes were observed following m beta CD perfusion of kidneys from vasopressin-deficient Brattleboro rats. No effect of m beta CD treatment on the basolateral distribution of AQP3 and AQP4 was detected. These data indicate that AQP2 constitutively recycles between the apical membrane and intracellular vesicles in principal cells in situ and that inducing apical AQP2 accumulation by inhibiting AQP2 endocytosis is a feasible goal for bypassing the defective V2R signaling pathway in X-linked NDI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Simches Res Ctr,Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Russo, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Simches Res Ctr,Program Membrane Biol, 185 Cambridge St,Rm 8100, Boston, MA 02114 USA. EM leileata.russo@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK-43341, DK-38452, DK-57521] NR 35 TC 27 Z9 28 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2006 VL 291 IS 1 BP F246 EP F253 DI 10.1152/ajprenal.00437.2005 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 050XB UT WOS:000238121900026 PM 16449354 ER PT J AU Inagami, S Cohen, DA Finch, BK Asch, SM AF Inagami, Sanae Cohen, Deborah A. Finch, Brian Karl Asch, Steven M. TI You are where you shop - Grocery store locations, weight, and neighborhoods SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SOCIOECONOMIC DIFFERENCES; MULTILEVEL ANALYSIS; RISK-FACTORS; ENVIRONMENT; SUPERMARKETS; DEPRIVATION; CONSUMPTION; MORTALITY; PREGNANCY; OBESITY AB Background: Residents in poor neighborhoods have higher body mass index (BMI) and eat less healthfully. One possible reason might be the quality of available foods in their area. Location of grocery stores where individuals shop and its association with BMI were examined. Methods: The 2000 U.S. Census data were linked with the Los Angeles Family and Neighborhood Study (L.A.FANS) database, which consists of 2620 adults sampled from 65 neighborhoods in Los Angeles County between 2000 and 2002. In 2005, multilevel linear regressions were used to estimate the associations between BMI and socioeconomic characteristics of grocery store locations after adjustment for individual-level factors and socioeconomic characteristics of residential neighborhoods. Results: Individuals have higher BMI if they reside in disadvantaged areas and in areas where the average person frequents grocery stores located in more disadvantaged neighborhoods. Those who own cars and travel farther to their grocery stores also have higher BMI. When controlling for grocery store census tract socioeconomic status (SES), the association between residential census tract SES and BMI becomes stronger. Conclusions: Where people shop for groceries and distance traveled to grocery stores are independently associated with BMI. Exposure to grocery store mediates and suppresses the association of residential neighborhoods with BMI and could explain why previous studies may not have found robust associations between residential neighborhood predictors and BMI. C1 VA Greater Los Angeles Hlth Care Syst, Vet Affairs Hlth Serv & Res Dev, Div Gen Int Med 111G, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. San Diego State Univ, Social Sci Res Lab, San Diego, CA 92182 USA. RP Inagami, S (reprint author), VA Greater Los Angeles Hlth Care Syst, Vet Affairs Hlth Serv & Res Dev, Div Gen Int Med 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sinagami@ucla.edu RI Mavoa, Suzanne/B-5372-2010 FU NIMHD NIH HHS [R40MD00303] NR 36 TC 150 Z9 151 U1 2 U2 23 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 JUL PY 2006 VL 31 IS 1 BP 10 EP 17 DI 10.1016/j.amepre.2006.03.019 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 059GM UT WOS:000238721300002 PM 16777537 ER PT J AU Fava, M Rush, AJ Wisniewski, SR Nierenberg, AA Alpert, JE McGrath, PJ Thase, ME Warden, D Biggs, M Luther, JF Niederehe, G Ritz, L Trivedi, MH AF Fava, M Rush, AJ Wisniewski, SR Nierenberg, AA Alpert, JE McGrath, PJ Thase, ME Warden, D Biggs, M Luther, JF Niederehe, G Ritz, L Trivedi, MH CA STAR D Study Team TI A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; TREATMENT-RESISTANT DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; QUALITY-OF-LIFE; REPORT QIDS-SR; QUICK INVENTORY; REMISSION RATES; PSYCHOMETRIC EVALUATION; RATING-SCALE; SYMPTOMATOLOGY AB Objective: Few controlled studies have addressed the issue of which antidepressant medications should be recommended for outpatients who have not responded to multiple treatment trials. This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant ( nortriptyline) following two prospective, consecutive, unsuccessful medication treatments for nonpsychotic major depressive disorder. Method: Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks ( first step) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone ( second step), adult outpatients ( N= 235) with nonpsychotic major depressive disorder were randomly assigned to 14 weeks of treatment with mirtazapine ( up to 60 mg/ day) ( N= 114) or nortriptyline ( up to 200 mg/ day) ( N= 121). The primary outcome, symptom remission, was defined a priori as a total exit score of <= 7 on the 17- item Hamilton Rating Scale for Depression. The 16- item Quick Inventory of Depressive Symptomatology - Self- Report ( QIDS- SR16), obtained at treatment visits, provided secondary outcomes of remission ( score = 5 at exit) and response (= 50% reduction in score from baseline). Results: For mirtazapine, remission rates were 12.3% and 8.0% per the Hamilton and QIDS- SR16 scores, respectively. For nortriptyline, remission rates were 19.8% and 12.4%, respectively. QIDS- SR16 response rates were 13.4% for mirtazapine and 16.5% for nortriptyline. Neither response nor remission rates statistically differed by treatment, nor did these two treatments differ in tolerability or adverse events. Conclusions: Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials resulted in low remission rates (< 20%) among patients with major depressive disorder. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. NIMH, Bethesda, MD 20892 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Bullfinch 351,55 Fruit St, Boston, MA 02114 USA. EM MFava@Partners.org RI Biggs, Dr. Melanie/C-1468-2010; McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 37 TC 152 Z9 153 U1 0 U2 1 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 JUL PY 2006 VL 163 IS 7 BP 1161 EP 1172 DI 10.1176/appi.ajp.163.7.1161 PG 12 WC Psychiatry SC Psychiatry GA 059CX UT WOS:000238712000012 PM 16816220 ER PT J AU Bowden, CL Calabrese, JR Ketter, TA Sachs, GS White, RL Thompson, TR AF Bowden, CL Calabrese, JR Ketter, TA Sachs, GS White, RL Thompson, TR TI Impact of lamotrigine and lithium on weight in obese and nonobese patients with bipolar I disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAINTENANCE AB Objective: This study assessed weight changes in a large cohort of patients with bipolar disorder who were treated with randomly assigned maintenance monotherapies. Method: A post hoc analysis was conducted to assess the effects of lamotrigine, lithium, and placebo administration on body weight in obese and nonobese patients with bipolar disorder from two double-blind, placebo-controlled, 18-month studies. Results: Mean changes in weight among obese patients (N=155) at week 52 were 4.2, +6.1, and -0.6 kg with lamotrigine, lithium, and placebo, respectively (lamotrigine versus lithium and lithium versus placebo). Among nonobese patients (N= 399), mean changes in weight ( kg) at week 52 were -0.5, +1.1, and +0.7 with lamotrigine, lithium, and placebo, respectively, with no significant differences among groups. Conclusions: Obese patients with bipolar I disorder lost weight while taking lamotrigine and gained weight while taking lithium. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Stanford Univ, Med Ctr, Sch Med, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Bowden, CL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM bowdenc@uthscsa.edu NR 10 TC 50 Z9 51 U1 0 U2 2 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 JUL PY 2006 VL 163 IS 7 BP 1199 EP 1201 DI 10.1176/appi.ajp.163.7.1199 PG 3 WC Psychiatry SC Psychiatry GA 059CX UT WOS:000238712000016 PM 16816224 ER PT J AU Silveira, MJ Copeland, LA Feudtner, C AF Silveira, MJ Copeland, LA Feudtner, C TI Likelihood of home death associated with local rates of home birth: Influence of local area healthcare preferences on site of death SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OF-HOSPITAL BIRTHS; PLACE; TRENDS AB Objectives. We tested whether local cultural and social values regarding the use of health care are associated with the likelihood of home death, using variation in local rates of home births as a proxy for geographic variation in these values. Methods. For each of 351110 adult decedents in Washington state who died from 1989 through 1998, we calculated the home birth rate in each zip code during the year of death and then used multivariate regression modeling to estimate the relation between the likelihood of home death and the local rate of home births. Results. Individuals residing in local areas with higher home birth rates had greater adjusted likelihood of dying at home (odds ratio [OR] = 1.04 for each percentage point increase in home birth rate; 95% confidence interval [CI] = 1.03, 1.05). Moreover, the likelihood of dying at home increased with local wealth (OR = 1.04 per $10000; 95% CI = 1.02, 1.06) but decreased with local hospital bed availability (OR = 0.96 per 1000 beds; 95% CI = 0.95, 0.97). Conclusions. The likelihood of home death is associated with local rates of home births, suggesting the influence of health care use preferences. C1 VA Hlth Serv Res & Dev Ctr Excellence, VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Univ Michigan, Div Gen Med, Ann Arbor, MI 48109 USA. Univ Michigan, Bioeth Program, Ann Arbor, MI 48109 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, VERDICT Res Program, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Pediat Generalist Res Grp, Dept Pediat, Ctr Bioeth,Leonard Davis Inst, Philadelphia, PA 19104 USA. RP Silveira, MJ (reprint author), 300 N Ingalls Bldg,Room 7C27,Box 0429, Ann Arbor, MI 48109 USA. EM mariajs@umich.edu FU AHRQ HHS [K08 HS000002, KO8-HS0000002] NR 24 TC 2 Z9 2 U1 2 U2 2 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 JUL PY 2006 VL 96 IS 7 BP 1243 EP 1248 DI 10.2105/AJPH.2005.063057 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 058IO UT WOS:000238658900025 PM 16735639 ER PT J AU Woodworth, BA Lathers, D Neal, JG Skinner, M Richardson, M Young, MR Schlosser, RJ AF Woodworth, Bradford A. Lathers, Deanne Neal, Jeffery G. Skinner, Margaret Richardson, Mary Young, M. Rita Schlosser, Rodney J. TI Immunolocalization of surfactant protein A and D in sinonasal mucosa SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article ID PSEUDOMONAS-AERUGINOSA; ALVEOLAR MACROPHAGES; HOST-DEFENSE; IN-VIVO; EXPRESSION; LOCALIZATION; PHAGOCYTOSIS; COLLECTINS; CELLS; INFECTION AB Background: Surfactant-associated proteins (SP) A and D are in the family of collectin proteins that play an integral part in the innate defense system. SP-A and SP-D expression and function are altered in a variety of inflammatory and infectious diseases of the lungs, such as asthma, allergies, and cystic fibrosis. Our prior studies are the first to identify the presence of these proteins in the human sinonasal cavity. The objective of this study was to immunolocalize SP-A and SP-D in human sinonasal tissue. Methods: Sinonasal mucosal biopsies were performed in patients with various forms of chronic hyperplastic rhinosinusitis with nasal polyposis and nondiseased mucosa from patients undergoing transsphenoidal hypophysectomy. (n = 10) Immunolocalization of surfactant proteins was performed with antibodies to SP-A and SP-D using immunoperoxidase staining technique, Isotype-negative controls were performed on all, specimens. Results: Analyses of mucosal biopsy specimens from human sinonasal tissue reveals staining within respiratory and intermediate (metaplastic)-type surface unit. In addition, staining was intense in the submucosal ductal epithelium of the seromucinous glands. These properties appear to be consistent regardless of disease state and location within the sinuses. Conclusion: This is the first study to immunolocalize SP-A and SP-D in sinonasal human mucosa. These are secreted proteins that are intricately involved in innate immunity in the lungs. Their secretion in the upper airway indicates that future studies may allow manipulation of these proteins and development of novel treatments for sinonasal pathology. C1 Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med & Immunol, 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 Woodworth, BA (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Suite 1130,POB 250550, Charleston, SC 29425 USA. EM woodwort@musc.edu NR 27 TC 24 Z9 27 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD JUL-AUG PY 2006 VL 20 IS 4 BP 461 EP 465 DI 10.2500/ajr.2006.20.2892 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 077RJ UT WOS:000240047200019 PM 16955780 ER PT J AU Golshan, M Miron, A Nixon, AJ Garber, JE Cash, EP Iglehart, JD Harris, JR Wong, JS AF Golshan, M Miron, A Nixon, AJ Garber, JE Cash, EP Iglehart, JD Harris, JR Wong, JS TI The prevalence of germline BRCA1 and BRCA2 mutations in young women with breast cancer undergoing breast-conservation therapy SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE breast cancer; BRCA1; BRCA2; prior probability; breast conservation ID FOLLOW-UP; STAGE-I; MASTECTOMY; GENE; CARRIERS AB Background: Germline mutations of BRCA1 and BRCA2 increase the risk for breast cancer. Mutation carriers selecting breast-conservation therapy (BCT) for treatment of operable breast cancer experience a higher rate of new primary breast cancers. We sought to determine the frequency of BRCA1/BRCA2 mutations in women who underwent BCT. Genetic testing results were compared with the prior probability of mutations in either gene. Methods: Eighty-nine patients age 39 or younger entered the study. Genetic testing was performed for BRCA1 and BRCA2 and the BRCAPRO model determined the probability of carrying a mutation. Results: Eight mutations were discovered (prevalence, 9.0%). Twenty (22%) uncharacterized sequence variants were found. The prior probability of carrying a mutation was 14%. Mutation carriers had a higher prior probability (.49) compared with women with uncharacterized variants (.09) or with normal genes (.11). Conclusions: BRCA1 and BRCA2 mutations are common (9%) among unselected young breast cancer patients undergoing BCT. (c) 2006 Excerpta Medica Inc. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Golshan, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 19 TC 15 Z9 15 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2006 VL 192 IS 1 BP 58 EP 62 DI 10.1016/j.amjsurg.2005.12.005 PG 5 WC Surgery SC Surgery GA 056UB UT WOS:000238549500011 PM 16769276 ER PT J AU Dorfman, DM Brown, JA Shahsafaei, A Freeman, GJ AF Dorfman, DM Brown, JA Shahsafaei, A Freeman, GJ TI Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE non-Hodgkin lymphoma; CD28 family; nodular lymphocyte predominant; Hodgkin lymphoma ID B-CELLS; DENDRITIC CELLS; TRANSCRIPTION FACTOR; EXPRESSION; ACTIVATION; DISEASE; HODGKIN; SUBSET; CD10; BET AB Programmed death-1 (PD-1), a member of the CD28 costimulatory receptor family, is expressed by germinal center-associated T cells in reactive lymphoid tissue. In a study of a wide range of lymphoproliferative disorders, neoplastic T cells in 23 cases of angioimmunoblastic lymphoma were immunoreactive for PD-1, but other subtypes of T cell and B cell non-Hodgkin lymphoma, as well as classic Hodgkin lymphoma, did not express PD-1. The pattern of PD-1 immunostaining of neoplastic cells in angioimmunoblastic lymphoma was similar to that reported for CD10, a recently described marker of neoplastic T cells in angioimmunoblastic lymphoma. Tumor-associated follicular dendritic cells in cases of angioimmunoblastic lymphoma were found to express PD-L1, the PD-1 ligand. In addition, PD-1-positive reactive T cells formed rosettes around neoplastic L&H cells in 14 cases of nodular lymphocyte predominant Hodgkin lymphoma studied. These findings, along with data from previous studies, suggest that angioimmunoblastic lymphoma is a neoplasm of germinal center-associated T cells and that there is an association of germinal center-associated T cells and neoplastic cells in nodular lymphocyte predominant Hodgkin lymphoma. PD-1 is a useful new marker for angioimmunoblastic lymphoma and lends further support to a model of T-cell lymphomagenesis in which specific subtypes of T cells may undergo neoplastic transformation and result in specific, distinct histologic, immunophenotypic, and clinical subtypes of T-cell neoplasia. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Dorfman, DM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ddorfman@partners.org FU NIAID NIH HHS [AI 39671, AI 56299, P01 AI039671, P01 AI039671-04, P01 AI056299, P01 AI056299-01, P01 AI056299-02, P01 AI056299-03] NR 20 TC 181 Z9 192 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 2006 VL 30 IS 7 BP 802 EP 810 DI 10.1097/01.pas.0000209855.28282.ce PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 059OX UT WOS:000238743200003 PM 16819321 ER PT J AU Hoch, BL Nielsen, GP Liebsch, NJ Rosenberg, AE AF Hoch, BL Nielsen, GP Liebsch, NJ Rosenberg, AE TI Base of skull chordomas in children and adolescents - A clinicopathologic study of 73 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE chordoma; skull base; children; adolescents ID INTRACRANIAL CHORDOMA; RADIATION-THERAPY; CRANIAL CHORDOMAS; CLIVUS CHORDOMA; INFANCY; CHILDHOOD; TUMORS; ULTRASTRUCTURE; CHONDROSARCOMA; METASTASIS AB Chordomas in children and adolescents comprise < 5% of all chordomas and most frequently develop in the skull base. These tumors are believed to behave more aggressively than chordomas in adults and may have unusual morphology. This study examines a large series of pediatric skull base chordomas treated with a standardized protocol to characterize the behavior and morphology of these tumors. There were 31 males and 42 females ranging from I to 18 (mean 9.7) years. Forty-two cases (58%) were conventional chordomas, some of which had unusual histopathologic features. Chondroid chordomas comprised 23% of cases. Fourteen tumors (19%) were highly cellular and had a solid growth pattern with no myxoid matrix or lobular architecture. Eight of these had cytologic features of conventional chordoma cells including physaliferous cells (cellular chordoma). The remaining cellular tumors were composed of poorly differentiated epithelioid cells set in a fibrous stroma and lacked physaliferous cells (poorly differentiated chordoma). All variants studied by immunohistochemistry showed positive staining for cytokeratin, epithelial membrane antigen, S100 protein, and vimentin. Mitoses and necrosis were seen in all variants. Follow-up data were available for all patients and ranged from I to 21 (mean 7.25) years. The survival rate was 81%. All but I patient with poorly differentiated chordoma died of disease. Overall, base of skull chordomas in children and adolescents treated with proton beam radiation have better survival than chordomas in adults. However, poorly differentiated chordomas are highly aggressive tumors. C1 Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Hoch, BL (reprint author), Mt Sinai Med Ctr, Dept Pathol, Box 1194,1 Gustave Levy Pl, New York, NY 10029 USA. EM benjamin.hoch@msnyuhealth.org NR 62 TC 42 Z9 45 U1 0 U2 4 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 JUL PY 2006 VL 30 IS 7 BP 811 EP 818 DI 10.1097/01.pas.0000209828.39477.ab PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 059OX UT WOS:000238743200004 PM 16819322 ER PT J AU Davis, LL Frazier, E Husain, MM Warden, D Trivedi, M Fava, M Cassano, P McGrath, PJ Balasubramani, GK Wisniewski, SR Rush, AJ AF Davis, Lori L. Frazier, Elizabeth Husain, Mustafa M. Warden, Diane Trivedi, Madhukar Fava, Maurizio Cassano, Paolo McGrath, Patrick J. Balasubramani, G. K. Wisniewski, Stephen R. Rush, A. John TI Substance use disorder comorbidity in major depressive disorder: A confirmatory analysis of the STAR*D cohort SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; ALCOHOL-USE DISORDERS; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; PSYCHIATRIC-DISORDERS; GENDER DIFFERENCES; QUICK INVENTORY; SYMPTOMATOLOGY; OUTPATIENTS; SCALE AB The demographics and clinical features were compared between those with (29.4%) and without concurrent substance use disorder (SUD) in 2541 outpatients with major depression (MDD) enrolled in the Sequenced Treatment Alternatives to Relieve Depression study. Compared to those without SUD, MDD patients with concurrent SUD were more likely to be younger, male, divorced or never married, and at greater current suicide risk, and have an earlier age of onset of depression, greater depressive symptomatology, more previous suicide attempts, more frequent concurrent anxiety disorders, and greater functional impairment (p = 0.048 to < 0.0001). They were also less likely to be Hispanic and endorse general medical comorbidities (p = 0.006 and 0.002, respectively). C1 VA Med Ctr, Tuscaloosa, AL 35404 USA. Univ Alabama, Birmingham, AL USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. RP Davis, LL (reprint author), VA Med Ctr, 151,3701 Loop Rd E, Tuscaloosa, AL 35404 USA. EM lori.davis@med.va.gov RI Cassano, Paolo/I-6959-2012; McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [N01 MH90003] NR 28 TC 43 Z9 44 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2006 VL 15 IS 4 BP 278 EP 285 DI 10.1080/10550490600754317 PG 8 WC Substance Abuse SC Substance Abuse GA 067BG UT WOS:000239274900003 PM 16867922 ER PT J AU Kane, BJ Zinner, MJ Yarmush, ML Toner, M AF Kane, BJ Zinner, MJ Yarmush, ML Toner, M TI Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes SO ANALYTICAL CHEMISTRY LA English DT Article ID ADULT-RAT HEPATOCYTES; CELL-INTERACTIONS; SANDWICH CONFIGURATION; PRIMARY CULTURES; MAINTENANCE; COCULTURES; CYTOCHROME-P-450; EXPRESSION; FIBROBLASTS; BIOREACTOR AB Nearly half a billion dollars in resources are lost each time a drug candidate is withdrawn from the market by the Food and Drug Administration (FDA) for reasons of liver toxicity. The number of late-phase drug developmental failures due to liver toxicity could potentially be reduced through the use of hepatocyte-based systems capable of modeling the response of in vivo liver tissue to toxic insults. With this article, we report progress toward the goal of realizing an array of primary hepatocytes for use in high-throughput liver toxicity studies. Described herein is the development of a 64 ( 8 x 8) element array of microfluidic wells capable of supporting micropatterned primary rat hepatocytes in coculture with 3T3-J2 fibroblasts. Each of the wells within the array was continuously perfused with medium and oxygen in a nonaddressable format. The key features of the system design and fabrication are described, including the use of two microfluidic perfusion networks to provide the coculture with an independent and continuous supply of cell culture medium and oxygen. Also described are the fabrication techniques used to selectively pattern hepatocytes and 3T3-J2 fibroblasts within the wells of the array. The functional studies used to demonstrate the synthetic and metabolic capacity of the array are outlined in this article. These studies demonstrate that the hepatocytes contained within the array are capable of continuous, steady-state albumin synthesis (78.4 mu g/day, sigma = 3.98 mu g/ day, N = 8) and urea production (109.8 mu g/day, sigma = 11.9 mu g/day, N) 8). In the final section of the article, these results are discussed as they relate to the final goal of this research effort, the development of an array of primary hepatocytes for use in physiologically relevant toxicology studies. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. 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. RP Toner, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM mtoner@sbi.org RI Yu, weiting/I-7417-2013 FU NIBIB NIH HHS [5P41EB002503-02, P41 EB002503]; NIDDK NIH HHS [R01DK43371] NR 30 TC 141 Z9 148 U1 3 U2 39 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 JUL 1 PY 2006 VL 78 IS 13 BP 4291 EP 4298 DI 10.1021/ac051856v PG 8 WC Chemistry, Analytical SC Chemistry GA 058KZ UT WOS:000238665200013 PM 16808435 ER PT J AU Adams, MS Alston, TA Walker, JD AF Adams, Mark S. Alston, Theodore A. Walker, Jennifer D. TI Detection of an III-poised thread of lint by transesophageal echocardiography after aortic valve replacement SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material 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 Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM talston@partners.org NR 2 TC 2 Z9 2 U1 0 U2 3 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 JUL PY 2006 VL 103 IS 1 BP 40 EP 40 DI 10.1213/01.ane.0000221165.57776.c7 PG 1 WC Anesthesiology SC Anesthesiology GA 058JS UT WOS:000238661900006 PM 16790621 ER PT J AU Brosnan, R Gong, D Cotten, J Keshavaprasad, B Yost, CS Eger, EI Sonner, JM AF Brosnan, R Gong, D Cotten, J Keshavaprasad, B Yost, CS Eger, EI Sonner, JM TI Chirality in anesthesia II: Stereoselective modulation of ton-channel function by secondary alcohol enantiomers SO ANESTHESIA AND ANALGESIA LA English DT Article ID GABA(A) RECEPTOR; VOLATILE ANESTHETICS; IN-VIVO; ISOFLURANE; IMMOBILITY; KETAMINE; RATS AB Chirality has been proposed as a means for distinguishing relevant from irrelevant molecular targets of action, but the sensitivity and specificity of this test is unknown for volatile anesthetics. We applied enantiomers of two chiral anesthetic alcohols (2-butanol and 2-pentanol) that are enantioselective for the minimum alveolar concentration (MAC) preventing movement in 50% of animals and one (2-hexanol) that was not to frog oocytes. Each oocyte expressed one of three anesthetic-sensitive ion channels: a Twik-related-spinal cord K+ (TRESK) channel, a gamma-amino butyric acid type A (GABA(A)) receptor and an N-methyl-D-aspartate (NMDA) receptor. Using voltage-clamp techniques, we found that 2-butanol was not enantioselective for any channel (e.g., 16 mM 2-butanol R(-) and S(-) enantiomers decreased current through an NMDA receptors by 44% +/- 3% [mean +/- SE] and 37% +/- 4%, respectively); 2-pentanol was enantioselective for one channel (the GABAA receptor, the enantiomers increasing current by 277% +/- 20% and 141% +/- 30%); 2-hexanol was enantioselective for both GABA(A) and NMDA receptors (e.g., decreasing current through the NMDA receptor by 19% +/- 3% and 43% +/- 5%). We calculated the sensitivity and specificity of chirality as a test of anesthetic relevance under two scenarios: 1) all three channels were relevant mediators of MAC and 2) no channel was a mediator of MAC. These sensitivities and specificities were poor because there is no consistent correspondence between receptor and whole animal results. We recommend that enantioselectivity not be used as a test of relevance for inhaled anesthetic targets. C1 Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA. Univ Texas, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Sonner, JM (reprint author), Univ Calif San Francisco, Dept Anesthesia, S-455I, San Francisco, CA 94143 USA. EM sonnerj@anesthesia.ucsf.edu FU NIGMS NIH HHS [R01 GM069379, T32 GM08440] NR 21 TC 15 Z9 15 U1 1 U2 3 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 JUL PY 2006 VL 103 IS 1 BP 86 EP 91 DI 10.1213/01.ane.0000221437.87338.af PG 6 WC Anesthesiology SC Anesthesiology GA 058JS UT WOS:000238661900018 PM 16790632 ER PT J AU Hong, J Grecu, L AF Hong, J Grecu, L TI Laryngospasm after autologous blood transfusion SO ANESTHESIA AND ANALGESIA LA English DT Article ID FEBRILE; REDUCTION; SURGERY; LEUKOREDUCTION; PLATELETS; PLASMA; CELLS; RBCS AB Although perioperative autologous blood transfusions are associated with few side effects, transfusion reactions can occur and can be life-threatening. We report the occurrence of postoperative laryngospasm in a patient who underwent spinal anesthesia for hip surgery. The laryngospasm. could not be attributed to any cause other than the autologous blood transfusion and recurred when the transfusion was restarted. Laryngospasm was successfully treated both times with positive pressure ventilation. Autologous transfusions can trigger febrile nonhemolytic transfusion reactions, which may result in airway compromise. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Grecu, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM lgrecu@partners.org NR 13 TC 0 Z9 1 U1 0 U2 0 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 JUL PY 2006 VL 103 IS 1 BP 200 EP 202 DI 10.1213/01.ane.0000221443.99505.80 PG 3 WC Anesthesiology SC Anesthesiology GA 058JS UT WOS:000238661900039 PM 16790653 ER PT J AU Becerra, L Harter, K Gonzalez, RG Borsook, D AF Becerra, L Harter, K Gonzalez, RG Borsook, D TI Functional magnetic resonance imaging measures of the effects of morphine on central nervous system circuitry in opioid-naive healthy volunteers SO ANESTHESIA AND ANALGESIA LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN BRAIN ACTIVITY; CEREBRAL-BLOOD-FLOW; REWARD CIRCUITRY; ANALGESIA; STRIATUM; PAIN; ACTIVATION; ADDICTION; HUMANS AB In this pilot study, we used functional magnetic resonance imaging (fMRI) to study the effects of morphine in 8 healthy, opioid-naive volunteers. Intravenous small-dose morphine (4 mg/70 kg) or saline was administered to volunteers undergoing a fMRI scan. Infusion of morphine, but not saline, elicited mild euphoria without aversive symptoms and resulted in positive signal changes in reward structures including the nucleus accumbens, sublenticular extended amygdala, orbitofrontal cortex, and hippocampus. The positive signal in the accumbens was opposite to the signal previously reported for noxious stimuli. Morphine produces a decreased signal in cortical areas in a similar manner to sedative-hypnotic drugs such as propofol or midazolam. Activation in endogenous analgesic regions was observed in the periaqueductal gray, the anterior cingulate gyrus (decreased signal), and hypothalamus (increased signals). The pattern of activation in reward circuitry was similar to that reported for euphoric drugs of abuse, providing a model to evaluate the initial effects of morphine on the central nervous system components of the circuitry involved in addiction. The segregation of fMRI response that was observed in cortical versus subcortical regions suggests a dissociation of reward from sensory-motor and cognitive functions. Activation patterns were opposite to those previously observed for the mu antagonist, naloxone. C1 McLean Hosp, PAIN Grp, Brain Imaging Ctr, Belmont, MA 02478 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Athinoula Martinos Biomed Imaging Ctr, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Athinoula Martinos Biomed Imaging Ctr, Dept Neuroradiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Borsook, D (reprint author), McLean Hosp, PAIN Grp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM dborsook@mclean.harvard.edu FU PHS HHS [13650, 012581] NR 26 TC 73 Z9 77 U1 0 U2 3 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 JUL PY 2006 VL 103 IS 1 BP 208 EP 216 DI 10.1213/01.ane.0000221457.71536.e0 PG 9 WC Anesthesiology SC Anesthesiology GA 058JS UT WOS:000238661900041 PM 16790655 ER PT J AU Tung, RH Camargo, CA Krauser, D Anwaruddin, S Baggish, A Chen, A Januzzi, JL AF Tung, Roderick H. Camargo, Carlos A., Jr. Krauser, Dan Anwaruddin, Saif Baggish, Aaron Chen, Annabel Januzzi, James L., Jr. TI Amino-terminal pro-brain natriuretic peptide for the diagnosis of acute heart failure in patients with previous obstructive airway disease SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY DIAGNOSIS; MORTALITY; DYSPNEA; ENALAPRIL; SURVIVAL; ASTHMA AB Study objective: We evaluate results from amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing with or without those of clinical judgment for the evaluation of dyspneic patients with previous chronic obstructive pulmonary disease or asthma. Methods: As a secondary analysis of previously collected observational data from a convenience sample of 599 breathless patients, 216 patients with previous chronic obstructive pulmonary disease or asthma who presented to the emergency department were analyzed according to results of NT-proBNP, clinical impression, and their final diagnosis. Test performance of NT-proBNP in these patients with chronic obstructive pulmonary disease or asthma was examined for the group as a whole, as well as in patients with and without previous heart failure. NT-proBNP results were compared to clinician-estimated likelihood for heart failure using receiver operating curves and as a function of NT-proBNP plus clinical evaluation. The final diagnosis was determined by 2 independent cardiologists blinded to NT-proBNP using all available data from the 60-day follow-up period. Results: Overall, 55 patients (25%) had acute heart failure; the median value of NT-proBNP was higher in these patients compared with those without acute heart failure (2,238 vs 178 pg/mL); use of cut points of 450 pg/mL for patients younger than 50 years and 900 pg/mL for patients 50 years or older yielded a sensitivity of 87% (95% confidence interval [CI] 72% to 93%) and a specificity of 84% (95% CI 76% to 88%). In patients without previous heart failure (n=164), median NT-proBNP levels were also higher in patients with heart failure of new onset compared with those with chronic obstructive pulmonary disease or asthma exacerbation (1561 versus 168 pg/mL). High clinical suspicion for acute heart failure (probability > 80%) detected only 23% of patients with new-onset heart failure, whereas 82% of these patients had elevated NT-proBNP levels. In patients who had both previous acute heart failure and chronic obstructive pulmonary disease or asthma (n=52), median NT-proBNP levels were significantly higher in those with acute heart failure (4,435 pg/mL) than patients with chronic obstructive pulmonary disease or asthma exacerbation (536 pg/mL). In patients with acute-on-chronic heart failure, NT-proBNP levels were elevated in 91%, whereas clinical impression considered only 39% of cases as high likelihood for acute heart failure. Conclusion: NT-proBNP may be a useful adjunct to standard clinical evaluation of dyspneic patients with previous obstructive airway disease. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Yawkey 5800,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org NR 23 TC 15 Z9 15 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2006 VL 48 IS 1 BP 66 EP 74 DI 10.1016/j.annemergmed.2005.12.022 PG 9 WC Emergency Medicine SC Emergency Medicine GA 059MP UT WOS:000238737200011 PM 16781921 ER PT J AU Camargo, CA Clark, S AF Camargo, Carlos A., Jr. Clark, Sunday TI Increasing diversity among the American College of Epidemiology membership SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE diversity AB PURPOSE: Our objective is to describe the American College of Epidemiology (College) membership, including recent trends in member demographic profile and professional characteristics. METHODS: College members were divided into two groups: i) year 2000 member (i.e., member as of December 31, 2000), and ii) new member admitted into the College between January 1, 2001, and January 1, 2005. The two groups were compared by using descriptive statistics. Proportions are reported with 95% confidence intervals. RESULTS: As of December 31, 2000, there were 859 active members. During the next 48 months, an additional 300 members joined the College. Compared with members on December 31, 2000, new members were younger (57 versus 43 years; p < 0.001). New members also were less likely to be men (66% versus 53%; p = 0.002) and white (87% versus 69%; p < 0.001). The full race/ethnicity breakdown for year 2000 was 87% white, 4% black, 2% Hispanic, and 7% other, whereas that of new members was 69% white, 11% black, 2% Hispanic, and 18% other. CONCLUSIONS: In recent years, the College has become more diverse in terms of sex and race/ethnicity. Continued improvements in membership diversity across these and other domains bode well for the College as it strives to maintain a vital membership base representing all aspects of epidemiology. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 2006 VL 16 IS 7 BP 529 EP 532 DI 10.1016/j.annepidem.2005.10.009 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 062RC UT WOS:000238961200006 PM 16516493 ER PT J AU Cudkowicz, ME Shefner, JM Schoenfeld, DA Zhang, H Andreasson, KI Rothstein, JD Drachman, DB AF Cudkowicz, Merit E. Shefner, Jeremy M. Schoenfeld, David A. Zhang, Hui Andreasson, Katrin I. Rothstein, Jeffrey D. Drachman, Daniel B. CA NE ALS Consortium TI Trial of celecoxib in amyotrophic lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID TRANSGENIC MOUSE MODEL; PROTECTS MOTOR-NEURONS; PGE(2) EP2 RECEPTOR; CEREBRAL-ISCHEMIA; CYCLOOXYGENASE-2 INHIBITORS; ALS PATIENTS; SPINAL-CORD; EXPRESSION; CREATINE; BRAIN AB Objective: To determine whether chronic treatment with celecoxib, a cyclooxygenase-2 inhibitor that has been shown to be beneficial in preclinical testing, is safe and effective in amyotrophic lateral sclerosis (ALS). Methods: A double-blind, placebo-controlled, clinical trial was conducted. Three hundred research subjects with ALS were randomized (2:1) to receive celecoxib (800mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function measured by the maximum voluntary isometric contraction strength. Secondary end points included safety, survival, change in cerebrospinal fluid prostaglandin E, levels, and changes in the rate of decline of leg and grip strength, vital capacity, ALS Functional Rating Scale-Revised, and motor unit number estimates. Results: Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival. Celecoxib was well tolerated and was not associated with an increased frequency of adverse events. Prostaglandin E, levels in cerebrospinal fluid were not elevated at baseline and did not decline with treatment. Interpretation: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800mg/day in ALS are not warranted. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Charlestown, MA 02172 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02172 USA. Upstate Med Univ, Syracuse, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biostat Ctr,Dept Med, Boston, MA USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Cudkowicz, ME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Bldg 149,13th St,Room 2274, Charlestown, MA 02172 USA. EM mcudkowicz@partners.org RI rothstein, jeffrey/C-9470-2013 FU NCRR NIH HHS [M01 RR01032, M01 RR01346, M01-RR-01066, M01-RR02602, M01-RR07122, M01RR00036, M01RR00109, M01RR06192] NR 35 TC 156 Z9 161 U1 0 U2 7 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 JUL PY 2006 VL 60 IS 1 BP 22 EP 31 DI 10.1002/ana.20903 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 060TW UT WOS:000238825500008 PM 16802291 ER PT J AU Ariyarajah, V Apiyasawat, S Spodick, DH AF Ariyarajah, V Apiyasawat, S Spodick, DH TI Optimal P-wave duration for bedside diagnosis of interatrial block SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE interatrial block; P-wave duration; electrocardiogram ID GENERAL-HOSPITAL POPULATION; ATRIAL-FIBRILLATION; PREVALENCE AB Background: Interatrial block (IAB; P wave >= 110 ms) is highly prevalent and associated with atrial tachyarrhythmias, left atrial electromechanical dysfunction and is a potential risk for embolism. Investigators have often used different parameters for P-wave duration to define IAB, and this causes confusion further adding to clinician ignorance of IAB. We therefore appraised the mode P-wave duration in IAB and evaluated the sensitivity and specificity of using previously used durations. Methods: We prospectively evaluated 225 electrocardiograms (ECGs) of patients at a tertiary care general hospital for P-wave duration. Of these, 49 were excluded because of severe motion artifact, errors in lead placement, absence of adequate patient identification, and atrial flutter or fibrillation. Mean, standard error of mean (SEM), standard deviation (SD), mode P-wave duration, specificity, and sensitivity were calculated of the remaining 176 ECGs. Results: From the sample (N = 176; ages 15-95 years; mean +/- SD = 69.15 +/- 16.53 years, female 50.3%), measured P-wave durations ranged from 50 ms to 230 ms (mean +/- SD = 113.75 +/- 30.56 ms, SEM 2.30 ms). 96 patients (54.55%) showed IAB (P wave >= 110 ms) with the mode P-wave duration being 120 ms. Sensitivity and specificity of using P wave >= 110 ms is 100% and 88.9%, respectively (accuracy 94.31%), while P wave >= 130 ms yielded 64% and 100%, respectively (accuracy 82.38%). Conclusions: Mode P-wave duration in IAB is 120 ms, and thus, for all practical reasons, it may be used to clinically diagnose IAB using ECGs recorded at the bedside at 25 mm/s with 10 mm/mV standardization. C1 VA Boston Hlth Care Syst, MAVERIC, Boston, MA 02130 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. St Vincent Hosp, Div Cardiol, Worcester, MA 01604 USA. Univ Massachusetts, Sch Med, Div Cardiovasc Med, Dept Med, Worcester, MA 01605 USA. RP Ariyarajah, V (reprint author), VA Boston Hlth Care Syst, MAVERIC, 150 S Huntington Ave, Boston, MA 02130 USA. EM vignendra@hotmail.com NR 13 TC 10 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JUL PY 2006 VL 11 IS 3 BP 259 EP 262 DI 10.1111/j.1542-474X.2006.00113.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 059QS UT WOS:000238747900010 PM 16846442 ER PT J AU Zeitels, SM Kobler, JB Heaton, JT Faquin, W AF Zeitels, Steven M. Kobler, James B. Heaton, James T. Faquin, William TI Carbon dioxide laser fiber for laryngeal cancer surgery SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the American-Broncho-Esophagological-Association CY MAY 13-14, 2005 CL Boca Raton, FL SP Amer Broncho Esophagol Assoc DE cancer; carbon dioxide laser; glottis; larynx; laser; microlaryngoscopy; photonic bandgap fiber; vocal fold ID CLINICAL EXPERIENCE; CO2-LASER; CARCINOMA AB Objectives: The carbon dioxide laser has evolved to be the premier dissecting instrument for hemostatic cutting during endolaryngeal cancer resection. However, dissection is limited to mirror-reflected line-of-sight delivery of the laser. A recently developed flexible, hollow photonic bandgap fiber (PBF) appears to offer advantages in endolaryngeal dissection. Methods: The suitability of the PBF for human application was evaluated in a canine experiment in which human surgical procedures for microlaryngoscopic en bloc partial laryngectomy were simulated. The specimens that were resected endoscopically and the completion laryngectomy specimen were evaluated histologically. Results: Observations from this experiment revealed that en bloc partial laryngectomy procedures were substantially easier to achieve as compared with prior experience in humans. This improvement resulted from three factors: 1) enhanced tangential dissection due to increased angulation of the laser energy, 2) enhanced procedural orientation due to proprioception of the tissues in contact mode, and 3) improved hemostasis. Histopathologic analysis of the resection margins revealed minimal thermal trauma. Conclusions: The PBF shows substantial promise for human application in endoscopic partial laryngectomy. It will likely enhance the ability of any surgeon to extend his or her indications for performing endoscopic laryngeal cancer resections regardless of philosophy (en bloc resection or piecemeal). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Med Sch, Dept Pathol, 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,11th Floor, Boston, MA 02114 USA. NR 37 TC 21 Z9 21 U1 1 U2 2 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 JUL PY 2006 VL 115 IS 7 BP 535 EP 541 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 064DI UT WOS:000239069000009 PM 16900808 ER PT J AU Gelber, RP McCarthy, EP Davis, JW Seto, TB AF Gelber, RP McCarthy, EP Davis, JW Seto, TB TI Ethnic disparities in breast cancer management among Asian Americans and Pacific Islanders SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE breast cancer; ethnicity; disease management; Pacific Islanders; Asian Americans ID CONSERVING SURGERY; REGISTRY DATA; WOMEN; CARCINOMA; SURVIVAL; STAGE; VALIDATION; QUALITY; TRIALS; TRENDS AB Background: Little is known about breast cancer management among Asian Americans and Pacific Islanders (AAPI). Methods: We performed a retrospective analysis of 2030 women (935 Japanese, 144 Chinese, 235 Filipino, 293 Hawaiian, and 423 white; mean age +/- SD, 59 +/- 13 years) with a diagnosis of early breast cancer (stages I, II, and IIIA) in Hawaii from 1995 to 2001. We linked data from the Surveillance, Epidemiology, and End Results program's Hawaii Tumor Registry to administrative health care claims. We evaluated (1) breast-conserving surgery (BCS); (2) radiotherapy after BCS; and (3) chemotherapy for node-positive disease. We used logistic regression to examine the association between AAPI ethnicity and treatment, adjusting for age, year, rural residence, tumor size, grade, nodal status, receptor status, prior cancer, comorbidity index, health plan type, and income. Results: Overall, 60.3% of women had stage I disease, 36.8% had stage II, and 2.9% had stage IIIA. Only 55.6% received BCS, and 85.1% of these women also received radiation. Of those with nodal involvement (n = 521), 82.7% received chemotherapy. Japanese and Filipino women were significantly less likely than white women to undergo BCS (for Japanese: adjusted odds ratio, 0.62; 95% confidence interval, 0.48-0.80; for Filipinos: adjusted odds ratio, 0.47; 95% confidence interval, 0.33-0.66). Filipinos tended to be less likely than white women to receive radiation after BCS (adjusted odds ratio, 0.80; 95% confidence interval, 0.42-1.49). AAPI women were as likely as white women to receive adjuvant chemotherapy for nodal spread. Conclusions: We found disparities in the management of early-stage breast cancer among AAPI women, particularly among Japanese and Filipinos. Further study is needed to determine the reasons for the observed disparities and to understand their effect on health outcomes. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96813 USA. Harvard Univ, Sch Med, Dept Med,Div Gen Med & Primary Care, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Hawaii Med Serv Assoc, Honolulu, HI 96814 USA. Queens Med Ctr, Ctr Best Healthcare Practice, Honolulu, HI 96813 USA. RP Gelber, RP (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, 150 S Huntington Ave,151MAV, Boston, MA 02130 USA. EM rgelber@hsph.harvard.edu FU AHRQ HHS [R24 HS11627] NR 26 TC 16 Z9 16 U1 0 U2 1 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 JUL PY 2006 VL 13 IS 7 BP 977 EP 984 DI 10.1245/ASO.2006.08.036 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 055MH UT WOS:000238454300012 PM 16788760 ER PT J AU Schumacher, HR Becker, MA Wortmann, RL Lloyd, E MacDonald, PA Joseph-Ridge, N AF Schumacher, H. R. Becker, M. A. Wortmann, R. L. Lloyd, E. MacDonald, P. A. Joseph-Ridge, N. TI The focus trial 48-month interim analysis: Long-term clinical outcomes of treatment with febuxostat in subjects with gout in an ongoing phase 2, open-label extension study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2006) CY JUN 21-24, 2006 CL Amsterdam, NETHERLANDS C1 Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Oklahoma, Tulsa, OK USA. TAP, Lake Forest, England. NR 2 TC 2 Z9 3 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2006 VL 65 SU 2 BP 93 EP 93 PG 1 WC Rheumatology SC Rheumatology GA 209ET UT WOS:000249372500276 ER PT J AU Kay, J Matteson, EL Dasgupta, B Nash, P Durezs, P Hall, S Han, J Rahman, MU AF Kay, J. Matteson, E. L. Dasgupta, B. Nash, P. Durezs, P. Hall, S. Han, J. Rahman, M. U. TI Das28 responses in patients with active rheumatoid arthritis who received golimumab and methotrexate: A randomized, double-blind, placebo-controlled phase 2 trial SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2006) CY JUN 21-24, 2006 CL Amsterdam, NETHERLANDS C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. Mayo Coll Med, Div Rheumatol, Rochester, MN USA. Southend Hosp, Dept Rheumatol, Westcliff S East, England. Clin Univ St Luc, Serv Rhumatol, B-1200 Brussels, Belgium. Carini Med Ctr, Melbourne, Vic, Australia. Centocor Res & Dev Inc, Malvern, PA USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2006 VL 65 SU 2 BP 323 EP 323 PG 1 WC Rheumatology SC Rheumatology GA 209ET UT WOS:000249372501306 ER PT J AU Becker, MA Schumacher, HR Wortmann, RL Lloyd, E Streit, J Joseph-Ridge, N AF Becker, M. A. Schumacher, H. R. Wortmann, R. L. Lloyd, E. Streit, J. Joseph-Ridge, N. TI The long-term clinical benefits of febuxostat vs allopurinol in subjects with gout: Interim analysis of the excel trial, an ongoing phase 3, open-label extension study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2006) CY JUN 21-24, 2006 CL Amsterdam, NETHERLANDS C1 Univ Chicago, Chicago, IL 60637 USA. Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Oklahoma, Tulsa, OK USA. TAP, Lake Forest, IL USA. NR 0 TC 1 Z9 1 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 JUL PY 2006 VL 65 SU 2 BP 431 EP 431 PG 1 WC Rheumatology SC Rheumatology GA 209ET UT WOS:000249372501662 ER PT J AU Rashad, SMOH Schumacher, RH Williams, GH Mahmoud, EABD AF Rashad, S. M. O. H. Schumacher, R. H. Williams, G. H. Mahmoud, E. A. B. D. TI A calcified intraarticular mass in a man with severe shoulder osteoarthritis. What are the implications? SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2006) CY JUN 21-24, 2006 CL Amsterdam, NETHERLANDS C1 Assiut Univ Hosp, Assiut, Egypt. Univ Penn, Sch Med, Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 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 JUL PY 2006 VL 65 SU 2 BP 436 EP 437 PG 2 WC Rheumatology SC Rheumatology GA 209ET UT WOS:000249372501682 ER PT J AU Cho, MH Malhotra, A Donahue, DM Wain, JC Harris, RS Karmpaliotis, D Patel, SR AF Cho, MH Malhotra, A Donahue, DM Wain, JC Harris, RS Karmpaliotis, D Patel, SR TI Mechanical ventilation and air leaks after lung biopsy for acute respiratory distress syndrome SO ANNALS OF THORACIC SURGERY LA English DT Article ID VOLUME REDUCTION SURGERY; RANDOMIZED-TRIAL; PULMONARY LOBECTOMY; SEVERE EMPHYSEMA; BAROTRAUMA; PREDICTORS; SUCTION; ARDS; MANAGEMENT; INJURY AB Background. Open lung biopsy in acute respiratory distress syndrome (ARDS) may provide a specific etiology and change clinical management, yet concerns about complications remain. Persistent air leak is the most common postoperative complication. Risk factors in this setting are not known. Methods. We performed a retrospective analysis of 53 patients who underwent open lung biopsy for clinical ARDS (based on American European Consensus Conference criteria) between 1989 and 2000. Results. Sixteen patients (30.2%) developed an air leak lasting more than 7 days or died with an air leak. Univariate analyses showed no significant correlation with age, gender, sex, corticosteroid use, diabetes, immunocompromised status, or pathologic diagnosis. A lower risk of air leak was associated with lower peak airway pressure and tidal volume, use of pressure-cycled ventilation, and use of an endoscopic stapling device. In multivariate analyses, only peak airway pressure remained a significant predictor. The risk of prolonged air leak was reduced by 42% (95% confidence interval [CI: 17% to 60%]) for every 5 cm H2O reduction in peak airway pressure. Conclusions. The use of a lung-protective ventilatory strategy that limits peak airway pressures is strongly associated with a reduced risk of postoperative air leak after open lung biopsy in ARDS. Using such a strategy may allow physicians to obtain information from open lung biopsy to make therapeutic decisions without undue harm to ARDS patients. C1 Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Hosp Cleveland, Div Pulm & Crit Care, Cleveland, OH USA. RP Cho, MH (reprint author), Brookline Ave KS-B23, Boston, MA 02215 USA. EM mcho@bidmc.harvard.edu OI Patel, Sanjay/0000-0002-9142-5172 FU NHLBI NIH HHS [R01 HL073146, R01 HL073146-02]; NIA NIH HHS [K23 AG024837, K23 AG024837-02] NR 29 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2006 VL 82 IS 1 BP 261 EP 267 DI 10.1016/j.athoracsur.2006.02.022 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 056KL UT WOS:000238521600041 PM 16798226 ER PT J AU Gaissert, HA Grillo, HC Shadmehr, MB Wright, CD Gokhale, M Wain, JC Mathisen, DJ AF Gaissert, HA Grillo, HC Shadmehr, MB Wright, CD Gokhale, M Wain, JC Mathisen, DJ TI Uncommon primary tracheal tumors SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 10-12, 2005 CL Orlando, FL SP So Thorac Surg Assoc ID EXPERIENCE; MANAGEMENT; CARCINOMA; RESECTION; CARINA; TREE AB Background. Primary tracheal tumors other than adenoid cystic or squamous cell carcinoma are uncommon and have a heterogeneous histologic appearance. The experience regarding their treatment and long-term outcome is limited, and alternatives to segmental tracheal resection, including endoscopic treatment or radiation, continue to be explored. Mrthods. A retrospective analysis was performed of uncommon tracheal tumors among 360 primary tracheal tumors seen over 40 years, excluding adenoid cystic and squamous cell carcinoma. Results. Of 90 patients, 34 (38%) had benign tumors and 56 malignant: 11 carcinoid tumors, 14 mucoepidermoid carcinomas, 13 sarcomas, 15 nonsquamous bronchogenic carcinomas, 2 lymphomas, and 1 melanoma. Three patients had a second tracheal malignancy. Dyspnea was the most common symptom in benign tumors and hemoptysis in malignant tumors. Twelve patients did not undergo tracheal resection (13.3%) and 1 died before resection. Surgical therapy in 77 patients (85%) consisted of laryngectomy in 3, laryngotracheal resection in 9, tracheal resection in 46, and carinal resection in 19. Hospital mortality was 2.6% (2 of 77 patients) and major complications occurred in 16% (12 of 77 patients). Mean follow-up was 9.7 years. After resection, survival at 10 years was 94% for benign and 83% for carcinoid tumors, and at 5 years survival was 60% for bronchogenic carcinoma, 100% for mucoepidermoid tumors, and 78% for sarcomas. Patients with lymphomas and melanoma are alive more than 8 years after resection. Ten patients experienced recurrence (14%). Conclusions. Surgical resection of uncommon primary tracheal tumors alleviates airway obstruction, is curative in patients with benign or slow-growing malignant lesions, and prolongs survival in highly malignant lesions. C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Clin Effect Surg, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Policy Anal Inc, Brookline, MA USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org OI shadmehr, mohammad behgam/0000-0002-3303-6750 NR 14 TC 39 Z9 50 U1 0 U2 5 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 JUL PY 2006 VL 82 IS 1 BP 268 EP 273 DI 10.1016/j.athoracsur.2006.01.065 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 056KL UT WOS:000238521600042 PM 16798228 ER PT J AU Keith, RL Geraci, MW Nana-Sinkam, SP Breyer, RM Hudish, TM Meyer, AM Malkinson, AM Dwyer-Nield, LD AF Keith, Robert L. Geraci, Mark W. Nana-Sinkam, S. Patrick Breyer, Richard M. Hudish, Tyler M. Meyer, Amy M. Malkinson, Alvin M. Dwyer-Nield, Lori D. TI Prostaglandin E-2 receptor subtype 2 (EP2) null mice are protected against murine lung tumorigenesis SO ANTICANCER RESEARCH LA English DT Article DE EP2; two-stage carcinogenesis; chronic pulmonary inflammation; downstream prostaglandin receptors ID BUTYLATED HYDROXYTOLUENE BHT; PHASE-II TRIAL; PULMONARY INFLAMMATION; COLON CARCINOGENESIS; CANCER CELLS; RECEPTOR; CELECOXIB; E-2; EXPRESSION; CYCLOOXYGENASE-2 AB Background: Manipulating prostaglandin (PG) production modulates tumor development. Elevated PGI(2) production prevents murine lung cancer, while decreasing PGE(2) content protects against colon cancer. PGE(2) receptor subtype 2 (EP2)-deficient mice were hypothesized to be resistant to lung tumorigenesis. Materials and Methods: EP2 null BALB/c mice and their wild-type littermates were exposed to an initiation-promotion carcinogenesis protocol and lung tumorigenesis was examined. Chronic lung inflammation was induced to determine whether EP2 ablation influenced inflammatory cell infiltration. Results: Tumor multiplicity in EP2 null mice was 34% lower than in their wild-type littermates (21.9 +/- 3.0 vs. 14.5 +/- 2.9 tumors/mouse,p < 0.001). The lung tumor burden, anindicator of growth rate, also declined (57%, p < 0.05). All the mice exhibited similar inflammatory cell infiltration. Conclusion: PGE(2), acting through EP2, enhanced lung tumorigenesis through a mechanism that may be distinct from its pro-inflammatory activity. Thus, EP2 is a potential target for novel chemoprevention strategies. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA. Denver VA Med Ctr, Div Pulm Sci & Crit Care Med, Dept Med, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Dept Med, Denver, CO 80262 USA. Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37232 USA. RP Dwyer-Nield, LD (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, 4200 E 9th Ave, Denver, CO 80262 USA. FU NCI NIH HHS [CA 33497] NR 43 TC 16 Z9 16 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 2006 VL 26 IS 4B BP 2857 EP 2861 PG 5 WC Oncology SC Oncology GA 096QJ UT WOS:000241391600011 PM 16886605 ER PT J AU Fox, JG Taylor, NS Howe, S Tidd, M Xu, S Paster, BJ Dewhirst, FE AF Fox, James G. Taylor, Nancy S. Howe, Shelly Tidd, Michele Xu, Shilu Paster, Bruce J. Dewhirst, Floyd E. TI Helicobacter anseris sp nov and Helicobacter brantae sp nov., isolated from feces of resident Canada geese in the greater Boston area SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID CAMPYLOBACTER-JEJUNI; SWINE FECES; PYLORI; CANADENSIS; PREVALENCE; PULLORUM; PHYLOGENY; PATHOGEN; CANCER; HUMANS AB Numbers of nonmigratory Canada geese have increased substantially in the past decade, and they have become a nuisance in some urban areas. Because of their close contact with humans in parks and areas adjacent to surface waterways, contact with their feces poses a zoonotic risk. A total of 97 geese from 10 separate geographic locales in the greater Boston area had their feces sampled for detection of Helicobacter spp. Identification of Helicobacter spp. based on 16S rRNA genus-specific helicobacter primers was noted in 39 of 97 (40.2%) DNA fecal extracts. Twenty-seven (27.8%) of these geese had helicobacters isolated from their feces. A urease-positive novel species, Helicobacter anseris, based on phenotypic, biochemical, and 16S rRNA analyses, was isolated from 20 geese from seven different flocks. A second, novel, urease-negative Helicobacter sp., H. brantae, was identified in seven geese. Four geese had both novel Helicobacter spp. cultured from their feces. Whether these two novel helicobacters pose a zoonotic risk, similar to other enteric helicobacters (e.g., H. canadensis, previously isolated from diarrheic and bacteremic humans and from geese in Europe), will require further studies. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Mass Ave,Bldg 16,Room 825C, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NCI NIH HHS [CA067529, R01 CA067529]; NCRR NIH HHS [T32 RR007036, RR007036]; NIAID NIH HHS [AI0150952]; NIDCR NIH HHS [R01 DE010374, DE10374, R01 DE011443, DE11443] NR 23 TC 15 Z9 18 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2006 VL 72 IS 7 BP 4633 EP 4637 DI 10.1128/AEM.02876-05 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 062RA UT WOS:000238961000018 PM 16820454 ER PT J AU Custo, A Wells, WM Barnett, AH Hillman, EMC Boas, DA AF Custo, Anna Wells, William M., III Barnett, Alex H. Hillman, Elizabeth M. C. Boas, David A. TI Effective scattering coefficient of the cerebral spinal fluid in adult head models for diffuse optical imaging SO APPLIED OPTICS LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; PHOTON MIGRATION; MONTE-CARLO; EXPERIMENTAL VALIDATION; OXYGEN-SATURATION; LIGHT TRANSPORT; BREAST-CANCER; IN-VIVO; TOMOGRAPHY; MAMMOGRAPHY AB An efficient computation of the time-dependent forward solution for photon transport in a head model is a key capability for performing accurate inversion for functional diffuse optical imaging of the brain. The diffusion approximation to photon transport is much faster to simulate than the physically correct radiative transpart equation (RTE); however, it is commonly assumed that scattering lengths must be much smaller than all system dimensions and all absorption lengths for the approximation to be accurate. Neither of these conditions is satisfied in the cerebrospinal fluid (CSF). Since line-of-sight distances in the CSF are small, of the order of a few millimeters, we explore the idea that the CSF scattering coefficient may be modeled by any value from zero up to the order of the typical inverse line-of-sight distance, or approximately 0.3 mm(-1), without significantly altering the calculated detector signals or the partial path lengths relevant for functional measurements. We demonstrate this in detail by using a Monte Carlo simulation of the RTE in a three-dimensional head model based on clinical magnetic resonance imaging data, with realistic optode geometries. Our findings lead us to expect that the diffusion approximation will be valid even in the presence of the CSF, with consequences for faster solution of the inverse problem. (c) 2006 Optical Society of America. C1 MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Engn, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Custo, A (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM custom@csail.mit.edu RI Hillman, Elizabeth/B-9854-2009; OI Hillman, Elizabeth M. C./0000-0001-5511-1451 FU NCRR NIH HHS [P41-RR14075]; NIBIB NIH HHS [R01-EB002482] NR 51 TC 66 Z9 66 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 2006 VL 45 IS 19 BP 4747 EP 4755 DI 10.1364/AO.45.004747 PG 9 WC Optics SC Optics GA 058LG UT WOS:000238665900031 PM 16799690 ER PT J AU Belogrudov, GI AF Belogrudov, GI TI Bovine factor B: Cloning, expression, and characterization SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE factor B; energy coupling; proton leaks vicinal dithiol; mitochondria; oxidative phosphorylation; ATP synthase ID MITOCHONDRIAL ATP SYNTHASE; COUPLING FACTOR-B; F-1-ATPASE; PROTEIN; PHOSPHORYLATION; INHIBITOR; SEQUENCE AB Bovine factor B, a polypeptide required for the coupled activity of the mitochondrial ATP synthase complex, was cloned. A novel expression system for overproducing the recombinant bovine factor B was developed, which yielded the recombinant polypeptide at a level of 12-15 mg of protein per liter of bacterial culture. Reconstitution of the recombinant polypeptide with factor B-depleted ammonia, EDTA-treated submitochondrial particles (AE-SMP) restored the formation of substrate-driven Delta pH gradient across vesicular membranes, presumably by blocking a proton leak. The proton leak in the AE-SMP could also be blocked by the F-0 inhibitors oligomycin and dicyclohexylcarbodiimide, but not the F-1-ATPase inhibitors efrapeptin and aurovertin B. The six factor B thiols titrated rapidly with Ellman's reagent, and two of these, presumably Cys92 and Cys94, gained protection following treatment of factor B with a vicinal dithiol-specific reagent phenylarsine oxide (PAO). Similarly, Cd, whose binding to factor B is believed to also involve a vicinal dithiol, and PAO, protected similar to 2 Cys residues against labeling with sulfhydryl-specific fluorescent reagent fluorescein-5'-maleimide. The circular dichroism spectra showed that binding of Cd2+ and Zn2+, but not Ca2+ to bovine factor B caused small but reproducible changes in the secondary structure elements of the polypeptide. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Belogrudov, GI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM gbclo@ucla.edu FU NIGMS NIH HHS [GM66085] NR 21 TC 8 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 1 PY 2006 VL 451 IS 1 BP 68 EP 78 DI 10.1016/j.abb.2006.02.021 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 060IT UT WOS:000238796600009 PM 16579955 ER PT J AU Profit, J Zupancic, JAF McCormick, MC Richardson, DK Escobar, GJ Tucker, J Tarnow-Mordi, W Parry, G AF Profit, J. Zupancic, J. A. F. McCormick, M. C. Richardson, D. K. Escobar, G. J. Tucker, J. Tarnow-Mordi, W. Parry, G. TI Moderately premature infants at Kaiser Permanente Medical Care Program in California are discharged home earlier than their peers in Massachusetts and the United Kingdom SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION LA English DT Article ID NEONATAL INTENSIVE-CARE; MANAGED CARE; NHS; MORTALITY; INDEX; SEVERITY; OUTCOMES; DOLLAR; APNEA; PRICE AB Objective: To compare gestational age at discharge between infants born at 30-34(+6) weeks gestational age who were admitted to neonatal intensive care units (NICUs) in California, Massachusetts, and the United Kingdom. Design: Prospective observational cohort study. Setting: Fifty four United Kingdom, five California, and five Massachusetts NICUs. Subjects: A total of 4359 infants who survived to discharge home after admission to an NICU. Main outcome measures: Gestational age at discharge home. Results: The mean (SD) postmenstrual age at discharge of the infants in California, Massachusetts, and the United Kingdom were 35.9 (1.3), 36.3 (1.3), and 36.3 (1.9) weeks respectively (p = 0.001). Compared with the United Kingdom, adjusted discharge of infants occurred 3.9 (95% confidence interval (CI) 1.4 to 6.5) days earlier in California, and 0.9 (95% CI - 1.2 to 3.0) days earlier in Massachusetts. Conclusions: Infants of 30-34(+6) weeks gestation at birth admitted and cared for In hospitals in California have a shorter length of stay than those in the United Kingdom. Certain characteristics of the integrated healthcare approach pursued by the health maintenance organisation of the NICUs in California may foster earlier discharge. The California system may provide opportunities for identifying practices for reducing the length of stay of moderately premature infants. C1 Childrens Hosp Boston, Harvard Newborn Med Program, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Neonatol, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Dept Vet Affairs, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Kaiser Permanente Med Care Program, Perinatal Res Unit, Oakland, CA 94612 USA. Univ Aberdeen, Dept Obstet & Gynaecol, Dugald Baird Ctr Res Womens Hlth, Aberdeen AB25 2ZL, Scotland. Univ Sydney, Westmead Hosp, Westmead & Childrens Hosp, Wentworthville, NSW, Australia. Univ Sheffield, Sch Hlth & Related Res, Hlth Serv Res, Sheffield, S Yorkshire, England. RP Profit, J (reprint author), Houston Ctr Qual Care & Utilizat Studies, Div Hlth Policy & Qual, VA HSR&D 152, 2002 Holcombe, Houston, TX 77030 USA. EM profit@bcm.edu OI McCormmick, Marie/0000-0002-3938-1707; Zupancic, John/0000-0003-1734-7193 FU AHRQ HHS [R01 HS010131, R01 HS10131, T32 HS000063] NR 47 TC 17 Z9 17 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1359-2998 J9 ARCH DIS CHILD-FETAL JI Arch. Dis. Child.-Fetal Neonatal Ed. PD JUL PY 2006 VL 91 IS 4 BP F245 EP F250 DI 10.1136/adc.2005.075093 PG 6 WC Pediatrics SC Pediatrics GA 061BI UT WOS:000238845800003 PM 16449257 ER PT J AU Brody, AL Mandelkern, MA Olmstead, RE Scheibal, D Hahn, E Shiraga, S Zamora-Paja, E Farahi, J Saxena, S London, ED McCracken, JT AF Brody, Arthur L. Mandelkern, Mark A. Olmstead, Richard E. Scheibal, David Hahn, Emily Shiraga, Sharon Zamora-Paja, Eleanor Farahi, Judah Saxena, Sanjaya London, Edythe D. McCracken, James T. TI Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 11th Annual Duke Nicotine Research Conference CY NOV 10, 2005 CL Durham, NC ID POSITRON-EMISSION-TOMOGRAPHY; D2 RECEPTOR GENE; RAT NUCLEUS-ACCUMBENS; CEREBRAL-BLOOD-FLOW; FREELY MOVING RATS; CIGARETTE-SMOKING; TRANSPORTER GENE; CONTINUOUS-INFUSION; HEALTHY-VOLUNTEERS; IN-VIVO AB Context: Preclinical studies demonstrate that nicotine administration leads to dopamine release in the ventral striatum. However, human studies reveal considerable interindividual variability in the extent of smoking-induced dopamine release. Objective: To determine whether common gene variants of the brain dopamine pathway explain this observed phenotypic variability in humans. Design: Blood samples were drawn to determine gene variants of dopamine system components, and positron emission tomography scanning with the radiotracer raclopride labeled with radioactive carbon (C-11) was performed to measure smoking-induced dopamine release. Setting: Academic brain imaging center. Participants: Forty-five tobacco-dependent smokers. Interventions: Subjects either smoked a cigarette (n=35) or did not smoke (n=10) during positron emission tomography scanning. Main Outcome Measures: Gene variants of dopamine system components (the dopamine transporter variable nucleotide tandem repeat, D-2 receptor Taq A(1)/A(2), D-4 receptor variable nucleotide tandem repeat, and catechol-O-methyltransferase Val158Met polymorphisms) and change in [C-11] raclopride binding potential in the ventral caudate/nucleus accumbens on positron emission tomography scans. Results: For subjects who smoked during scanning, those with at least one 9 allele of the dopamine transporter variable nucleotide tandem repeat, fewer than 7 repeats of the D-4 variable nucleotide tandem repeat, and the Val/Val catechol-O-methyltransferase genotype had greater decreases in binding potential (an indirect measure of dopamine release) with smoking than those with the alternate genotypes. An overall decrease in ventral caudate/nucleus accumbens binding potential in those who smoked compared with those who did not smoke was also found but was smaller in magnitude than previously reported. Conclusions: Smokers with genes associated with low resting dopamine tone have greater smoking-induced (phasic) dopamine release than those with alternate genotypes. These findings suggest that dopamine system genotype variabilities explain a significant proportion of the interindividual variability in smoking-induced dopamine release and indicate that smoking-induced dopamine release has a genetic predisposition. C1 Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Positron Emiss Tomog Ctr, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, 300 UCLA Med Pl,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU NIDA NIH HHS [R01 DA015059, DA14093, DA20872, R01 DA014093, R01 DA015059-04, R01 DA020872, R01 DA020872-02, R01 DA15059]; NIMH NIH HHS [K24 MH001805, K24 MH01805] NR 98 TC 137 Z9 141 U1 4 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2006 VL 63 IS 7 BP 808 EP 816 DI 10.1001/archpsyc.63.7.808 PG 9 WC Psychiatry SC Psychiatry GA 059RJ UT WOS:000238749600013 PM 16818870 ER PT J AU Peskind, ER Li, G Shofer, J Quinn, JF Kaye, JA Clark, CM Farlow, MR DeCarli, C Raskind, MA Schellenberg, GD Lee, VMY Galasko, DR AF Peskind, Elaine R. Li, Ge Shofer, Jane Quinn, Joseph F. Kaye, Jeffrey A. Clark, Chris M. Farlow, Martin R. DeCarli, Charles Raskind, Murray A. Schellenberg, Gerard D. Lee, Virginia M. -Y. Galasko, Douglas R. TI Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition SO ARCHIVES OF NEUROLOGY LA English DT Article ID AMYLOID-BETA PROTEIN; APOE EPSILON-4 ALLELE; ALZHEIMERS-DISEASE; A-BETA; TAU; CSF; BRAIN; A-BETA-42(43) AB Background: Decreased cerebrospinal fluid (CSF) beta-amyloid 42 (A beta(42)) concentration, but not A beta(40) concentration, is a biomarker for Alzheimer disease. This A beta(42) concentration decrease in CSF likely reflects precipitation of A beta(42) in amyloid plaques in brain parenchyma. This pathogenic plaque deposition begins years before the clinical expression of dementia in Alzheimer disease. Normal aging and the presence of the apolipoprotein E (APOE*4) allele are the most important known risk factors for Alzheimer disease. Objective: To estimate the interactive effects of normal aging and presence of the APOE*4 allele on CSF A beta(42) concentration in adults with normal cognition across the life span. Design: The CSF was collected in the morning after an overnight fast using Sprotte 24-g atraumatic spinal needles. The CSF A beta(42) and A beta(40) concentrations were measured in the 10th milliliter of CSF collected by sandwich enzyme-linked immunosorbent assay. The APOE genotype was determined by a restriction digest method. Subjects: One hundred eighty-four community volunteers with normal cognition aged 21 to 88 years. Results: The CSF A beta(42), but not the A beta(40), concentration decreased significantly with age. There was a sharp decrease in CSF A beta(42) concentration beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF A beta(42) concentration was significantly and substantially greater in subjects with the APOE*4 allele compared with those without the APOE*4 allele. Conclusion: These CSF A beta(42) findings are consistent with acceleration by the APOE*4 allele of pathogenic A beta(42) brain deposition starting in later middle age in persons with normal cognition. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Ctr Geriatr Res Educ & Clin, Sch Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Univ Penn, Dept Neurol, Inst Aging, Philadelphia, PA 19104 USA. Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. VA Med Ctr, San Diego, CA USA. RP Peskind, ER (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, S-116MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM peskind@u.washington.edu RI DeCarli, Charles/B-5541-2009; OI Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [M01 RR00034]; NIA NIH HHS [AG05136, AG08017, AG08419, AG10124, AG10133, AG23185] NR 22 TC 86 Z9 89 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2006 VL 63 IS 7 BP 936 EP 939 DI 10.1001/archneur.63.7.936 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 062AQ UT WOS:000238917100003 PM 16831961 ER PT J AU Yaffe, K Vittinghoff, E Ensrud, KE Johnson, KC Diem, S Hanes, V Grady, D AF Yaffe, Kristine Vittinghoff, Eric Ensrud, Kristine E. Johnson, Karen C. Diem, Susan Hanes, Vladimir Grady, Deborah TI Effects of ultra-low-dose transdermal estradiol on cognition and health-related quality of life SO ARCHIVES OF NEUROLOGY LA English DT Article ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGENS; SURGICALLY MENOPAUSAL WOMEN; ALZHEIMERS-DISEASE CERAD; POSTMENOPAUSAL WOMEN; INITIATIVE MEMORY; ESTROGEN/PROGESTIN REPLACEMENT; HORMONE-THERAPY; CLINICAL-TRIAL AB Background: Several small trials and many observational studies suggest that estrogen treatment in postmenopausal women improves cognition, but 2 large randomized trials have shown harm. The effect of an ultra low- dose of unopposed transdermal estradiol on cognition and health-related quality of life is unknown. Objective: To investigate the effect of unopposed ultra low- dose transdermal estradiol on cognitive function and quality of life in postmenopausal women. Design: Randomized, placebo-controlled, double-blind trial with 2-year follow-up. The main outcome of the trial was change in bone density. Changes in cognitive function and quality of life were preplanned secondary outcomes of the trial. Setting: Nine clinical centers in the United States. Participants: Postmenopausal women (N = 417), aged 60 to 80 years, with a normal bone density for age and an intact uterus. Intervention: A weekly transdermal patch that delivers estradiol, 0.014 mg/d (n = 208), or placebo (n = 209). Main Outcome Measures: Seven standardized cognitive tests (a total of 10 scores) administered at baseline and years 1 and 2 to test global cognitive function, verbal and visuospatial memory, language, executive function, and semantic memory. The 36-Item Short-Form General Health Survey was administered to assess health-related quality of life in physical and mental domains. The sample size provided 80% power to detect a standardized effect of 0.29 SD, a small-to-moderate difference. Results: Baseline characteristics were similar in the 2 treatment groups. At 2 years of follow-up, we found no statistically significant differences between treatment groups in change on any of the cognitive test scores or on the 36-Item Short- Form General Health Survey (P > .12 for all). There was no consistent evidence that the effect of treatment on change in cognitive or 36-Item Short-Form General Health Survey scores depended on the level of baseline endogenous estradiol. Conclusion: Postmenopausal treatment with ultra-lowdose unopposed transdermal estradiol for 2 years had no effect on change in cognitive function or in health-related quality of life over 2 years of treatment. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Womens Hlth Clin Res Ctr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Minnesota, Dept Med, Div Epidemiol, Minneapolis, MN 55455 USA. Vet Adm Med Ctr, Minneapolis, MN 55417 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Berlex Inc, Montville, NJ USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Campus Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu RI Diem, Susan/B-6479-2013 FU NIA NIH HHS [R01 AG021918] NR 32 TC 55 Z9 61 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2006 VL 63 IS 7 BP 945 EP 950 DI 10.1001/archneur.63.7.945 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 062AQ UT WOS:000238917100005 PM 16831962 ER PT J AU Weintraub, D Siderowf, AD Potenza, MN Goveas, J Morales, KH Duda, JE Moberg, PJ Stern, MB AF Weintraub, Daniel Siderowf, Andrew D. Potenza, Marc N. Goveas, Joseph Morales, Knashawn H. Duda, John E. Moberg, Paul J. Stern, Matthew B. TI Association of dopamine agonist use with impulse control disorders in Parkinson disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID THERAPY AB Objective: To determine the frequency and correlates of impulse control disorders (ICDs) in Parkinson disease (PD). Design: An unstructured screening interview for ICDs (compulsive gambling, buying, and sexual behavior) followed by a telephone-administered structured interview for screen- positive patients. Setting: Two university-affiliated movement disorders centers. Participants: A convenience sample of 272 patients with idiopathic PD who were screened for psychiatric complications. Main Outcome Measures: Presence of compulsive gambling, buying, or sexual behavior as assessed by the Minnesota Impulsive Disorders Interview. Results: Eighteen patients (6.6%) with PD met criteria for an ICD at some point during the course of PD, including (4.0%) with an active ICD. Compulsive gambling and compulsive sexual behavior were equally common. In a multivariate model, treatment with a dopamine agonist (P = .01) and a history of ICD symptoms prior to PD onset (P = .02) predicted current ICD. There were no differences between the dopamine agonists in their association with ICDs (P = .21), and daily doses of dopamine agonists were higher in patients with an ICD than in dopamine agonist-treated patients without an ICD (P < .001). Conclusions: Patients with PD treated with a dopamine agonist should be made aware of the risk of developing an ICD and monitored clinically. Because dopamine agonists are increasingly being used for other indications, future research should assess the dopamine agonist-associated risk for ICDs in other populations. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Educ & Clin Ctr, Philadelphia, PA USA. Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Weintraub, D (reprint author), 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23 MH067894, K23MH067894] NR 15 TC 337 Z9 344 U1 4 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2006 VL 63 IS 7 BP 969 EP 973 DI 10.1001/archneur.63.7.969 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 062AQ UT WOS:000238917100010 PM 16831966 ER PT J AU Ament, CS Zacks, DN Lane, AM Krzystolik, M D'Amico, DJ Mukai, S Young, LH Loewenstein, J Arroyo, J Miller, JW AF Ament, Christine Shortsleeve Zacks, David N. Lane, Anne Marie Krzystolik, Magdalena D'Amico, Donald J. Mukai, Shizuo Young, Lucy H. Loewenstein, John Arroyo, Jorge Miller, Joan W. TI Predictors of visual outcome and choroidal neovascular membrane formation after traumatic choroidal rupture SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OCULAR HISTOPLASMOSIS SYNDROME; RETINAL PIGMENT EPITHELIUM; PHOTODYNAMIC THERAPY; MACULAR DEGENERATION; DISCIFORM DEGENERATION; LASER PHOTOCOAGULATION; SUBMACULAR SURGERY; AGE; SUBFOVEAL; VERTEPORFIN AB Objective: To determine predictors of choroidal neovascularization (CNV) and visual outcome after traumatic choroidal rupture. Methods: A retrospective review of patients with traumatic choroidal rupture diagnosed in the Retina Service, Massachusetts Eye and Ear Infirmary, Boston, between January 1993 and August 2001 was performed. Parametric and nonparametric statistical methods were used to evaluate visual prognosis, CNV, and retinal detachment after traumatic choroidal rupture. Results: One hundred eleven cases were identified and reviewed. Visual acuity (VA) changes were recorded in all of the cases. Thirty-eight (34%) of the 111 patients recovered driving vision (VA >= 20/40). Rupture location was recorded in 107 cases. Recovery of driving vision was seen in 20 (59%) of 34 eyes with peripheral choroidal ruptures, 17 (22%) of 73 eyes with macular choroidal ruptures, 38 (38%) of 99 eyes without CNV, 1 (8%) of 12 eyes with CNV, 38 (40%) of 96 eyes without retinal detachment, and 1 (7%) of 15 eyes with retinal detachment. Older age and location of rupture within the arcades were positively associated with CNV formation (P=.04 and .03, respectively). Foveal location of rupture, multiple ruptures, and poor baseline VA were associated with failure to recover driving vision in univariate regression analyses. In multivariate analysis, rupture location and baseline VA were independently associated with visual outcome. Of 12 patients diagnosed with CNV, 5 were not treated, 4 were treated with argon laser photocoagulation, 1 was treated with surgery, 1 was treated with argon laser photocoagulation followed by surgery, and 1 was treated with verteporfin photodynamic therapy. Conclusions: Most patients with traumatic choroidal rupture do not achieve final VA of 20/40 or better. Poor visual outcome was most highly associated with a macular rupture and baseline VA of less than 20/40. The formation of CNV was most strongly associated with older age and macular choroidal rupture. C1 Harvard Univ, Retina Serv, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Angiogenesis Lab, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Retina Serv, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM joan_miller@meei.harvard.edu RI Zacks, David/I-4394-2013; OI Zacks, David/0000-0001-8592-5165 NR 31 TC 12 Z9 15 U1 0 U2 1 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 JUL PY 2006 VL 124 IS 7 BP 957 EP 966 DI 10.1001/archopht.124.7.957 PG 10 WC Ophthalmology SC Ophthalmology GA 064XE UT WOS:000239123200003 PM 16832018 ER PT J AU D'Amico, DJ Lit, ES Viola, F AF D'Amico, Donald J. Lit, Eugene S. Viola, Francesco TI Lamina puncture for central retinal vein occlusion - Results of a pilot trial SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RADIAL OPTIC NEUROTOMY; MACULAR EDEMA; ANASTOMOSIS; VITRECTOMY AB Objective: To evaluate the effect of treatment by lamina puncture, a novel procedure to create a perivascular opening within the optic nerve head by a transvitreal approach, on visual acuity after central retinal vein occlusion (CRVO) in older patients. Methods: The patients comprised a nonrandomized, consecutive, interventional case series of older patients being seen with CRVO. Patients 65 years or older with CRVO and a visual acuity of 20/200 or worse were treated with vitrectomy and lamina puncture of the optic disc. Preoperative visual acuity, clinical examination results, and fluorescein angiography results were compared with postoperative results. Results: Twenty patients (12 men and 8 women), an average age of 72 years, were enrolled. The mean duration of CRVO was 5.4 months; 14 eyes had nonischemic CRVO when first seen, while 6 had substantial ischemia. The mean preoperative visual acuity was in the counting fingers range, and the mean postoperative visual acuity was also in the counting fingers range. Complications included 5 eyes with iris neovascularization, of which 4 progressed to neovascular glaucoma; also, preoperative ischemia seemed to predispose to neovascular complications. Conclusion: Lamina puncture does not restore visual acuity in older patients with CRVO. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP D'Amico, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM djdamico@meei.harvard.edu NR 30 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2006 VL 124 IS 7 BP 972 EP 977 DI 10.1001/archopht.124.7.972 PG 6 WC Ophthalmology SC Ophthalmology GA 064XE UT WOS:000239123200005 PM 16832020 ER PT J AU Haan, MN Klein, R Klein, BE Deng, YZ Blythe, LK Seddon, JM Musch, DC Kuller, LH Hyman, LG Wallace, RB AF Haan, Mary N. Klein, Ronald Klein, Barbara E. Deng, Yingzi Blythe, Lynn K. Seddon, Johanna M. Musch, David C. Kuller, Lewis H. Hyman, Leslie G. Wallace, Robert B. TI Hormone therapy and age-related macular degeneration - The women's health initiative sight exam study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID C-REACTIVE PROTEIN; ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; BEAVER DAM EYE; POSTMENOPAUSAL WOMEN; REPRODUCTIVE FACTORS; VISUAL IMPAIRMENT; 5-YEAR INCIDENCE; UNITED-STATES; RISK-FACTORS AB Objective: To determine the effectiveness of treatment with conjugated equine estrogens (CEE) or with CEE combined with progestin (CEE + P) on age-related macular degeneration (AMD). Methods: In an ancillary study to the Women's Health Initiative clinical trial of hormone therapy, 4262 women 65 years and older underwent fundus photography for the determination of AMD. Participants were recruited from April 2000 to June 2002 at 21 clinical sites an average of 5 years after randomization. Participants were randomized to treatment with CEE, CEE + P, or placebo. Participants had been treated for an average of 5 years at the ophthalmic evaluation for AMD. Results: The overall prevalence of any AMD was 21.0%. No association was found between CEE + P (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.75-1.11) or CEE alone (OR, 0.98; 95% CI, 0.78-1.25) and early-stage AMD. The CEE + P was associated with a reduced risk of soft drusen (OR, 0.83; 95% CI, 0.68-1.00) after adjustment for covariates and with a reduced risk of neovascular AMD (OR, 0.29; 95% CI, 0.09-0.92). Conclusions: Treatment with CEE alone or CEE + P does not affect early- or late-stage AMD. Treatment with CEE + P may reduce the risk of soft drusen or neovascular AMD. C1 Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48104 USA. Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48104 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Epidemiol, Boston, MA 02115 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. RP Haan, MN (reprint author), Univ Michigan, Dept Epidemiol, 611 Church St,Room 311, Ann Arbor, MI 48104 USA. EM mnhaan@umich.edu FU WHI NIH HHS [N01 WH032113] NR 40 TC 30 Z9 30 U1 1 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 JUL PY 2006 VL 124 IS 7 BP 988 EP 992 DI 10.1001/archopht.124.7.988 PG 5 WC Ophthalmology SC Ophthalmology GA 064XE UT WOS:000239123200007 PM 16832022 ER PT J AU Seddon, JM George, S Rosner, B AF Seddon, Johanna M. George, Sarah Rosner, Bernard TI Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with Age-Related Macular Degeneration - The US twin study age-related macular degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID COMPLEMENT FACTOR-H; FOOD FREQUENCY QUESTIONNAIRE; C-REACTIVE PROTEIN; DIETARY-FAT; CLASSIFICATION-SYSTEM; RISK-FACTORS; MACULOPATHY; DISEASE; REPRODUCIBILITY; POLYMORPHISM AB Objective: To evaluate modifiable risk and protective factors for age-related macular degeneration (AMD) among elderly twins. Methods: The US Twin Study of Age-Related Macular Degeneration comprises elderly male twins from the National Academy of Sciences-National Research Council World War II Veteran Twin Registry. To determine genetic and environmental risk factors for AMD, twins were surveyed for a prior diagnosis of AMD and underwent an eye examination, fundus photography, and food frequency and risk factor questionnaires. This environmental component of the study includes 681 twins: 222 twins with AMD (intermediate or late stages) and 459 twins with no maculopathy or early signs. Risk for AMD according to cigarette smoking and dietary fat intake was estimated using logistic regression analyses. past smokers had about a 1.7-fold increased risk (95% confidence interval, 1.2-2.6, P=.009). Increased intake of fish reduced risk of AMD, particularly for 2 or more servings per week (P trend =.04). Dietary omega-3 fatty intake was inversely associated with AMD (odds ratio, 0.55; 95% confidence interval, 0.32-0.95) comparing the highest vs lowest quartile. Reduction in risk of AMD with higher intake of omega-3 fatty acids was seen primarily among subjects with low levels (below median) of linoleic acid intake, an omega-6 fatty acid (P trend <.001). The attributable risk percentage was 32% for smoking and the preventive fraction was 22% for higher omega-3 intake. Conclusions: This study of twins provides further evidence that cigarette smoking increases risk while fish consumption and omega-3 fatty acid intake reduce risk of AMD. Results: Current smokers had a 1.9-fold increased risk (95% confidence interval, 0.99-3.68, P=.06) of AMD while past smokers had about a 1.7-fold increased risk (95% confidence interval, 1.2-2.6, P=.009). Increased intake of fish reduced risk of AMD, particularly for 2 or more servings per week (P trend =.04). Dietary omega-3 fatty intake was inversely associated with AMD (odds ratio, 0.55; 95% confidence interval, 0.32-0.95) comparing the highest vs lowest quartile. Reduction in risk of AMD with higher intake of omega-3 fatty acids was seen primarily among subjects with low levels (below median) of linoleic acid intake, an omega-6 fatty acid (P trend <.001). The attributable risk percentage was 32% for smoking and the preventive fraction was 22% for higher omega-3 intake. Conclusions: This study of twins provides further evidence that cigarette smoking increases risk while fish consumption and omega-3 fatty acid intake reduce risk of AMD. C1 Harvard Univ, Epidemiol Unit, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Seddon, JM (reprint author), Harvard Univ, Epidemiol Unit, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02115 USA. EM johanna_seddon@meei.harvard.edu FU NEI NIH HHS [EY 10012] NR 43 TC 176 Z9 187 U1 2 U2 11 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 JUL PY 2006 VL 124 IS 7 BP 995 EP 1001 DI 10.1001/archopht.124.7.995 PG 7 WC Ophthalmology SC Ophthalmology GA 064XE UT WOS:000239123200008 PM 16832023 ER PT J AU Miller, JW AF Miller, Joan W. TI Using a drug before the risks and benefits are known from a phase 3 clinical trial - Thoughts on caompassion SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID MULTIPLE-SCLEROSIS; OPTIC NEURITIS C1 Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM jwmiller@meei.harvard.edu NR 13 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2006 VL 124 IS 7 BP 1029 EP 1031 DI 10.1001/archopht.124.7.1029 PG 3 WC Ophthalmology SC Ophthalmology GA 064XE UT WOS:000239123200012 PM 16832027 ER PT J AU Boseley, ME Cunningham, MJ Volk, MS Hartnick, CJ AF Boseley, Mark E. Cunningham, Michael J. Volk, Mark S. Hartnick, Christopher J. TI Validation of the pediatric voice-related quality-of-life survey SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID OUTCOME SURVEY; POPULATION; INSTRUMENT AB Objective: To validate the Pediatric Voice-Related Quality-of-Life (PVRQOL) survey, which was designed to assess voice changes over time in the pediatric population. Design: Prospective longitudinal study. Setting: Outpatient pediatric otolaryngology office practice. Participants: One hundred twenty parents of children aged 2 through 18 years having a variety of otolaryngological diagnoses including disorders that affect the voice. Interventions: The previously validated Pediatric Voice Outcomes Survey and the PVRQOL were jointly administered to the parents of the study participants. Test-retest reliability was accomplished by having 70 caregivers repeat the instrument 2 weeks after the initial visit. The Cronbach alpha value was calculated to determine reliability. Instrument validity was determined by examining convergent and discriminant validity. Main Outcome Measure: Correlation of PVRQOL scores with Pediatric Voice Outcomes Survey scores. Results: Reliability of the PVRQOL was established by evaluating the Cronbach alpha value (.96; P<.001) and by test-retest reliability (weighted kappa value, 0.8). Validity of the PVQROL was tested by evaluating its ability to show significant change in voice-related quality-of-life. after adenoidectomy (discriminant validity) (P<.001). The PVQROL also proved valid when the overall score was correlated with the previously validated Pediatric Voice Outcomes Survey (r=0.7; P<.001). Conclusion: The PVRQOL is a. more comprehensive survey than the previously validated Pediatric Voice Outcomes Survey and is another valid instrument to examine the health-related quality-of-life issues in pediatric voice disorders. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Childrens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu OI Volk, Mark/0000-0001-5708-5808 NR 9 TC 50 Z9 55 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2006 VL 132 IS 7 BP 717 EP 720 DI 10.1001/archotol.132.7.717 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 062ME UT WOS:000238948400002 PM 16847178 ER PT J AU Brown, I Mino-Kenudson, M Deshpande, V Lauwers, GY AF Brown, Ian Mino-Kenudson, Mari Deshpande, Vikram Lauwers, Gregory Y. TI Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID GLUTEN-SENSITIVE ENTEROPATHY; LATENT CELIAC-DISEASE; T-CELL LYMPHOMA; VILLOUS ARCHITECTURE; AUTOIMMUNE ENTEROPATHY; COLLAGENOUS COLITIS; JEJUNAL MUCOSA; BIOPSY; ANTIBODIES; SPRUE AB Context.-An increased intraepithelial lymphocyte density in an architecturally normal proximal small intestinal mucosal biopsy is a common finding facing surgical pathologists dealing with gastrointestinal biopsy specimens. Approximately 1% to 2% of all proximal small intestinal biopsies will show this change. It is increasingly recognized by surgical pathologists that gluten-sensitive enteropathy is an important cause of this pattern; however, gluten-sensitive enteropathy accounts for the minority of all cases. A wide variety of immunologic stimuli can raise intraepithelial lymphocyte numbers. Among the other common associations are enteric infection, autoimmune disease, drugs, and gastric Helicobacter infection. Objective.-To outline the causes of intraepithelial lymphocytosis, to highlight the importance and the difficulties faced in establishing gluten-sensitive enteropathy as the cause, and to aid the surgical pathologist in the routine sign out of these cases. Data Sources.-A review of the literature detailing the causes or associations of proximal small intestinal intraepithelial lymphocytosis is presented. Conclusions.-Increased lymphocyte numbers in the epithelium of architecturally preserved proximal small intestinal biopsies is a morphologic feature associated with a broad differential diagnosis. C1 Sullivan Nicolaides Pathol, Taringa, Qld, Australia. Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA USA. RP Brown, I (reprint author), Sullivan Nicolaides Pathol, Taringa, Qld, Australia. EM ian_brown@snp.com.au RI Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 NR 59 TC 79 Z9 80 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 2006 VL 130 IS 7 BP 1020 EP 1025 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 062ZA UT WOS:000238984300017 PM 16831028 ER PT J AU Pysher, TJ Bach, PR Geaghan, SM Hamilton, MS Laposata, M Lockitch, G Brugnara, C Coffin, CM Pasquali, M Rinaldo, P Roberts, WL Rutledge, JC Ashwood, ER Blaylock, RC Campos, JM Goldsmith, B Jones, PM Lim, M Meikle, AW Perkins, SL Perry, DA Petti, CA Rogers, BB Steele, PE Weiss, RL Woods, G AF Pysher, Theodore J. Bach, Philip R. Geaghan, Sharon M. Hamilton, Marilyn S. Laposata, Michael Lockitch, Gillian Brugnara, Carlo Coffin, Cheryl M. Pasquali, Marzia Rinaldo, Piero Roberts, William L. Rutledge, Joe C. Ashwood, Edward R. Blaylock, Robert C. Campos, Joseph M. Goldsmith, Barbara Jones, Patricia M. Lim, Megan Meikle, A. Wayne Perkins, Sherrie L. Perry, Deborah A. Petti, Cathy A. Rogers, Beverly B. Steele, Paul E. Weiss, Ronald L. Woods, Gail TI Teaching pediatric laboratory medicine to pathology residents SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID CLINICAL PATHOLOGY; OBJECTIVES; PROGRAMS; GOALS AB Context.-Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine. Objective.-Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs. Data Sources.-Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine. Conclusions.-Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training. C1 Primary Childrens Med Ctr, Dept Pathol, Div Pediat Pathol, Salt Lake City, UT 84113 USA. Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. Childrens Mercy Hosp, Dept Pathol, Kansas City, MO 64108 USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Childrens & Womens Hlth Ctr, Dept Pathol & Lab Med, Vancouver, BC, Canada. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84112 USA. ARUP Labs, Salt Lake City, UT USA. Mayo Clin, Coll Med, Dept Lab Med & Pathol, Div Lab Genet, Rochester, MN USA. Mayo Med Labs, Rochester, MN USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Childrens Hosp & Reg Med Ctr, Dept Labs, Seattle, WA 98195 USA. Childrens Hosp, Natl Med Ctr, Dept Lab Med, Washington, DC 20010 USA. Childrens Hosp, Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. Childrens Hosp, Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. Childrens Hosp, Natl Med Ctr, Dept Microbiol Trop Med, Washington, DC 20010 USA. George Washington Univ, Med Ctr, Washington, DC 20052 USA. St Elizabeths Med Ctr, Dept Pathol, Boston, MA USA. Univ Texas, SW Med Sch, Dallas, TX 75230 USA. Childrens Med Ctr, Dept Pathol, Dallas, TX 75230 USA. Childrens Hosp, Dept Pathol, Omaha, NE USA. Childrens Med Ctr, Dept Pathol, Dallas, TX 75235 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Cincinnati Childrens Hosp, Med Ctr, Dept Pathol & Lab Med, Cincinnati, OH 45221 USA. Univ Arkansas Med Sci, Dept Pathol & Lab Serv, Fayetteville, AR 72701 USA. RP Pysher, TJ (reprint author), Primary Childrens Med Ctr, Dept Pathol, Div Pediat Pathol, 100 N Med Dr, Salt Lake City, UT 84113 USA. EM theodore.pysher@intermountainmail.org RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 14 TC 7 Z9 7 U1 1 U2 6 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 JUL PY 2006 VL 130 IS 7 BP 1031 EP 1038 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 062ZA UT WOS:000238984300019 PM 16831030 ER PT J AU McCarthy, ML Dikmen, SS Langlois, JA Selassie, AW Gu, JK Horner, MD AF McCarthy, ML Dikmen, SS Langlois, JA Selassie, AW Gu, JK Horner, MD TI Self-reported psychosocial health among adults with traumatic brain injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE brain injuries; rehabilitation ID QUALITY-OF-LIFE; HEAD-INJURY; PSYCHIATRIC-DISORDERS; SURVEY SF-36; SOCIOECONOMIC-STATUS; DEPRESSION; VALIDITY; 1-YEAR; PRODUCTIVITY; INDIVIDUALS AB Objective: To measure the subjective psychosocial health of a population-based sample of adults with traumatic brain injury (TBI). Design: Retrospective, cohort study involving a 1-year postinjury interview. Setting: Sixty-two acute care, nonfederal hospitals in South Carolina. Participants: Persons (>= 15y) hospitalized with TBI. Interventions: Not applicable. Main Outcome Measure: The psychosocial health scales of the Medical Outcomes Study 36-Item Short-Form Health Survey. Results: Of the 7612 participants, 29% reported poor psychosocial health. Factors associated with poor psychosocial well-being included younger age, female sex, Medicaid coverage, no health insurance, inadequate or moderate social support, comorbidities (eg, a preinjury substance abuse problem), cognitive complaints, and some or a lot of limitation with activities of daily living. Only 36% of participants who reported poor psychosocial health reported receiving any mental health services. Conclusions: A substantial proportion of persons hospitalized with TBI reported poor psychosocial health at 1 year postinjury. To optimize recovery, clinicians need to ensure that patients' psychosocial health needs are addressed during the postacute period. C1 Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21209 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Natl Ctr Injury Prevent & Control, Atlanta, GA USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. RP McCarthy, ML (reprint author), Johns Hopkins Univ, Sch Med, Dept Emergency Med, 5801 Smith Ave,Davis Bldg,Ste 3220, Baltimore, MD 21209 USA. EM mmccarth@jhmi.edu FU PHS HHS [U17/CCU421926] NR 76 TC 52 Z9 52 U1 10 U2 17 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 JUL PY 2006 VL 87 IS 7 BP 953 EP 961 DI 10.1016/j.apmr.2006.03.007 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 059MY UT WOS:000238738100011 PM 16813783 ER PT J AU Williams, RM Turner, AP Orendurff, M Segal, AD Klute, GK Pecoraro, J Czerniecki, J AF Williams, RM Turner, AP Orendurff, M Segal, AD Klute, GK Pecoraro, J Czerniecki, J TI Does having a computerized prosthetic knee influence cognitive performance during amputee walking? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE amputees; artificial limbs; attention; memory; mental fatigue; rehabilitation ID LOWER-LIMB AMPUTATION; LOWER-EXTREMITY AMPUTATION; ATTENTIONAL DEMANDS; BALANCE CONFIDENCE; POSTURAL CONTROL; TASK; QUESTIONNAIRE; INDIVIDUALS; PROFILE; PEOPLE AB Objective: To compare objective cognitive performance and perception of cognitive burden during walking tasks using 2 different prosthetic knees: a computerized hydraulic knee (Otto Bock C-leg) and a noncomputerized hydraulic knee (Ossur Mauch SNS). Design: Two-group crossover trial, with participants randomly assigned to order of prosthesis. Participants completed assessments under 2 conditions, a self-selected speed walk and a controlled speed walk, on 2 separate occasions (precrossover, postcrossover). Setting: Veterans Health Administration hospital. Participants: Eight transfemoral amputees. Intervention: Computerized versus noncomputerized prosthetic knee. Main Outcome Measures: Objective cognitive performance measures included verbal fluency (Controlled Oral Word Association Test, Category Test), attention and working memory (serial subtraction), and walking speed during cognitive tasks. Measures of perceived cognitive burden included subjective attentional requirements of walking and cognitive tasks and subjective general cognitive burden of prosthesis. Results: There were no significant differences in objective cognitive performance on any task between prostheses, nor did walking speed vary by prosthesis during the free-speed walk. Participants reported that walking required less attention while wearing the C-leg and that the C-leg was less of a cognitive burden than the noncomputerized prosthesis. Conclusions: In nondemanding walking conditions with experienced amputees. participants reported that the more costly C-leg required less cognitive attention than the noncomputerized knee. However, this subjective experience did not translate to improved performance on neuropsychologic screening instruments or on walking speed. Noncomputerized prostheses may be adequate for a majority of amputees, and further research is needed to identify particular groups of amputees (ie, new amputees, amputees with complex physical or cognitive demands) who may benefit from computerized prostheses. C1 VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. Ctr Excellence Limb Loss Prevent & Prosthet Engn, Dept Vet Affairs, Seattle, WA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Williams, RM (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-1117 S Columbian Way, Seattle, WA 98108 USA. EM Rhonda.Williams1@med.va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 32 TC 16 Z9 16 U1 1 U2 5 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 JUL PY 2006 VL 87 IS 7 BP 989 EP 994 DI 10.1016/j.apmr.2006.03.006 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 059MY UT WOS:000238738100016 PM 16813788 ER PT J AU Alsfasser, G Warshaw, AL Thayer, SP Antoniu, B Laposata, M Lewandrowski, KB Fernandez-del Castillo, C AF Alsfasser, Guido Warshaw, Andrew L. Thayer, Sarah P. Antoniu, Bozena Laposata, Michael Lewandrowski, Kent B. Fernandez-del Castillo, Carlos TI Decreased inflammation and improved survival with recombinant human activated protein C treatment in experimental acute pancreatitis SO ARCHIVES OF SURGERY LA English DT Article ID DISSEMINATED INTRAVASCULAR COAGULATION; PULMONARY VASCULAR INJURY; MICROARTERIAL THROMBOSIS; PLASMINOGEN-ACTIVATOR; ESCHERICHIA-COLI; SEVERE SEPSIS; RABBIT MODEL; FACTOR-XA; RATS; INHIBITION AB Hypothesis: Drotrecogin alfa (activated), the pharmacologic form of activated protein C and the first Food and Drug Administration-approved drug for treatment of severe sepsis, is beneficial in experimental acute pancreatitis (AP). Design: Animal study. Setting: Laboratory Subjects: Male Sprague-Dawley rats. Subjects: Male Sprague-Dawley rats. Interventions: Mild (intravenous cerulein) or severe (intravenous cerulein plus intraductal glycodeoxycholic acid) AP was induced in 72 rats, and coagulation evaluated. Rats with severe AP were randomized to treatment with drotrecogin alfa (activated), 100 mu g/kg per hour, or isotonic sodium chloride. Main Outcome Measures: Histologic scoring of pancreatic necrosis, inflammation of the pancreas and lung (measured by myeloperoxidase concentration), coagulation measures, and 24-hour survival. Results: Severe consumptive coagulopathy, hemoconcentration, and leukocytosis were observed 6 hours after induction of severe AP, but not in mild AP. Treatment of AP with drotrecogin did not worsen coagulation measures. Although the degree of pancreatic necrosis was comparable in treated and untreated animals with severe AP, drotrecogin significantly reduced myeloperoxidase levels in the pancreas (P=.009) and lungs (P=.03). The 24-hour survival in severe AP was markedly improved in animals treated with drotrecogin (86% vs 38%; P=.05). Conclusions: Animals with severe AP have severe consumptive coagulopathy, but administration of drotrecogin alfa (activated), 100 mu g/kg per hour, does not worsen coagulation abnormalities. Drotrecogin treatment reduces inflammation in the pancreas and lungs and significantly improves survival. These results encourage clinical investigation of drotrecogin in the treatment of severe AP. C1 Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, WACC336,15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org FU NIDDK NIH HHS [K08 DK071329] NR 37 TC 19 Z9 20 U1 0 U2 2 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 JUL PY 2006 VL 141 IS 7 BP 670 EP 676 DI 10.1001/archsurg.141.7.670 PG 7 WC Surgery SC Surgery GA 061ZU UT WOS:000238914400011 PM 16847238 ER PT J AU Alsfasser, G Warshaw, AL Fernandez-del Castillo, C AF Alsfasser, Guido Warshaw, Andrew L. Fernandez-del Castillo, Carlos TI Decreased inflammation and improved survival with recombinant human activated protein C treatment in experimental acute pancreatitis - Invited response SO ARCHIVES OF SURGERY LA English DT Editorial Material ID MODEL C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, WACC 336,15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org NR 3 TC 0 Z9 0 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 JUL PY 2006 VL 141 IS 7 BP 677 EP 677 DI 10.1001/archsurg.141.7.677 PG 1 WC Surgery SC Surgery GA 061ZU UT WOS:000238914400013 ER PT J AU Kuhlencordt, PJ Hotten, S Schodel, J Rutzel, S Hu, K Widder, J Marx, A Huang, PL Ertl, G AF Kuhlencordt, Peter J. Hoetten, Stefanie Schoedel, Johannes Ruetzel, Sebastian Hu, Kai Widder, Julian Marx, Alexander Huang, Paul L. Ertl, Georg TI Atheroprotective effects of neuronal nitric oxide synthase in apolipoprotein E knockout mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE nitric oxide; nitric oxide synthase; arteriosclerosis; blood pressure; gene expression ID VASCULAR SMOOTH-MUSCLE; BLOOD-PRESSURE; RNA DIVERSITY; IN-VITRO; SUPEROXIDE; ATHEROSCLEROSIS; MODULATION; GENERATION; ISOFORM; GENE AB Objective - All 3 isoforms of the nitric oxide synthase (NOS) are expressed in atherosclerotic lesions. To test whether neuronal NOS (nNOS) deficiency affects atherosclerosis, we studied apoE/nNOS alpha double knockout (DKO) and apolipoprotein E (apoE) knockout (KO) control mice. Methods and Results - Lesion area was significantly increased in male DKO (66%) mice after 14 weeks and in female DKO animals (31%) after 24 weeks of "western" diet. Moreover, mean arterial blood pressure was significantly reduced in female DKO animals. Immunohistochemistry revealed nNOS expression in the neointima of KO mice. In DKO animals, residual nNOS staining was caused by the presence of nNOS splice variants. Whereas nNOS alpha was present in vessels of KO and absent in DKO animals, nNOS gamma was expressed in KO and DKO mice. Conclusion - nNOS alpha protects against atherosclerosis as nNOS alpha deletion leads to an increase in plaque formation in apoE/nNOS alpha DKO mice. Female DKO mice showed a significant reduction in mean arterial blood pressure. Additionally, we found expression of nNOS splice variants in vessels of apoE KO mice. Our data highlights nNOS alpha overexpression as a potential therapeutic strategy and naturally occurring splice variants that lack exon 2 of the nNOS gene as a potential risk factor for vascular disease. C1 Univ Wurzburg, Med Klin 1, Wurzburg, Germany. Univ Wurzburg, Ctr Cardiovasc, Wurzburg, Germany. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kuhlencordt, PJ (reprint author), Univ Hosp Wurzburg, Dept Med, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM kuhlencord_p@klink.uni-wuerzburg.de OI Schodel, Johannes/0000-0002-3587-8839 FU NHLBI NIH HHS [HL57818, R01 HL057818, R01 HL057818-09]; NINDS NIH HHS [R01 NS048426, NS33335, R01 NS033335, R01 NS033335-13, R01 NS048426-04] NR 33 TC 41 Z9 41 U1 0 U2 1 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 JUL PY 2006 VL 26 IS 7 BP 1539 EP 1544 DI 10.1161/01.ATV.0000223143.88128.19 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 124YO UT WOS:000243408900020 PM 16627802 ER PT J AU Qing, XP Zavadil, J Crosby, MB Hogarth, MP Hahn, BH Mohan, C Gilkeson, GS Bottinger, EP Putterman, C AF Qing, Xiaoping Zavadil, Jiri Crosby, Michelle B. Hogarth, Mark P. Hahn, Bevra H. Mohan, Chandra Gilkeson, Gary S. Bottinger, Erwin P. Putterman, Chaim TI Nephritogenic anti-DNA antibodies regulate gene expression in MRL/lpr mouse glomerular mesangial cells SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NITRIC-OXIDE SYNTHASE; GELATINASE-ASSOCIATED LIPOCALIN; GROWTH-FACTOR-BETA; AUTOIMMUNE GLOMERULONEPHRITIS; STRUCTURAL CHARACTERISTICS; ALPHA-ACTININ; RENAL INJURY; AUTOANTIBODIES; MICE AB Objective. Lupus-associated IgG anti-double-stranded DNA antibodies are thought to be pathogenic in the kidney due to cross-reaction with glomerular antigens, leading subsequently to immune complex formation in situ and complement activation. We undertook this study to determine if pathogenic anti-DNA antibodies may also contribute to renal damage by directly influencing mesangial gene expression. Methods. Complementary DNA microarray gene profiling was performed in primary mesangial cells (derived from lupus-prone MRL/lpr mice) treated with pathogenic, noncomplexed anti-DNA antibodies. Significant gene up-regulation induced by anti-DNA antibodies as determined by microarray analysis was further investigated by real-time polymerase chain reaction and methods to detect the relevant proteins. Induction of proinflammatory genes by pathogenic antibodies was confirmed by comparing gene expression in glomeruli of old versus young MRL/lpr mice, and by antibody injection in vivo. Results. Pathogenic, but not nonpathogenic, antibodies significantly induced a number of transcripts, including CXCL1/KC, LCN2, iNOS, CX3CL1/fractalkine, SERPINA3G, and I kappa B alpha ("marker genes"). Blocking of Fc gamma receptors or using Fc gamma chain-knockout mesangial cells had no effect on the gene regulation effect of the pathogenic antibody R4A, indicating a non-Fc-dependent mechanism. The glomerular expression of these marker genes increased over time with the development of glomerular antibody deposition and active nephritis in MRL/lpr mice. Moreover, injection of R4A into SCID mice in vivo significantly up-regulated glomerular marker gene expression. Conclusion. These findings indicate that the renal pathogenicity of anti-DNA antibodies may be attributed in part to their ability to directly modulate gene expression in kidney mesangial cells through both Fc-dependent and non-Fc-dependent mechanisms. C1 Albert Einstein Coll Med, Div Rheumatol, Bronx, NY 10461 USA. NYU, Sch Med, New York, NY USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Med Res Serv, Charleston, SC USA. Austin & Repatriat Med Ctr, Heidelberg, Germany. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Mt Sinai Sch Med, New York, NY USA. RP Putterman, C (reprint author), Albert Einstein Coll Med, Div Rheumatol, Forchheimer 701N,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM putterma@aecom.yu.edu OI Zavadil, Jiri/0000-0003-0640-5562 FU NIAID NIH HHS [P01-AI-51392, R37-AI/AR-46776]; NIAMS NIH HHS [R01-AR-48692]; NIDDK NIH HHS [DK-58768-02] NR 42 TC 50 Z9 52 U1 0 U2 1 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 JUL PY 2006 VL 54 IS 7 BP 2198 EP 2210 DI 10.1002/art.21934 PG 13 WC Rheumatology SC Rheumatology GA 062IY UT WOS:000238939000018 PM 16804897 ER PT J AU Nowling, TK Gilkeson, GS AF Nowling, Tamara K. Gilkeson, Gary S. TI Regulation of Fli1 gene expression and lupus SO AUTOIMMUNITY REVIEWS LA English DT Article; Proceedings Paper CT 9th International Workshop on Autoantibodies and Autoimmunity CY SEP 29-OCT 02, 2005 CL Gainesville, FL DE Ets; Fli1 gene expression; transcription; lupus; lymphocytes ID MURINE LEUKEMIA-VIRUS; ETS FAMILY; TRANSCRIPTION FACTOR; RENAL-DISEASE; DNA-BINDING; PROMOTER; ERYTHROLEUKEMIA; PROTEIN; MEMBER; CELLS AB Ets transcription factors function throughout development in such varied processes as cellular proliferation, apoptosis, differentiation and migration. Many have been implicated to play important roles in hematopoiesis, vasculogenesis/angiogenesis and myogenesis. Fli1 is an Ets family member that is essential for development and increasing evidence suggests modulating Fli1 gene expression impacts lymphocyte function and is important in the autoimmune disease lupus. Presently, it is unknown how Fli1 gene expression is controlled in lymphocytes. Identifying upstream regulators of Fli1 in lymphocytes will be critical for understanding lymphocyte development and the consequences of dysregulation and may be of value in developing future treatments for Jupus. Published by Elsevier B.V. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Med Res Serv, Charleston, SC 29425 USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Ste 912 CSB, Charleston, SC 29425 USA. EM gilkeson@musc.edu FU NIAMS NIH HHS [AR47451] NR 23 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD JUL PY 2006 VL 5 IS 6 BP 377 EP 382 DI 10.1016/j/autrev.2005.10.005 PG 6 WC Immunology SC Immunology GA 079KL UT WOS:000240174700004 PM 16890890 ER PT J AU Fitzsimons, MG Parrado, C AF Fitzsimons, Michael G. Parrado, Carlos TI ECG and thallium imaging abnormalities with normal coronary angiogram in a male flight surgeon SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Article DE CAD; cardiac abnormalities; thallium imaging ID PERFORMANCE; DISEASE AB Coronary artery disease and cardiac anomalies have the potential to cause sudden incapacitation in the flight environment with potentially disastrous consequences. Flight surgeons are responsible for screening for these potential diseases. We report a case of a healthy, active, asymptomatic U.S. flight surgeon returning for duty who demonstrated an abnormal ECG, graded exercise test, and thallium imaging. He was ultimately referred for cardiac catheterization that revealed normal coronary arteries. We discuss the sensitivity of non-invasive screening studies in healthy young individuals and potential causes of "false-positive" thallium imaging. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Div Cardiac Anesthesia & Crit Care, Boston, MA 02114 USA. Martin Army Community Hosp, Dept Family Med, Boston, MA USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Div Cardiac Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org RI Parrado, Concepcion/K-9270-2014 OI Parrado, Concepcion/0000-0002-7627-4310 NR 10 TC 0 Z9 2 U1 0 U2 0 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD JUL PY 2006 VL 77 IS 7 BP 749 EP 752 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA 063VZ UT WOS:000239049300013 PM 16856363 ER PT J AU Duan, XB Berthiaume, F Yarmush, D Yarmush, ML AF Duan, XB Berthiaume, F Yarmush, D Yarmush, ML TI Proteomic analysis of altered protein expression in skeletal muscle of rats in a hypermetabolic state induced by burn sepsis SO BIOCHEMICAL JOURNAL LA English DT Article DE burn sepsis; heat-shock protein; metabolic enzyme; muscle atrophy; proteomic analysis; skeletal muscle ID UBIQUITIN-CONJUGATING ACTIVITY; SMALL STRESS-PROTEINS; NF-KAPPA-B; GENE-EXPRESSION; OXIDATIVE STRESS; MESSENGER-RNA; SOLEUS MUSCLE; TNF-ALPHA; MUSCULAR-DYSTROPHY; PROTEASOME PATHWAY AB mRNA profiling has been extensively used to study muscle wasting :. mRNA level changes may not reflect that of proteins, especially in catabolic muscle where there is decreased synthesis and increased degradation. As sepsis is often associated with burn injury, and burn superimposed by sepsis has been shown to result in significant loss of lean tissues, we characterized changes in the skeletal-muscle proteome of rats subjected to a cutaneous burn covering 20 % of the total body surface area, followed 2 days later by sepsis induced by CLP (caecal ligation and puncture). EDL (extensor digitorum longus) muscles were dissected from Burn-CLP animals (n = 4) and controls (sham-bumed and sham-CLP-treated, n = 4). Burn-CLP injury resulted in a rapid loss of EDL weight, increased ubiquitin-conjugated proteins and increased protein carbonyl groups. EDL protein profiles were obtained by two-dimensional gel electrophoresis using two immobilized pH gradient strips with overlapping pH range covering a pH 3-8 range. Seventeen spots were significantly altered in the Burn-CLP compared with the control group, representing 15 different proteins identified by peptide mass fingerprinting. The identities of three proteins including transferrin were further confirmed by liquid chromatography-tandem MS. The significant changes in transferrin and HSP27 (heat-shock protein 27) were verified by Westem-blot analysis. HSP60, HSP27 and HSPP6 were down-regulated, along with HSP70, as detected by Western blotting. Six metabolic enzymes related to energy production were also down-regulated. A simultaneous decrease in chaperone proteins and metabolic enzymes could decrease protein synthesis. Furthermore, decreased HSPs could increase oxidative damage, thus accelerating protein degradation. Using cultured C2C12 myotubes, we showed that H2O2-induced protein degradation in vitro could be partially attenuated by prior heat-shock treatment, consistent with a protective role of HSP70 and/or other HSPs against proteolysis. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv,Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-11]; PHS HHS [R01 A1063795] NR 67 TC 35 Z9 37 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 2006 VL 397 BP 149 EP 158 DI 10.1042/BJ20051710 PN 1 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 058XZ UT WOS:000238699200017 PM 16483253 ER PT J AU Milad, MR Rauch, SL Pitman, RK Quirk, GJ AF Milad, MR Rauch, SL Pitman, RK Quirk, GJ TI Fear extinction in rats: Implications for human brain imaging and anxiety disorders SO BIOLOGICAL PSYCHOLOGY LA English DT Review DE fear extinction; rats; human brain ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL-ABUSE; LONG-TERM POTENTIATION; SCRIPT-DRIVEN IMAGERY; TRANSCRANIAL MAGNETIC STIMULATION; CEREBRAL-BLOOD-FLOW; EVENT-RELATED FMRI; CONDITIONED FEAR AB Fear extinction is the decrease in conditioned fear responses that normally occurs when a conditioned stimulus (CS) is repeatedly presented in the absence of the aversive unconditioned stimulus (US). Extinction does not erase the initial CS-US association, but is thought to form a new memory. After extinction training, extinction memory competes with conditioning memory for control of fear expression. Deficits in fear extinction are thought to contribute to post-traumatic stress disorder (PTSD). Herein, we review studies performed in rats showing that the medial prefrontal cortex plays a critical role in the retention and expression of extinction memory. We also review human studies indicating that prefrontal areas homologous to those critical for extinction in rats are structurally and functionally deficient in patients with PTSD. We then discuss how findings from rat studies may allow us to: (1) develop new fear extinction paradigms in humans, (2) make specific predictions as to the location of extinction-related areas in humans, and (3) improve current extinction-based behavioral therapies for anxiety disorders. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Ponce Sch Med, Dept Physiol, Ponce, PR 00732 USA. RP Quirk, GJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St, Charlestown, MA 02129 USA. EM gjquirk@yahoo.com RI 蔡, 阿燕/K-6744-2013 NR 151 TC 311 Z9 326 U1 7 U2 47 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JUL PY 2006 VL 73 IS 1 BP 61 EP 71 DI 10.1016/j.biopsycho.2006.01.008 PG 11 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 053JX UT WOS:000238302500006 PM 16476517 ER PT J AU Engler, DA Mohapatra, G Louis, DN Betensky, RA AF Engler, DA Mohapatra, G Louis, DN Betensky, RA TI A pseudolikelihood approach for simultaneous analysis of array comparative genomic hybridizations SO BIOSTATISTICS LA English DT Article ID HIDDEN MARKOV-MODELS; CGH DATA; BREAST-CANCER; MICROARRAY ANALYSIS; SURVIVAL; TUMORS; OLIGODENDROGLIOMAS; AMPLIFICATION; ASSOCIATION; PREDICTORS AB DNA sequence copy number has been shown to be associated with cancer development and progression. Array-based comparative genomic hybridization (aCGH) is a recent development that seeks to identify the copy number ratio at large numbers of markers across the genome. Due to experimental and biological variations across chromosomes and hybridizations, current methods are limited to analyses of single chromosomes. We propose a more powerful approach that borrows strength across chromosomes and hybridizations. We assume a Gaussian mixture model, with a hidden Markov dependence structure and with random effects to allow for intertumoral variation, as well as intratumoral clonal variation. For ease of computation, we base estimation on a pseudolikelihood function. The method produces quantitative assessments of the likelihood of genetic alterations at each clone, along with a graphical display for simple visual interpretation. We assess the characteristics of the method through simulation studies and analysis of a brain tumor aCGH data set. We show that the pseudolikelihood approach is superior to existing methods both in detecting small regions of copy number alteration and in accurately classifying regions of change when intratumoral clonal variation is present. Software for this approach is available at http://www.biostat.harvard.edu/similar to betensky/papers.html. C1 Harvard Univ, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Mol Pathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. RP Betensky, RA (reprint author), Harvard Univ, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM engler@fas.harvard.edu; betensky@hsph.harvard.edu FU NCI NIH HHS [CA075971, CA106695, CA121884]; NINDS NIH HHS [NS048005] NR 39 TC 37 Z9 37 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JUL PY 2006 VL 7 IS 3 BP 399 EP 421 DI 10.1093/biostatistics/kxj015 PG 23 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 056PG UT WOS:000238537000005 PM 16401686 ER PT J AU Fitzmaurice, GM Lipsitz, SR Ibrahim, JG Gelber, R Lipshultz, S AF Fitzmaurice, GM Lipsitz, SR Ibrahim, JG Gelber, R Lipshultz, S TI Estimation in regression models for longitudinal binary data with outcome-dependent follow-up SO BIOSTATISTICS LA English DT Article DE follow-up time process; generalized estimating equations; maximum likelihood; multinomial distribution; pseudolikelihood ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DOXORUBICIN THERAPY; CHILDHOOD; CANCER AB In many observational studies, individuals are measured repeatedly over time, although not necessarily at a set of pre-specified occasions. Instead, individuals may be measured at irregular intervals, with those having a history of poorer health outcomes being measured with somewhat greater frequency and regularity. In this paper, we consider likelihood-based estimation of the regression parameters in marginal models for longitudinal binary data when the follow-up times are not fixed by design, but can depend on previous outcomes. In particular, we consider assumptions regarding the follow-up time process that result in the likelihood function separating into two components: one for the follow-up time process, the other for the outcome measurement process. The practical implication of this separation is that the follow-up time process can be ignored when making likelihood-based inferences about the marginal regression model parameters. That is, maximum likelihood (ML) estimation of the regression parameters relating the probability of success at a given time to covariates does not require that a model for the distribution of follow-up times be specified. However, to obtain consistent parameter estimates, the multinomial distribution for the vector of repeated binary outcomes must be correctly specified. In general, ML estimation requires specification of all higher-order moments and the likelihood for a marginal model can be intractable except in cases where the number of repeated measurements is relatively small. To circumvent these difficulties, we propose a pseudolikelihood for estimation of the marginal model parameters. The pseudolikelihood uses a linear approximation for the conditional distribution of the response at any occasion, given the history of previous responses. The appeal of this approximation is that the conditional distributions are functions of the first two moments of the binary responses only. When the follow-up times depend only on the previous outcome, the pseudolikelihood requires correct specification of the conditional distribution of the current outcome given the outcome at the previous occasion only. Results from a simulation study and a study of asymptotic bias are presented. Finally, we illustrate the main results using data from a longitudinal observational study that explored the cardiotoxic effects of doxorubicin chemotherapy for the treatment of acute lymphoblastic leukemia in children. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Miami, Sch Med, Miami, FL USA. RP Fitzmaurice, GM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM fitzmaur@hsph.harvard.edu FU NCI NIH HHS [CA 68484, CA 70101, CA 74015, CA 79063]; NHLBI NIH HHS [HL 69800, HL 72705, HL 53392, HL 78522, HR 96041]; NIAID NIH HHS [AI 60373]; NIGMS NIH HHS [GM 70335, GM 29745] NR 20 TC 10 Z9 10 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JUL PY 2006 VL 7 IS 3 BP 469 EP 485 DI 10.1093/biostatistics/kxj019 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 056PG UT WOS:000238537000009 PM 16428260 ER PT J AU Yang, CC Porter, MP Penson, DF AF Yang, Claire C. Porter, Michael P. Penson, David F. TI Comparison of the International Index of Erectile Function erectile domain scores and nocturnal penile tumescence and rigidity measurements: does one predict the other? SO BJU INTERNATIONAL LA English DT Article DE RigiScan; International Index of Erectile Function; nocturnal penile tumescence and rigidity; erectile function; impotence ID FUNCTION IIEF; DYSFUNCTION; POTENT; ULTRASONOGRAPHY; CAVERNOSOMETRY; DIAGNOSIS; IMPOTENCE; CRITERIA; MEN AB OBJECTIVE To describe the relationship between the International Index of Erectile Function (IIEF) erectile domain score, and nocturnal penile tumescence and rigidity values measured by RigiScan (Timm Medical Technologies, Eden Prairie, MN). PATIENTS AND METHODS In all, 73 men were evaluated with the IIEF and 2 nights of continuous penile monitoring with the RigiScan. Twenty-six men were evaluated before and after prostatectomy, for a total of 99 pairs of data points. We dichotomized the RigiScan results as 'adequate' (no erectile dysfunction, ED), or 'inadequate' (having ED), based on the 'best erectile event' over the 2 nights of monitoring. Two separate criteria for adequate erectile function were used, one of > 70% rigidity for >= 10 min, and the other > 600/6 rigidity for >= 10 min. The erectile domain score of the IIEF was calculated in the standard fashion. RESULTS Using both the 70% and the 60% rigidity criteria, there was a statistically significant association between the IIEF erectile domain scores and the RigiScan data (r= 0.27, P = 0.008 and r = 0.29, P = 0.003, respectively). However, the sensitivity of the IIEF to predict ED based on RigiScan results using the 70% rigidity criteria was 68.90/6, and the specificity was 57.1%. When the IIEF was used as a continuous predictor of RigiScan results, the area under the receiver-operating characteristic (ROC) curve was 0.66. Using the 60% criteria, the sensitivity was 55.8% and the specificity was 73.2%; the area under the ROC curve was 0.72. CONCLUSIONS IIEF erectile domain scores and nocturnal penile tumescence and rigidity measurements are weakly associated, and the clinical utility of one test to predict the other is limited. However, because of the differences in the measured outcomes (perception of erectile function vs physiological capacity), a weak association does not disqualify either test's individual utility. C1 Univ Washington, Dept Urol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ So Calif, Keck Sch Med, Dept Urol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. RP Yang, CC (reprint author), Univ Washington, Dept Urol, Box 356510, Seattle, WA 98195 USA. EM cyang@u.washington.edu FU NIDDK NIH HHS [1R21DK069315] NR 22 TC 13 Z9 15 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 2006 VL 98 IS 1 BP 105 EP 109 DI 10.1111/j.1464-410X.2006.06246.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 062MJ UT WOS:000238948900024 PM 16831153 ER PT J AU Farag, SS Archer, KJ Mrozek, K Ruppert, AS Carroll, AJ Vardiman, JW Pettenati, MJ Baer, MR Qumsiyeh, MB Koduru, PR Ning, Y Mayer, RJ Stone, RM Larson, RA Bloomfield, CD AF Farag, SS Archer, KJ Mrozek, K Ruppert, AS Carroll, AJ Vardiman, JW Pettenati, MJ Baer, MR Qumsiyeh, MB Koduru, PR Ning, Y Mayer, RJ Stone, RM Larson, RA Bloomfield, CD TI Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461 SO BLOOD LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; ACUTE NONLYMPHOCYTIC LEUKEMIA; RESISTANCE MODULATOR PSC-833; DOUBLE MINUTE CHROMOSOMES; COUNCIL AML11 TRIAL; STUDY-GROUP ULM; ELDERLY-PATIENTS; POSTREMISSION THERAPY AB We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5% achieved complete remission (CR); 6.6% survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex a 3) and a group including "rare aberrations" predicted lower CR rates (25% and 30%) versus other patients (56%). Compared with complex >= 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex >= 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex >= 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P <.001), with 5-year survivals of 0%, 0%, and 19.4%, respectively, and 7.5% for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex >= 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care. C1 Ohio State Univ, Dept Internal Med, Div Hematol & Oncol, Columbus, OH 43210 USA. Virginia Commonwealth Univ, Richmond, VA USA. Ctr Stat, Canc Leukemia Grp B CALGB, Durham, NC USA. Univ Alabama, Birmingham, AL USA. Univ Chicago, Chicago, IL 60637 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Duke Univ, Durham, NC USA. N Shore Univ, Manhasset, NY USA. Univ Maryland, Baltimore, MD 21201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Farag, SS (reprint author), Ohio State Univ, Dept Internal Med, Div Hematol & Oncol, B312 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM sherif.farag@osumc.edu RI Mrozek, Krzysztof/A-3142-2008; OI Qumsiyeh, Mazin/0000-0003-2002-3026; Larson, Richard/0000-0001-9168-3203 NR 71 TC 171 Z9 180 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 JUL 1 PY 2006 VL 108 IS 1 BP 63 EP 73 DI 10.1182/blood-2005-11-4354 PG 11 WC Hematology SC Hematology GA 057LI UT WOS:000238596900018 ER PT J AU Campese, AF Garbe, AI Zhang, FR Grassi, F Screpanti, I von Boehmer, H AF Campese, AF Garbe, AI Zhang, FR Grassi, F Screpanti, I von Boehmer, H TI Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling SO BLOOD LA English DT Article ID T-CELL LEUKEMIA; LYMPHOCYTE DEVELOPMENT; ALPHA-BETA; PT-ALPHA; NOTCH; EXPRESSION; MICE; THYMOCYTES; INDUCTION; NEOPLASMS AB Overexpression of intracellular Notch plays an important role in the generation of human acute lymphoblastic T cell leukemia (T-ALL). In mouse models, it was shown that Notch-dependent T-ALL required pre-TCR signaling. Here we show that pre-TCR signaling is required to condition mice for Notch-dependent transformation but that it is not required to sustain malignant growth of T-ALL. In contrast to previous studies, we found that disease development does not require pre-TCR but that it can be accelerated in Rag2(-/-) mice by transient mimicking of pre-TCR signals. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy. Inst Res Biomed, Bellinzona, Switzerland. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Smith 736,44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Garbe, Annette/A-4824-2014; Campese, Antonio /A-9783-2015; OI CAMPESE, Antonio Francesco/0000-0002-8535-6609 FU NCI NIH HHS [P01 CA109901, P01CA 109901]; NIAID NIH HHS [R01AI 45846] NR 21 TC 41 Z9 42 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 JUL 1 PY 2006 VL 108 IS 1 BP 305 EP 310 DI 10.1182/blood-2006-01-0143 PG 6 WC Hematology SC Hematology GA 057LI UT WOS:000238596900049 PM 16507772 ER PT J AU Wells, WA Schwartz, GN Morganelli, PM Cole, BF Gibson, JJ Kinlaw, WB AF Wells, Wendy A. Schwartz, Gary N. Morganelli, Peter M. Cole, Bernard F. Gibson, Jennifer J. Kinlaw, William B. TI Expression of "Spot 14" (THRSP) predicts disease free survival in invasive breast cancer: immunohistochemical analysis of a new molecular marker SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE chromosome 11q13; gene amplification; lipogenesis; tumor markers ID FATTY-ACID SYNTHESIS; CYCLIN D1; LIPID-SYNTHESIS; CELL-DEATH; PROTEIN; GENE; AMPLIFICATION; INHIBITION; PROGNOSIS; SYNTHASE AB Most breast cancers are "lipogenic'', defined by high fatty acid synthase (FAS) content and dependence on fatty acid synthesis for growth and survival. S14 (Spot 14; THRSP) is a nuclear protein that activates genes required for fatty acid synthesis. The S14 gene is amplified in (similar to)15% of breast cancers, but clinical correlates of its expression were unknown. We analyzed 131 breast cancers by immunohistochemistry for S14 and FAS. Staining was graded 0, 1, or 2+, and scores were correlated with traditional tumor markers, histological features, and outcome. S14 and FAS staining were related to tumor size (p = 0.05 for S14, p = 0.038 for FAS), but not to stage. S14 but not FAS scores correlated with tumor grade in both DCIS (p = 0.003) and invasive cases (p < 0.001). Invasive cases (pooled node) and +) with weak S14 staining (n = 21) showed no recurrence over 3000 d follow-up, including 10 cases with lymph node involvement, whereas 32% of 67 strongly-staining tumors recurred ( log rank p < 0.0001). S14 scores did not cosegregate with sex steroid receptors, Her2/neu, or cyclin D1. Low level S14 expression is associated with prolonged disease-free survival in invasive cases, including those with nodal metastasis. High-level expression of S14 identifies a subset of high-risk breast cancers that is not specified by analysis of sex steroid receptors, Her2/neu, or cyclin D1, and provides a molecular correlate to histologic features that predict recurrence. C1 Dartmouth Coll Sch Med, Div Endocrinol & Metab, Dept Pathol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Med, Lebanon, NH 03756 USA. VA Hosp, US Dept Vet Affairs, White River Jct, VT USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Lebanon, NH 03756 USA. RP Kinlaw, WB (reprint author), Dartmouth Coll Sch Med, Div Endocrinol & Metab, Dept Pathol, 606 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM william.kinlaw@hitchcock.org FU NIDDK NIH HHS [R01 DK 058961, R01 DK058961] NR 35 TC 26 Z9 29 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2006 VL 98 IS 2 BP 231 EP 240 DI 10.1007/s10549-005-9154-z PG 10 WC Oncology SC Oncology GA 071IL UT WOS:000239593700015 PM 16552628 ER PT J AU Neri, P Yasui, H Hideshima, T Tassone, P Raje, N Laurence, CP Ishitsuka, K Blotta, S Kiziltepe, T Ocio, EM Fulciniti, M Kanekal, S Elliott, GT Munshi, NC Anderson, KC AF Neri, P Yasui, H Hideshima, T Tassone, P Raje, N Laurence, CP Ishitsuka, K Blotta, S Kiziltepe, T Ocio, EM Fulciniti, M Kanekal, S Elliott, GT Munshi, NC Anderson, KC TI In vivo and in vitro cytotoxicity of R-etodolac with dexamethasone in glucocorticoid-resistant multiple myeloma cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE R-etodolac; multiple myeloma; dexamethasone; drug resistance; in vivo mouse model ID NF-KAPPA-B; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CHRONIC LYMPHOCYTIC-LEUKEMIA; PROTEASOME INHIBITOR PS-341; MOLECULAR-MECHANISMS; INDUCED APOPTOSIS; MM CELLS; GROWTH; INDUCTION; CHEMOTHERAPY AB Glucocorticoids have been widely used in the treatment of multiple myeloma (MM) both as single agents and in combination with other drugs. However, primary or acquired glucocorticoid resistance occurs in most cases. It was recently reported that R-etodolac induced in vitro cytotoxicity in MM cell lines and in primary MM cells, as well as synergistically enhanced dexamethasone (Dex)-induced apoptosis in Dex-sensitive MM.1S cells. This study examined the in vitro and in vivo effects of combination treatment with R-etodolac and Dex on Dex-resistant OPM1 cells. Treatment with R-etodolac and Dex was found to enhance cytotoxicity, inhibit nuclear factor kappa B activity via upregulation of I kappa B alpha, as well as enhance Dex-induced caspase activation and poly (ADP)-ribose polymerase cleavage in OPM1 cells. R-etodolac also enhanced Dex cytotoxicity in patient MM cells that were resistant to glucocorticoids. The in vivo anti-tumour effect of this combination on MM cells was evaluated by using severe combined immunodeficient mice engrafted with OPM1. Treatment with R-etodolac or Dex alone did not induce a significant reduction of tumour volume; in contrast, combination treatment with R-etodolac and Dex induced significant synergistic inhibition of tumour growth. These data indicate that R-etodolac overcomes resistance to Dex in glucocorticoid-resistant MM cells, providing the framework for clinical trials of R-etodolac combined with Dex, to improve patient outcome in MM. C1 Harvard Univ, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Groecia, Dept Expt & Clin Med, Catanzaro, Italy. Ctr Canc, Catanzaro, Italy. Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Salmedix Inc, San Diego, CA USA. RP Anderson, KC (reprint author), Harvard Univ, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [P0-1 CA78378, R0-1 CA50947, IP50 CA10070-01] NR 46 TC 14 Z9 17 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2006 VL 134 IS 1 BP 37 EP 44 DI 10.1111/j.1365-2141.2006.06122.x PG 8 WC Hematology SC Hematology GA 047IB UT WOS:000237871900004 PM 16803565 ER PT J AU Shringarpure, R Catley, L Bhole, D Burger, R Podar, K Tai, YT Kessler, B Galardy, P Ploegh, H Tassone, P Hideshima, T Mitsiades, C Munshi, NC Chauhan, D Anderson, KC AF Shringarpure, R Catley, L Bhole, D Burger, R Podar, K Tai, YT Kessler, B Galardy, P Ploegh, H Tassone, P Hideshima, T Mitsiades, C Munshi, NC Chauhan, D Anderson, KC TI Gene expression analysis of B-lymphoma cells resistant and sensitive to bortezomib SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE proteasome inhibition; drug resistance; bortezomib; TCF-4; B-cell lymphoma ID PROTEASOME INHIBITOR PS-341; ACTIVATING TRANSCRIPTION FACTOR-3; MULTIPLE-MYELOMA CELLS; PHASE-I TRIAL; BETA-CATENIN; HEPATOCELLULAR-CARCINOMA; COLON-CARCINOMA; CANCER; APOPTOSIS; GROWTH AB The proteasome inhibitor bortezomib has shown impressive clinical activity alone and in combination with conventional and other novel agents for the treatment of multiple myeloma (MM). Although bortezomib is known to be a selective proteasome inhibitor, the downstream mechanisms of cytotoxicity and drug resistance are poorly understood. However, resistance to bortezomib as a single agent develops in the majority of patients, and activity in other malignancies has been less impressive. To elucidate mechanisms of bortezomib resistance, we compared differential gene expression profiles of bortezomib-resistant SUDHL-4 and bortezomib-sensitive SUDHL-6 diffuse large B-cell lymphoma lines in response to bortezomib. At concentrations that effectively inhibited proteasome activity, bortezomib induced apoptosis in SUDHL-6 cells, but not in SUDHL-4 cells. We showed that overexpression of activating transcription factor 3 (ATF3), ATF4, ATF5, c-Jun, JunD and caspase-3 is associated with sensitivity to bortezomib-induced apoptosis, whereas overexpression of heat shock protein (HSP)27, HSP70, HSP90 and T-cell factor 4 is associated with bortezomib resistance. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Amylin Pharmaceut Inc, San Diego, CA USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, 44 Binney St,Mayer 557, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013; OI Kessler, Benedikt/0000-0002-8160-2446 FU NCI NIH HHS [P50 CA100707]; PHS HHS [P0-1 78378] NR 53 TC 76 Z9 81 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2006 VL 134 IS 2 BP 145 EP 156 DI 10.1111/j.1365-2141.2006.06132.x PG 12 WC Hematology SC Hematology GA 053LO UT WOS:000238306800003 PM 16846475 ER PT J AU Otto, MW Simon, NM Wisniewski, SR Miklowitz, DJ Kogan, JN Reilly-Harrington, NA Frank, E Nierenberg, AA Marangell, LB Sagduyu, K Weiss, RD Miyahara, S Thase, ME Sachs, GS Pollack, MH AF Otto, M. W. Simon, N. M. Wisniewski, S. R. Miklowitz, D. J. Kogan, J. N. Reilly-Harrington, N. A. Frank, E. Nierenberg, A. A. Marangell, L. B. Sagduyu, K. Weiss, R. D. Miyahara, S. Thase, M. E. Sachs, G. S. Pollack, M. H. CA STEP-BD Investigators TI Prospective 12-month course of bipolar disorder in out-patients with and without comorbid anxiety disorders SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; I DISORDER; STEP-BD; PSYCHIATRIC COMORBIDITY; SPECTRUM SYMPTOMS; MAJOR DEPRESSION; PANIC DISORDER; SUBSTANCE USE; PREVALENCE; SCALE AB Background The impact of anxiety disorders has not been well delineated in prospective studies of bipolar disorder. Aims To examine the association between anxiety and course of bipolar disorder, as defined by mood episodes, quality of life and role functioning. Method A thousand out-patients with bipolar disorder were followed prospectively for 1 year. Results A current comorbid anxiety disorder (present in 31.9% of participants) was associated with fewer days well, a lower likelihood of timely recovery from depression, risk of earlier relapse, lower quality of life and diminished role function over 1 year of prospective study. The negative impact was greater with multiple anxiety disorders. Conclusions Anxiety disorders, including those present during relative euthymia, predicted a poorer bipolar course. The detrimental effects of anxiety were not simply a feature of mood state. Treatment studies targeting anxiety disorders will help to clarify the nature of the impact of anxiety on bipolar course. Declaration of interest None. Funding detailed in Acknowledgements. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. Univ Colorado, Boulder, CO 80309 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Missouri, Sch Med, Kansas City, MO USA. Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. RP Otto, MW (reprint author), Boston Univ, Ctr Anxiety & Relates Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM mwotto@bu.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIDA NIH HHS [DA15968, DA00326]; NIMH NIH HHS [MH-01831-01, N01MH80001] NR 28 TC 123 Z9 124 U1 2 U2 5 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 JUL PY 2006 VL 189 BP 20 EP 25 DI 10.1192/bjp.bp.104.007773 PG 6 WC Psychiatry SC Psychiatry GA 062CD UT WOS:000238921100004 PM 16816301 ER PT J AU Kimmel, AD Losina, E Freedberg, KA Goldie, SJ AF Kimmel, April D. Losina, Elena Freedberg, Kenneth A. Goldie, Sue J. TI Diagnostic tests in HIV management: a review of clinical and laboratory strategies to monitor HIV-infected individuals in developing countries SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Review ID RESOURCE-POOR SETTINGS; TOTAL LYMPHOCYTE COUNT; CD4 COUNTS; ANTIRETROVIRAL THERAPY; RESEARCH AGENDA; STAGING SYSTEM; RNA; MARKERS; ADULTS; ASSAYS AB We conducted asystematic review on the performance of diagnostic tests for clinical and laboratory monitoring of HIV-infected adults in developing countries. Diagnostic test information collected from computerized databases, bibliographies and the Internet were, categorized a's clinical (non-laboratory patient information), immunologic (information from immunologic laboratory tests), or virologic,(information from virologic laboratory tests). Of the 51 studies selected for the review 28 assessed immunologic tests, 12 virologic tests and seven clinical and immunologic tests. Methods of performance evaluation were primarily sensitivity and specificity for the clinical category and correlation coefficients for immunologic and virologic categories. In the clinical category, the majority of test performance measures was reported as > 70% sensitive and > 65% specific. In the immunologic category, correlation coefficients ranged from r = 0.54 to r = 0.99 for different CD4 count enumeration techniques, while correlation for CD4 and total lymphocyte counts was between r = 0.23 and r = 0.74. In the virologic category, correlation coefficients for different human immunodeficiency virus (HIV) ribonucleic acid (RNA) quantification techniques ranged from r = 0.54 to r = 0.90. Future research requires consensus on designing studies, and collecting and reporting data useful for decision-makers. We recommend classifying information into clinically relevant categories, using a consistent definition of disease across studies and providing measures of both association and accuracy. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. RP Kimmel, AD (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM akimmel@partners.org FU AHRQ HHS [T32 HS00055]; NIAID NIH HHS [P30 AI042851, P30 AI42851, K24 AI062476, K25 AI050436, K25 AI50436, R01 AI058736] NR 40 TC 3 Z9 3 U1 0 U2 1 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD JUL PY 2006 VL 84 IS 7 BP 581 EP 588 DI 10.2471/BLT.05.021865 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 063SK UT WOS:000239039700017 PM 16878233 ER PT J AU Walters, DK Mercher, T Gu, TL O'Hare, T Tyner, JW Loriaux, M Goss, VL Lee, KA Eide, CA Wong, MJ Stoffregen, EP McGreevey, L Nardone, J Moore, SA Crispino, J Boggon, TJ Heinrich, MC Deininger, MW Polakiewicz, RD Gilliland, DG Druker, BJ AF Walters, Denise K. Mercher, Thomas Gu, Ting-Lei O'Hare, Thomas Tyner, Jeffrey W. Loriaux, Marc Goss, Valerie L. Lee, Kimberly A. Eide, Christopher A. Wong, Matthew J. Stoffregen, Eric P. McGreevey, Laura Nardone, Julie Moore, Sandra A. Crispino, John Boggon, Titus J. Heinrich, Michael C. Deininger, Michael W. Polakiewicz, Roberto D. Gilliland, D. Gary Druker, Brian J. TI Activating alleles of JAK3 in acute megakaryoblastic leukemia SO CANCER CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE JAK2; MICE LACKING JAK3; POLYCYTHEMIA-VERA; MYELOPROLIFERATIVE DISORDERS; CONSTITUTIVE ACTIVATION; JANUS KINASE; CELL-LINES; PSEUDOKINASE DOMAIN; ALLOGRAFT-REJECTION AB Tyrosine kinases are aberrantly activated in numerous malignancies, including acute myeloid leukemia (AML). To identify tyrosine kinases activated in AML, we developed a screening strategy that rapidly identifies tyrosine-phosphorylated proteins using mass spectrometry. This allowed the identification of an activating mutation (A572V) in the JAK3 pseudokinase domain in the acute megakaryoblastic leukemia (AMKL) cell line CMK. Subsequent analysis identified two additional JAK3 alleles, V722I and P132T, in AMKL patients. JAK3(A572V), JAK3(P132T), and JAK3P132T each transform Ba/F3 cells to factor-independent growth, and JAK3 A572V confers features of megakaryoblastic leukemia in a murine model. These findings illustrate the biological importance of gain-of-function JAK3 mutations in leukemogenesis and demonstrate the utility of proteomic approaches to identifying clinically relevant mutations. C1 Howard Hughes Med Inst, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Hematol & Med Oncol, Portland, OR 97239 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. Cell Signaling Technol Inc, Danvers, MA 01923 USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. RP Druker, BJ (reprint author), Howard Hughes Med Inst, Portland, OR 97239 USA. EM drukerb@ohsu.edu RI Mercher, Thomas/J-2446-2014; OI Mercher, Thomas/0000-0003-1552-087X; Tyner, Jeffrey/0000-0002-2133-0960; Crispino, John/0000-0002-8182-8306 FU NCI NIH HHS [R01 CA101774, R01 CA101774-04] NR 66 TC 188 Z9 191 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2006 VL 10 IS 1 BP 65 EP 75 DI 10.1016/j.ccr.2006.06.002 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 066AW UT WOS:000239202800009 PM 16843266 ER PT J AU Eder, JP Ryan, DP Appleman, L Zhu, AX Puchalski, T He, XY Sonnichsen, DS Cooper, M Wright, J Clark, JW Supko, JG AF Eder, JP Ryan, DP Appleman, L Zhu, AX Puchalski, T He, XY Sonnichsen, DS Cooper, M Wright, J Clark, JW Supko, JG TI Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 administered as a weekly 24 h continuous intravenous infusion in patients with advanced solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol DE cancer; chemotherapy; human; pharmacokinetics; pharmacodynamics ID PRECLINICAL ANTITUMOR-ACTIVITY; CANCER-THERAPY; ONCOGENIC RAS AB Purpose: BMS-214662 is a novel farnesyltransferase ( FT) inhibitor that has shown promising suggestions of single agent activity in patients with advanced solid tumors when administered as a 1 h intravenous (i.v.) infusion every 3 weeks. The degree of FT inhibition in peripheral blood mononuclear cells (PBMCs) was greatest at the end of the infusion and rapidly reversed as the concentration of the drug in the plasma decayed. A second phase I trial of BMS-214662 administered as a weekly 24 h i.v. infusion was initiated to determine if the duration of maximum FT inhibition could be significantly extended by prolonging the infusion time and increasing the frequency of administration. Patients and methods: Infusion of BMS-214662 was prolonged from 2, 4, 8, 16, 24 h in single patient cohorts and repeated weekly for 3 out of 4 weeks. The initial dose was 56 mg/m(2). When the infusion duration reached 24 h, the dose was escalated at a constant multiples of 1.4 in single patient cohorts until the occurrence of toxicity greater than grade 1, upon which groups of at least three patients were evaluated at each dose level. The plasma pharmacokinetics and FT inhibition in PBMCs were measured in all patients at the prospective maximum tolerated dose. Results: Nineteen patients participated in the study ( 11 males/8 females) and the weekly dose was increased to a maximum of 300 mg/m(2) given as a 24 h i.v. infusion. Drug-related toxicity greater than grade 1 first occurred at 300 mg/m(2), with two patients experiencing dose-limiting toxicity. One patient developed a grade 3 hyponatremia and another developed reversible grade 3 diarrhea, grade 2 renal toxicity, and grade 3 transaminitis. A 275 mg/m(2) dose was then evaluated, where one of the three patients treated experienced reversible grade 4 renal toxicity and grade 3 diarrhea. In view of the identical renal toxicity at 275 mg/m(2) in another study and limited drug availability, there was no further accrual to this dose level and the study was closed. No evidence of antitumor activity was observed. The plasma pharmacokinetics of BMS-214662 was linear with high interpatient variability. In the three patients evaluated at the 275 mg/m(2) dose level, the maximum inhibition of FT activity in PBMCs was 47 +/- 23% of the baseline. Conclusion: Administering BMS-214662 as a weekly 24 h continuous i.v. infusion permitted a considerably greater dose intensity to be delivered as compared to a single 1 h infusion given once every 3 weeks. The more prolonged infusion schedule resulted in a much lower degree of maximum FT inhibition in PBMCs than achieved with the 1 h infusion, although the duration of enzyme inhibition was longer, consistent with the lower peak plasma concentration of the drug provided by comparably tolerated doses when given as a 24 h infusion. Similarly, delivering the drug with increased dose intensity permitted by this weekly administration schedule did not appear to enhance its therapeutic benefit, at least in this phase I trial. Continued development of BMS-214662 may depend upon the potential for using it in combination with other anticancer drugs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Harvard Canc Ctr,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Bristol Myers Squibb Co, Princeton, NJ USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. RP Eder, JP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Shields Warren Bldg 460,44 Binney St, Boston, MA 02115 USA. EM jeder@partners.org OI Appleman, Leonard/0000-0003-4951-7388 FU NCI NIH HHS [P30-CA-0516, U01-CA-62490] NR 16 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 2006 VL 58 IS 1 BP 107 EP 116 DI 10.1007/s00280-005-0134-0 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 035AP UT WOS:000236972400012 PM 16362299 ER PT J AU Ford, BM Evans, JS Stoffel, EM Balmana, J Regan, MM Syngal, S AF Ford, Beth M. Evans, James S. Stoffel, Elena M. Balmana, Judith Regan, Meredith M. Syngal, Sapna TI Factors associated with enrollment in cancer genetics research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; INFORMED-CONSENT; BREAST-CANCER; PARTICIPATION; ATTITUDES; BARRIERS; AGE; RECRUITMENT; ONCOLOGY; RACE AB Previous studies have identified low patient accrual in large-scale cancer clinical trials, particularly for underrepresented groups, such as ethnic minorities, females, and patients > 65 years. As there have been few studies examining participation in cancer genetics epidemiologic research, our objective was to identify clinical and demographic factors predicting enrollment in these studies. A total of 1,111 patients diagnosed with colorectal cancer presenting to a gastrointestinal oncology clinic were approached to enroll in a study investigating the role of the MSH6 gene in familial colorectal cancer. Patient consent was sought for providing a blood specimen for DNA analysis and review of medical records/tumor specimens and contacting family members to confirm the family history of cancer. Seven predictor variables for enrollment (age, sex, ethnicity, family history of colorectal cancer in a first-degree relative, presence of children, insurance type, and type of visit) were analyzed using logistic regression analysis to determine the effect on decision to enroll. Of 1,111 patients approached, 696 (62.6%) enrolled in the study. Of these approached individuals, 4.2% were of nonwhite ethnicity and 33.5% were age >= 65 years. Patients of white ethnicity [odds ratio (OR), 2.10; P = 0.018], males (OR, 1.47; P = 0.002), those ages >= 65 years (OR, 1.42; P = 0.009), and those with a first-degree relative with colorectal cancer (OR, 1.57; P = 0.005) were significantly more likely to enroll. Fewer than 4% of all participants denied permission for the study researchers to access information from medical records or to be recontacted by researchers to discuss the enrollment of additional family members. Our data suggest that, once subjects decided to enroll, the majority (88%) was comfortable with consenting to all study components, including the creation of cell lines and future recontact. Low participation rates for ethnic minorities, females, and elderly patients are similar for both cancer genetics and clinical trial studies. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Mt Auburn Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Autonoma Barcelona, Hosp Univ Vall Hebron, Barcelona, Spain. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 1 Jimmy Fund Way,SM 209, Boston, MA 02115 USA. EM ssyngal@partners.org FU NCI NIH HHS [R01CA85759] NR 34 TC 21 Z9 21 U1 0 U2 3 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 JUL PY 2006 VL 15 IS 7 BP 1355 EP 1359 DI 10.1158/1055-9965.EPI-05-0816 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 061OB UT WOS:000238880800020 PM 16835336 ER PT J AU Shimamura, T Ji, HB Minami, Y Thomas, RK Lowell, AM Shah, K Greulich, H Glatt, KA Meyerson, M Shapiro, GI Wong, KK AF Shimamura, Takeshi Ji, Hongbin Minami, Yuko Thomas, Roman K. Lowell, April M. Shah, Kinjal Greulich, Heidi Glatt, Karen A. Meyerson, Matthew Shapiro, Geoffrey I. Wong, Kwok-Kin TI Non-small-cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272 SO CANCER RESEARCH LA English DT Article ID IRREVERSIBLE INHIBITORS; KINASE DOMAIN; EGF RECEPTOR; GEFITINIB; RESISTANCE; EXPRESSION; ERLOTINIB; MUTANTS; TUMORS AB Mutation-specific cancer therapy has shown promising clinical efficacy. In non-small-cell lung cancer (NSCLC), the presence of mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase correlates with clinical response to small-molecule tyrosine kinase inhibitors. Here, we show that cells harboring the G776insV_G/C mutation in the related ERBB2 tyrosine kinase (also known as HER2 or Neu), present in a small percentage of NSCLCs, are sensitive to HKI-272, an irreversible dual-specific kinase inhibitor targeting both EGFR and ERBB2. In the ERBB2-matant NCI-H1781 cell line, HKI-272 treatment inhibited proliferation by induction of G(I) arrest and apoptotic cell death. Furthermore, HKI-272 abrogated autophosphorylation of both ERBB2 and EGFR. Finally, Ba/F3 murine pro-B cells, engineered to express mutant EABB2, became independent of interleukin-3 and sensitive to HKI-272. Thus, the subset of NSCLC patients with tumors carrying the ERBB2 G776insV_G/C mutation may benefit from treatment with HKI-272. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Broad Inst MIT & Harvard, Cambridge, MA USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 810B,44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu; kwong1@partners.org RI Meyerson, Matthew/E-7123-2012; OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [CA 116020, CA 90679, CA 90687, P20 CA 90578]; NIA NIH HHS [AG 24004-01, AG 24379] NR 22 TC 82 Z9 88 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2006 VL 66 IS 13 BP 6487 EP 6491 DI 10.1158/0008-5472.CAN-06-0971 PG 5 WC Oncology SC Oncology GA 060TZ UT WOS:000238825800007 PM 16818618 ER PT J AU Farazi, PA Zeisberg, M Glickman, J Zhang, Y Kalluri, R DePinho, RA AF Farazi, Paraskevi A. Zeisberg, Michael Glickman, Jonathan Zhang, Yan Kalluri, Raghu DePinho, Ronald A. TI Chronic bile duct injury associated with fibrotic matrix microenvironment provokes cholangiocarcinoma in p53-deficient mice SO CANCER RESEARCH LA English DT Article ID PRIMARY SCLEROSING CHOLANGITIS; INTRAHEPATIC CHOLANGIOCARCINOMA; NITRIC-OXIDE; CARBON-TETRACHLORIDE; MICROSATELLITE INSTABILITY; HEPATOCELLULAR-CARCINOMA; GENETIC ALTERATIONS; RECENT PROGRESS; RAT-LIVER; P53 AB Intrahepatic cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium associated with p53 mutations, bile duct injury, inflammation, and fibrosis. Here, to validate these processes in CCA, we developed a liver cirrhosis model driven by chronic intermittent toxin exposure, which provokes bile duct injury/necrosis and proliferation, fibroblast recruitment, and progressive extracellular matrix (ECM) changes. Fibrotic changes in the matrix microenvironment, typified by increased type I and III collagens and fibroblast recruitment, were shown to stimulate biliary epithelium hyperplasia with subsequent progression to malignant intrahepatic CCA only in mice harboring a p53 mutant allele. These murine CCAs bear histologic and genetic features of human intrahepatic CCA, including dense peritumoral fibrosis, increased inducible nitric oxide synthase, nitrotyrosine, and cyclooxygenase-2 expression, c-Met activation, cErbB2 overexpression, down-regulation of membrane-associated E-cadherin, and p53 codon 248 mutation. Thus, p53 deficiency, chronic bile duct injury/proliferation, and the fibrotic matrix microenvironment cooperate to induce intrahepatic CCA, highlighting the key role of the ECM microenvironment in this common liver cancer. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Matrix Biol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Div Med Sci, Dept Genet, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med & Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci, 44 Binney St M413, Boston, MA 02115 USA. EM rkalluri@bidmc.harvard.edu; ron_depinho@dfci.harvard.edu RI Kalluri, Raghu/E-2677-2015 OI Kalluri, Raghu/0000-0002-2190-547X FU NCI NIH HHS [U01 CA 84313]; NIAAA NIH HHS [AA 13913]; NIDDK NIH HHS [5T32 DK 07760, DK 62987] NR 48 TC 46 Z9 50 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 JUL 1 PY 2006 VL 66 IS 13 BP 6622 EP 6627 DI 10.1158/0008-5472.CAN-05-4609 PG 6 WC Oncology SC Oncology GA 060TZ UT WOS:000238825800024 PM 16818635 ER PT J AU Tai, YT Li, XF Breitkreutz, I Song, WH Neri, P Catley, L Podar, K Hideshima, T Chauhan, D Raje, N Schlossman, R Richardson, P Munshi, NC Anderson, KC AF Tai, Yu-Tzu Li, Xian-Feng Breitkreutz, Iris Song, Weihua Neri, Paola Catley, Laurence Podar, Klaus Hideshima, Tern Chauhan, Dharminder Raje, Noopur Schlossman, Robert Richardson, Paul Munshi, Nikhil C. Anderson, Kenneth C. TI Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR FAMILY; GENE-EXPRESSION; PLASMA-CELLS; BAFF-R; APRIL; BCMA; SURVIVAL; TACI; RECEPTOR AB Recent studies have underscored the role of B-cell-activating factor (BAFF), a member of the tumor necrosis factor superfamily, in promoting the survival of malignant B cells, including human multiple myeloma. We here characterized the functional significance of BAFF in the interaction between multiple myeloma and bone marrow stromal cells (BMSC) and further defined the molecular mechanisms regulating these processes. BAFF is detected on BMSCs derived from multiple myeloma patients as evidenced by flow cytometry. RAFF secretion is 3- to 10-fold higher in BMSCs than in multiple myeloma cells, and tumor cell adhesion to BMSCs augments BAFF secretion by 2- to 5-fold, confirmed by both ELISA and immunoblotting. Adhesion of MMIS and MCCAR multiple myeloma cell lines to KM104 BMSC line transfected with a luciferase reporter vector carrying the BAFF gene promoter (BAFF-LUC) significantly enhanced luciferase activity, suggesting that nuclear factor-kappa B (NF-kappa B) activation induced by multiple myeloma adhesion to BMSCs mediates BAFF up-regulation. Moreover, BAFF (0-100 ng/mL) increases adhesion of multiple myeloma lines to BMSCs in a dose-dependent manner; conversely, transmembrane activator and calcium modulator and cyclophylin ligand interactor-Ig or B-cell maturation antigen/Fc blocked BAFF stimulation. Using adenoviruses expressing dominant-negative and constitutively expressed AKT as well as NF-kappa B inhibitors, we further showed that BAFF-induced multiple myeloma cell adhesion is primarily mediated via activation of AKT and NF-kappa B signaling. Importantly, BAFF similarly increased adhesion of CD138-expressing patient multiple myeloma cells to BMSCs. These studies establish a role for BAFF in localization and survival of multiple mycloma cells in the bone marrow microenvironment and strongly support novel therapeutics, targeting the interaction between BAFF and its receptors in human multiple myeloma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02215 USA. RP Tai, YT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, M551,44 Binney St, Boston, MA 02215 USA. EM yu-tzu_tai@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU PHS HHS [R01 50947, P01 78378] NR 40 TC 127 Z9 136 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2006 VL 66 IS 13 BP 6675 EP 6682 DI 10.1158/0008-5472.CAN-06-0190 PG 8 WC Oncology SC Oncology GA 060TZ UT WOS:000238825800030 PM 16818641 ER PT J AU Dang, H Dehghan, PL Goodwiler, K Chen, S Zardeneta, G Zhang, BX Yeh, CK AF Dang, Howard Dehghan, Parastou Lizeth Goodwiler, Kai Chen, Shuo Zardeneta, Gustavo Zhang, Bin-Xian Yeh, Chih-Ko TI Inhibition of CD95-mediated apoptosis through beta 1 integrin in the HSG epithelial cell line SO CELL COMMUNICATION AND ADHESION LA English DT Article DE salivary gland; Bcl-2; apoptosis; CD95; integrins; p63 ID SUBMANDIBULAR-GLAND; SALIVARY-GLAND; EGF RECEPTOR; SURVIVAL; ANOIKIS; PROTEIN; INTEGRINS; P63; ACTIVATION; MECHANISMS AB The HSG cell line serves as a model for salivary gland epithelial progenitor cell differentiation. In order for a progenitor cell to differentiate, the cell must maintain viability within its niche. Studies were designed to elucidate the mechanism for integrin-mediated HSG cell survival. HSG cells, grown on Matrigel(R), were resistant to CD95-mediated apoptosis. Western blot analysis showed that Matrigel(R) induced the expression of bcl-2, bcl-xL, p63, and Delta Np63. This induction occurred by as early as 2 hrs and remained for 24 hrs. CD95-mediated apoptosis resistance was dependent, however, upon the expression of the bcl-2 family. Furthermore, Matrigel(R) induced bcl-2 family expression was dependent on the transactivation of the EGF receptor pathway since PD98059 and AG1478 inhibited Matrigel(R) induced bcl-2 family expression and caused HSG cells to be sensitive to CD95-mediated apoptosis. Activation of the EGF receptor pathway, by itself, however, was not sufficient to inhibit apoptosis. Blocking antibody showed that bcl-2 family expression was mediated through beta 1 integrin. These studies show that salivary progenitor epithelial cell survival is integrin dependent and involves the transactivation of the EGF receptor pathway. C1 Univ Texas, Hlth Sci Ctr, Dept Community Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Oral & Maxillofacial Surg, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res Serv, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Dang, H (reprint author), Univ Texas, Hlth Sci Ctr, Dept Community Dent, Mail Code 7917, San Antonio, TX 78229 USA. EM dang@uthscsa.edu FU NIDCR NIH HHS [DE-017333, DE-15381] NR 34 TC 2 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1541-9061 J9 CELL COMMUN ADHES JI Cell Commun. Adhes. PD JUL-AUG PY 2006 VL 13 IS 4 BP 223 EP 232 DI 10.1080/15419060600848532 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 074OC UT WOS:000239820700003 PM 16916750 ER PT J AU Lacy-Hulbert, A Moore, KJ AF Lacy-Hulbert, Adam Moore, Kathryn J. TI Designer macrophages: Oxidative metabolism fuels inflammation repair SO CELL METABOLISM LA English DT Editorial Material ID ACTIVATION; DISEASE AB Macrophages play a central role in immunity, contributing to both the initiation and resolution of inflammation. In this issue of Cell Metabolism, Vats et al. provide insight into the mechanisms by which reparative macrophages are generated and reveal a previously unappreciated link between this anti-inflammatory axis and mitochondrial oxidative metabolism (Vats et al., 2006). C1 Univ Edinburgh, Ctr Inflammat Res, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Lacy-Hulbert, A (reprint author), Univ Edinburgh, Ctr Inflammat Res, Queens Med Res Inst, 47 Little France Crescent, Edinburgh EH16 4TJ, Midlothian, Scotland. OI Lacy-Hulbert, Adam/0000-0003-2162-0156; Moore, kathryn/0000-0003-2505-2547 NR 10 TC 18 Z9 20 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUL PY 2006 VL 4 IS 1 BP 7 EP 8 DI 10.1016/j.cmet.2006.06.001 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 060SL UT WOS:000238821800004 PM 16814727 ER PT J AU Uldry, M Yang, WL St-Pierre, J Lin, JD Seale, P Spiegelman, BM AF Uldry, Marc Yang, Wenli St-Pierre, Julie Lin, Jiandie Seale, Patrick Spiegelman, Bruce M. TI Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation (vol 3, pg 333, 2006) SO CELL METABOLISM LA English DT Correction ID OLIGONUCLEOTIDE ARRAYS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu NR 3 TC 0 Z9 0 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUL PY 2006 VL 4 IS 1 BP 97 EP 97 DI 10.1016/j.cmet.2006.06.005 PG 1 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 060SL UT WOS:000238821800013 ER PT J AU Altmann, SM Muryshev, A Fossale, E Maxwell, MM Norflus, FN Fox, J Hersch, SM Young, AB MacDonald, ME Abagyan, R Kazantsev, AG AF Altmann, Stephen M. Muryshev, Andrey Fossale, Elisa Maxwell, Michele M. Norflus, Francine N. Fox, Jonathan Hersch, Steven M. Young, Anne B. MacDonald, Marcy E. Abagyan, Ruben Kazantsev, Aleksey G. TI Discovery of bioactive small-molecule inhibitor of poly ADP-ribose polymerase: Implications for energy-deficient cells SO CHEMISTRY & BIOLOGY LA English DT Article ID HUNTINGTONS-DISEASE; POLY(ADP-RIBOSE) POLYMERASE-1; DNA-DAMAGE; OXIDATIVE DAMAGE; PROTEINS; STRESS; REPAIR; DEATH AB Poly (ADP-ribose) polymerase (PARP1) is a nuclear protein that, when overactivated by oxidative stress-induced DNA damage, ADP ribosylates target proteins leading to dramatic cellular ATP depletion. We have discovered a biologically active small-molecule inhibitor of PARP1. The discovered compound inhibited PARP1 enzymatic activity in vitro and prevented ATP loss and cell death in a surrogate model of oxidative stress in vivo. We also investigated a new use for PARP1 inhibitors in energy-deficient cells by using Huntington's disease as a model. Our results showed that insult with the oxidant hydrogen peroxide depleted cellular ATP in mutant cells below the threshold of viability. The protective role of PARP1 inhibitors against oxidative stress has been shown in this model system. C1 Massachusetts Gen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Inst Mol Phys, Moscow 123182, Russia. Molsoft LLC, La Jolla, CA 92037 USA. Richard B Simches Res Ctr, Boston, MA 02114 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Kazantsev, AG (reprint author), Massachusetts Gen Inst Neurodegenerat Dis, Bldg 114,3300 16th St, Charlestown, MA 02129 USA. EM akazantsev@partners.org FU NIGMS NIH HHS [GM071872-02]; NINDS NIH HHS [NS32765, NS16367] NR 21 TC 7 Z9 7 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JUL PY 2006 VL 13 IS 7 BP 765 EP 770 DI 10.1016/j.chembiol.2006.05.012 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 070TJ UT WOS:000239546800011 PM 16873024 ER PT J AU Okram, B Nagle, A Adrian, FJ Lee, C Ren, P Wang, X Sim, T Xie, YP Wang, X Xia, G Spraggon, G Warmuth, M Liu, Y Gray, NS AF Okram, Barun Nagle, Advait Adrian, Francisco J. Lee, Christian Ren, Pingda Wang, Xia Sim, Taebo Xie, Yongping Wang, Xing Xia, Gang Spraggon, Glen Warmuth, Markus Liu, Yi Gray, Nathanael S. TI A general strategy for creating "Inactive-conformation" Abl inhibitors SO CHEMISTRY & BIOLOGY LA English DT Article ID TYROSINE KINASE INHIBITORS; CHRONIC MYELOID-LEUKEMIA; P38 MAP KINASE; CLINICAL DEVELOPMENT; BIOLOGICAL-ACTIVITY; STRUCTURAL BIOLOGY; IN-VIVO; DESIGN; POTENT; STI-571 AB Kinase inhibitors that bind to the ATP cleft can be broadly classified into two groups: those that bind exclusively to the ATP site with the kinase assuming a conformation otherwise conducive to phosphotransfer-(type 1), and those that exploit a hydrophobic site immediately adjacent to the ATP pocket made accessible by a conformational rearrangement of the activation loop (type II). To date, all type II inhibitors were discovered by using structure-activity-guided optimization strategies. Here, we describe a general pharmacophore model of type II inhibition that enables a rational "hybrid-design" approach whereby a 3-trifluoromethylbenzamide functionality is appended to four distinct type I scaffolds in order to convert them into their corresponding type II counterparts. We demonstrate that the designed compounds function as type II inhibitors by using biochemical and cellular kinase assays and by cocrystallography with Abl. C1 Novartis Res Fdn, Genom Inst, Dept Biol Chem, San Diego, CA 92121 USA. Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Liu, Y (reprint author), Novartis Res Fdn, Genom Inst, Dept Biol Chem, 10675 Joh Jay Hopkins Dr, San Diego, CA 92121 USA. EM yliu@gnf.org; nathanael_gray@dfci.harvard.edu NR 35 TC 118 Z9 121 U1 1 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 JUL PY 2006 VL 13 IS 7 BP 779 EP 786 DI 10.1016/j.chembiol.2006.05.015 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 070TJ UT WOS:000239546800013 PM 16873026 ER PT J AU Choi, Y Weissleder, R Tung, CH AF Choi, Yongdoo Weissleder, Ralph Tung, Ching-Hsuan TI Protease-mediated phototoxicity of a polylysine-chlorin(e6) conjugate SO CHEMMEDCHEM LA English DT Article AB Photodynamic therapy with a molecular switch: Both singlet oxygen generation and near-infrared fluorescence from a photosensitizer were markedly decreased by conjugating multiple chlorine, photosensitizers onto a polypeptide backbone. Protease-mediated cleavage of the backbone results in the formation of degraded probes, which are highly phototoxic and fluorescent. RP Choi, Y (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu FU NCI NIH HHS [P50-CA86355, R01 CA99385] NR 14 TC 23 Z9 24 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD JUL PY 2006 VL 1 IS 7 BP 698 EP + DI 10.1002/cmdc.200600053 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V43PC UT WOS:000202946000005 PM 16902920 ER PT J AU Schatz, M Camargo, CA AF Schatz, Michael Camargo, Carlos A., Jr. TI Follow-up after an asthma hospitalization - Who can prevent subsequent exacerbations? SO CHEST LA English DT Editorial Material ID EMERGENCY-DEPARTMENT VISITS; INTERVENTION PROGRAM; CONTROLLED-TRIAL; HEALTH OUTCOMES; ADULT ASTHMA; RISK-FACTORS; CARE; ADMISSIONS; CHILDREN; MANAGEMENT C1 Kaiser Permanente Med Care Program, Dept Allergy, San Diego, CA 92111 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Cambridge, MA 02138 USA. RP Schatz, M (reprint author), Kaiser Permanente Med Care Program, Dept Allergy, 7060 Clairemont Mesa Blvd, San Diego, CA 92111 USA. EM michael.x.schalz@kp.org NR 23 TC 6 Z9 6 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2006 VL 130 IS 1 BP 8 EP 10 DI 10.1378/chest.130.1.8. PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 066HC UT WOS:000239219300005 PM 16840375 ER PT J AU Stoddard, FJ Usher, CT Abrams, AN AF Stoddard, Frederick J. Usher, Craigan T. Abrams, Annah N. TI Psychopharmacology in pediatric critical care SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; MINI-MENTAL-STATE; CLINICAL PHARMACOKINETICS; BURNED CHILDREN; FLUOXETINE PHARMACOKINETICS; ATYPICAL ANTIPSYCHOTICS; MECHANICAL VENTILATION; RISPERIDONE TREATMENT; HYPERACTIVE-CHILDREN AB The use of psychopharmacologic drugs in critical care is rapidly expanding. Compassionate prescribing of medications for children who have sustained major injuries or suffer life-threatening illness dramatically reduces the pain and suffering which they endure. The potential benefits of psychopharmacologic interventions must be weighed against risks for adverse effects, toxicity, or untoward drug interactions. Unfortunately most clinical trials have not included children under 12, or the critically ill. This overview addresses the following: (1) general psychopharmacologic principles; (2) classes of psychotropic drugs; (3) the basics of child psychiatric consultation in critical care; (4) the treatment of delirium, pain and psychiatric disorders; and (5) palliative care. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Child Psychiat Consultat Liaison Serv, Boston, MA 02114 USA. RP Stoddard, FJ (reprint author), Massachusetts Gen Hosp, 51 Blossom St, Boston, MA 02114 USA. EM fstoddard@partners.org NR 149 TC 13 Z9 13 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2006 VL 15 IS 3 BP 611 EP + DI 10.1016/j.chc.2006.02.005 PG 46 WC Psychiatry SC Psychiatry GA 065AK UT WOS:000239131600007 PM 16797442 ER PT J AU Duncan, J Joselow, M Hilden, JM AF Duncan, Janet Joselow, Marsha Hilden, Joanne M. TI Program interventions for children at the end of life and their siblings SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID BEREAVED SIBLINGS; WEEKEND; CANCER; DEATH; CARE AB An analogy may be drawn between readying a family for the birth of a child and readying a family for the death of a child. Both experiences bring about an intense fusion of the emotional, physical, and spiritual realms for those bearing witness. Preparation, communication, and collaboration are essential to provide optimal support for the children at the end of life, the parents, and the brothers and sisters. C1 Childrens Hosp, Pediat Adv Care Team, Boston, MA 02116 USA. Dana Farber Canc Inst, Boston, MA 02116 USA. Childrens Hosp, Cleveland Clin, Cleveland, OH 44195 USA. RP Duncan, J (reprint author), Childrens Hosp, Pediat Adv Care Team, 44 Binney St,Dana 3, Boston, MA 02116 USA. EM janet.duncan@childrens.harvard.edu NR 23 TC 6 Z9 6 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2006 VL 15 IS 3 BP 739 EP + DI 10.1016/j.chc.2006.02.002 PG 21 WC Psychiatry SC Psychiatry GA 065AK UT WOS:000239131600012 PM 16797447 ER PT J AU Swick, SD Rauch, PK AF Swick, Susan D. Rauch, Paula K. TI Children facing the death of a parent: The experiences of a parent guidance program at the Massachusetts General Hospital Cancer Center SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID CHILDHOOD BEREAVEMENT; PSYCHOLOGICAL DISTRESS; TERMINAL CANCER; IMPACT; MOM; DAD AB Children facing the death of a parent are facing a major upheaval, a loss that will bring them emotional pain and will resonate in different ways at important points throughout their lives. Given the proper supports, most children can expect to adjust well to this enormous change and live happy, productive, and meaningful lives. The goal is to help parents relocate their bearings and realize they can use the parenting skills they already have in helping their children make this adjustment. Guided by the goal of protecting their children, these parents can find purpose and strength. Reframing their circumstances as a painful and unavoidable challenge, but one that they can actively face, is organizing and fortifying for these families buffeted by loss. C1 Massachusetts Gen Hosp, Child Psychiat Consultat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Canc Ctr, Parenting Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Rauch, PK (reprint author), Massachusetts Gen Hosp, Child Psychiat Consultat Serv, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM prauch@partners.org NR 16 TC 6 Z9 7 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2006 VL 15 IS 3 BP 779 EP + DI 10.1016/j.chc.2006.02.007 PG 18 WC Psychiatry SC Psychiatry GA 065AK UT WOS:000239131600014 PM 16797449 ER PT J AU Bell, DW Haber, DA AF Bell, Daphne W. Haber, Daniel A. TI A blood-based test for epidermal growth factor receptor mutations in lung cancer - Commentary SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; GENE-MUTATIONS; KINASE DOMAIN; EGF RECEPTOR; GEFITINIB; ADENOCARCINOMAS; ERLOTINIB; SURVIVAL; FEATURES C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY7,149 13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu NR 16 TC 10 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2006 VL 12 IS 13 BP 3875 EP 3877 DI 10.1158/1078-0432.CCR-06-0670 PG 3 WC Oncology SC Oncology GA 062FR UT WOS:000238930500002 PM 16818680 ER PT J AU Jackman, DM Yeap, BY Sequist, LV Lindeman, N Holmes, AJ Joshi, VA Bell, DW Huberman, MS Halmos, B Rabin, MS Haber, DA Lynch, TJ Meyerson, M Johnson, BE Janne, PA AF Jackman, David M. Yeap, Beow Y. Sequist, Lecia V. Lindeman, Neal Holmes, Alison J. Joshi, Victoria A. Bell, Daphne W. Huberman, Mark S. Halmos, Balazs Rabin, Michael S. Haber, Daniel A. Lynch, Thomas J. Meyerson, Matthew Johnson, Bruce E. Jaenne, Pasi A. TI Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib SO CLINICAL CANCER RESEARCH LA English DT Article ID ACTIVATING MUTATIONS; GENE-MUTATIONS; TYROSINE KINASE; SENSITIVITY; TUMORS; ADENOCARCINOMAS; RESISTANCE; THERAPY; DOMAIN; TABLES AB Purpose: Somatic mutations in the epidermal growth factor receptor (EGFR) have been detected in patients with non - small cell lung cancer (NSCLC) and are associated with sensitivity to treatment with gefitinib or erlotinib. Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib. Experimental Design: Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations. Patients with exon 19 deletion or L858R mutations were identified. The response rate, time to progression, and overall survival were determined for the two groups. Results: We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib. Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation (38 versus 17 months; P = 0.04). There were also trends toward higher response rate (73% versus 50%) and improved time to progression (24 versus 10 months) for the patients with an exon 19 deletion, although these were not independently significant in a multivariate analysis. A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [18 of 23 (78%) versus 3 of 9 (33%); P = 0.04]. No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients. Conclusions: Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation. Pooling of greater numbers of patients and completion of prospective trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib, erlotinib, and other EGFR inhibitors. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Partners Ctr Genet & Genom, Mol Med Lab, Cambridge, MA USA. Univ Hosp Cleveland, Case Sch Med, Ireland Canc Ctr, Cleveland, OH 44106 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, D1234,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org RI Meyerson, Matthew/E-7123-2012; Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU NCI NIH HHS [1K 12CA87723-01, 1R01CA114465-01, P20CA90578-02] NR 37 TC 305 Z9 325 U1 1 U2 12 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 JUL 1 PY 2006 VL 12 IS 13 BP 3908 EP 3914 DI 10.1158/1078-0432.CCR-06-0462 PG 7 WC Oncology SC Oncology GA 062FR UT WOS:000238930500008 PM 16818686 ER PT J AU Pelloski, CE Lin, E Zhang, L Yung, WKA Colman, H Liu, JL Woo, SY Heimberger, AB Suki, D Prados, M Chang, S Barker, FG Fuller, GN Aldape, KD AF Pelloski, Christopher E. Lin, E. Zhang, Li Yung, W. K. Alfred Colman, Howard Liu, Juinn-Lin Woo, Shaio Y. Heimberger, Amy B. Suki, Dima Prados, Michael Chang, Susan Barker, Fredrick G., III Fuller, Gregory N. Aldape, Kenneth D. TI Prognostic associations of activated mitogen-activated protein kinase and Akt pathways in glioblastoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RECURSIVE PARTITIONING ANALYSIS; MALIGNANT BRAIN-TUMORS; GROWTH-FACTOR RECEPTOR; RADIATION-THERAPY; IONIZING-RADIATION; SIGNALING PATHWAYS; GENE-EXPRESSION; IN-VITRO; CELL-PROLIFERATION; DOWN-REGULATION AB Purpose: Activation of mitogen-activated protein kinase (MAPK) and members of the Akt pathway have been shown to promote cell proliferation, survival, and resistance to radiation. This study was conducted to determine whether any of these markers are associated with survival time and response to radiation in glioblastoma. Experimental Design: The expression of phosphorylated (p-)Akt, mammalian target of rapamycin (p-mTOR), p-p70S6K, and p-MAPK were assessed by immunohistochemical staining in 268 cases of newly diagnosed glioblastoma. YKL-40, a prognostic marker previously examined in these tumors, was also included in the analysis. Expression data were tested for correlations with response to radiation therapy in 131 subtotally resected cases and overall survival (in all cases). Results were validated in an analysis of 60 patients enrolled in clinical trials at a second institution. Results: Elevated p-MAPK expression was most strongly associated with poor response to radiotherapy, a finding corroborated in the validation cohort. For survival, higher expressions of p-mTOR, p-p70S6K, and p-MAPK were associated with worse outcome (all P < 0.03). YKL-40 expression was associated with the expressions of p-MAPK, p-mTOR, and p-p70S6K (all P < 0.02), with a trend toward association with p-Akt expression (P = 0.095). When known clinical variables were added to a multivariate analysis, only age, Karnofsky performance score, and p-MAPK expression emerged as independent prognostic factors. Conclusions: p-MAPK and activated members of the Akt pathway are markers of outcome in glioblastoma. Elevated expression of p-MAPK is associated with increased radiation resistance and represents an independent prognostic factor in these tumors. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. Univ Calif San Francisco, Sch Med, Dept Neurosurg, San Francisco, CA USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Aldape, KD (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd,Box 85, Houston, TX 77030 USA. EM kaldape@mdanderson.org OI Fuller, Gregory/0000-0001-9447-2647 NR 41 TC 128 Z9 131 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 JUL 1 PY 2006 VL 12 IS 13 BP 3935 EP 3941 DI 10.1158/1078-0432.CCR-05-2202 PG 7 WC Oncology SC Oncology GA 062FR UT WOS:000238930500012 PM 16818690 ER PT J AU Rubio, MT Zhao, GL Buchli, J Chittenden, M Sykes, M AF Rubio, MT Zhao, GL Buchli, J Chittenden, M Sykes, M TI Role of indirect allo- and autoreactivity in anti-tumor responses induced by recipient leukocyte infusions (RLI) in mixed chimeras prepared with nonmyeloablative conditioning SO CLINICAL IMMUNOLOGY LA English DT Article DE bone marrow transplantation; recipient lymphocyte infusions; mixed chimeras; anti-tumor effects; cytotoxicity; proliferative responses; lymphocytes; indirect presentation; alloresponse; cytotoxic T lymphocyte ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; LYMPHOHEMATOPOIETIC CHIMERISM; MYELOABLATIVE THERAPY; INDUCTION; TOLERANCE; LEUKEMIA; DISEASE AB In mixed chimeras prepared with nonmyetoablative conditioning, we previously showed that recipient leukocyte infusions (RLI) induced loss of donor chimerism and anti-tumor responses against the A20 BALB/c B cell lymphoma. We also previously showed that RLI-mediated tumor rejection involved IFN-gamma producing RLI-derived CD8(+) cells and non-RLI, recipient-derived CD4 T cells, leading to the generation of anti-tumor cytotoxic cells. However, the mechanisms of such paradoxical anti-tumor responses remained to be clarified. In the present study, we further explored the cellular mechanisms of the anti-tumor effects of RLI in fully MHC-mismatched and haploidentical strain combinations. In both cases, we show that RLI breaks the tolerance of chimeric T cells toward donor antigens, in association with the in vivo expansion of recipient splenic T, B and CD4(-)CD8(-) cells and the production of IFN-gamma. RLI leads to the development of two types of tumor-specific responses. The first is mediated by indirect presentation of donor antigens and occurs independently of tumor injection. The second is observed only in recipients of RLI and tumor and may involve responses to self antigens. Anti-tumor cytotoxicity was mediated by CD8(+) or CD4(-)CD8(-) effector cells. Thus, anti-tumor cytotoxic responses are generated following complex interactions between recipient APCs presenting donor and recipient antigens and host-type CD4(+), CD8(+) and CD4(-)CD8(-) cells. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Bone Marrow Transplanta, MGH-E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [R01 CA79989] NR 27 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2006 VL 120 IS 1 BP 33 EP 44 DI 10.1016/j.clim.2006.03.004 PG 12 WC Immunology SC Immunology GA 057ZE UT WOS:000238632900004 PM 16675304 ER PT J AU Martin, SI Marty, FM Fiumara, K Treon, SP Gribben, JG Baden, LR AF Martin, SI Marty, FM Fiumara, K Treon, SP Gribben, JG Baden, LR TI Infectious complications associated with alemtuzumab use for lymphoproliferative disorders SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ANTI-CD52 MONOCLONAL-ANTIBODY; STEM-CELL TRANSPLANTATION; NON-HODGKINS-LYMPHOMAS; PHASE-II MULTICENTER; RESIDUAL DISEASE; CAMPATH-1H; FLUDARABINE; THERAPY; GRADE AB Background. Alemtuzumab is an emerging therapy for refractory lymphoproliferative disorders. The associated long-term risks of infection remain poorly defined. Methods. From July 2001 through December 2003, all patients who received alemtuzumab for the treatment of lymphoproliferative disorders at 1 institution underwent a retrospective evaluation to document infectious complications until death or end of follow-up in October 2004. Alemtuzumab recipients who underwent allogeneic hematopoietic stem cell transplantation were compared with a concurrent cohort who also underwent allogeneic hematopoietic stem cell transplantation but did not receive alemtuzumab. Results. Twenty-seven patients were identified ( 21 with chronic lymphocytic leukemia and 6 with plasma cell disorders). The overall mortality was 37%, with 7 of 10 deaths being related to infection. Significant opportunistic infections occurred in 9 patients ( 43%) with chronic lymphocytic leukemia, including cytomegalovirus, progressive multifocal leukoencephalopathy, adenovirus, toxoplasmosis, and acanthamaebiasis. Thirty nonopportunistic infections in 22 patients ( 82%) were also identified. The 3 deaths related to nonopportunistic infections all involved Enterococcus species bacteremia. When compared with a concurrent chronic lymphocytic leukemia cohort that underwent allogeneic hematopoietic stem cell transplantation, alemtuzumab recipients had an incidence of cytomegalovirus reactivation of 66.7% ( 6 of 9 patients), compared with 37% in the non-alemtuzumab group ( 10 of 27 patients;), and an incidence of post-transplant opportunistic infections ( excluding herpesviruses) P= .15 of 44.4% ( compared with 29.6% in the non-alemtuzumab group;). P = .41 Conclusions. Despite the use of herpesvirus and Pneumocystis pneumonia prophylaxis, serious infectious complications occur in patients receiving alemtuzumab for lymphoproliferative disorders. Infectious complications are more varied and diverse in patients receiving alemtuzumab than has been reported in trials to date. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pharm, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Barts & London Sch Med, Canc Res UK, Med Oncol Unit, London, England. RP Martin, SI (reprint author), Ohio State Univ, Med Ctr, Div Infect Dis, 410 W 10th Ave,Rm N-1147 Doan Hall, Columbus, OH 43210 USA. EM simartin100@gmail.com RI Martin, Stanley/E-3600-2011 NR 28 TC 146 Z9 152 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2006 VL 43 IS 1 BP 16 EP 24 DI 10.1086/504811 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 049PY UT WOS:000238030000003 PM 16758413 ER PT J AU Felsenfeld, AJ Levine, BS AF Felsenfeld, Arnold J. Levine, Barton S. TI Milk alkali syndrome and the dynamics of calcium homeostasis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID SENSING RECEPTOR REGULATION; GASTRIC-ACID SECRETION; EXTRACELLULAR CA2+-SENSING RECEPTOR; PARATHYROID-HORMONE LEVELS; CHRONIC METABOLIC-ACIDOSIS; CONVOLUTED TUBULE CELLS; CHRONIC-RENAL-FAILURE; THICK ASCENDING LIMB; RAT PROXIMAL TUBULE; PEAK BONE MASS C1 Univ Calif Los Angeles, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. RP Felsenfeld, AJ (reprint author), Va Greater Los Angeles Healthcare Syst, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Arnold.Felsenfeld@med.va.gov NR 134 TC 33 Z9 34 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2006 VL 1 IS 4 BP 641 EP 654 DI 10.2215/CJN.01451005 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 108LQ UT WOS:000242241700006 PM 17699269 ER PT J AU Karayiannis, NB Tao, GZ Frost, JD Wise, MS Hrachovy, RA Mizrahi, EM AF Karayiannis, Nicolaos B. Tao, Guozhi Frost, James D., Jr. Wise, Merrill S. Hrachovy, Richard A. Mizrahi, Eli M. TI Automated detection of videotaped neonatal seizures based on motion segmentation methods SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE clustering; motion segmentation; motion strength signal; neonatal seizure; optical flow; quantitative feature; velocity field; videorecording ID MOTOR-ACTIVITY SIGNALS; QUANTIFYING MOTION; OPTICAL-FLOW; RECORDINGS; EEG; EXTRACTION; NEWBORN AB Objective: This study was aimed at the development of a seizure detection system by training neural networks using quantitative motion information extracted by motion segmentation methods from short video recordings of infants monitored for seizures. Methods: The motion of the infants' body parts was quantified by temporal motion strength signals extracted from video recordings by motion segmentation methods based on optical flow computation. The area of each frame occupied by the infants' moving body parts was segmented by direct thresholding, by clustering of the pixel velocities, and by clustering the motion parameters obtained by fitting an affine model to the pixel velocities. The computational tools and procedures developed for automated seizure detection were tested and evaluated on 240 short video segments selected and labeled by physicians from a set of video recordings of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). Results: The experimental study described in this paper provided the basis for selecting the most effective strategy for training neural networks to detect neonatal seizures as well as the decision scheme used for interpreting the responses of the trained neural networks. Depending on the decision scheme used for interpreting the responses of the trained neural networks, the best neural networks exhibited sensitivity above 90% or specificity above 90%. Conclusions: The best among the motion segmentation methods developed in this study produced quantitative features that constitute a reliable basis for detecting myoclonic and focal clonic neonatal seizures. The performance targets of this phase of the project may be achieved by combining the quantitative features described in this paper with those obtained by analyzing motion trajectory signals produced by motion tracking methods. Significance: A video system based upon automated analysis potentially offers a number of advantages. Infants who are at risk for seizures could be monitored continuously using relatively inexpensive and non-invasive video techniques that supplement direct observation by nursery personnel. This would represent a major advance in seizure surveillance and offers the possibility for earlier identification of potential neurological problems and subsequent intervention. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. Baylor Coll Med, Dept Neurol, Peter Kellaway Sect Neurophysiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Karayiannis, NB (reprint author), Univ Houston, Dept Elect & Comp Engn, N308 Engn Bldg 1, Houston, TX 77204 USA. EM karayiannis@uh.edu FU NIBIB NIH HHS [1 R01 EB00183]; NINDS NIH HHS [N01-NS-2316] NR 24 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUL PY 2006 VL 117 IS 7 BP 1585 EP 1594 DI 10.1016/j.clinph.2005.12.030 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KB UT WOS:000239227100022 PM 16684619 ER PT J AU Bragdon, CR Thanner, J Greene, ME Malchau, H Digas, G Harris, WH Karrholm, J AF Bragdon, Charles R. Thanner, Jonas Greene, Meridith E. Malchau, Henrik Digas, Georgios Harris, William H. Karrholm, Johan TI Standing versus supine radiographs in RSA evaluation of femoral head penetration SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Radiostereometry Meeting 2003 CY FEB 04, 2003 CL New Orleans, LA ID TOTAL HIP-ARTHROPLASTY; RADIO STEREOMETRIC ANALYSIS; POLYETHYLENE WEAR; WEIGHT-BEARING; REPLACEMENT; PRECISION AB Evaluation of polyethylene acetabular component wear in total hip arthroplasties commonly is performed using serial radiographs of the hip by measuring the change in the location of the center of the femoral head in relation to the acetabular component. Of the different methods currently used for this purpose, radiostereometric analysis (RSA) is considered the most accurate and precise. In all such radiographic studies, it is assumed the femoral head is seated into the deepest portion of the acetabular component during all radiographic examinations. Although most radiographs used for wear measurements are taken with the patient supine, we questioned whether standing radiographs, with substantial joint load, are better suited for these measurements. We evaluated two groups of patients having total hip arthroplasty who had radiostereometric radiographs taken in supine and standing positions. The average femoral head penetration that occurred between the 6-month and 2-year time interval was measured with radiographs taken in the standing or supine position. We found no difference between the average total femoral head penetration when using supine or standing radiographs. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Gothenburg, Inst Surg Sci, Dept Orthoped, Gothenburg, Sweden. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Jackson 1125, Boston, MA 02114 USA. EM cbragdon@partners.org NR 13 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 2006 IS 448 BP 46 EP 51 DI 10.1097/01.blo.0000224012.50292.67 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119OD UT WOS:000243020700008 PM 16826095 ER PT J AU Bragdon, CR Martell, JM Greene, ME Estok, DM Thanner, J Karrholm, J Harris, WH Malchau, H AF Bragdon, Charles R. Martell, John M. Greene, Meridith E. Estok, Daniel M., II Thanner, Jonas Karrholm, Johan Harris, William H. Malchau, Henrik TI Comparison of femoral head penetration using RSA and the Martell method SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Radiostereometry Meeting 2003 CY FEB 04, 2003 CL New Orleans, LA ID TOTAL HIP-ARTHROPLASTY; POLYETHYLENE WEAR; GROWTH-RATE; REPLACEMENT; PROSTHESES; RADIOSTEREOMETRY; RADIOGRAPHS; ACCURACY; CHILDREN AB Radiostereometry has high precision and accuracy measuring polyethylene wear in total hip arthroplasty but requires a specialized setup. The Martell method is simpler and can be used on larger populations. The hypothesis that the radiostereometry analysis and the Martell analysis would yield comparable wear data from the same group of patients having total hip arthroplasty was tested. A group of twenty-five total hip arthroplasty patients who had both radiostereometry and standard anterior-posterior pelvic and cross-table lateral radiographs of sufficient quality for analysis were identified. The films were taken at postoperative periods of 6 weeks, 1 year, 2 years, and 5 years. Femoral head penetration was measured by both methods at each time point. The median penetration rates measured by each method decreased over time. Penetration results were affected by method of analysis, time, and dimension, with greater penetration for Martell compared with radiostereometry at each time point, greater penetration with increasing time for each method, and larger three-dimensional magnitude compared with two-dimensional analysis. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Chicago, Sect Orthopaed, Chicago, IL 60637 USA. Univ Gothenburg, Inst Surg Sci, Dept Orthoped, Gothenburg, Sweden. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Jackson 1125, Boston, MA 02114 USA. EM cbragdon@partners.org NR 26 TC 31 Z9 31 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 2006 IS 448 BP 52 EP 57 DI 10.1097/01.blo.0000224018.88410.83 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119OD UT WOS:000243020700009 PM 16826096 ER PT J AU Chaipat, L Palmer, WE AF Chaipat, Lida Palmer, William E. TI Shoulder magnetic resonance imaging SO CLINICS IN SPORTS MEDICINE LA English DT Article ID GLENOID LABRUM; ROTATOR CUFF; MR ARTHROGRAPHY; EXTERNAL ROTATION; TEARS; ABDUCTION; CADAVERS; ARM AB MRI provides excellent soft tissue contrast and allows for multiplanar imaging in anatomic planes. Because of these advantages MRI has become the study of choice for imaging of shoulder pathology. Some structures, such as the rotator cuff, humeral head contour, and glenoid shape, are evaluated well with conventional MRI. When more sensitive evaluation of the labrum, capsule, articular cartilage, and glenohumeral ligaments is required or when a partial-thickness rotator cuff tear is suspected, magnetic resonance arthrography with intra-articular contrast can be performed. For MR arthrography contrast is injected directly into the glenohumeral joint. This article reviews the appearances of normal anatomic structures in MRI of the shoulder and disorders involving the rotator cuff and glenoid labrum. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Palmer, WE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6030, Boston, MA 02114 USA. EM palmer.william@mgh.harvard.edu NR 22 TC 13 Z9 13 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 0278-5919 J9 CLIN SPORT MED JI Clin. Sports Med. PD JUL PY 2006 VL 25 IS 3 BP 371 EP + DI 10.1016/j.csm.2006.03.002 PG 17 WC Sport Sciences SC Sport Sciences GA 099TH UT WOS:000241618300003 PM 16798133 ER PT J AU McCloskey, M Valtonen, J Sherman, JC AF McCloskey, Michael Valtonen, Jussi Sherman, Janet Cohen TI Representing orientation: A coordinate-system hypothesis and evidence from developmental deficits SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID OBJECT ORIENTATION; AGNOSIA; LOCALIZATION; RECOGNITION; DISSOCIATION; PERCEPTION; KNOWLEDGE; LOCATION; PATTERNS; FAILURE AB This article concerns how the orientations of objects are represented in the human brain. We propose a coordinate-system hypothesis of orientation representation (COR) and show that the hypothesis provides an explicit basis for interpreting orientation errors. Next, we report results from three studies of individuals with developmental deficits in the processing of orientation information, demonstrating that the COR hypothesis can interpret the error patterns in each study. We conclude by discussing several issues concerning the interpretation of our results, the COR hypothesis, and the use of developmental deficits as a basis for inferences about normal cognition. C1 Johns Hopkins Univ, Dept Cognit Sci, Baltimore, MD 21218 USA. Univ Helsinki, Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP McCloskey, M (reprint author), Johns Hopkins Univ, Dept Cognit Sci, Krieger Hall,3400 N Charles St, Baltimore, MD 21218 USA. EM michael.mccloskey@jhu.edu NR 49 TC 6 Z9 6 U1 1 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD JUL PY 2006 VL 23 IS 5 BP 680 EP 713 DI 10.1080/02643290500537356 PG 34 WC Psychology; Psychology, Experimental SC Psychology GA 070DF UT WOS:000239499800002 PM 21049350 ER PT J AU Bromley, E Johnson, JG Cohen, P AF Bromley, Elizabeth Johnson, Jeffrey G. Cohen, Patricia TI Personality strengths in adolescence and decreased risk of developing mental health problems in early adulthood SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID STRESSFUL LIFE EVENTS; EGO-RESILIENCY; 5-FACTOR MODEL; CHILDHOOD PERSONALITY; SUICIDE ATTEMPTS; CHILDREN; DISORDERS; ADAPTATION; PREDICTORS; DEPRESSION AB The aim of this study was to investigate whether personality strengths during adolescence are associated with decreased risk of developing psychiatric disorders, educational or occupational problems, violent or criminal behaviors, and interpersonal difficulties during early adulthood. A representative community sample of 688 mothers from upstate New York and their offspring was interviewed in the period of 1985-1986 (mean offspring age = 16 years) and in that of 1991-1993 (mean offspring age = 22 years). Results showed that youths with numerous personality strengths at the mean age of 16 years were at a decreased risk of developing psychiatric disorders, educational and occupational problems, interpersonal difficulties, and criminal behaviors at the mean age of 22 years. These associations remained significant after controlling for age, sex, socioeconomic status, verbal intelligence, preexisting psychiatric disorders, and corresponding problems at the mean age of 16 years. Although youths with fewer personality strengths who experienced numerous stressful events were at elevated risk of developing psychiatric disorders during early adulthood, those with a higher number of personality strengths at the mean age of 16 years did not share this vulnerability. We conclude that personality strengths during adolescence may contribute to a decreased risk of developing a wide range of adverse outcomes during early adulthood. Systematic evaluation of character strengths may improve the clinical assessment of adolescents. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90024 USA. Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. VA Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. Columbia Univ, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Bromley, E (reprint author), Univ Calif Los Angeles, Dept Anthropol, 911 Broxton Plaza,3rd Floor, Los Angeles, CA 90024 USA. EM ebromley@ucla.edu NR 59 TC 5 Z9 5 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2006 VL 47 IS 4 BP 317 EP 326 DI 10.1016/j.comppsych.2005.11.003 PG 10 WC Psychiatry SC Psychiatry GA 058BL UT WOS:000238639000012 ER PT J AU Peretti, GM Campo-Ruiz, V Gonzalez, S Randolph, MA Xu, JW Morse, KR Roses, RE Yaremchuk, MJ AF Peretti, Giuseppe M. Campo-Ruiz, Vanessa Gonzalez, Salvador Randolph, Mark A. Xu, Jian Wei Morse, Kenneth R. Roses, Robert E. Yaremchuk, Michael J. TI Tissue engineered cartilage integration to live and devitalized cartilage: A study by reflectance mode confocal microscopy and standard histology SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE cartilage; confocal microscope; integration; reflectance mode; tissue engineering ID ARTICULAR-CARTILAGE; FIBRIN GLUE; CHONDROCYTES; REPAIR; ADHESION; DEFECTS; MATRIX AB This study investigated the in vivo formation of engineering cartilage within living or devitalized cartilage discs using reflectance mode confocal microscopy and conventional light microscopy. Pig articular chondrocytes were suspended in fibrin glue and placed between two cartilage discs. Four experimental groups were prepared: in groups 1 and 2, the cell-hydrogel composite was placed between two live or between two devitalized cartilage discs, respectively; in groups 3 and 4, acellular fibrin glue was placed between two live or between two devitalized cartilage discs, respectively. Samples were implanted in the back of nude mice and analyzed after 2, 5, and 8 weeks. Results showed that engineered cartilage seems to grow more homogenously when the cell-seeded gel was placed between devitalized cartilages than when it was placed between live cartilage matrices. Confocal microscopy provides valuable information on the integration of tissue-engineered cartilage with native tissue and could be useful for nondestructive imaging in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Milan, Italy. Univ Milan, Fac Exercise Sci, Milan, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA USA. Zhongshan Hosp, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China. Fudan Univ, Shanghai 200433, Peoples R China. RP Randolph, MA (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, 15 Parkman St,WACC 453, Boston, MA 02114 USA. EM Randolph.mark@mgh.harvard.edu RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 NR 21 TC 12 Z9 18 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PD JUL-SEP PY 2006 VL 47 IS 4 BP 190 EP 199 DI 10.1080/03008200600809935 PG 10 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 085XA UT WOS:000240636500002 PM 16987750 ER PT J AU Dunfee, R Thomas, ER Gorry, PR Wang, JB Ancuta, P Gabuzda, D AF Dunfee, Rebecca Thomas, Elaine R. Gorry, Paul R. Wang, Jianbin Ancuta, Petronela Gabuzda, Dana TI Mechanisms of HIV-1 neurotropism SO CURRENT HIV RESEARCH LA English DT Review DE HIV; CCR5; macrophages; microglia; neurotropism ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; ACTIVE ANTIRETROVIRAL THERAPY; AIDS DEMENTIA COMPLEX; MONOCYTE-DERIVED MACROPHAGES; POLYMERASE CHAIN-REACTION; CHEMOKINE RECEPTORS CCR3; CEREBROSPINAL-FLUID; TYPE-1 INFECTION; IN-VIVO AB Human immunodeficiency virus type 1 (HIV) infects macrophages and microglia in the CNS and frequently causes neurocognitive impairment. Although antiviral therapy generally reduces the viral load in the CNS and improves HIV-associated neurological dysfunction, most current antiviral drugs have poor CNS penetrance and cannot completely suppress viral replication. Furthermore, drug-resistance mutations can evolve independently in the CNS. Thus, a long-lived viral reservoir persists in macrophages and microglia in the brain despite antiviral therapy. This review discusses mechanisms underlying the neurotropism of HIV, focusing on the role of the HIV envelope glycoproteins and their interactions with CD4 and the chemokine receptors CCR5 and CXCR4. We review data from studies of neurotropic HIV derived from the brains of patients with HIV-associated neurocognitive impairment as well as studies of nonhuman primate models. Understanding mechanisms that underlie HIV neurotropism and neurovirulence is critical for development of therapeutics to inhibit CNS infection and preventing neurological injury in HIV-infected individuals. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JF816, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIAID NIH HHS [AI054207]; NIDA NIH HHS [DA16549]; NINDS NIH HHS [NS37277, NS35734] NR 171 TC 57 Z9 61 U1 2 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JUL PY 2006 VL 4 IS 3 BP 267 EP 278 DI 10.2174/157016206777709500 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 063LY UT WOS:000239020900005 PM 16842080 ER PT J AU Niess, JH Reinecker, HC AF Niess, JH Reinecker, HC TI Dendritic cells: the commanders-in-chief of mucosal immune defenses SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE adaptive immunity; dendritic cells; inflammatory bowel disease; innate immunity; intestinal microbiota; pathogen defense; tolerance ID INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; T-HELPER TYPE-1; ULCERATIVE-COLITIS; CROHNS-DISEASE; PEYERS PATCH; LAMINA PROPRIA; ORAL TOLERANCE AB Purpose of review Intestinal dendritic cells have emerged as key regulators of immunity to pathogens, oral tolerance and intestinal inflammation. Studies have begun to elucidate the regulatory mechanisms responsible for defining region- and compartment-specific phenotypes and functions of dendritic cells in mucosal tissues. Recent findings Specific subsets of dendritic cells appear to be associated with the various routes for antigen acquisition in the intestine. The constant sampling of intestinal antigenic content ensures establishment of tolerance to commensal bacteria and food antigens. Tolerance development to oral antigens is restricted to the mucosal immune system. Other advances have provided insight into the molecular basis of microbial recognition and innate immune responses by intestinal dendritic cells. Differences in the involvement of dendritic cell's have be gun to emerge in Crohn's disease and ulcerative colitis and link gene regulation in dendritic cells to therapeutic responses. Summary A major focus of mucosal immunology I Will be to understand,how diverse dendritic cell subsets cooperate in regulating homeostasis and host defense in the different intestinal immune compartments. This will be pivotal to understanding how the mucosal immune system makes the distinction between commensal microbiota, pathogens and self antigens. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Jackson 711, Boston, MA 02114 USA. EM hans-christian_reinecker@hms.harvard.edu RI Niess, Jan /E-8361-2017 OI Niess, Jan /0000-0001-6902-5650 FU NIDDK NIH HHS [DK68181, DK33506] NR 87 TC 50 Z9 51 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 2006 VL 22 IS 4 BP 354 EP 360 DI 10.1097/01.mog.0000231807.03149.54 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 059MO UT WOS:000238737100004 PM 16760749 ER PT J AU Peralta, CA Kurella, M Lo, JC Chertow, GM AF Peralta, Carmen A. Kurella, Manjula Lo, Joan C. Chertow, Glenn M. TI The metabolic syndrome and chronic kidney disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Editorial Material DE chronic kidney disease; hyperglycemia; hypertension; metabolic syndrome; microalbuminuria; obesity ID GLOMERULAR-FILTRATION-RATE; TARGET ORGAN DAMAGE; INSULIN-RESISTANCE; US ADULTS; RENAL-DISEASE; RHESUS-MONKEYS; OBESITY; HYPERINSULINEMIA; ASSOCIATION; RISK AB Purpose of review The metabolic syndrome is a constellation of physical and laboratory abnormalities including hypertension, hyperglycemia, hyperlipidemia and abdominal obesity. Over the past decade, the metabolic syndrome has emerged as a critically important risk factor for cardiovascular disease. Recent findings A large population-based cross-sectional analysis (the National Health and Nutrition Evaluation Survey III) found that the presence of the metabolic syndrome was associated with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m(2) and was also associated with proteinuria. More recently, a prospective cohort study found that the presence of the metabolic syndrome was associated with incident chronic kidney disease by the same definition, even when excluding individuals with diabetes mellitus and hypertension. More studies are required to determine whether the relationship between the metabolic syndrome and chronic kidney disease is mainly mediated by hyperglycemia (with insulin resistance) and hypertension, or other metabolic or hemodynamic factors. Summary The metabolic syndrome is associated with chronic kidney disease. Efforts aimed at determining the mechanisms underlying this association and strategies for the prevention of chronic kidney disease (or slowing the progression of chronic kidney disease) in affected patients should be research priorities in the future. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Chertow, GM (reprint author), Dept Med Res, UCSF Laurel Hts,Suite 430,3333 Calif St, San Francisco, CA 94118 USA. EM chertowg@medicine.ucsf.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 NR 24 TC 43 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 EI 1473-6543 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JUL PY 2006 VL 15 IS 4 BP 361 EP 365 DI 10.1097/01.mnh.0000232875.27846.7e PG 5 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 064QA UT WOS:000239103000002 PM 16775449 ER PT J AU LeBleu, VS Thornton, M Gonda, SR Helmstetter, CE AF LeBleu, Valerie S. Thornton, Maureen Gonda, Steven R. Helmstetter, Charles E. TI Technology for cell cycle research with unstressed steady-state cultures SO CYTOTECHNOLOGY LA English DT Article DE steady-state culture; cell cycle; continuous culture; rotating culture ID BABY MACHINE; MAMMALIAN-CELLS; SYNCHRONOUS CULTURES; HEMATOPOIETIC-CELLS; DNA-REPLICATION; HELA-CELLS; SYNCHRONIZATION; DIVISION; GROWTH AB A culture system for performing cell cycle analyses on cells in undisturbed steady-state populations was designed and tested. In this system, newborn cells are shed continuously from an immobilized, perfused culture rotating about the horizontal axis. As a result of this arrangement, the number of newborn cells released into the effluent medium each generation is identical to the number of cells residing in the immobilized population, indicating that one of the two new daughter cells is shed at each cell division. Thus, the immobilized cells constitute a continuous, steady-state culture because the concentrations, locations and microenvironments of the cells in the culture vessel do not vary with time. In tests with mouse L1210 lymphocytic leukemia cells, about 10(8) newborn cells were produced per day. This new culture system enables a multiplicity of cell cycle analyses on large numbers of cells assured to be from populations in steady-state growth. C1 Harvard Univ, Sch Med, Div Matrix Biol, Kalluri Lab,Biol & Biomed Sci Program,BIDMC, Boston, MA 02446 USA. Florida Inst Technol, Dept Biol Sci, Melbourne, FL 32901 USA. Midwest Res Inst, Florida Div, Palm Bay, FL 32909 USA. NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. RP LeBleu, VS (reprint author), Harvard Univ, Sch Med, Div Matrix Biol, Kalluri Lab,Biol & Biomed Sci Program,BIDMC, DANA 515,330 Brookline Ave, Boston, MA 02446 USA. EM valerie_lebleu@hms.harvard.edu RI LeBleu, Valerie /E-2991-2015 FU NIA NIH HHS [R01 AG021508] NR 24 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-9069 J9 CYTOTECHNOLOGY JI Cytotechnology PD JUL PY 2006 VL 51 IS 3 BP 149 EP 157 DI 10.1007/s10616-006-9024-5 PG 9 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 111AH UT WOS:000242422300004 PM 19002885 ER PT J AU Abe, Y Chen, W Huang, W Nishino, M Li, YP AF Abe, Yoko Chen, Wei Huang, Wei Nishino, Mizuho Li, Yi-Ping TI CNBP regulates forebrain fon-nation at organogenesis stage in chick embryos SO DEVELOPMENTAL BIOLOGY LA English DT Article DE CNBP; gene expression; forebrain development; organogenesis stage; RNAi; mixepression; chick embyros ID ANTERIOR NEUROECTODERM; VISCERAL ENDODERM; MOUSE EMBRYO; GENE; EXPRESSION; OTX2; NOTCH1; ELECTROPORATION; SPECIFICATION; GASTRULATION AB We recently demonstrated that Cellular Nucleic acid Binding Protein (CNBP)(-/-) mouse embryos exhibit forebrain truncation due to a lack of proper morphogenetic movements of the anterior visceral endoderm (AVE) during pre-gastrulation stage (Chen, W., Liang, Y., Deng, W., Shimizu, K., Ashique, A.M., Li, E., Li, Y.P., 2003. The zinc-finger protein CNBP is required for forebrain formation in the mouse, Development 130, 1367-1379). However, CNBP expression pattern in the mouse forebrain suggests that CNBP may have more direct effects during forebrain development. Our data show that CNBP is expressed in tissues of early chick embryo that are the equivalent to the mouse embryo. Using a combination of RNAi-silencing and Retrovirus-misexpression approaches, we investigated the temporal function of CNBP in the specification/development of the chick forebrain during organogenesis. The silencing of CNBP expression resulted in forebrain truncation and the absence of BF-1, Six3 and Hesx1 expression, but not Otx2 in chick embryos. Misexpression of CNBP induced the expression of BE-1, Six3 and Hesx1 in the hindbrain, but not the expression of Otx2. These results offer novel insights into the function of CNBP during organogenesis as the regulator of forebrain formation and a number of rostral head transcription factors. Moreover, CNBP and Otx2 may play roles as regulators of forebrain formation in two parallel pathways. These new insights into CNBP functions underscore the essential role of CNBP in forebrain formation during chick embryo organogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Zhejiang Univ, Coll Life Sci, Hangzhou 310027, Peoples R China. Univ Tokushima, Sch Dent, Dept Pediat Dent, Tokushima 770, Japan. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM ypli@forsyth.org FU NIAMS NIH HHS [AR44741, AR48133] NR 26 TC 20 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 BP 116 EP 127 DI 10.1016/j.ydbio.2006.03.012 PG 12 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200010 PM 16626683 ER PT J AU Oviedo, NJ Levin, M AF Oviedo, Nestor J. Levin, Michael TI SMEDXIN-1: A specific innexin that regulates planarian stem cells SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Harvard Univ, Sch Dent Med, Ctr Regenerat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 18 BP 329 EP 329 DI 10.1016/j.ydbio.2006.04.028 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200042 ER PT J AU Levin, M Adams, D Aw, S Morokuma, J Oviedo, N AF Levin, Michael Adams, Dany Aw, Sherry Morokuma, Junji Oviedo, Nestor TI Bioelectrical controls of morphogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Forsyth Inst Harvard, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 25 BP 331 EP 332 DI 10.1016/j.ydbio.2006.04.036 PG 2 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200049 ER PT J AU Adams, DS Masi, A Levin, M AF Adams, Dany S. Masi, Alessio Levin, Michael TI Xenopus tadpole tail regeneration requires the activity of the proton pump V-ATPase, and proton pumping is sufficient to partially rescue the loss of function phenotype SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Forsyth Ctr Regenerat & Dev Biol, Boston, MA USA. Forsyth Inst, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 76 BP 355 EP 356 DI 10.1016/j.ydbio.2006.04.094 PG 2 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200099 ER PT J AU Blum, M Schweickert, A Beyer, T Weber, T Andre, P Fischer, A Viebahn, C Levin, M AF Blum, M. Schweickert, A. Beyer, T. Weber, T. Andre, P. Fischer, A. Viebahn, C. Levin, M. TI A leftward fluid flow precedes nodal induction in Xenopus SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Univ Hohenheim, D-7000 Stuttgart, Germany. Univ Gottingen, D-3400 Gottingen, Germany. Forsyth Inst, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 334 BP 443 EP 443 DI 10.1016/j.ydbio.2006.04.364 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200351 ER PT J AU Morokuma, J Levin, M AF Morokuma, Junji Levin, Michael TI Role of KvLQT-1/minK K+ channel in early embryonic patterning SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Forsyth Inst, Ctr Dev & Regenerat Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 360 BP 451 EP 451 DI 10.1016/j.ydbio.2006.04.390 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200377 ER PT J AU Jasinski, JM Yu, L Nakayama, M Li, MM Lipes, MA Eisenbarth, GS Liu, E AF Jasinski, JM Yu, L Nakayama, M Li, MM Lipes, MA Eisenbarth, GS Liu, E TI Transgenic insulin (B : 9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2(g7) homozygosity, and insulin 2 gene knockout SO DIABETES LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE-65; NOD MICE; COSTIMULATOR B7-1; PEPTIDE; AUTOANTIGEN; EXPRESSION; TOLERANCE; EPITOPE; PROGRESSION; INDUCTION AB A series of recent studies in humans and the NOD mouse model have highlighted the central role that autoimmunity directed against insulin, in particular the insulin B chain 9-23 peptide, may play in the pathogenesis of type 1 diabetes. Both pathogenic and protective T-cell clones recognizing the B:9-23 peptide have been produced. This report describes the successful creation of BDC12-4.1 T-cell receptor (TCR) transgenic mice with spontaneous insulitis in F1 mice (FVB x NOD) and spontaneous diabetes in NOD.RAG(-/-) (backcross 1 generation). Disease progression is heterogeneous and is modified by a series of genetic factors including heterozygosity (H-2(g7)/H-2(q)) versus homozygosity for H-2g', the presence of additional T-/B-cell receptor-rearranged genes (RAG(+) versus RAG(-/-)), and the insulin 2 gene knockout (the insulin gene expressed in the NOD thymus). Despite lymphopenia, 40% of H-2(g7/g7) BDC12-4.1 TCR+ RAG(-/-) Ins2(-/-) mice are diabetic by 10 weeks of age. As few as 13,500 transgenic T-cells from a diabetic TCR+ RAG(-/-) mouse can transfer diabetes to an NOD.scid mouse. The current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes at NOD backcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis. C1 Univ Colorado, Barbara Davis Ctr Childhood Diabet, Hlth Sci Ctr, Aurora, CO 80045 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Liu, E (reprint author), Univ Colorado, Barbara Davis Ctr Childhood Diabet, Hlth Sci Ctr, POB 6511,MS B140, Aurora, CO 80045 USA. EM edwin.liu@uchsc.edu FU NIAID NIH HHS [AI50864]; NIDDK NIH HHS [DK064605, DK32083, DK55969, DK62718, P30 DK57516] NR 40 TC 45 Z9 45 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2006 VL 55 IS 7 BP 1978 EP 1984 DI 10.2337/db06-0058 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 059XD UT WOS:000238764600010 PM 16804066 ER PT J AU Biddinger, SB Miyazaki, M Boucher, J Ntambi, JM Kahn, CR AF Biddinger, SB Miyazaki, M Boucher, J Ntambi, JM Kahn, CR TI Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c SO DIABETES LA English DT Article ID STEAROYL-COA DESATURASE-1; FATTY-ACID SYNTHESIS; GENE-EXPRESSION; MOUSE-LIVER; X-RECEPTOR; MICE; RAT; TRANSCRIPTION; METABOLISM; CELLS AB Stearoyl-CoA desaturase (SCD)1 catalyzes the rate-limiting reaction of monounsaturated fatty acid (MUFA) synthesis and plays an important role in the development of obesity. SCD1 is suppressed by leptin but induced by insulin. We have used animal models to dissect the effects of these hormones on SCD1. In the first model, leptin-deficient ob/ob mice were treated with either leptin alone or with both leptin and insulin to prevent the leptin-mediated fall in insulin. In the second model, mice with a liver-specific knockout of the insulin receptor (LIRKO) and their littermate controls (LOXs) were treated with leptin. As expected, leptin decreased SCD1 transcript, protein, and activity by > 60% in ob/ob and LOX mice. However, the effects of leptin were not diminished by the continued presence of hyperinsulinemia in ob/ob mice treated with both leptin and insulin or the absence of insulin signaling in LIRKO mice. Furthermore, genetic knockout of sterol regulatory element-binding protein (SREBP)-1c, the lipogenic transcription factor that mediates the effects of insulin on SCD1, also had no effect on the ability of leptin to decrease either SCD1 transcript or activity. Thus, the effect of leptin on SCD1 in liver is independent of insulin and SREBP-1c, and leptin, rather than insulin, is the major regulator of hepatic MUFA synthesis in obesity-linked diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK45935, DK31036, DK59637-01, DK60837-02, DK62388, T32 DK63702-01] NR 38 TC 61 Z9 67 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2006 VL 55 IS 7 BP 2032 EP 2041 DI 10.2337/db05-0742 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 059XD UT WOS:000238764600017 PM 16804073 ER PT J AU Kramer, HF Witczak, CA Fujii, N Jessen, N Taylor, EB Arnolds, DE Sakamoto, K Hirshman, MF Goodyear, LJ AF Kramer, HF Witczak, CA Fujii, N Jessen, N Taylor, EB Arnolds, DE Sakamoto, K Hirshman, MF Goodyear, LJ TI Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle SO DIABETES LA English DT Article ID GTPASE-ACTIVATING-PROTEIN; STIMULATED GLUCOSE-TRANSPORT; AKT/PROTEIN KINASE-B; GLUT4 TRANSLOCATION; AKT SUBSTRATE; SEQUENCE MOTIFS; EXERCISE; DOMAIN AB Insulin and contraction increase GLUT4 translocation in skeletal muscle via distinct signaling mechanisms. Akt substrate of 160 kDa (AS160) mediates insulin-stimulated GLUT4 translocation in L6 myotubes, presumably through activation of Akt. Using in vivo, in vitro, and in situ methods, insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR all increased AS160 phosphorylation in mouse skeletal muscle. Insulin-stimulated AS160 phosphorylation was fully blunted by wortmannin in vitro and in Akt2 knockout (KO) mice in vivo. In contrast, contraction-stimulated AS160 phosphorylation was only partially decreased by wortmannin and unaffected in Akt2 KO mice, suggesting additional regulatory mechanisms. To determine if AMPK mediates AS160 signaling, we used AMPK alpha 2-inactive (alpha 2i) transgenic mice. AICAR-stimulated AS160 phosphorylation was fully inhibited, whereas contraction-stimulated AS160 phosphorylation was partially reduced in the AMPK alpha 2i transgenic mice. Combined AMPK alpha 2 and Akt inhibition by wortmannin treatment of AMPK alpha 2 transgenic mice did not fully ablate contraction-stimulated AS160 phosphorylation. Maximal insulin, together with either AICAR or contraction, increased AS160 phosphorylation in an additive manner. In conclusion, AS160 may be a point of convergence linking insulin, contraction, and AICAR signaling. While Akt and AMPK alpha 2 activities are essential for AS160 phosphorylation by insulin and AICAR, respectively, neither kinase is indispensable for the entire effects of contraction on AS160 phosphorylation. C1 Joslin Diabet Ctr, Metab Res Div, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Metab Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Jessen, Niels/E-1731-2011; Fujii, Nobuharu/J-2724-2014; OI Fujii, Nobuharu/0000-0002-0974-3033; Jessen, Niels/0000-0001-5613-7274 FU NIAMS NIH HHS [AR42238, AR45670, F32 AR051663]; NIDDK NIH HHS [DK36836] NR 30 TC 191 Z9 198 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2006 VL 55 IS 7 BP 2067 EP 2076 DI 10.2337/db06-0150 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 059XD UT WOS:000238764600021 PM 16804077 ER PT J AU Mahimainathan, L Das, F Venkatesan, B Choudhury, GG AF Mahimainathan, L Das, F Venkatesan, B Choudhury, GG TI Mesangial cell hypertrophy by high glucose is mediated by downregulation of the tumor suppressor PTEN SO DIABETES LA English DT Article ID GROWTH-FACTOR-BETA; DIABETIC RENAL HYPERTROPHY; ACTIVATED PROTEIN-KINASE; LHERMITTE-DUCLOS-DISEASE; TGF-BETA; PHOSPHOINOSITIDE 3-KINASE; GENE-EXPRESSION; TRANSFORMING GROWTH-FACTOR-BETA-1; FIBRONECTIN EXPRESSION; INSULIN-RESISTANCE AB Diabetic nephropathy is characterized early in its course by glomerular hypertrophy and, importantly, mesangial hypertrophy, which correlate with eventual glomerulosclerosis. The mechanism of hypertrophy, however, is not known. Gene disruption of the tumor suppressor PTEN, a negative regulator of the phosphatidylinositol 3-kinase/Akt pathway, in fruit flies and mice demonstrated its role in size control in a cell-specific manner. Here, we investigated the mechanism of mesangial hypertrophy in response to high extracellular glucose. We link early renal hypertrophy with significant reduction in PTEN expression in the streptozotocin-induced diabetic kidney cortex and glomeruli, concomitant with activation of Akt. Similarly, exposure of mesangial cells to high concentrations of glucose also decreased PTEN expression and its phosphatase activity, resulting in increased AM activity. Expression of PTEN inhibited high-glucose-induced mesangial cell hypertrophy, and expression of dominant-negative PTEN was sufficient to induce hypertrophy. In diabetic nephropathy, the hypertrophic effect of hyperglycemia is thought to be mediated by transforming growth factor-beta (TGF-beta). TGF-beta significantly reduced PTEN expression in mesangial cells, with a reduction in its phosphatase activity and an increase in Akt activation. PTEN and dominant-negative Akt attenuated TGF-beta-induced hypertrophy of mesangial cells. Finally, we show that inhibition of TGF-beta signal transduction blocks the effect of high glucose on PTEN downregulation. These data identify a novel mechanism placing PTEN as a key regulator of diabetic mesangial hypertrophy involving TGF-beta signaling. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu OI /0000-0001-5077-3552 FU NIDDK NIH HHS [R01 DK50190, R01 DK 55815] NR 71 TC 88 Z9 103 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2006 VL 55 IS 7 BP 2115 EP 2125 DI 10.2337/db05-1326 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 059XD UT WOS:000238764600027 PM 16804083 ER PT J AU Qi, L Meigs, JB Liu, SM Manson, JE Mantzoros, C Hu, FB AF Qi, Lu Meigs, James B. Liu, Simin Manson, JoAnn E. Mantzoros, Christos Hu, Frank B. TI Dietarary fibers and glycemic load, obesity, and plasma adiponectin levels in women with type 2 diabetes SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; MESSENGER-RNA LEVELS; INSULIN-RESISTANCE; INFLAMMATORY MARKERS; RISK; MEN; DIET; MELLITUS; ADIPOSE; INDEX AB OBJECTIVE - The purpose of this study was to examine the associations of dietary fibers and glycemic load with plasma adiponectin in diabetic women and investigate the modification effect of obesity. RESEARCH DESIGN AND METHODS - We conducted a cross-sectional analysis in 902 women with type 2 diabetes from the Nurses' Health Study. Dietary information was obtained using semiquantitative food frequency questionnaires. RESULTS - After adjustment for age, smoking, alcohol consumption, physical activity, aspirin use, HbA(1c) history of hypertension and hypercholesterolemia, and postmenopausal hormone use, intakes of cereal fiber and fruit fiber (P for trend = 0.002 and 0.036, respectively) were Significantly associated with an increasing trend of plasma adiponectin concentrations. Further adjustment for BMI did not appreciably change the associations for cereal fiber but attenuated the associations for fruit fiber. Adiponectin concentrations were 24% higher in the highest compared with the lowest quintile of cereal fiber. Dietary glycemic load and glycemic index were significantly associated with lower plasma adiponectin levels, after adjustment for BMI and other covariates (P for trend = 0.01 and 0.03, respectively). The percent differences in adiponectin concentration between the highest and the lowest quintiles of dietary glycemic load and glycemic index were 17 and 18%, respectively. The associations between dietary factors and plasma adiponectin were consistent across lean (BMI < 25 kg/m(2)), overweight (25 <= BMI < 30 kg/m(2)), and obese subjects (BMI >= 30 kg/m(2)). CONCLUSIONS - Our data indicate that dietary cereal fiber and glycemic load/index are associated with the circulating adiponectin concentration. Such associations were not modified by obesity status. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Dept Med, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464, HL65582] NR 29 TC 68 Z9 74 U1 0 U2 4 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 JUL PY 2006 VL 29 IS 7 BP 1501 EP 1505 DI 10.2337/dc-0221 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061EM UT WOS:000238854000006 PM 16801569 ER PT J AU Novak, V Last, D Alsop, DC Abduljalil, AM Hu, K Lepicovsky, L Cavallerano, J Lipsitz, LA AF Novak, Vera Last, David Alsop, David C. Abduljalil, Amir M. Hu, Kun Lepicovsky, Lukas Cavallerano, Jerry Lipsitz, Lewis A. TI Cerebral blood flow velocity and periventricular white matter hyperintensities in type 2 diabetes SO DIABETES CARE LA English DT Article ID CEREBROVASCULAR REACTIVITY; ATHEROSCLEROSIS RISK; MELLITUS; MRI; RATS; HYPERGLYCEMIA; COMMUNITIES; BARRIER; LESIONS; ADULTS AB OBJECTIVE - Diabetes increases the risk for cerebromicrovascular disease, possibly through its effects on blood flow regulation. The aim of this study was to assess the effects of type 2 diabetes on blood flow velocities (BFVs) in the middle cerebral arteries and to determine the relationship between white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) and BFVs. RESEARCH DESIGN AND METHODS - We measured BFVs in 28 type 2 diabetic and 22 control subjects (aged 62.3 +/- 7.2 years) using transcranial Doppler ultrasound during baseline, hyperventilation, and CO2 rebreathing. WMHs were graded, and their volume was quantified from fluid-attenuated inversion recovery images on a 3.0 Tesla MRI. RESULTS - The diabetic group demonstrated decreased mean BFVs and increased cerebrovascular resistance during baseline, hypo- and hypercapnia (P < 0.0001), and impaired CO, reactivity (P = 0.05). WMH volume was negatively correlated with baseline BFV (P < 0.0001). A regression model revealed that baseline BFVs were negatively associated with periventricular WMHs, HbA(1c) (A1C), and inflammatory markers and positively associated with systolic blood pressure (R-2 = 0.86, P < 0.0001). CONCLUSIONS - Microvascular disease in type 2 diabetes, which manifests as white matter abnormalities on MRI, is associated with reduced cerebral BFvs, increased resistance in middle cerebral arteries, and inflammation. These findings are clinically relevant as a potential mechanism for cerebrovascular disease in elderly with type 2 diabetes. C1 Harvard Univ, Div Gerontol, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Dept Radiol, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Hebrow SeniorLife, Boston, MA USA. RP Novak, V (reprint author), Harvard Univ, Div Gerontol, Sch Med, Beth Israel Deaconess Med Ctr, 110 Francis St, Boston, MA 02215 USA. EM vnovak@bidmc.harvard.edu RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 FU NCRR NIH HHS [M01 RR001032, M01 RR001032-316097, M01 RR001032-316142, M01-RR01032]; NIA NIH HHS [P60 AG008812, 2P60 AG08812, AG004390, P01 AG004390, P01 AG004390-23, P60 AG008812-15]; NINDS NIH HHS [R01 NS045745, R01 NS045745-04] NR 32 TC 66 Z9 66 U1 0 U2 4 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 JUL PY 2006 VL 29 IS 7 BP 1529 EP 1534 DI 10.2337/dc06-0261 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061EM UT WOS:000238854000011 PM 16801574 ER PT J AU Liu, SM Choi, HK Ford, E Song, YQ Klevak, A Buring, JE Manson, JE AF Liu, Simin Choi, Hyon K. Ford, Earl Song, Yiqing Klevak, Anna Buring, Julie E. Manson, JoAnn E. TI A prospective study of dairy intake and the risk of type 2 diabetes in women SO DIABETES CARE LA English DT Article ID POSTMENOPAUSAL WOMEN; MILK CONSUMPTION; HEART-DISEASE; VITAMIN-D; CALCIUM; INTERVENTION; MORTALITY AB OBJECTIVE - Although studies have indicated that increased dairy intake may reduce risk of overweight and insulin resistance syndrome, data directly relating dairy intake to type 2 diabetes remain sparse. RESEARCH DESIGN AND METHODS - We prospectively examined the associations between intake of dairy foods and calcium and incident type 2 diabetes in 37,183 women without a history of diabetes, cardiovascular disease, and/or cancer at baseline. RESULTS - During an average of 10 years of follow-up, we documented 1,603 incident cases. After adjusting for potential confounders including BMI, smoking status, physical activity, family history of diabetes, alcohol consumption, history of hypertension, use of hormones, and high cholesterol, the relative risk for type 2 diabetes among women in the highest quintile of dairy intake was 0.79 (95% CI 0.67-0.94; P for trend = 0.007) compared with those in the lowest quintile. Each serving-per-clay increase in dairy intake was associated with a 4% lower risk (0.96[10.93-1-01]). The inverse association with type 2 diabetes appeared to be mainly attributed to low-fat dairy intake; the Multivariate relative risks comparing the highest to the lowest quintiles was 0.79 (0.67-0.93; P for trend = 0.002) for low-fat dairy. The inverse relation between dairy intake and incident type 2 diabetes remained unchanged after further adjustment for dietary calcium, vitamin D, glycemic load, fat, fiber, and magnesium intake. These associations also did not vary significantly according to BMI. CONCLUSIONS - A dietary pattern that incorporates higher low-fat dairy products may lower the risk of type 2 diabetes in middle-aged or older women. C1 Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA 90095 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Div Adult & Community Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. RP Liu, SM (reprint author), Univ Calif Los Angeles, Dept Epidemiol, 650 Charles E Young Dr S,71-254 CHS Box 951772, Los Angeles, CA 90095 USA. EM siminliu@ucla.edu RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA-47988]; NHLBI NIH HHS [HL-43851]; NIDDK NIH HHS [DK66401, P30 DK040561] NR 19 TC 132 Z9 136 U1 2 U2 23 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 JUL PY 2006 VL 29 IS 7 BP 1579 EP 1584 DI 10.2337/dc06-0256 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061EM UT WOS:000238854000019 PM 16801582 ER PT J AU Smaldone, A Ganda, OP McMurrich, S Hannagan, K Lin, S Caballero, AE Weinger, K AF Smaldone, Arlene Ganda, Om P. McMurrich, Sheila Hannagan, Keri Lin, Susan Caballero, A. Enrique Weinger, Katie TI Should group education classes be separated by type of diabetes? SO DIABETES CARE LA English DT Article ID ENERGY-EXPENDITURE; SELF-MANAGEMENT; INTERVENTIONS; ADULTS; METAANALYSIS; INVENTORY C1 Joslin Diabet Ctr, Sect Behav & Mental Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02115 USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Sect Behav & Mental Hlth, 1 Joslin Pl, Boston, MA 02115 USA. EM katie.weinger@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK36836, P30 DK036836, R01 DK060115, R01 DK60115, DK07260, T32 DK007260]; PHS HHS [M01 01032] NR 29 TC 3 Z9 3 U1 3 U2 3 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 JUL PY 2006 VL 29 IS 7 BP 1656 EP 1658 DI 10.2337/dc06-0356 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061EM UT WOS:000238854000032 PM 16801595 ER EF